2011 PRER Elsevier - Podoleanu - Retina OCT

ARTICLE IN PRESS
Progress in Retinal and Eye Research 27 (2008) 464 499
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Progress in Retinal and Eye Research

journal homepage: www.elsevier.com/locate/prer
Combinations of techniques in imaging the retina with high resolution

Adrian Gh. Podoleanu a,, Richard B. Rosen b
a b
Applied Optics Group, University of Kent, Canterbury, UK New York Eye and Ear Inrmary, NY, USA
a b s t r a c t
Developments in optical coherence tomography (OCT) have expanded its clinical applications for high-resolution imaging of the retina, as a standalone diagnostic and in combination with other optical imaging modalities. This review presents currently explored combinations of OCT technology with a variety of complementary imaging modalities along with augmentational technologies such as adaptive optics (AO) and tracking. Some emphasis is on the combination of OCT technology with scanning laser ophthalmoscopy (SLO) as well as on using OCT to produce an SLO-like image. Different OCT modalities such as time domain and spectral domain are discussed in terms of their performance and suitability for imaging the retina. Each modality admits several implementations, such as ying spot or using an area or line illumination. Flying spot has taken two principle forms, en-face and longitudinal OCT. The review presents the advantages and disadvantages of different possible combinations of OCT and SLO with AO, evaluating criteria in choosing the best OCT method to t a specic combination of techniques. Some of these combinations of techniques evolved from bench systems into the clinic, their merit can be judged on images showing different pathologies of the retina. Other potential combinations of techniques are still in their infancy, in which case the discussion will be limited to their technical principles. The potential of any combined implementation to provide clinical relevant data is described by three parameters, which take into account the number of voxels acquired in unit time, the minimum time required to produce or infer an en-face OCT image (or an SLO-like image) and the number of different types of information provided. The current clinically used technologies as well as those under research are comparatively evaluated based on these three parameters. As the technology has matured over the years, their evolution is discussed as well with their potential for further improvements. & 2008 Elsevier Ltd. All rights reserved.
Contents 1. 2. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . High-resolution imaging technologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Optical coherence tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Scanning laser ophthalmoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Adaptive optics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Tracking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Different scanning procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. The one letter terminology of scanning, A, B, C, T . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.1. Longitudinal OCT or A-scan-based B-scan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.2. T-scan-based B-scan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.3. C-scan images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Different OCT imaging methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Time domain optical coherence tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Spectral domain optical coherence tomography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465 466 466 466 468 468 468 468 469 469 469 469 469 469
3.
4.
Abbreviations: 3D, three-dimensional; AMD, age-related macular degeneration; AO, adaptive optics; APD, avalanche photodiode; cSLO, confocal scanning laser ophthalmoscopy; dB, decibel; D-OCA, Doppler-optical coherence angiography; ERG, electroretinography; FA, uorescein angiography; FD, Fourier domain; FF, full eld; FFT, fast Fourier transformation; I, imaging content units, or number of channels simultaneously working in a combined conguration; ICG, indocyanine-green; IS, inner segments; LF, line eld; L-SLO, line-scanning laser ophthalmoscopy; mfERG, multifocal electroretinography; Mv/s, megavoxels per second; NA, numerical aperture; n.a., non-applicable; OCA, optical coherence angiography; OCT/SLO, combined OCT and scanning laser ophthalmoscopy; OCT, optical coherence tomography; ODT, optical Doppler tomography; OPD, optical path difference; OS, outer segment; PED, pigment epithelium detachment; RNFL, retinal nerve ber layer; RPE, retinal pigment epithelium; S-OCA, scattering-optical coherence angiography; SD, spectral domain; SLD, superluminescent diode; SLO, scanning laser ophthalmoscopy; SS, swept source; TD, time domain; mm, micron; ms, millisecond; X, Y, Z, rectangular axes, with X- and Y-oriented lateral to the retina and Z along the depth. Corresponding author. Tel.: +44 1227823272; fax: +44 1227827558. E-mail addresses: ap11@kent.ac.uk (A.Gh. Podoleanu), r.b.rosen@nyeei.edu (R.B. Rosen). 1350-9462/$ - see front matter & 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.preteyeres.2008.03.002
ARTICLE IN PRESS
A.Gh. Podoleanu, R.B. Rosen / Progress in Retinal and Eye Research 27 (2008) 464499 465
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4.2.1. Fourier domain optical coherence tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470 4.2.2. Swept source optical coherence tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470 4.3. Full eld or en-face non-scanning systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470 4.4. Line-eld-SD-OCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471 4.5. Multiplexing in OCT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471 4.5.1. Multiplexing in A-scan-based OCT imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471 4.5.2. Multiplexing in T-scan-based OCT imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471 4.6. Comparative assessment of the OCT methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 Depth of focus range and dynamic focus in OCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473 Combining OCT with SLO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474 6.1. Simultaneous OCT/SLO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475 6.1.1. Recognizable patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477 6.2. No splitter OCT/SLO conguration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477 6.3. Sequential generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477 6.3.1. Sequential OCT C-scan/SLO C-scan, sequential OCT B-scan/SLO B-scan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477 6.3.2. OCT/line-SLO (sequential B-scan OCT with C-scan SLO). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478 6.4. Quasi-simultaneous operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 6.5. Generation of an SLO-like image using OCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480 6.5.1. Real-time generation by using a low coherent source with sufciently long coherence length. . . . . . . . . . . . . . . . . . . . . . . . 480 6.5.2. Generation of an SLO-like image from OCT stacks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483 Combination of high-resolution modalities with uorescence imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 7.1. SLO/uorescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 7.2. OCT/uorescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 7.3. OCT/SLO/uorescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 7.4. No-dye uorescence-based OCT imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486 Combinations of high-resolution imaging procedures with AO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487 8.1. SLO+AO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487 8.1.1. SLO/uorescence+AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488 8.2. OCT+AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488 8.2.1. Trade-off between depth resolution in OCT and level of correction using AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488 8.2.2. Incompatibility between A-scan-based OCT and AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 8.2.3. Small size imaging using TD-en-face OCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 8.2.4. Full eld TD-OCT+AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 8.2.5. Longitudinal TD-OCT+AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 8.2.6. FD-OCT+AO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 8.2.7. FD-OCT+AO equipped with two mirrors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 8.3. OCT+SLO+AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 8.3.1. Simultaneous OCT/SLO+AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 8.3.2. Sequential OCT/SLO+AO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 Combination of high-resolution imaging technologies with tracking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492 9.1. SLO+AO+tracking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492 9.2. TD-OCT+lateral tracking. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 9.3. TD-OCT+AO+axial tracking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 Combination of high-resolution imaging technologies with other techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 10.1. Combinations with physiology methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 10.1.1. Multifocal ERG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 10.1.2. Combinations with optophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 10.2. Combinations with polarization information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494 10.3. Combinations with ow information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494 10.4. Combinations with spectroscopy imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495 10.5. Polarization/ow/optophysiology/spectroscopy imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495 Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495 11.1. Potential of existing technologies and trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496 11.2. Synergies provided by the combination of techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497
1. Introduction Today, ocular imaging technology has reached high heights of sophistication, building on the tremendous progress in the last 5 years. However, none of the current imaging methods available fulll all the ideal requirements of the ophthalmologist faced with the need for rapid and accurate diagnosis. This has led to exploration of combinations of imaging and assistive techniques by groups attempting to solve these deciencies. The goals driving the combination of different imaging technologies are diverse, including the need for precise targeting and real-time focusing of the en-face optical coherence tomo-
graphy (OCT) (which lead to the addition of a scanning laser ophthalmoscopy (SLO) channel to the OCT channel), the need for correlation of retinal blood ow with changes in morphology (such as in the combination of OCT with uorescence imaging) or the need for enhancing the imaging performance (such as the addition of adaptive optics (AO) and tracking to SLO or OCT or combined OCT/SLO). Expansion of a familiar perspective found in one type of instrument may stimulate interest in combining it with an additional modality, which shares the same viewpoint. For example, en-face imaging (C-scan) has the advantage that ophthalmologists are more familiar with the interpretation of
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466 A.Gh. Podoleanu, R.B. Rosen / Progress in Retinal and Eye Research 27 (2008) 464499
transversal images since they are of similar orientation as those found in ophthalmoscopes, fundus cameras and SLOs. This was an important factor that stimulated research into combining the OCT with SLO technology. This review will focus primarily on combinations of techniques where the core technology is OCT. Initially, OCT technology advanced towards enhancing the acquisition rate along a line in depth in the image. Nowadays, OCT imaging is found into an evergrowing collection of combinations, which pair OCT with techniques such as SLO, ow imaging, polarization, multifocal electroretinography (mfERG), optophysiology, oximetry, microperimetry, etc. A major goal of current research is scanning a target volume of the retina as fast as possible. Signicant progress has been achieved in terms of line-scanning rate, which increased from tens of Hz in the rst OCT implementation (Huang et al., 1991) to tens of kHz (Nassif et al., 2004) to using the channelled spectrum or the Fourier domain OCT (FDOCT), and to hundreds of kHz (Huber et al., 2007) using the swept source OCT (SS-OCT) method (see Table 1). However, a fast line-scanning rate may not be sufcient to guarantee superiority in respect of all performances required by an accurate diagnosis. For instance, imaging methods that are recognized as very fast in the modern OCT imaging today, such as spectral domain OCT (SD-OCT), operate under xed focus, limiting the accuracy of three-dimensional (3D) acquisition. If the same sensitivity is required within the whole 3D volume, then repetition of acquisitions under several different positions of the focus could lead to longer acquisition times for high-density, high-resolution volumes than the time required by slower line-scanning methods, which allow focus change. Therefore, specic imaging requirements may take precedence over the raw line-scanning rate in order to respond to the need of good sensitivity and sufcient sampling data. In the discussion, which follows, different imaging modalities and specic implementations are compared in their performance taking into consideration three parameters: 1. Mv/s: The number of pixels along three rectangular directions (two lateral and one in depth) acquired in the unit of time. Sometimes, in order to shorten the overall scanning time required to capture a given retina volume, a coarse sampling size is chosen for one of the axes, leading to enlargement of the pixel size along that particular direction, trade-off best described by the parameter Mv/s. 2. Tenface: The time to produce a two-dimensional (2D) OCT image with the SLO orientation. 3. Imaging content units (I): The number of different types of information provided in a system by a specic conguration. As combination of techniques compound different types of information (OCT, SLO, uorescence), the performance Mv/s is multiplied by I to obtain an overall performance of a given combination of techniques, as IMv. For instance for a combined system incorporating OCT, SLO and uorescence channels which can deliver images simultaneously, I 3. The combination of techniques is evolving in two principal directions: combination of channels providing multiple information and combination of imaging techniques with assisting technologies, such as AO and tracking. Both lines of development will be presented here. The quest for faster and more complete acquisition of information from the eye demands evaluation of several tradeoffs in the performance of the technologies combined. Such different demands and trade-offs will be discussed, presenting the
problems raised by the hardware combination as well as the challenges in developing synergistic interpretations of composite images collected from several imaging channels.
2. High-resolution imaging technologies 2.1. Optical coherence tomography OCT is a non-invasive high-resolution imaging modality, which employs non-ionizing optical radiation. OCT derives from lowcoherence interferometry. This is an absolute measurement technique that was developed for high-resolution ranging and characterization of optoelectronic components (Al-Chalabi et al., 1983, Youngquist et al., 1987). The rst application of the lowcoherence interferometry in the biomedical optics eld was for the measurement of the eye length (Fercher et al., 1988). Adding lateral scanning to a low-coherence interferometer, allows depthresolved acquisition of 3D information from the volume of biologic material (Huang et al, 1991). The concept was initially employed in heterodyne scanning microscopy (Sawatari, 1973). OCT has the potential of achieving high depth resolution, which is determined by the coherence length of the source. This is the length over which a process or a wave maintains strict phase relations; an ideal laser source for instance, emits light with more than a few km coherence length while the coherence length of light emitted by a tungsten lamp could be as short as 1 mm. More intense optical sources, suitable for use in scanning the eye are now available with coherence lengths below 1 mm (Drexler, 2004). Using sources with extremely short coherence length, submicron depth resolution is achievable even when the microscope objective is far away from the investigated target, feature not achievable with confocal microscopy. This is one of the most important advantage of OCT, which explains the high level of interest for OCT in ophthalmology. OCT delivers fast, non-contact images of the cornea, lens and the retina with depth resolutions better than 3 mm (Drexler, 2004).
2.2. Scanning laser ophthalmoscopy Confocal imaging was the rst high-resolution imaging technology applied to the eye (Webb, 1990). The inuence of scattered light from outside the focus point within the target is suppressed by a pinhole in front of the photodetector and conjugate to the focal plane (Elsner et al., 1996). 3D imaging (Masters, 1998) is performed by acquiring en-face images (Cscans) at different positions of the focusing element, each position corresponding to a different depth. Increasing the beam diameter of the beam sent to a lens leads to a better connement of the light in the focus of the lens and therefore to better transversal and depth resolution. The key gure in following these changes is the numerical aperture (NA), a quantity proportional with the beam diameter and inversely proportional with the focal length of the lens used in imaging. The transversal resolution varies inverse proportional to NA while the depth resolution varies inverse proportional to the square of the NA. Therefore, to improve the resolutions, it will be desirable to work with a large eye opening. However, in practice, increasing the eye pupil only leads to cumulative addition of aberrations. Therefore, with or without the pupil dilated, an SLO will provide approximately 15 mm transversal resolution and larger than 300 mm axial resolution (Bartsch and Freeman, 1994; Woon et al., 1992). Similarly, a relatively low NA of the anterior chamber limits the achievable resolution in imaging the eye lens.
Table 1 Evolution of the OCT technology in imaging the retina in terms of number of Megavoxel/s and Tenface Method employed Line rate (kHz) Frame rate (Hz) Pixels in the B-scan (Nx, Nz) Pixels in the C-scan (Nx, Ny) n.a. n.a. n.a. 196 196 512 512 256 128 n.a. n.a. n.a. n.a. n.a. n.a. n.a. n.a. Tenface (s) (time to produce an OCT C-scan image) Megavoxel/s NxNyNz/total time for 3D imaging A.Gh. Podoleanu, R.B. Rosen / Progress in Retinal and Eye Research 27 (2008) 464499
1 2 3 4 5 6 7 8 9 10 11 12 13 14
a
TD-OCT longitudinal OCT, rst report on OCT, in-vitro (Huang et al., 1991) TD-OCT longitudinal OCT, in-vivo (Swanson et al., 1993) TD-OCT longitudinal OCT with fast axial scanning (Rollins et al., 1998)e En-face TD-OCT (Podoleanu et al, 1998b) En-face TD-OCT (van Velthoven et al., 2006) En-face TD-OCT using a resonant galvo-scanner (Hitzenberger et al., 2003) FD-OCT (Wojtkowski et al., 2004) FD-OCT (Nassif et al., 2004) FD-OCT Gotzinger et al., 2005) FD-OCT/Line-eld SLO (Iftimia et al., 2006) Line-eld FD-OCT (Nakamura et al., 2007) SS-OCT at 850 nm (Lim et al., 2006) SS-OCT at 1050 nm (Huber et al., 2007) Fastest SS-OCT (Moon and Kim, 2006)
0.0008 0.042 8 0.6 1 4 16 29 20 Not specied 51.5 (single frame: 823.2) 43.2 236 5000
0.0053a 0.42 16 (32 possible) 1.18 2 (8) 53.3 6.7 (or 31) 29 (real-time display 10) 20 15 201 84 461 105
150 118b 100 285

c
Not contemplated 6095

d
0.000094 0.012 1 0.045 0.52 (1.04 as OCT/SLO) 1.75 21 (or 16.2) 9.3 5.84 (polarization sensitive, at least two channels so I 2) which gives: 11.7) 7.87 in the OCT 15.7 in the SLO 2.8 6 122 345
250 250 196 100 512 250 Not contemplated, but possible 3000 1024 (or 512 1024) 1000 320 1000 292f 1024 512 128g 108h 512 140i 512 512 50 69
16 (8)c 0.85 0.5 0.019 38.2c(or 8.25) 8.83c 12.8d 17

c
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1.27 3j 0.56c 0.0026d
Although potential to 5 Hz was also mentioned. Evaluated using the values quoted in the paper of 2 mm depth range and 17 mm depth resolution in air. Evaluated using the values quoted in the paper of 3 mm depth range and 10.5 mm depth resolution in air. d Not contemplated and evaluated for 256 frames using the frame rate for B-scan imaging. e Although images from the anterior chamber of a murine eye are presented only and not from the retina, the fast scanning delay line method presents sufcient sensitivity to image the retina and was included here for comparison of technologies. f Evaluated from 1.75 mm depth range with 6 mm resolution quoted. g Dividing the line of 2.1 mm with the indicated value of transversal resolution, of 16.4 mm. h Evaluated from 0.8 mm depth range and 7.4 mm resolution quoted. i Evaluated from 1.4 mm depth range and 10 mm resolution in tissue. j Evaluated for 256 B-scan frames.
b c
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2.3. Adaptive optics AO uses a wavefront sensor, which instructs a corrector, usually a deformable mirror, to alter the wavefront in order to compensate for the aberrations in the eye and in the instrument (Liang et al., 1997; Dreher et al., 1989; Roorda et al., 2002). However, if aberrations are compensated using AO, the transversal resolution of a confocal-SLO (cSLO) through a 6 mm pupil could be improved to less then 3 mm (Zhang and Roorda, 2006) and the axial resolution could be reduced to 40 mm (Venkateswaran et al., 2004). For an 8 mm pupil size, resolution is even more improved (Miller et al., 2003). These levels of resolution pose compatibility considerations when added to other imaging modalities, such as OCT. After AO correction is applied, a xed focus scanning approach may adversely affect the signal strength of points not far from the focus, due to the shrinkage of the confocal prole produced by the correction of aberrations.
T-scan
Y -Z X B-scan
A-scan C-scan
Fig. 1. Relative orientation of the axial scan (A-scan), transverse scan (T-scan), longitudinal slice (B-scan) and en-face or transverse slice (C-scan).
A-scans
FAST SLOW -Z X SLOW FAST -Z
(i) B-SCAN IMAGE GENERATED FROM A-SCANS (CONVENTIONAL) LONGITUDINAL OCT SCANNING) (ii) B-SCAN IMAGE GENERATED FROM T-SCANS (METHOD COMPATIBLE WITH C-SCANNING)
2.4. Tracking Tracking is an assisting technology to high-resolution imaging, which has seen impressive evolution in the last 5 years. Tracking is essential when information to be extracted needs a stationary target. This is often the case in high-resolution or small size imaging and especially when the signal returned from the retina is weak. With weak signals, information from a single frame may be insufcient, necessitating some form of aligned multiple image collection and averaging. Tracking also enables psychophysical and neurophysiological techniques, which require accurate eye motion compensation, such as micro-perimetry and laser surgery. Tracking is a complex technology which raises several issues including: (i) selection of the reference region used for tracking, either retina or cornea or both; (ii) wavelength of operation; (iii) integration of the tracking system into the imaging system, requiring modication of the interface optics to handle both tracking and imaging beams; and (iv) adjustment of power safety levels to compensate for at least two beams launched into the eye.
T-scans
FAST -Z SLOW (iii) C-SCAN IMAGES AND 3D SCANNING BASED ON C-SCANS (CONVENTIONAL cSLO OPERATION
X Y
SLOWEST
SLOWEST SLOW FAST X

Z
(iv) 3D SCANNING BASED ON B-SCAN SLICES AT DIFFERENT POSITIONS Y CURRENTLY USED BY SD-OCT SYSTEMS
3. Different scanning procedures To obtain 3D information about the retina, any imaging system is equipped with three scanning means, one to scan the object in depth and two others to scan the object transversally. Depending on the order these scanners are operated and on the scanning direction associated with the line displayed in the raster of the nal image delivered, different possibilities exist. One-dimensional (1D) and 2D scans are known. 1D scans are labeled as: Aand T-scans, while 2D scans are labeled as B- and C-scans and this terminology will be explained below. A- and T-scans are 1D reectivity proles while B and C are 2D reectivity maps or images. In terms of the strength, the brightness in the SLO image is proportional to the reectivity while in the OCT with the square root of the reectivity. While in the SLO, the display is generally linear, in OCT, especially for B-scans, the display often represents the logarithm of the reectivity. OCT systems, using CCD cameras or arrays of sensors or arrays of emitters eliminate the need of scanning the beam. However, the terminology below applies in such cases as well, where the ray scanning has been replaced by different forms of electronic scanning. The scanning terminology is illustrated in Fig. 1 and the utilization of the three scanners described in Fig. 2.
Fig. 2. Different modes of operation of the three scanners in a 3D imaging system. Lateral scanning along the X- and Y-axes are implemented using an XY or 2D transverse scanner in both cSLO and OCT systems. The scanning in depth, along the axis Z differs, implemented using focus change in cSLO and OPD change in OCT. (i) B-scan image generated from A-scans (conventional longitudinal OCT scanning). (ii) B-scan image generated from T-scans (method compatible with C-scanning). (iii) C-scan images and 3D scanning based on C-scans (conventional cSLO operation. (iv) 3D scanning based on B-scan slices at different positions y currently used by SD-OCT systems.
3.1. The one letter terminology of scanning, A, B, C, T A-scan: represents a reectivity prole in depth. This scanning technology is used clinically for determining the eye length. In principle, an A-scan can be provided by cSLO (Bartsch and Freeman, 1994) as well. The depth scanning requires the axial movement of a lens to alter the focus, as the lens is heavy, the scanning cannot be fast. Electrically adjustable lenses may provide a solution for fast axial scanning in cSLO, however, there is no motivation for development in that direction in view of the much better resolution obtained using OCT. T-scans: represent the reectivity (SLO) or square root of reectivity (OCT) obtained by scanning the beam transversally across the target. B-scan: represents a cross-section image, a (lateral depth) map. This could be obtained by grouping T-scans together from different depth values or A-scans together for different lateral
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positions, both in use in the OCT practice. Historically, the rst OCT image was a B-scan image of the retina (Huang et al., 1991) made from A-scans, using ying spot longitudinal OCT technology (see below). Although possible in the cSLO, B-scans are not used in the imaging of patients. cSLO can provide only T-scan-based cSLO B-scan images. (An A-scan-based B-scan would require fast focus change; see the comment above in connection to the A-scans in cSLO). However, such a B-scan image is inferred in the practice of glaucoma imaging in a post-acquisition process after collection of C-scan images (Mikelberg et al., 1995). B-scan images, analogous to ultrasound B-scan are generated by collecting many A-scans (Fig. 1) for different and adjacent transverse positions, as shown in Fig. 2(i). The lines in the raster generated correspond to A-scans, i.e. the lines are oriented along the depth coordinate. The transverse scanner (operating along X or Y, or along the polar angle y in polar coordinates in Fig. 1 right, with X shown in Fig. 2(i)) advances at a slower pace to build a Bscan image. The majority of OCT reports in literature refer to this mode of operation. 3.1.1. Longitudinal OCT or A-scan-based B-scan Development of the longitudinal OCT based on A-scans was facilitated by a technical advantage: in time domain OCT (TDOCT), when moving the mirror in the reference path of the interferometer, not only is the depth scanned, but a carrier is also generated (Huang et al., 1991; Swanson et al., 1993). The reectivity information is superposed on a carrier signal, having a frequency equal to the Doppler shift produced by the longitudinal scanner itself (moving along the axis of the system, Z, to explore the retina in depth). In longitudinal OCT, the axial scanner is the fastest and its movement is synchronous with displaying the pixels along the line in the raster, while the lateral scanning determines the frame rate. Longitudinal OCT is performed as explained here in TD and is also provided by SD-OCT methods (see Section 4.2.) 3.1.2. T-scan-based B-scan In this case, the transverse scanners (or scanner) determine(s) the fast lines in the image (Podoleanu et al., 1996, 1998a, b). These image lines represent T-scans (Fig. 1). A T-scan can be produced by controlling either the transverse scanner to scan along the X-coordinate, or the Y-scanner to scan along the Y-coordinate with the other two scanners xed, or controlling both transverse scanners, along the polar angle y, with the axial scanner xed. The example in Fig. 2(ii) illustrates the generation of a T-scan-based B-scan, where the X-scanner produces the T-scans and the axial scanner advances slower in depth, along the Z-coordinate. This procedure has a net advantage in comparison with the A-scanbased B-scan procedure as it allows production of OCT transverse (or 2D en-face) images for a xed reference path, images called C-scans. In this way, the system can be easily switched from B to C-scan, procedure incompatible with A-scan-based OCT imaging mentioned above. 3.1.3. C-scan images A C-scan represents a raster image, with the same orientation as a TV image or image provided by microscopy, a (lateral lateral) scanned map. Historically, the C-scan was the native orientation for fundus cameras, SLOs and cSLOs. C-scans are provided by the ying spot en-face OCT and the full-eld (FF) OCT. They can also be inferred post-acquisition in longitudinal OCT, either TD or SD. C-scans are made from many T-scans along either of X, Y, r or y coordinates, repeated for different values of the other transverse coordinate, Y, X, y or r, respectively in the transverse
plane (with the most used case, oriented along the horizontal axis, X). The repetition of T-scans along the other transverse coordinate is performed at a slower rate than that of the T-scans (Fig. 2(iii)), which determines the frame rate. In this way, a complete raster is generated. For 3D imaging, different transversal slices can be collected at different depths Z, either by advancing the optical path difference in the OCT in steps after each complete transverse (XY) or (r,y) scan, or continuously at a much slower speed than the frame rate. The depth scanning is the slowest in this case. In cSLO, the focus is changed to select a C-can from a different depth position and this is the typical procedure for 3D cSLO imaging (Masters, 1998). It is more difcult to generate en-face OCT images than longitudinal OCT images as the reference mirror is xed and no carrier is produced. Therefore, in order to generate T-scans and T-scan-based OCT images, a phase modulator is needed in order to create a carrier for the image bandwidth (Hitzenberger et al., 2003). This complicates the design and introduces dispersion. Research has shown that the X or Y-scanning device itself introduces a path modulation (Podoleanu et al., 1996, 1998a, b), which plays a similar role to the path modulation created by the longitudinal scanner employed to produce A-scans or A-scanbased B-scans.
4. Different OCT imaging methods There are two main OCT methods, TD-OCT and SD-OCT. SDOCT can be implemented in two formats, FD-OCT and SS-OCT. Their utility for retinal imaging has been presented in several recent review articles in this journal (Costa et al., 2006; Drexler and Fujimoto, 2008; van Velthoven et al., 2007). We will shortly review them, to compare their performance and discuss how they can be best combined with other retinal imaging modalities. Each method has its own merits and decits.
4.1. Time domain optical coherence tomography An A-scan is produced by varying the optical path difference (OPD) in the interferometer to output a square root of reectivity prole in depth. En-face ying spot OCT belongs to the same category. A T-scan is produced by transversally scanning the beam over the target maintaining the reference mirror xed to output a square root of reectivity prole versus angle or lateral position. In both cases, the envelope of the interferometric temporal signal is processed in time.
4.2. Spectral domain optical coherence tomography In the last 5 years, considerable research has been devoted by different groups developing OCT for tissue imaging into the spectral OCT method. SD-OCT is attractive because it eliminates the need for depth scanning in TD-OCT, performed usually by mechanical means. Recent studies (Choma et al., 2003) have shown that SD-OCT can provide a sensitivity, which is more than 10 times higher than that of TD-OCT. FD-OCT and SS-OCT output A-scans, therefore they do not allow real-time C-scan imaging. En-face (C-scan) sections can only be obtained in FD-OCT and SS-OCT by sectioning the 3D volume generated from a series of B-scan images taken at different transverse coordinates, i.e. as a post-acquisition process only. Therefore, essential in comparing the different OCT technologies is the time required to complete a volume acquisition of the retina, which is then sectioned to create C-scan slices
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4.2.1. Fourier domain optical coherence tomography This refers to Fourier transformation of the optical spectrum of a low-coherence interferometer (Hausler and Lindner, 1998). This method is an extension of the work on white light interferometry with initial applications in absolute ranging and sensing (Smith and Dobson, 1981). The operation of FD-OCT is based on the demodulation of the optical spectrum output of an interferometer. The spectrum exhibits peaks and troughs (channeled spectrum) and the period of such a modulation is proportional to the OPD in the interferometer (Jenkins and White 1957). If multi-layered objects are imaged, such as retina, each layer imprints its own modulation periodicity, depending on its depth. A linear CCD camera can be used to transform the optical spectrum into an electrical signal, which exhibits ripple of different frequencies. A fast Fourier transform (FFT) of the spectrum of the CCD signal translates the periodicity of the channeled spectrum into peaks of different frequency, related to the path imbalance (Costa et al., 2006). Such a prole is essentially the A-scan prole of the square root of reectivity in depth. Due to its sensitivity advantage, the FD-OCT became the method of choice in current OCT investigation of the retina (at least in the past 3 years) with video-rate images from the retina demonstrated (Nassif et al., 2004; Cense et al., 2004; Wojtkowski et al., 2004; Gotzinger et al., 2005; Jiao et al., 2005, 2006). The majority of FD-OCT reports employ linear cameras at 29 kHz (and faster rates are already available), which represents a line scan rate at least twice faster than en-face imaging using a resonant scanner at 16 kHz and more than 30 times faster than line scan rates in en-face OCT using galvanometer scanners. This also reects in large values of the voxel number Mv/s $10 to a few tens (Wojtkowski et al., 2004). Using line eld (LF) FD-OCT, where a line is projected to the retina, eliminating the mechanical transverse scanner, frame rates as high as hundred of Hz have been achieved (Nakamura et al., 2007). However, even with such fast line scan rates, because C-scans are perpendicular to the main scanning direction, which is axial, the time to provide a C-scan, Tenface, is several seconds (Table 1), much larger than the time achievable with en-face OCT (tens of ms to sub-seconds, Table 1). 4.2.2. Swept source optical coherence tomography Recent progress in the fast tuneability of laser sources has revived the interest in SS-OCT. The achievable signal-to-noise (S/N) ratio is similar to that of FD-OCT, i.e. at least 10 times better than TD-OCT (Choma et al., 2003). The time required to tune the wavelength determines the time to produce an A-scan. Tuning speeds in excess of 10 MHz makes the SS-OCT the fastest scanning OCT method (Moon and Kim, 2006) to date. Lower rates, of a few hundred kHz have been reported in imaging the retina in-vivo. These values are close to one order of magnitude higher than those achievable using a CCD camera implementing FD-OCT. This method leads to much larger values of Mv/s$100 ((Huber et al., 2007) achieved a Mv/s 122 for 400 frames of 512 512 pixels cross sections collected in 0.87 s) and to a reduced value for the Tenface, of subsecond to second. This value is comparable to that reported in typical en-face OCT, but still larger than the ultrafast Tenface$20 ms achievable with resonant scanners (Hitzenberger et al., 2003). 4.3. Full eld or en-face non-scanning systems Full-eld or coherence radar (Dresel et al., 1992) operates according to the scanning operation described in Fig. 2(iii). The XY scanning is provided in the process of reading a 2D chargecoupled device (CCD) photodetector array. The eye is ood illuminated, i.e. all pixels in transversal section are simultaneously lit, in contrast to the ying spot method where each
transverse pixel in transversal section is independently lit at a certain time only. The information acquired along a line of pixels is equivalent to a T-scan in Fig. 1. Telecentric optics are used to transfer the object beam from the target to the camera. Practically, everything happens as for each pixel in the transversal section, an object beam ray can be identied in the object beam, which interferes with one ray within the cluster of reference rays. C-scans and B-scans can be produced with no need for lateral scanning. The line rate is that of reading 2D CCD cameras, which at video rate means more than 10 kHz. The frame rate is in the range of tens to hundreds of Hz and the depth scanning is the slowest, the OPD change rate being slower than the CCD-frame rate. One of the main advantages of the method is that it can use incoherent spatial optical sources, such as tungsten lamps. These represent low-cost versions of low coherent sources and easily exhibit bandwidths larger than 300 nm. Using such large band spatial incoherent sources, and a Linnik interference microscope (Dubois et al, 2002), images with submicron lateral and depth resolutions have been reported (Grieve et al., 2004) from ocular tissue in-vitro. Images from bovine retina in-vitro have also been obtained using a superluminescent diode (SLD) (Qu et al., 2004). The same system with AO enhancement (see Section 8.2.4. below) was used to produce C- and B-scans of a living eye (Miller et al., 2003). Tremendous progress in sensitivity allowed the imaging of the anterior chamber of rat eyes (Grieve et al., 2005) with a very high value of Mv/s 33328 (depending on the frame averaging mode) and a Tenface 4 ms. As a disadvantage of the FF-OCT, the amplitude of the interference signal is recovered using phase-stepping algorithms. Phase shifts are introduced by exact path difference steps, which in total add up to a wavelength, or by a continuous change of the OPD and comparing the sequences obtained. This means that real-time processing is not possible, however, this is not important for fast acquisition systems where this leads to a mere short delay in the display, equal to the number of frames used for phase shifting multiplied by the frame acquisition time. Using a fast acquisition camera (Miller et al., 2003; Grieve et al., 2005), this amounts to some tens of ms. As another disadvantage, the detection of reective interfaces in a multilayer object using the coherence radar method is limited by the dynamic range of the analog to digital (A/D) converter of the combination CCD-frame grabber system. The interference signal sits on a large constant value, which consumes a large part of the dynamic range of the CCD cameras. The limited dynamic range of 16 bit CCD cameras, limits the smallest signal to 1/65,365 of the digital value, which makes the FF-OCT method less sensitive than the ying spot imaging method. In principle, the ying spot can provide signals for variations in the interference of less than 1013 in a 1 Hz electric bandwidth (Takada et al., 1991). A faster processing method uses an array of photodetectors in a smart chip (Ducros et al., 2002). A photodetector is employed for each pixel in the en-face image, followed by a processing electronics channel (demodulation, rectier, amplier, conditioning). One pixel consists of a small silicon photodiode coupled to a complementary metal-oxide semiconductor electronic circuit. A maximum size chip of 58 58 smart pixels was reported, which limits the numbers of pixels in the images to similar values. Because there is no transverse scanning to alter the OPD, a phase modulator is used. The reading is sequential, similar to the reading of a CCD camera in a coherence radar system but the output is a fully demodulated OCT signal. The amplitude of the signal provided by each channel is proportional to the envelope of the OCT interference signal. The smart chip can also operate in the C- and B-scan regimes. The technology still evolves; for the moment there is no report on using the smart sensor on ocular tissue. Medium values of Mv/s 2.5 have been achieved, however, with a record Tenface 1.33 ms.
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4.4. Line-eld-SD-OCT This is a combination of the FF and SD-OCT, where instead of a 2D image, a lD transversal image is collected using principles of SD-OCT. A recent report on combining the line imaging and FDOCT has been developed (Nakamura et al., 2007) for very highspeed 3D retinal imaging. By this technique, the A-line rate signicantly improved to 823,200 A-lines/s for single frame imaging and 51,500 A-lines/ s for continues frame imaging. A high-speed 2D CMOS area camera with effective pixels of 1104 (horizontal) 256 (vertical) was used. The columns of 256 pixels are oriented along the vertical lateral size of the image while the horizontal arrays of pixels are used for spectral analysis of the channeled spectrum, supplying the depth information in the B-scan. With an image size (the length of the vertical line projected on the retina) of 2.1 mm and a pixel size of 16.4 mm, the number of pixels along the vertical line is 128. Due to the decay of sensitivity of the FD-OCT method with depth, a maximum depth range of 2.88 mm was achieved and images with sufcient contrast presented up to 0.8 mm in depth, which gives 108 pixels of 7 mm depth resolution (Table 1). The frame rate at continues frame imaging is 201 fps. This 3D acquisition speed is more than two-fold higher than the acquisition speed of standard ying spot SD-OCT. To enhance the sensitivity, pulse illumination was used for the duration of the frame, of 0.3 ms. The in-vivo 3D retinal imaging with 256 B-scan image frames was successfully performed in 1.27 s, which gives a Mv/s 2.8 for a collection of 128 140 256 pixels. The time to produce a C-scan image, Tenface, is quoted as 1.27 s in Table 1 considering the number of lateral pixels of 128 256 in the images reported. However, if 512 512 C-scan images are required, Tenface scales eight times larger to over 10 s. 4.5. Multiplexing in OCT Multiplexing refers to acquisition of data from several points at the same time. Extending this notion to OCT, would mean acquisition of several OCT images simultaneously. 4.5.1. Multiplexing in A-scan-based OCT imaging One reason for the recent success of SD-OCT method in the eye imaging is the fact that the depth information is somehow multiplexed, i.e. one FFT of the photodetected spectrum contains the OPD of all resolved scattering points along the depth of the Ascan. One spectrum contains all depth information, where each depth is coded in the number of peaks in the channeled spectrum at the interferometer output. This is not the case in TD-OCT, where when scanning the depth, the same Doppler shift is obtained, for any of the scattering points resolved. To a larger extent, multiplexing of images means different procedures in A-scan-based OCT and T-scan-based OCT. 3D complete information could be collected in different ways, either acquiring many B-scan OCT images at different en-face positions, as shown in Fig. 2(iv) or many C-scan OCT images at many depth positions, as illustrated in Fig. 2(iii). Different possibilities exist and the choice will depend on the best way to use the available S/N ratio and the available bandwidth to collect simultaneous images from the retina. Collecting several B-scan OCT images as in Fig. 2(iv) would involve splitting the light in the sensing arm, possible by using mirrors and beam-splitters. The optical elements in the sensing arm have to be arranged in such a way that in each new arm the optical path is the same. Consequently, such a procedure would involve cumbersome optics before the transverse scanner along with matching the optical paths of the
different sensing arms within a few wavelengths. Additionally, the signal in each sensing arm and so in each channel decreases proportionally with the number of channels.
4.5.2. Multiplexing in T-scan-based OCT imaging In the case of T-scan-based imaging, the reference paths can be split instead, thus avoiding any disturbances with the transverse scanner in the object arm. Different optical paths can be employed to obtain C-scan slices at different depths. This is why the en-face OCT imaging is more tolerant to simultaneous collection of slices. Although apparently it should be equivalent to build the 3D prole from either longitudinal slices or en-face slices, the latter procedure is less cumbersome in terms of technical implementation and less lossy in term of the object signal power. For the same voxel volume (resolution) and number of voxels, the time taken and the amount of memory required for storage is the same irrespective of the method, Fig. 2(iii) or (iv). Such a procedure, of dividing the power in the reference path has been explored in two prior reports. Two OCT channels have been demonstrated using a two splitter conguration (Podoleanu et al., 1997). A different conguration employed an integrated MachZehnder modulator, where two delays have been introduced in the reference arm, each with its own RF modulation (Podoleanu et al., 2001). The frequency modulation limit of the rst and the dispersion of the modulator of the second rendered these approaches unsuitable for in-vivo applications. Another possibility is to split both the object and reference arms as shown in Fig. 3 (Podoleanu et al., 2004b). In this way, two independent OCT imaging channels are assembled. The depth scanning proceeds simultaneously in the two OCT channels and from the same range, however, a differential optical path difference can be introduced between the two channels. In this way, two simultaneous images are generated where the depth differs in each transversal pixel by the differential optical path difference. A dual OCT system, OCT/OCT, working at 850 nm was devised and its capability demonstrated by simultaneously acquiring images from the optic nerve and fovea of a volunteer. The conguration ensures a strict pixel-to-pixel correspondence between the two images irrespective of the axial eye movements, while the depth difference between the corresponding pixels is exactly the set differential optical path difference. The images are collected by fast en-face scanning (T-scan), which allows both B- and C-scan acquisitions. The reference light is passed via mirrors M1 and M2 and the depth is selected in both channels at the same time. A differential path difference between the two interferometers is created by moving the mirrors M1 and M2. In this way, any differential delay, d, of 1 to 1500 mm could be introduced.
Control of depth 1
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Fig. 3. Schematic diagram of the OCT/OCT system to provide C-scan images at different depths. The output beam from the low-coherence source is sent to two interferometers, 1 and 2, with independent adjustment of the imaging depth, using mirrors M1 and M2, which are simultaneously and synchronously controlled by a personal computer, PC.
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Fig. 4. Images from the optic nerve. Separation between pairs: D 100 mm. Separation between images in the pair: d 100 mm. Lateral size: 2.5 mm 2.5 mm. Pairs collected at 2 Hz (Podoleanu et al., 2004b).
Fig. 4 presents images from the optic nerve of a volunteer. Pairs of images have been collected at D 100 mm OPD steps, obtained by moving the two mirrors M1 and M2 simultaneously, while maintaining their differential separation d. The separation between the pairs may be different from D in reality due to axial eye movement. However, the images in each pair are from depths separated by d 100 mm exactly (the bottom image is deeper by 100 mm), because d is independent to the eye movement. Within each pair, the differential depth difference is certain because the two images are collected simultaneously, while the depth difference between the pairs is only approximate due to eye movements. Therefore, the images should be interpreted strictly within the pair, on each vertical in Fig. 4, as associated pairs of pixels displaced in depth by 100 mm. The problem for the current technology is how to produce at the same time 10 or 100 of such images from different depths. If such a technological difculty can be overcome, en-face OCT could reach Mv/s values similar to those obtained with the SD-OCT method. So far, only two channels could be successfully demonstrated.
4.6. Comparative assessment of the OCT methods Each method has several advantages and disadvantages. Advantages of SD-OCT: The main performance that dictates the supremacy of SD-OCT in comparison with the TD-OCT is its superior sensitivity or enhanced S/N ratio. This reects in better penetration and/or faster acquisition speed. Theoretical models estimate that SD-OCT is better than TD-OCT by a factor of 10 at least which will be considered for our comparative analysis in what follows. Disadvantages of SD-OCT: Although the SD-OCT method is currently favored for its speed, it has inherent limitations. In both formats (FD-OCT and SS-OCT), SD-OCT has three main disadvantages: (i) decay of sensitivity with the OPD, which means that the relative intensity of layers along the depth in the retina is not real, in fact their intensity depends on how far the retina is from the value of OPD 0, which varies due to head position relative to the chin rest; (ii) dynamic focus not possible (see below), i.e. ensuring that each depth in the OCT depth is in focus when acquiring signal from that depth; (iii) the optical spectrum of the interferometer output consists of symmetric spectral terms, i.e. the same image results for positive and negative OPDs. For the latter, an initial adjustment of the OPD 0 outside the range of interest is required. This is not possible all the time, especially when imaging moving thick organs or tissue, and this is a problem for
imaging the eye too. Different methods have been devised to attenuate the symmetric terms in order to obtain a correct image such as phase-shifting interferometry, or complex signal processing (Targowski et al, 2004), which are cancellation techniques (and so sensitive to movement) requiring several images or steps (at least 3). An independent method to the target movement was also developed (Podoleanu and Woods, 2007). Unexploited potential in multiplexing of en-face OCT images: This refers to the possibility of improving the overall number of Mv/s. In terms of line rate, TD-OCT could reach fast line-scanning rates using resonant scanners (4, 8 and 16 kHz are available). This is 27 times less than the scanning rate of modern line scan cameras used in FD-OCT and more than an order of magnitude smaller than the rate achievable using SS-OCT. It looks unlikely that the line rate in en-face OCT can be further increased. Polygon mirrors may achieve faster line-scanning rates, but they introduce a nonlinear dependence of the OPD with scanning and the main limitation is the S/N ratio in TD-OCT. However, for any given line rate, en-face OCT has an unexploited potential in the possibility of simultaneous acquisition of several C-scan images, at the expense of power division in the reference path, where power is normally attenuated to reduce the noise, as explained above in the Section 4.5.2. Table 1 presents the performance of the OCT technology in imaging the retina in-vivo as presented in a selection of reports. The rst columns show the acquisition rate and number of pixels in the image, depending whether B-scan or C-scan, while the last two columns on the right are the most signicant. They display two main parameters: the number of Mv/s and the time required to produce a C-scan image, Tenface. The table starts with the 1st report of OCT from retina at MIT (Huang et al., 1991) and ends with the highest OCT speed reported using chirped laser technology (Moon and Kim, 2006) to implement SS-OCT method (although not on the eye). Where the authors have not specied the numbers of pixels, such numbers were inferred from the data available in each report, as detailed in the footnotes. The size of the image varies from report to report, therefore the number of Mv/s represents a suitable performance to compare the different methods. The number of pixels in Table 1 are those specied in the images presented in the reports. A rigorous comparison would require an evaluation of the techniques mentioned based on a similar size image, however, this was not possible. Anyway, the important numbers are the order of magnitude of the Mv/s and Tenface and not their exact value. The time to produce an OCT cross-section (B-scan) image is not used as a comparison criterion because on one hand is the inverse of the frame rate in A-scan-based systems and on the other,
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345:
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Fig. 5. Evolution of OCT technology including TD (time domain), FD (Fourier domain), SS (swept source) and LF (line eld) for imaging the retina in terms of Megavoxel/s. The horizontal line at 345 Megavoxel/s represents the maximum achieved today in terms of Megavoxel/s, using SS-OCT (Moon and Kim, 2006).
Fig. 6. Evolution of Tenface, the time required to produce a C-scan image of the retina, using longitudinal OCT (including TD and SD). The horizontal line at 19 ms represents the time reported for en-face OCT using a resonant scanner (Hitzenberger et al., 2003).
a T-scan-based OCT system can be switched into B-scan regime and produce a B-scan in the same time as for generating a C-scan, Tenface. In other words, producing a B-scan image is not a challenge for T-scan-based OCT systems while producing a C-scan from A-scan-based OCT systems is. The parameter Tenface also represents the time required to produce an SLO-like image in the A-scan-based OCT systems, and this has clinical relevance in the case of SD-OCT, which generates B-scans and not C-scans. The graph in Fig. 5 is assembled based on the exemplary reports in Table 1 only, for simplicity. In reality, a large spread of points could be placed in the graph based on the articles mentioned in the reference list, however, when this is completed, they display the same trend as shown using only the few points representing the publications in Table 1. The graph shows extraordinary progress in terms of the number of Megavoxels imaged in a time unit, due to the progress in SD-OCT and especially in the case of SS-OCT imaging using mode-locked SS technology (Huber et al., 2007). The SS-OCT has further potential for improvement in data acquisition rate since the chirped laser principle allows line rates in excess of tens of MHz. However, the increase in the line rate is currently accompanied by reduction in the signal and increase in noise due to large electronic bandwidth required. For A-scan-based OCT systems, the time to collect the whole volume of voxels determines the time required to produce a C-scan image, Tenface, since such an image is only available once all data have been acquired. Where data were not available, Tenface was inferred considering a number of 256 frames. The graph in Fig. 6 illustrates the progress over the years in reducing Tenface. For A-scan-based TD-OCT systems, Tenface exceeds tens of seconds, too long for imaging a moving eye (although the majority of reports on OCT before 1998 required such large time intervals for acquiring multivoxel data). To the right of the graph, progress in mode-locked SS-OCT lead to a time of less than 1 s, which becomes useful in practice. However, even if the progress was substantial in the last few years, this value is still more than an order of magnitude larger than the time to produce a C-scan image using an en-face OCT system equipped with resonant scanners (Hitzenberger et al., 2003).
In the past few years, progress has been reported not only in the improvement of the two parameters, Mv/s and Tenface, but in the depth resolution too. Excellent accounts on the resolution improvement in OCT are presented elsewhere (Drexler, 2004). This is however implied in the number of pixels in depth in the Table 1.
5. Depth of focus range and dynamic focus in OCT In order to obtain images with high transverse resolution throughout the whole depth of the retina, dynamic focus is essential. Dynamic focus means maintaining the coherence gate and the focus gate in synchrony in OCT. The confocal core of the OCT channel is what determines the depth of focus in the OCT, and this is an important issue in the progress towards high resolution, sometimes ignored. A good S/N ratio requires that the confocal core of the OCT channel focuses at the same depth where the coherence gate of the OCT selects signal from. The procedure is often utilized in the TD-OCT, where the focus and the coherence gate can be synchronously scanned. A TD-OCT A-scan-based system requires that the focus scanning be performed at the line rate. In an A-scan-based TD-OCT system, dynamic focus is in principle possible, but unachievable technically due to the high speed required for focus change (it is difcult to move a lens at kHz rate). A T-scan-based OCT system relaxes this demand, as the focus needs to be changed at the frame rate, of the order of Hz or tens of Hz, which is much smaller. In opposition to the TD-OCT methods, dynamic focus is not applicable to FD-OCT and SS-OCT due to the very principle employed. Therefore, for such systems, the interface optics are devised with a large depth of focus, to accommodate the entire range of the A-scan, usually, 12 mm. Not providing focus change with depth is visible especially in imaging the optic nerve, which extends for more than 2 mm, and where the contrast in the image decreases at the image edges. The constant focus in SD-OCT precludes the possibility of using a high NA objective to enhance the transverse resolution and also limits the efciency of the combined SD-OCT/AO method as detailed below. Dynamic focus applied to a TD transversal (en-face) scanning system for retinal imaging (Pircher et al., 2006b) demonstrated that a transverse resolution of 4.4 mm can be achieved over an optical depth of 1 mm in a model eye.
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6. Combining OCT with SLO OCT has mainly evolved in the direction of producing crosssectional images, most commonly perpendicular to the plane orientation of images delivered by a microscope or by an SLO. Several groups have shown that the ying spot concept, utilized in the SLO hardware can be combined with the OCT technology to produce en-face OCT images from the anterior and posterior pole. The depth resolution in SLO is 30100 mm coarser than that in OCT while the transversal resolution in OCT is affected by random interference effects from different scattering centers (speckle), inexistent in SLO images. Therefore, there is scope in combining SLO with OCT. Once C-scan OCT images have had been demonstrated, sharing the same natural orientation to that of SLO systems, the next step was to combine OCT with SLO. Different avenues have been evaluated, to provide SLO and en-face OCT images simultaneously, quasi-simultaneously or sequentially. The simultaneous OCT/confocal technology has been extensively evaluated on more than 2000 eyes with pathology, using what is now called the OCT/SLO or the OCT/Ophthalmoscope instrument (Rosen et al., 2003). A variant of this instrument, the OCT/SLO/indocyanine-green (ICG), has also been tested proving the potential of multi-modal imaging. This allows collection of simultaneous en-face OCT and ICG uorescence images from the retina. The sequential OCT-confocal imaging procedure is still in laboratory phase. This concept provides better S/N ratio in the OCT channel and better depth resolution in the confocal (SLO) channel than the OCT/SLO system. The performances of the sequential procedure will be discussed in comparison with the simultaneous procedure. Different solutions have been provided to assemble OCT/SLO systems, depending on the scanning type and on the OCT regime of operation. The main motivation for OCT/SLO combination is to provide orientation to the OCT channel. Crucial for the operation is pixel-to-pixel correspondence between the two channels, OCT and SLO, which can only be ensured if both channels share the same transverse scanner to scan the beam across the eye. Different possible congurations are shown in Fig. 7. Any OCT system is constructed around an interferometer illuminated by a lowcoherence source. The interferometer is equipped with some means to adjust the OPD to determine the axial (or depth) scanning. To send the signal towards the eye, the OCT is equipped with an interface optics, which contains lenses or curved mirrors and the XY scanner. Light collected from the eye is received either in a pinhole or via a single-mode ber in order to ensure a high visibility for the interference signal. This acts also as a confocal core, which can be used for implementing an SLO channel, however, this is not possible all the time as explained below, therefore different possibilities exist. Fig. 7(i) illustrates the principle of the OCT/SLO instrument where the confocal core of the OCT is used to produce the SLO signal. No splitting of the light from the eye is performed. Fig. 7(ii) shows a different conguration, where light for the SLO channel is produced using a separate optical source and light received from the eye is diverted towards a separate confocal receiver. This requires a splitter to divert light into the two paths, OCT and SLO. Fig. 7(iii) is a simplication of Fig. 7(ii) where the same optical source is shared by both channels. Again, this requires a splitter to divert light into the two paths, OCT and SLO. Historically, while the simplest conguration looks like that in Fig. 7(i), the rst OCT/SLO (Podoleanu and Jackson, 1998) implemented employed the conguration in Fig. 7(iii). It was 7 years before a sequential version of Fig. 7(i) to be described, and a simultaneous implementation has not yet been reported, the main problem being the associated noise with the high reference power.
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Fig. 7. Generic congurations used in the combination of OCT with SLO.
Fig. 7(ii) is useful in combining OCT with uorescence. In this case, the separate SLO source excites uorescence, which is processed in a separate SLO receiver. Such a conguration would be useful in combining OCT with uorescein angiography (FA), where the OCT operates at 700900 nm and the separate source operates in greenblue to excite uorescein. Such a OCT/ uorescence conguration has been reported in endoscopy (Barton et al., 2004). The three generic congurations presented in Fig. 7 help to reveal the diversity of possible combinations of OCT with SLO in terms of the scanning regimes. SLO provides C-scan images. Therefore the natural combination of the two channels would be that where the two images generated are both C-scans. However, solutions have been provided where the SLO channel maintains its natural C-scan orientation while the OCT channel operates in B-scan regime, in order to implement SD-OCT. In time, the two images can be generated simultaneously or sequentially. Simultaneous generation could be implemented in C-scan orientation by both channels. C-scan SLO and B-scan OCT, however, can only be sequential, if the same source and transverse scanner is to be shared. (The operation in C-scan SLO and B-scan OCT can also be achieved by combining an OCT channel and an SLO channel each equipped with its own XY scanner, via a splitter, however, such a conguration is not practical and will be difcult to ensure pixelto-pixel correspondence when using two different, independently ran XY scanners). The main advantage of the en-face imaging is that it allows integration of SLO with OCT. This has proved useful in allowing ophthalmologists and visions scientists to associate features seen in cSLOs and SLOs with those highly fragmented due to enhanced depth resolution in en-face OCT. Such a method allows a dual presentation of high-resolution images (OCT and SLO) in different regimes of operation, B- or C-scan, providing cross sections in depth or constant depth images, respectively. Other current
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developments include sequential OCT-confocal regime of operation, dual OCT/confocal uorescence imaging and triple OCT/SLO/ confocal uorescence imaging.
6.1. Simultaneous OCT/SLO Simultaneous acquisition of images in two channels, OCT and SLO requires congurations using splitters, according to Fig. 7(iii). In (Podoleanu and Jackson, 1998), a small fraction of the light returned is diverted towards the SLO channel using a separate splitter. There is an optimum splitting ratio which ensures sufcient and similar S/N ratio in both channels (Podoleanu and Jackson, 1999). New imaging technology brings not only new information to the clinician, but with it, the requirement of interpretation. Enface OCT is no exception in this respect. The higher the depth resolution of the OCT system, the more fragmented the en-face OCT image looks like (Podoleanu et al., 1999). The fragmentation is especially visible when the plane of the retina is tilted in relation to the scanning plane. First, the en-face OCT image appears fragmented, and on its own, such an image is difcult to interpret. Second, variations in tissue inclination with respect to the coherence wave surface alters the sampling of structures within the depth in the retina, creating unbalanced distortions among the elements being sampled (Podoleanu et al., 2004a). The bright patches in the OCT image represent the intersection of the surface of OPD 0 with the tissue. Due to the particular way the retina is scanned, with the fan of rays converging on the eye
pupil, the surface of OPD 0 is an arc circle with the center in the eye pupil. Depth exploration requires that the radius of the arc is altered. If the arc has a small radius, it may just only intersect the top of the optic nerve with the rest of the arc in the aqueous. The radius of the arc is changed by changing the length of one of the arms of the interferometer in the OCT channel to explore the retina up to the RPE and choroid. The orientation of the retina tissue at the back of the eye is not planar and this complicates the interpretation of the image even further. Despite scanning images in an en-face plane, the result is that the images may display the structure in depth like in any B-scan OCT image. This is especially visible in the high-resolution en-face OCT as shown in Fig. 8 (Cucu et al., 2006), where the C-scan slice is very thin (3 mm). These two effects, (i) fragmentation and (ii) multiple depths simultaneously displayed in the C-scan images are present in a cSLO with high depth resolution as well, however, at a scale where they are regularly discarded. In a cSLO, the images do not look fragmented and the depth structure is barely visible due to the coarse depth resolution, 0.3 mm, comparable to the retina thickness. Going in and out of focus results in a smooth transition from dark to bright areas in the image. Both problems mentioned above are brought about by the high depth resolution of OCT. Providing an SLO image simultaneously guides the user and addresses the fragmentation problem. In terms of data acquisition, the confocal image adds further versatility. The design ensures a strict pixel-to-pixel correspondence between the two C-scan images, OCT and SLO. This helps in two respects: for small movements, the SLO image can be used to track the eye movements between frames and for subsequent
Fig. 8. Images acquired from the foveal region of the retina in-vivo using en-face technology and 120 nm band SLD source. SLO images on the left and en-face high-resolution OCT (3 mm depth resolution) images on the right for two different depths in the retina. The structure of layers normally encountered in B-scan OCT images is also visible here: ILM, the inner limiting membrane; NFL, nerve ber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ELM, external limiting membrane; IS/OS, junction between the inner and outer photoreceptors; RPE, retinal pigment epithelium; CC, choriocapillaris; C, choroid; V, the vitreous.
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Fig. 9. Illustration of synergy between C-scans and B-scans.
transversal alignment of the OCT image stacks; for large movements and blinks, the SLO image gives a clear indication of the OCT frames that need to be eliminated from the collected stack. As a reference for the aligning procedure, the rst artifact-free confocal image in the set is used. In the B-scan regime, movements of the eye are indicated by lateral shifts of the confocal traces (Podoleanu et al., 2004a). Each horizontal line in the SLO image when the OCT/SLO is switched to B-scan, corresponds to a depth position. The relative lateral eye movements lead to slight deviations of contours in the SLO image, which can be employed to correct the lateral shift of the lines in the B-scan OCT image (also illustrated here in left insets below the B-scan OCT images in Figs. 1014 below).
A bulk interferometer solution for simultaneous acquisition of an OCT and an SLO image was also reported (Pircher et al., 2006a). The bulk conguration allows placing the optical splitter close to the optical source with the advantage of no signal lost towards the OCT channel (however requiring to compensate for loss of power by increasing the optical source power). Using such a system equipped with dynamic focus, the cone mosaic was imaged simultaneously in the SLO and OCT channels without AO elements. Combination of techniques allows correlation of information in orthogonal planes and facilitates more accurate diagnosis. For instance, Fig. 9 top presents a B-scan OCT, which represents a 20 mm thick slice through the central macula. Since the slice is collected as the patient is instructed to xate on a specic target,
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the image captures a macular region where the visual acuity is best and suggests that the macular anatomy of this patient is normal. However, the pair of associated C-scans OCT/SLO from the same patient reveal a slightly eccentric perifoveal RPE cyst. This en-face perspective is able to redirect the investigation. In the subsequent step, the OCT/SLO is switched back to B-scan regime and a B-scan is collected from the horizontal line placed over the desired position indicated by the C-scans in the Fig. 9 middle. The image in Fig. 9 bottom is then obtained displaying the cyst.
6.1.1. Recognizable patterns Images from a diverse selection of patients from a large retinaspecialty practice were studied with the dual-channel OCT/SLO and correlated with clinical records. The standard protocol employed consisted of multi-slice sequences dual-channel sets of C-scan OCT and corresponding confocal ophthalmoscopic images. Selectively targeted sequences of B-scan OCT were also acquired. The OCT/SLO utilizes a single illumination source (according to Fig. 7(iii) that provides point-to-point correspondence between images of the retinal surface and at various depths below extending into the choroid. Advantages of the simultaneous OCT/confocal acquisition have been discussed (Podoleanu et al., 2004a; Van Velthoven et al., 2006) and utility of C-scan OCT was demonstrated on imaging a variety of pathologies including macular hole, diabetic retinopathy, choroidal neovascular membrane and macular pucker. Several remarkable new aspects of clinical anatomy were revealed using this new perspective. The versatility of selective capture of C-scan OCT images and B-scan OCT images at precise points on the confocal image affords the clinician a more complete and interactive tool for 3D imaging of retinal pathology. After examining a diverse array of common clinic pathologies including macular degeneration, central serous retinopathy, macular hole, macular pucker, cystoid macular edema, diabetic maculopathy, hereditary maculopathies and macular trauma, a series of specic and reoccurring patterns for several pathologic entities became evident. Observation of uniquely specic and reoccurring patterns for several pathologic entities have been reported for the rst time (Rosen et al., 2004), visible in the en-face display only. The most notable examples were: the chrysanthemum ower arrangement of cystic degeneration seen in macular holes, the Swiss cheese wheel cluster of cysts seen in cystoid macular edema, the Shining Star conguration of radiating epiretinal membrane folds, seen in macular pucker, the bullseye target pattern of concentric light and dark rings on the macula in central serous retinopathy, and the ring of light appearance of the slice through the bulge of a retinal pigment epithelium detachment (RPED). Other notable patterns, which were recognizable but often variable enough to defy simple categorization include the cluster of grapes footprint of multiple RPE bulges in polypoidal choroidopathy, and the islands in the stream array of edema residues in diabetic macula edema. Fig. 10 presents an example of RPE detachment (RPED). This is typied by hypo-reective circles, which are produced by the presence of the elevated edge of the RPE producing rings of light appearance. This is in contrast to the bullseye target appearance of the macula in central serious elevation, which may appear similar on clinical examination. They cannot be called rings in the SLO images, as the rings are lled in due to the poorer resolution of the SLO channel, which integrates the signal from a wider depth range. Fig. 11 shows the bullseye target pattern of concentric alternating dark and light rings seen in central serous retinopathy. This results from the convex splaying of adjacent hyper and hypo-
reective layers of the sensory retina. There is no border of intense hyper reectivity as seen in a RPE detachment. Fig. 12 displays the pattern, typical of full-thickness macular holes (Bartsch et al., 1989). Coronal sectioning of macular holes produces slices, which appear as a petaloid wreath of perifoveal cysts surrounding a dark circle simulating the oral pattern of chrysanthemum owers. This circle of cysts reveals a more complete picture of the cystic changes most commonly associated with B-scan OCT of macular holes. This pattern disappears at the RPE depth (C-scan OCT image at the bottom). Fig. 13 illustrates the Swiss cheese wheel pattern seen in cystoid macular edema. This foamy appearance corresponds to the petalloid pattern of cysts characteristically described on clinical examination. This pattern is differentiated from that of macular hole by the lack of a central well-dened dark circle. A B-scan OCT image demonstrates diffuse clumping of hypo-reective spaces within the middle retina. Epiretinal membranes often create a pattern, which resembles a shining star with radial lines due to centripetal contraction of the cellular elements, as seen in Fig. 14. In this case, the surface distortion has progressed to such extent as to create the appearance of a macular hole or pseudo-hole. These lines disappear when the membranes are surgically excised. In all images in Figs. 1014, the insets underneath the B-scan image represent the SLO images just before the OCT/SLO was switched from the C-scan to the B-scan regime (right) and after the switch, when the OCT/SLO operates in the B-scan regime (left). This is why the image in the left inset displays vertical stripes only, they provide information on the lateral movement of the eye during the 0.5 s the B-scan was acquired, as explained in the Section 6.1 above. 6.2. No splitter OCT/SLO conguration The main problem for the simultaneous operation using the confocal core, according to the generic conguration in Fig. 7(i) is the high value of intensity due to the reference beam and the noise associated with it. The balanced receiver at the output of a balanced OCT conguration can be conveniently used to generate both the SLO and OCT signals. The addition of the two photodetected signals produces the SLO signal and their difference produces the OCT signal (Podoleanu et al., 2005). In this way, the same photodetectors producing the OCT signal can be used for the SLO channel and the high reference power can be tolerated. Such congurations offer the advantage of simpler optics and better efciency in using the weak signal returned from the eye, eliminating the need for splitting into fractions for individual channels. 6.3. Sequential generation 6.3.1. Sequential OCT C-scan/SLO C-scan, sequential OCT B-scan/SLO B-scan Switching off the reference beam in a conguration as that in Fig. 7(i) removes the high value of photodetected intensity and the noise associated with the high-power reference beam falling on the photodetectors. In this way, the photodetectors can reproduce a noise-free SLO signal. Elimination of the constant terms means that high-gain photodetectors such as avalanche photodiodes (APD)s and photomultipliers can be employed, which however, need to be swapped for low-gain photodetectors such as pin diode when the reference beam is reinstated on the photodetectors in the OCT regime. A technical solution is presented in (Podoleanu et al., 2004c) where APDs are used in both regimes and a selfswitching APD regime is employed based on the voltage drop on
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Fig. 10. RPE detachment: top: B-scan OCT image; middle and bottom: C-scan images, SLO (left) and OCT (right), for two different axial positions.
the resistors in series with the APDs. Such pairs of images are presented in Fig. 15. The advantage of such a conguration is its simplicity and also its efciency in using the whole signal returned from the retina to produce either an OCT or an SLO image, i.e. no splitting of the signal is required. The conguration in Fig. 7(i) can operate either simultaneously or sequentially: (i) in C-scan regime in both channels, OCT and SLO as well as in (ii) B-scan regime in both channels, OCT and SLO.
6.3.2. OCT/line-SLO (sequential B-scan OCT with C-scan SLO) A different sequential method from those presented above is that where in the SLO regime, a C-scan image is produced while in the OCT regime, a B-scan. A conguration using line-SLO (L-SLO) and FD-OCT was reported (Iftimia et al., 2006), which shares the same imaging optics and line scan camera for both OCT and L-SLO imaging. Co-registered high-contrast wide-eld en-face retinal L-SLO and FD-OCT images are obtained
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Fig. 11. Central Serous Retinopathy: top: B-scan OCT image; middle and bottom: C-scan images, SLO (left) and OCT (right), for two different axial positions.
at 15 frames/s, as shown in Fig. 16. The instrument can run in three modes: L-SLO mode only, OCT mode only and frame/ interleaved L-SLO/FD-OCT mode. No moving parts are required to change imaging modes. There is no need to obstruct the reference beam, like in the previously presented solution because the conguration operates according to that in Fig. 7(ii), using different sources for the two channels, which are sequentially switched on and off synchronous with switching the operation regime of the camera.
6.4. Quasi-simultaneous operation The conguration used for sequential operation if equipped with a chopper, which obstructs the reference beam in synchronism with the transverse scanner allows quasisimultaneous OCT/SLO operation (Podoleanu et al., 2005). Half of the line in the nal raster displays the OCT signal and the other half the SLO channel, however time reverted. Simple inversion of the half of the lines in the raster leads to the display of
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Fig. 12. Macular hole: top: B-scan OCT image; middle and bottom: C-scan images, SLO (left) and OCT (right), for two different axial positions.
a pixel-to-pixel correspondent SLO image with the OCT image (Trifanov et al., 2008). 6.5. Generation of an SLO-like image using OCT 6.5.1. Real-time generation by using a low coherent source with sufciently long coherence length OCT can be used to generate an equivalent SLO image by using a low coherent source with a coherence length comparable with
the retina thickness. Long coherence light can be obtained by using a narrow band optical lter in front of a large bandwidth source. For instance, a lter centered at 800 nm with a FWHM of 10 nm provides 28 mm depth resolution. With a bandwidth narrowed to 1 nm, 280 mm depth resolution could be achieved on the expense of the loss of power due to the optical ltration. Alternatively, a laser diode below threshold exhibits similar linewidths and can deliver much higher power and be more efcient. Lasers are ideally suited for such applications with the condition
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Fig. 13. Cystoid macular edema: top: B-scan image; middle and bottom: C-scan images, SLO (left) and OCT (right), for two different axial positions.
that their cavity be longer than the depth range, which in the case of retina imaging should be larger than 2 mm. Optical sources exist whose coherence length can be adjustable, such as the multiple electrode semiconductor laser. By actuating on the different electrodes of such a laser, different
functionality can be achieved, including variation in the coherence length. Two C-scan images are presented in Fig. 17a and b, obtained with a SLD and a three electrode laser, respectively (Podoleanu et al., 1999). The image in Fig. 17b covers only one third of the optic nerve depth range, and with the coherence gate
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Fig. 14. Epiretinal membrane: top: B-scan image; middle and bottom: C-scan images, SLO (left) and OCT (right), for two different axial positions.
adjusted close to the supercial retina depth, lamina cribrosa is not visible. Development of such low noise optical sources with sufcient power in the near future may allow an instant SLO-like image using OCT technology. Such a method has the advantage of generating the SLO-like image in one frame, in comparison with the methods presented below in Section 6.5.2
where several frames are used, with the disadvantage of movement distortions. 6.5.1.1. Sequential high-resolution OCT/ low-resolution OCT. Two optical sources, such as a large band source and a laser, can be employed sequentially within an en-face OCT system to produce
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Fig. 15. Sequential OCT-confocal images from the optice nerve in vivo. Pairs of OCT (top) and SLO (bottom) images.
Fig. 16. Left: B-scan (FD-OCT) image and right: C-scan (L-SLO) image, which can be displayed separately or simultaneously (depending on the imaging mode. The FD-OCT scan can be positioned anywhere in the L-SLO raster (see the vertical line on the L-SLO image on the right). Reproduced in part from Iftimia et al. (2006) with the permission of the publisher (Optical Society of America).
matched high depth resolution C-scan images (mm range) and C-scan images with depth resolution comparable to the retina thickness (mm range).
6.5.1.2. Quasi-simultaneous high-resolution OCT /low-resolution OCT. Two optical sources can be employed, a large band source and a laser, with the difference that they are synchronously modulated with the transverse line-scanning system. Such a method was demonstrated using a superluminiscent diode (as the source with short coherence length) and a three electrode laser (as a source with long coherence length) (Podoleanu et al., 2003). The system displays a raster image, which is made of two images,
the left-hand side for instance is a high depth resolution C-scan OCT image, while the right-hand side image is an equivalent SLO image, which represents an integration of C-scans over the coherence length of the three electrode laser. The same set of images as those in Fig. 17a and b have been obtained in this way, however, at 700 Hz line rate, both in the same raster produced at 2 Hz, with one of them ipped horizontally.
6.5.2. Generation of an SLO-like image from OCT stacks An equivalent SLO image can be generated from several OCT C-scans or from several B-scans. Using any OCT method, a 3D stack is rst obtained. Then, by software means, an SLO image can
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Fig. 17. SLO-like images using ying spot T-scan-based OCT imaging. The high depth resolution OCT image in (a) is for comparison. (a) OCT C-scan image using a superluminescent diode determining 28 mm depth resolution and thickness of the C-scan slice (Podoleanu et al., 1999); (b) OCT C-scan image of the optic nerve using an optical source with long coherence length determining 340 mm depth resolution and thickness of the C-scan slice (Podoleanu et al, 1999); (c) SLO-like projection image obtained by summing C-scan OCT images (10(x) 10(y)) of the nerve head area. Reproduced from Hitzenberger et al. (2003) with the permission of the publisher (Optical Society of America).
be inferred without using a beam-splitter nor a separate confocal receiver. Such congurations t the description in Fig. 7(i). Both OCT and the inferred SLO image are obtained via the same aperture optics. Superposition of C-scans collected in a stack of C-scans leads to a C-scan of thickness similar to that of the stack. Similarly, C-scans inferred from 3D volumes of B-scans acquired using B-scan-based OCT systems can be summed to produce an equivalent SLO image. Either way, such an equivalent SLO image is obtained only after all the images in the stack have been acquired, which requires a time interval Tenface (Table 1). Therefore, such a method can be implemented on a fast OCT system only. 6.5.2.1. Generation of an SLO-like image from stacks of C-scan OCT images. A fast en-face OCT method (T-scan-based OCT method) was reported (Hitzenberger et al., 2003) using a stable high-frequency carrier (40 MHz) generated by use of an acousto-optic modulator and a resonant scanning mirror (4 kHz) for the priority scan (x-direction). In this way, 64 transverse images consisting of 256 128 pixels were acquired in 1.2 s. This means that the SLO image can be generated after 1.2 s only. 64 C-scans were sampled from a volume of 2 mm depth with a distance from slice to slice of 31 mm. Such an image is shown in Fig. 17c, in comparison with images created using similar en-face OCT, in Fig. 17a (short coherence length en-face OCT) and Fig. 17b (long coherence length en-face OCT). This method, in comparison to that of using an OCT with long coherence length (Fig. 17b), has the disadvantage of cumulated distortions due to eye movements. 6.5.2.2. Generation of an SLO-like image from stacks of B-scan OCT images. An SLO-like image can also be obtained from images captured with any A-scan OCT-based method. Because the equivalent SLO image is obtained by the end of acquisition, only after sufcient number of slices have been collected, it makes sense to use the fastest OCT method known today, based on spectral processing. Such a method has been demonstrated using both SD-OCT methods, FD-OCT and SS-OCT. After a 3D data set acquisition, an SLO-like image is generated and then the B-scan OCT images can be revisited through the 3D data set with simultaneous display of the synthesized SLO image. 6.5.2.2.1.Generation of an SLO-like image from stacks of B-scan FD-OCT images. Several groups have reported inference of an SLOlike image from B-scans using FD-OCT systems (Hong et al., 2007; Wojtkowski et al., 2005). A feature-based algorithm (Jiao et al., 2006) was developed, which can register a high-density OCT
image of the fundus image from normal density scans. The algorithm was successfully tested for both normal and diseased eyes. An elliptic high-pass lter of order 1 on the raw measured spectra was applied. The quality of the SLO-like image was improved by tuning the cut off frequency of the high-pass lter. Both large and small blood vessels around the optic disk were imaged with good contrast. The main advantage of the method relies on the speed of spectral OCT, which allows collection of a large data set of pixels. With a high density of 65,536 A-scans, obtained at 29 kHz, 2.25 s are required for the whole volume. The transversal resolution along the synthesis axis of the SLO image is given by the spatial sampling, i.e. by the lateral interval from a B-scan to the next B-scan along a rectangular direction to that contained in the B-scan image. Such SLO-like C-scan images exhibit the normal transversal resolution (1520 mm) along the B-scan lateral coordinate (X) and the coarse sampling interval, along the lateral rectangular direction (Y). Fig. 18a shows such an OCT fundus image for the optic nerve of a normal human of sufcient quality to guide a posteriori the OCT investigation through the stack of B-scan OCT images. The image is from an area of 4 mm 4 mm on the retina of 512 128 pixels. This means that the Y-pixel size is 4 mm/128 31 mm. This size could be reduced by increasing the acquisition time in order to capture more B-scan images but would also result in more cumulated artifacts due to movement. If correction is made for the large transversal pixel size along the Y-axis, to achieve the normal pixel size of 15 mm in an aberrated eye, acquisition time would increase to over 4.5 s. 6.5.2.2.2.Generation of an SLO-like image from stacks of B-scan SS-OCT images. Similar procedure was applied to generate an SLOlike image from a stack of SS-OCT images acquired with systems operating at 850 nm (Lim et al., 2006; Srinivasan et al., 2007) and at 1 mm (Yasuno et al., 2007). In the 3D measurement mode, a preview image of the fundus (fundus preview) was created immediately after acquisition. In Yasuno et al. (2007), the central 256 points were extracted from a single spectral interference signal, and the signal power was obtained by squaring followed by its summation. This operation provided only the power of the interference signal, because the non-interference offset of the spectrum gets rejected by a balance detection scheme and an RF high-pass lter. This operation was applied to all the spectral signals in the OCT volume, yielding the fundus preview image as shown in Fig. 18(b). This fundus preview is an analogoperation to its digital counterpart demonstrated using FD-OCT (Jiao et al. 2005).
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Fig. 18. SLO-like image using A-scan-based OCT imaging. (a) SLO-like image of the optic nerve obtained by summing depth information in FD-OCT images. Reproduced from Jiao et al. (2005) with the permission of the publisher (Optical Society of America). (b) SLO-like images of the optic nerve obtained from SS-OCT images, created by squared spectral integration. Reproduced from Yasuno et al. (2007) with the permission of the publisher (Optical Society of America).
7. Combination of high-resolution modalities with uorescence imaging 7.1. SLO/uorescence The SLO is widely used in uorescein and ICG angiography to examine human retinal diseases. SLOs have been used for ICG or uorescein imaging separately, or simultaneously (Holz et al., 1997), although more complex systems performing angiography on both uorescein and ICG, as well as autouorescence of the fundus (FAF) have also been reported (Jorzik et al, 2005). Separate optical sources were used to excite the uorescein (488 nm) and the ICG (790 nm). As with any combination of techniques straddling over a wide bandwidth, authors report a small focus difference between uorescein and ICG scans because of chromatic aberrations. This problem will become more acute in the combination of OCT with uorescence imaging (next paragraph). By enhancing the SLO sensitivity, new generation of SLO systems require lower levels of dye concentration to achieve sufcient quality in images for the diagnosis (Bindewald et al., 2005). Another interesting combination investigated the 2D measurement of the time-dependent autouorescence and time-correlated single photon counting to evaluate the metabolism state at the eye ground (Schweitzer et al., 2005). This represents a novel avenue in combining high-resolution imaging technology, where not only the spatial resolution is important, but the temporal one too. The fundus was excited at 446 nm with 100 ps full-width at half-maximum pulses and 40 MHz repetition rate. The autouorescence was detected with a time resolution of 25 ps for wavelengths 4500 nm. By measuring the uorescence lifetime, differences were noticed between age-related macular degeneration (AMD) patients and healthy subjects. 7.2. OCT/uorescence On one hand, ICG angiography and OCT appear well suited to operate together because they share similar spectral bands. The most widely used band for retinal OCT of the retina is 820920 nm, while ICG is usually excited at 806 nm and uoresces in the band 810860 nm with a peak at 830 nm. Operating in similar bands allows the same source to be used for ICG excitation as well as for the production of an OCT image, according to the generic conguration in Fig. 7(iii). On the other hand, the proximity of the excitation wavelength to the uorescence band
raises several optimization issues. It looks easier to combine OCT with FA, as the excitation wavelength and the uorescence band are well separated. However, this requires two optical sources, as shown in Fig. 7(ii).
7.3. OCT/SLO/uorescence An instrument combining OCT with SLO and ICG uorescence is presented in Fig. 19, and has versatile scanning and image display capabilities allowing the acquisition of pairs of OCT and confocal images in B- or C-scan regime of operation. This is a triple-channel OCT/SLO/ICG angiographer (Podoleanu et al., 2007), which represents an improved version of the dual-channel OCT/SLO (Dobre et al., 2005). The splitter used in the OCT/SLO conguration to divert some of the light to a separate confocal receiver was replaced in the present implementation by a chromatic splitter, CS1. This separates the retina-scattered light at the excitation wavelength, guided into the OCT channel, from the uorescence signal, guided towards the confocal receiver. The residual transmission of the chromatic splitter is sufcient to generate an image at the OCT wavelength, separated from the uorescence using a chromatic splitter, CS2. To enhance the contrast of uorescence, a supplementary emission lter is used in front of the photoreceiver in the uorescence channel to attenuate any excitation band light that gets past the CS1 and CS2. Such an instrument, providing three different pieces of information, has an imaging content units, I 3. However, supplementary screens can be provided simultaneously, by combining any OCT, ICG or SLO images. To minimize the distortion of the OCT depth sampling prole (determined by the correlation function of the source), CS1 is used in transmission by the ICG channel and in reection by the OCT channel. CS1 and CS2 are cold mirrors with a transition wavelength, ltr between the excitation band and uorescence band. The image in the OCT channel is generated using the phase modulation created by the transversal beam scan across the target (Podoleanu et al, 1996, 1998). Following the injection of ICG solution into the patients bloodstream (5 mg/ml), light from the SLD, guided through to the eye fundus by means of the interface optics, generates on one hand a reected/backscattered return at the same wavelength (793 nm), which coherently combines with reference light to produce the OCT images, and on the other hand serves to excite uorescence in any tissue structures containing the ICG dye contrast agent, such as retinal and choroidal blood vessels.
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MX Superluminiscent diode, 790 nm OCT Single mode couplers Chromatic Splitter 1 (CS) Chromatic Splitter 2 (CS)
MY
Interface Optics
Y Z
Signal processing unit
Reference path adjustment
Fluorescence emission filter ICG Optical Receiver
SLO Optical Receiver
X
Eye
Variable scan frame grabber
Personal computer
Fig. 19. General set-up of the combined OCT/SLO/ICG-system. MX, MY: galvanometer mirrors of the XY transverse scanner.
The acquisition of uorescent images has to proceed rapidly, in less than a minute, due to the fast ICG disappearance rate from the blood stream of between 18% and 24%/min. Generating OCT, SLO and ICG images at 2 Hz was found (Rosen et al., 2006) to be a reasonably good trade-off between the acquisition speed requirement and the quality of the OCT images in terms of their S/N ratio. The 12-bit grayscale images in the three channels are displayed simultaneously side-by-side. Optimization of the CS1 and CS2 lter parameters and choice of excitation wavelength (Podoleanu et al., 2007) required that by shifting the excitation wavelength from the optimum of 806793 nm, in combination with a chromatic splitter with ltr 810 nm, which has 90% transmission at 815 nm and reection close to 95% at 793 nm, the correlation function experiences little distortion. Fig. 20 shows OCT and ICG images of a case of choroidal neovascular membrane. The image in (a) left shows full ICG lling of the retina and choroidal vessels with a comma-shaped hyperuorescent lesion within the central foveal dark zone that represents a neovascular membrane. The corresponding C-scan OCT on the right reveals a slight posterior tilt of the scan to the right such that the vitreous is represented by the black region on the left. The adjacent bright circular region with attached arms represents the vitreousretinal interface-nerve ber layer region. It surrounds a gray region of concentric circles, which correspond to a serous elevation enveloping the neovascular complex. The double line of the retinaRPE interface is seen in the upper right. (b) Later in ICG transit sequence the smaller vascular structures become less distinct. The C-scan OCT shows the tilt has shifted in this pair such that the choroid is captured in the upper left corner and the vitreous is in the lower right. The larger apparent size and more central location of the neovascular membrane in relation to the surrounding retinal structures places the depth of this cut somewhere near the mid-thickness of the retina. The B-scan OCT image in (c) demonstrates the defect in the RPE layer through which the vascular lesion has grown. The two insets below the B-scan image represents the C-scan image just before the switch from the C- to B-scan regimes of operation (right), while that on the left the current C-scan, deprived from frame scanning, which provides information on the lateral eye movement during the acquisition of the B-scan. The T-scan principle is extremely useful in quick switching of the instrument from C- to B-scan and back, depending on the needs of investigation.
7.4. No-dye uorescence-based OCT imaging By using border detection in the processing of OCT images, the vessel structure can be inferred with no dye. This method is called optical coherence angiography (OCA) (Makita et al., 2006), with two versions: scattering OCA (S-OCA), which employs the lowscattering property of choroidal vessels and Doppler OCA (D-OCA) which uses a Doppler OCT signal as the contrast origin of the vessels (Yasuno et al., 2007). According to the difference between the contrast mechanisms, D-OCA is used to visualize the 3D distribution of blood ow in the retina and the choroids while S-OCA is used to visualize the 3D structure of the blood vessels in the choroids (Hong et al, 2007). The combined use of S-OCA and D-OCA is recommended because they have different contrast mechanisms and complement each other in non-invasive angiography. S-OCA is used to visualize the 3D structure of the blood vessels in the choroids and is based on the segmentation of the choroidal vessels by using intensity threshold-based binarization (Yasuno et al., 2007). D-OCA uses a phase-sensitive Doppler OCT scheme, hence, the phase stability of the OCT system is mandatory, while it is not required for S-OCA. Supplementary, axial motion between adjacent A-lines within one OCT image was compensated by the Doppler shift due to bulk sample motion. Axial displacements between neighboring images were compensated by a correlation-based algorithm. By selecting the integration range as the tissue region, the contrast of the images is slightly enhanced, as shown in Fig. 21C. Only retinal vessels are visible in the projection images of the retinal layers, as seen in Fig. 21D. On the other hand, the projection images of the choroidal part reveal not only the choroidal vessels but also the retinal vessels due to shadowing effect (Fig. 21E). For practical applications, composite false-colored images are created from these projection image sets to distinguish the retinal vessels and the choroidal vessels. For the colored images, each of the three layersred, green and blueare produced, according to the following steps. The images of the retina (blue) and the choroid (green) are normalized. The retinal images are inverted and multiplied with the images of the choroid in order to suppress the retinal vessel artifacts, giving the yellow channel. This process renders the retinal and choroidal vessels cyan and yellow, respectively (Fig. 21F). The software processing, allowing clear distinction between the retina and the choroid vessels empowers
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Fig. 20. En face OCT (right) and ICG uorescence (left) images of the fundus of a patient with a well-dened classic choroidal neovascular membrane in the post-injection phase at 10 s (a) and 15 s (b). The ICG images highlight the vascular component of the membrane, while the accompanying OCT C-scan in (a) and (b) and the B-scan OCT image in (c) reveal the surrounding serous retinal elevation. C-scan images in (a) and (b): 4 mm 4 mm. Axial distance between the OCT slices in (a) and (b): 0.2 mm. B-scan image: 4 mm 1.5 mm. The OCT images exhibit 11 mm depth resolution.
this combination of techniques with an imaging content units, I 3 (one unit for the OCT information and the other two for the angiography data).
8. Combinations of high-resolution imaging procedures with AO 8.1. SLO+AO Pioneering work on fundus cameras equipped with AO (Liang et al., 1997) and ying spot SLO systems equipped with AO (Dreher et al., 1989; Roorda et al., 2002) have demonstrated the
benets of AO correction for enhancing the transversal resolution in the image as well as the contrast. The fundus cameras studies (Rha et al., 2006) have paved the way towards combining FF-OCT with AO while the studies on the ying spot represented essential steps in extending this imaging technology towards combining it with OCT in different formats, TD or SD. The SLO+AO imaging technology mainly progressed along C-scan imaging, the familiar orientation for the SLO. Although there is an expected improvement on the depth resolution, emphasis was on the transversal resolution enhancement, which allows visualization of photoreceptors. Application of AO to SLOs, reduces the volume of the imaging voxel from (1015) (1015) (300500) mm3 to smaller values, which in depth should reach FWHM values as small as
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Fig. 21. Optical coherence angiography of the optic nerve head of the human eye. Each image is produced by the integration of (A) the entire depth, (C) tissue region, (D) retinal part and (E) choroidal part of the power of Doppler shift images. (F) is a combination of (D) and (E). In the cross-sectional ow image (B), each integration range is indicated. Reproduced from Makita et al. (2006) with the permission of the publisher (Optical Society of America).
40 mm for ideal correction using an eye opening of 6 mm (Dreher et al., 1989; Venkateswaran et al., 2004) and transversally less than 2.5 mm (Roorda et al., 2002; Zhang and Roorda, 2006). An SLO+AO multi-wavelength imaging system was demonstrated (Grieve et al., 2006), which can operate at 532, 658 and 840 nm. Typically, the instrument is used in dual-frame mode, performing imaging at 840 nm and precisely coincident retinal stimulation in one of the visible wavelengths. This makes the imaging content units for such a combination of techniques, I 2. 8.1.1. SLO/uorescence+AO The benets of confocal detection, AO, multispectral and uorescence imaging have been reported in a new instrument for high resolution, in-vivo imaging of the mammalian retina (Gray et al., 2006). The instrument demonstrates imaging single ganglion cells and their axons through retrograde transport in ganglion cells of uorescent dyes injected into the monkey lateral geniculate nucleus. AO allows imaging of the smallest retinal capillaries in FA and the mosaic of RPE cells with lipofuscin autouorescence. 8.2. OCT+AO OCT allows reduction of the voxel along the axial direction. OCT systems illuminated by superluminescent diodes could easily reach 10 mm depth resolution. This is practically better by more
than an order of magnitude than the experimental value of an aberration-corrected SLO, with a FWHM of $100 mm often reported. Furthermore, with wider sources as such used for ultra-high-resolution OCT, the axial dimension of the voxel could be further reduced to less than 3 mm in-vivo (Drexler et al., 2001, 2003) and to submicron resolution in-vitro (Grieve et al., 2004), which is again more than 10 times better than the ideal axial correction achievable with an SLO+AO for a 6 mm pupil, mentioned above (Venkateswaran et al., 2004). Practically, the marriage of OCT and AO leads to an improved imaging technology of microscopic retinal structures by combining the high lateral resolution of AO with the high axial resolution of OCT. OCT+AO has the narrowest 3D point-spread function (PSF) of all in-vivo retinal imaging techniques. With AO-OCT, retinal structures that are not resolvable with AO or OCT alone, such as bundles of retinal nerve ber layers, the mosaic pattern of photoreceptors, microvasculature structure and detailed structure of retinal disruptions can be visualized. Practically all variety of OCT methods have been tested in conjunction with AO elements, as presented below.
8.2.1. Trade-off between depth resolution in OCT and level of correction using AO An important consideration when combining techniques is the effect of one on the other. The broad spectrum required for OCT imaging impacts on the aberrations to be corrected by AO.
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In ophthalmic OCT applications, there is a supplementary demand for correcting chromatic aberrations as well, an issue, which is not as critical for narrow band fundus cameras and SLOs. The effects of chromatic ocular aberrations on the quality of retinal OCT tomograms, in respect to transverse resolution, sensitivity and contrast, have been theoretically studied and characterized ndez and Drexler, 2005). It has been found that losses in (Ferna the intensity of OCT images obtained with monochromatic aberration correction can be up to 80%. This occurred in the case of an 8 mm diameter pupil size in combination with a spectral bandwidth of 120 nm FWHM for AO ultra-high-resolution OCT. The reduction of the detected signal and the resulting transverse resolution caused by chromatic aberration of the human eye is found to be strongly dependent on the employed bandwidth and pupil size.
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8.2.2. Incompatibility between A-scan-based OCT and AO The dynamic focus mentioned above becomes important especially in the combination of OCT with AO. The sensitivity of an OCT+AO system drops off as we move away from the focus and this is dictated by the confocal core of the OCT interferometer. Using the theoretical model for a single-mode ber confocal receiver (Kimura and Wilson, 1991), the confocal proles for four different pupil sizes are graphically represented in Fig. 22 left (Tuohy et al., 2007), where z is the distance from the center of the prole. An alternative theoretical model involves a sinc-based model of the confocal prole (Izatt et al., 1996), which leads to the confocal proles in Fig. 22 right. As can be seen from both diagrams in Fig. 22, as the pupil size increases the confocal prole shrinks due to better AO correction. This results in lower signal at the depth extremities of an image when using xed focus, as illustrated in Fig. 23. Similar results for the confocal prole of the confocal core of the optical receiver due to AO correction have also been reported (Venkateswaran et al., 2004). A 20 dB gain is obtained using SD-OCT methods in comparison with the TD-OCT method in the focus. At 150 mm distance from the focus, as the pupil size increases in Fig. 23, lower signal is received in the SD-OCT channel. At pupil sizes larger than 5 mm, the initial advantage of 20 dB of the SD-OCT method is lost and above this pupil size the TD-OCT presents better sensitivity. SDOCT operates under xed focus while TD-OCT can operate under a non-xed focus, which allows the center of the confocal peak in Fig. 23 to follow the scanning of the coherence gate resulting in a higher signal. A larger pupil size is desirable as it gives a better lateral resolution as long as the aberrations are corrected via the AO loop. Since the objective of using AO is to compensate for
Fig. 23. Decay of the confocal signal strength at the core of an OCT system versus pupil size at 150 mm from the focus for Gaussian and sinc confocal proles. The horizontal line at 20 dB marks the pupil size where the SD-OCT sensitivity advantage is lost in comparison with TD-OCT equipped with dynamic focus.
aberrations in order to obtain the ideal confocal prole both in transversal and axial directions, control of the focus to maintain high sensitivity over the whole retina thickness becomes of paramount concern. 8.2.3. Small size imaging using TD-en-face OCT A precursor of combining technologies for high transversal and high axial resolution using T-scans (Pircher et al., 2006a) demonstrated the utility of dynamic focus and paved the way towards establishing the best combination of imaging technology with AO. A transverse-scanning OCT system was equipped with dynamic focus. The technique provides cross-sectional and transverse information about the cone distribution without any AO correction. Small lateral size C-scans (200 mm 225 mm) and B-scans (200 mm 370 mm) at 4 1 nasal were acquired from three healthy eyes with small aberrations. The cone mosaic was observed in good correspondence with a simultaneous recorded SLO image. This could be resolved due to the high transversal resolution ensured by the ying spot T-scan method and conditioned by the controllable focus feature in the dynamic focus. Although the associated resolutions have been estimated using a model eye, this report was essential in giving an OCTbased explanation to the origin in depth of the regular pattern observable with fundus cameras and SLO. It concluded that the regular structure seen in the C-scan fundus and SLO images is given by the inner and outer photoreceptor layer and the Verhoeffs membrane placed in front of the RPE.
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8.2.4. Full eld TD-OCT+AO C-scan slices were obtained using a phase-shifting interferometry set-up employing four-step phase shifts in a single-path AO correction system (Miller et al., 2003). Each en-face image was obtained from a sequence of four 4 ms images that approached one half the pixel well capacity of the retinal CCD. Forty-two reconstructions were collected, which were then used to infer B-scans. Although the dynamic range in the image was less than 25 dB, the through gating results demonstrated sufcient S/N ratio for capturing high spatial resolution en-face images of several bright tissue layers. However, in order to enhance the sensitivity from the eye in-vivo, the frame rate was made much slower, 3.4 Hz. In a related report (Qu et al., 2003) it was concluded that the set of parameters: axial width of the PSF and the sensitivity (10 mm and 76 dB, respectively) were substantially better than current ood-illuminated camera+AO and SLO+AO.
8.2.5. Longitudinal TD-OCT+AO Using a single-path correction AO in an A-scan based TD-OCT set-up (Hermann et al., 2004), the authors reported an improvement of the transverse resolution of two to three times, and an increase in the S/N ratio of up to 9 dB in comparison to the noncorrected case. Subsequent reports demonstrated signicant improvement in the transverse resolution as well as on using wider bandwidth optical sources, which resulted in the reduction of the axial dimension of the imaged voxel. This in principle could be reduced to submicron values, although it is accepted that for in-vivo targets, this cannot be smaller than a few microns due the compound effect of movement, scattering and chromatic aberrations. Historically, most of the current research in this direction employs A-scan-based OCT under AO correction. The natural image orientation, C-scan was sacriced for a while, in order to take advantage of spectral OCT, which yields higher sensitivity than TD-OCT. However, it is expected that with the continuous technological progress in the amount of AO correction, the need for dynamic focus will revive the interest to en-face OCT. When working under no aberration correction, the depth of focus is expected to be approx 300 mm, sufcient to collect good strength signal from all layers in the macula, where the retina is less than 500 mm. However, when AO is applied, if the AO works well, then the depth of focus will shrink so much that only the scattering points within the depth of focus of the confocal receiver at the core of the OCT channel will contribute signicantly to the image. Put differently, simple inspection of B-scan images in reports of xed focus-OCT+AO exposes the performance of the correction of aberrations. The better the correction, the larger is the contrast variation along the depth, with an easy-to-spot focus position.
8.2.7. FD-OCT+AO equipped with two mirrors Using two mirrors, one with a large and the other with a small stroke, better functionality and correction of aberrations was achieved (Chen et al., 2007). The large stroke mirror reduced the need for trial lens correction. Another advantage of using two correctors was that the focus of the AO correction can be varied within the retina using only one of the mirrors, leaving the full dynamic range of the second mirror for AO correction (Zawadzki et al., 2007). This resulted in narrowing the confocal prole of the confocal core of the OCT to a value close to the ideal value. To visualize the effect of axial focus position on imaged structures, two volumes from the same retinal location of the same subjects eye were acquired with two focus positions: rst, on the photoreceptor layer and then on upper retinal layers. As seen in Fig. 24, reconstructed C-scans show different microstructures. These results clearly demonstrate that for maximum contrast it is essential to set the axial focus of the AO-OCT at the plane that contains the structure of interest. A narrow confocal prole of less than 100 mm was obtained. The authors conclude that one cannot observe all retinal layers in a single volume. Thus, two to three volumes need to be acquired at a single retinal location to maintain maximum lateral resolution for structures of all retinal layers (in the spirit of discussion in the Section 8.2.2.). This compensates for the fact that FD-OCT is not compatible with dynamic focus.
8.3. OCT+SLO+AO 8.3.1. Simultaneous OCT/SLO+AO The application of AO correction to the OCT/SLO dual imaging system would appear to be a natural t, however, it is not straightforward. Matching the beam diameter to that of the corrector, to the aperture of the XY transverse scanner, with the size of the lenslet array in the ShackHartmann wavefront sensor and with the SLO confocal receiver aperture raises constructive and engineering problems. The OCT/SLO is based on T-scan imaging, in contrast to the other systems described above, but also allows B-scan imaging within the same combined system. Dynamic focus is also possible with such a conguration (although not reported as yet in combination with AO). Pairs of OCT and SLO images obtained under AO correction are shown in Fig. 25. Two pairs are selected at different depths in the OCT channel. Due to the use of path modulation introduced by the galvo scanner responsible for line scanning, the speckle size is comparable with the pixel size and therefore transversal pixel size improvement could not be evaluated. Clear distinction of the cones in the SLO image was however demonstrated. An interesting observation, allowed by the en-face principle of scanning, with no phase modulator, is the display of fringe pattern by very reective cones. Fig. 26 left shows a zoom of the OCT C-scan image in Fig. 25 left, which illustrates that even after round trip traversal of several hundred of microns through a scattering tissue such as the retina, the signal retains the specular reection characteristics. On the right in Fig. 26, a B-scan OCT image is shown obtained using the T-scan principle. Despite the speckle, regular structure in the I/O layer is seen. The OCT/SLO instrument is particularly well suited for identifying the depth origin of patterns seen in the SLO image. Using the pixel-to-pixel correspondence, these could be traced to the depth shown in either the OCT C-scan or in the OCT B-scan. Clear pattern regularity is seen in the SLO images in Fig. 25, which could then be associated with the layer exhibiting such regularity in the B-scan in Fig. 26 right. The determination of depth origin of patterns seen
8.2.6. FD-OCT+AO Several reports exist on combining FD-OCT with AO. Signicant for the strategy in combining OCT with AO and in the utilization procedure of the combined system is a study on the experimental shift of focus under AO loop (Zawadzki, et al., 2005). Theoretical calculation predicts that 1 diopter defocus should shift the focal plane within the retina for about 370 mm for the standard eye. The study demonstrates that high sensitivity and lateral resolution can be achieved over a depth range of approximately plus/minus 50 mm surrounding the focus position. The authors concluded that in order to exploit the superior lateral resolution of their AOOCT system, the focal plane of the instrument should always be shifted towards the structure of interest.
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Fig. 24. Reconstructed slow-axis B-scans and C-scans from two retinal volumes acquired with a longitudinal-OCT+AO system, with the focus set on photoreceptor layers (left column) and on upper retinal layers (right column). Arrow in each panel denotes estimated focus position. Rows show C-scan reconstruction of the same retinal layer (denoted by abbreviations) with the exact position indicated by a white line on the B-scan. Retinal layers in C-scans from top to bottom are nerve ber layer (NFL), ganglion cell layer (GCL), outer plexiform layer (OPL), inner/outer segment junction (I/OS), Verhoeffs membrane (VM), and retinal pigmented epithelium (RPE). Scale bars 100 mm (vertical and horizontal). Reproduced from Zawadzki, et al. (2007) with permission of the publisher (Optical Society of America).
The studies by the groups in Vienna and Kent on small size imaging employing T-scan-based OCT suggest that when combined with AO, this is superior to the A-scan-based OCT combinations because the T-scan-based OCT method is compatible with dynamic focus. Dynamic focus is critical if aberrations are well corrected, since the resulting confocal prole narrowing in the core of the OCT channel, markedly reduces the signal outside focus. Despite this, the majority of reports on OCT/AO refer to combinations of SD-OCT with AO emphasizing the better S/N ratio or higher acquisition speed of the SD-OCT method in comparison with the TD-OCT, without commenting on the relative small contribution of AO to the combination due to the limitations discussed above. 8.3.2. Sequential OCT/SLO+AO 8.3.2.1. Sequential en-face OCT/SLO with AO. The sequential conguration presented in the Section 6.3.1. appears more advantageous in the context of combination with AO. The AO requires a large number of mirrors in the object arm to route the signal via two scanners and at least a deformable mirror. The large number of optical components increases the light losses, mandating the need for an OCT/SLO with no beam-splitter. 8.3.2.2. Sequential FD-OCT/ood-illuminated camera +AO. A 2D camera was used to collect either images of a ood-illuminated
Fig. 25. Pairs of C-scan OCT and SLO images simultaneously acquired and displayed via AO closed loop correction in an OCT/SLO system. Each image size: 330 mm 500 mm. Top: OCT; bottom: SLO. The depth in the OCT channel is at the inner outer segment junction (left) and approx. 50 mm above (right), displaying microvasculature. (Merino et al., 2006).
in small size imaging of the fovea using fundus cameras and SLOs is consistent with the explanation previously given for an en-face OCT system without AO correction (Pircher et al., 2006a, b) and for an AO corrected FD-OCT system (Zhang et al., 2005).
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Fig. 26. Left: expanded view from the middle of the C-scan OCT image in Fig. 25 top left; Right: B-scan OCT image of the same lateral size as that in Fig. 25 top left.
retina or spectra from a line projected to the retina, in which case the same camera was part of a spectrometer in an FD-OCT set-up (Zhang et al., 2005). The regime switching requires several seconds and involves swapping the diffraction grating performing spectral analysis for FD-OCT with a mirror and blocking the reference path in the interferometer to obtain ood-illuminated images. A single-path AO correction was utilized in both regimes. Short bursts of narrow B-scans (100 560 mm) of the living retina were acquired at 500 Hz during dynamic compensation (up to 14 Hz) that successfully corrected the most signicant ocular aberrations across a 6 mm dilated pupil. The importance of focus control in AO research was emphasized here again. Conventional ood illumination was integrated into the system, ensuring accuracy of the focus position on the retina to 710.3 mm.
9. Combination of high-resolution imaging technologies with tracking Eye movements wash out the transverse resolution in both SLO and OCT systems and the axial resolution in OCT. Therefore, tracking must address all three dimensions for OCT while lateral tracking is sufcient for SLO and even for SLO+AO systems. Tracking has evolved from simple CCD-based devices stabilizing the eye via pupil alignment to sophisticated systems, which control the angular orientation of the scanning beam. 9.1. SLO+AO+tracking The benets of tracking become more evident with SLO+AO systems since AO correction reduces the transversal pixel size making image quality more vulnerable to eye movement. Both hardware-combined congurations and specialized tracking software have been developed as briey presented below. An instrument has been reported (Hammer et al., 2006), which consists of three main sub-systems: a retinal tracker with a wideeld line-scanning laser ophthalmoscope to stabilize retinal coordinates, a ying spot SLO and an AO sub-system that senses wavefront distortion and corrects ocular aberrations. Fig. 27 summarizes the stabilization accuracy of the tracking and software registration purposely developed. The degree to which tracking corrects eye motion can be seen by comparing Figs. 27(a and b), where a number of frames have been superimposed. The vessel is completely washed out in the superposed image shown in Fig. 27(a) but its boundaries are clear in the superimposed image presented in Fig. 27(b). The composite image in Fig. 27(c) illustrates residual position error elimination with software registration. Line proles through three cones in the composite image are shown in Fig. 27(d) as indicated in Fig. 27(c) in comparison to a single frame (not shown). The line proles for the composite image are smoother while there is only a small degradation in contrast, proving the tracking efciency. For comparison, the cone mosaic is not resolved in Fig. 27(b).
Fig. 27. Summary of tracking and registration results in an SLO system equipped with AO and tracking. Composite images generated from co-added frames (blinks excluded) for (a) non-tracking (52 frames), (b) tracking (67 frames), and (c) software registration (67 frames) cases. Line proles (d) through three cones labeled in (c) in a single unprocessed frame (28) and the composite image. Contrast values are shown below the curves. Reproduced from Hammer et al. (2006) with permission of the publisher (Optical Society of America).
For the SLO+AO, a novel computational technique known as the map-seeking circuit algorithm (Vogel et al., 2006) was developed to estimate the motion of the retina of the eye from a sequence of SLO frames. A scheme to dewarp and co-add frames of retinal images, given the estimated motion of data was also developed. The motion estimation and dewarping techniques have been applied to images obtained by an SLO+AO. Co-adding dewarped frames revealed a honeycomb structure which represents the cone mosaic. This feature could not be seen in the single raw image frame. A related method is that of projecting highly stabilized, aberration-corrected stimuli directly onto the retina by means of real-time retinal image motion signals in combination with highspeed modulation of a scanning laser (Arathorn et al., 2007). The delivered stimulus is corrected by the AO system, which makes it possible to conne the stimulus to a single cone. Real-time correction for image distortions in an SLO+AO is proved with an intra-frame accuracy of about 7 arcsec. The system is distinguished by the fact that it can target a specic cone as well as maintain the stimulus on that cone over time. In three subjects with good xation stability, stimulus location accuracy averaged 0.26 arcmin or approximately 1.3 mm, which is smaller than the cone-to-cone spacing at the fovea.
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According to the denition of imaging content units in Section 1, adding AO does not necessarily contribute novel type of information, but improves the quality of information retrieved. For the latter example, however, AO enables performance of an additional function beyond conventional SLO imaging, resulting in I 2. 9.2. TD-OCT+lateral tracking An A-scan-based TD-OCT (Hammer et al., 2005) was equipped with a similar tracker to that used on a previous SLO/tracking system that addressed only lateral eye movements. The system was able to achieve transverse scan registration with sub-pixel accuracy ($10 mm). Tracking allowed accurate composite scans averaged from multiple B-scans taken consecutively and several hours apart and 3D retinal maps of the fovea and optic disk. C-scans were produced by summing the A-scans of circular, line and raster scans. The improved spatial resolution was accompanied by an increase in the S/N ratio, and reduced speckle while maintaining well-dened boundaries and sharp ne structures. Precise reregistration of multiple scans over separate imaging sessions demonstrated the utility of tracking in longitudinal OCT studies. 9.3. TD-OCT+AO+axial tracking For axial tracking, a low-coherence interferometer can be used, based on OCT technology. This has been proposed in a combined OCT+AO system (Qu et al., 2003). Coherence gating is generated by a free-space Michelson interferometer employing a superluminescent diode for illuminating the retinal tissue and voice coil and piezo-electric translators for controlling the optical path length of the reference channel. The axial eye movement was tracked by a 1D OCT system, which utilized a feedback loop to correct the optical path difference in the imaging OCT set-up. Further work is expected to be reported along this avenue, of OCTbased axial tracking in the near future.
valuable in combining the information provided by three imaging technologies, they present the limitation of having no means of accurately correlating the structural and functional changes observed. Therefore, simultaneous observation using combinations of such technologies incorporated into one instrument is required.
10.1.1.1. cSLO/mfERG. A rst step in combining two of the technologies was accomplished using a cSLO to provide stimulation and trigger the unit to take mfERGs. The retinal function was topographically mapped under simultaneous control of xation in humans. SLO/mfERG was demonstrated to be a feasible and reliable new technique to investigate macular function under simultaneous fundus control (Rudolph et al., 2003). The main advantage demonstrated was that control of xation could be used in order to obtain more reliable results that correlate well with visible fundus abnormalities such as in patients with macular holes. Monitoring of the fundus was guaranteed by an infrared laser (780 nm). The stimulus matrix consisted of 61 hexagonal elements, covering 241 of the posterior pole. Patients with macular holes and healthy individuals have been imaged. Such a combination is characterized by an imaging content units, I 2.
10. Combination of high-resolution imaging technologies with other techniques Other combinations will be reviewed briey, such as combinations with physiology methods in both variants, electrical physiology and optophysiology, as well as combinations with polarization, ow imaging and spectroscopic analysis. 10.1. Combinations with physiology methods 10.1.1. Multifocal ERG Electrophysiological methods allow clinicians to distinguish between diseases of the outer and inner retina. FF-ERG methods portray the bulk retinal response, while mfERG attempts to localize functional variations by mapping the retinal physiology with a relatively coarse transverse resolution, larger than 0.5 mm. There is also some disagreement as to the contributions of various cell populations to the components of mfERG signals. The need to better understand the source of the signals certainly justies the combination of mfERG with higher-resolution imaging methods such as SLO or OCT. Studies conducted using separate OCT, SLO and mfERG instruments (Saito et al., 2003) demonstrated correlation between the information provided by each instrument separately. OCT and SLO provided macular structure while the mfERG functional changes in response to surgical or pharmacological interventions for various macular pathologies. While these studies have proved
10.1.1.2. OCT/SLO/mfERGs. A simultaneous three-channel instrument combining OCT, SLO and mfERG was assembled (Dudgeon et al., 2008), to implement a new technique, called by authors multi-modal imaging. Simultaneous OCT/SLO and mfERG enabled the development of a system, which provides more complete morphology analysis and function than any other known tool. A micro-mfERG stimulus was projected onto an organic lightemitting diode display integrated into an OCT/SLO ophthalmoscope (OTI, Toronto, Canada) device. A 19-hexagonal-element stimulus stimulated a 201 eld, which allowed high-resolution mfERG recording. The OCT/SLO imaging operated simultaneously and independently of the mfERG. Preliminary work in patients with macular holes showed that functional decits existed beyond the geographical area of apparent structural alterations and that macular hole size did not always correlate with the severity of functional loss. It was concluded that the multi-modal imaging approach could provide additional useful functional information that was not available using separate studies, which might be important when assessing prognosis in these patients. The morphology and visual function of the macula in 5 eyes with macular holes was tested rst with wide-eld mfERG (901) and then with the OCT/SLO/mfERG. Micro-mfERG revealed functional abnormalities in a larger number of areas than did wide-eld mfERG in all patients due to the approximately threefold higher spatial resolution of the stimulus, allowed by the combination. Correlations between macular structure and function is displayed in Fig. 28 for all patients. The results obtained with the three-channel system showed that micro-mfERG has approximately three times the spatial resolution of conventional wide-eld mfERG. Such a combination is characterized by an imaging content units, I 3.
10.1.2. Combinations with optophysiology In optophysiology, the response to the stimulus is sensed as an optical signal. FD-OCT was used to determine an increase in backscatter from the photoreceptor outer segments (OSs) in a dark adapted rabbit retina (Bizheva et al., 2006) and rat retina (Srinivasan et al., 2006) due to a white light stimulus. An extended review on OCT published recently in this journal presents the subject in more detail (Drexler and Fujimoto, 2008). Such
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Fig. 28. Images of (left to right): SLO, OCT C-scan, OCT B-scan, micro-mfERG trace array, schematic diagram of stimulated areas with normal (white), delayed only (gray) or delayed and reduced in amplitude (black) responses, and overlay of micro-mfERG stimulus on the C-scan image. The top row is from a healthy control subject. Rows 26 are from patients 15, respectively. Reproduced from Dudgeon et al. (2007) with permission of the publisher (Optical Society of America).
combined systems are characterized by imaging content units, I 2 or larger (see Section 10.5).
10.2. Combinations with polarization information Other combinations of techniques include channels providing polarization information, such as SLO/polarization (Choplin et al., 2003), A-scan-based OCT/polarization (Baumann et al., 2007; Cense et al., 2002), T-scan-based OCT/polarization (Pircher et al., 2004; Cucu et al., 2004). Polarization sensitive OCT systems can produce simultaneously a polarization insensitive image and the birefringence image when using uncorrelated channels (Cucu et al., 2004), which determines a polarization insensitive image and the map of retardation, i.e. a minimum I 2, or if adding the two original orthogonal polarized images, then I 4). When using correlated channels, polarization sensitive OCT can provide additionally the orientation of the birefringence axis (Pircher et al., 2004), in which case at the minimum, I 3 or if adding the two original orthogonal polarized images, I 5. If all Jones
parameters are displayed, and if all Mueller coefcients are produced simultaneously, with the required complexity in the hardware, then the imaging content units can expand to 16. Symmetry considerations reduce the number of meaningful Jones and Mueller parameters. Work is still required to extend such technologies to the retina, from research on combining confocal microscopy with Mueller polarimetry (Lara and Dainty, 2006), or from research on combining OCT with Mueller polarimetry (Yasuno et al., 2003).
10.3. Combinations with ow information Both SLO and OCT make use of the Doppler shift of the light scattered from a moving target. Beating the signal returned with that of the excitation optical wave leads to an electrical beating signal with frequency proportional with the ow. When combined with OCT, the OCT/ow system additionally provides depthresolved ow information. Given the high depth resolution of OCT, distribution of ow inside micro-vessels becomes possible.
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Because ow is pulsatile, average of measurements is required. In addition, the location has to be maintained during acquisition, both reasons justifying the addition of tracking. An SLO based on the LF principle, similar to that described in Section 6.3.2 was used for real-time, high-speed image stabilization (Ferguson et al., 2004). Large dynamic range, wide-eld stabilized Doppler owmetry imaging was demonstrated in initial human subject testing with a large frequency range and up to 401 elds of view. The line sensor integrates, as opposed to conventional SLO owmeters, thus minimizing aliasing that contributes to velocity errors. FFT power spectra at each image pixel were computed. Doppler frequency resolution from 14 Hz to 3.675 kHz, as well as pulsatile ow effects were observed. Beating of the signal returned from the vessel and a local signal is naturally implemented in any OCT system and therefore all OCT systems are sensitive to ow. This explains the abundance of OCT reports on measuring ow (Drexler and Fujimoto, 2008; van Velthoven et al., 2007). SD-OCT due to its fast acquisition rate is the most suitable method to allow reliable data collection, being compatible with averaging while is less affected by eye movements (White et al., 2003). Such combined methods, OCT and Doppler, have already been presented in the Section 7.4 on providing vessel imaging with no dye. Phase stability in the OCT system is now more important than in imaging to sense small Doppler shifts. Accurate determination of vessel boundaries and time-dependent bi-directional ow dynamics is possible in artery-vein pairs. SD-OCT systems made sensitive to the phase perform optical Doppler tomography (ODT). SD-ODT allows visualization of the pulsatile nature of retinal blood ow, detects blood ow within the retinal capillaries and the choroid (Makita et al., 2006). Color can be added to show the direction of ow based on the direction of carrier frequency change due to the ow (Yazdanfar et al., 2003) or by measuring the phase change in adjacent A-scans (Leitgeb et al., 2003). When ow needs to be assessed in micro-capillaries, AO correction of aberrations becomes important in either combination of SLO+AO (Martin and Roorda, 2005) or OCT+AO (Zawadzki et al., 2007).
processing without changing the measurement apparatus (Morgner et al., 2000). An alternative for accessing spectroscopic information in OCT without post-processing uses the FF-OCT concept implemented using the smart pixel detector mentioned by the end of Section 4.3, based on wavelength de-multiplexing using a diffraction grating (Laubscher et al., 2004). Conventional A-scans and spectrally resolved measurement can be acquired simultaneously. A proof-of-principle demonstration was given on a dynamically changing absorbing sample. A combined near-infrared spectroscopy/OCT instrument (Xu et al., 2006) was proposed, where some problems of diffusive optical imaging are addressed by using OCT. Diffusive optical imaging is hindered by the lack of spatial and depth resolution, therefore OCT is used to assess the relative distance between layers in the retina. This is an example of two image-processing technologies, which jointly provide one piece of information, hence the imaging content units, I 1. 10.5. Polarization/ow/optophysiology/spectroscopy imaging FD-OCT concept was extended to functional imaging by analyzing the spectroscopic tissue properties, polarization contrast and Doppler velocity imaging. Differential spectral contrast FD-OCT allows an equivalent of optical staining of retinal tomograms and contrast tissue of high pigmentation such as the RPE, with strong correlation with polarization sensitive OCT. Studies of retinal perfusion based on laser Doppler owmetry demonstrated the high sensitivity of blood ow to external stimuli. Retinal perfusion was assessed in response to icker stimulation. An increase in vessel diameter by 11% and of ow velocity by 49% was measured (Leitgeb et al., 2007). Hence, this combination is characterized by an imaging content units of at least I 6 (considering the OCT morphology and at least two dimensions provided by polarization).
11. Future directions 10.4. Combinations with spectroscopy imaging Spectroscopic data offers information on the concentration of different pigments or of the oxygen saturation in oximetry, with clinical relevance in diagnosis of various ophthalmic diseases including the detection of blood loss in trauma victims. Providing spectroscopic information requires large bandwidth optical systems in both SLO and OCT implementations. Evaluation of the oxygen saturation relies on absorption measurements at different wavelengths. Several absorption measurements need to be performed at wavelengths around the isosbestic point, 790 nm, where the oxy-hemoglobin and deoxy-hemoglobin manifest the same absorption. Several fundus cameras (Johnson et al., 2007) and SLOs have been reported operating on several wavelengths (Lompado et al., 2000). For OCT, such development proceeds hand in hand with the research on ultra-high resolution, which require a large bandwidth source as well as a large bandwidth OCT system. In comparison with SLO, like with ow, OCT can provide depthresolved spectroscopic data. Two possible avenues have been investigated, that of using separate bands, typical for SLO and spectrally analyzing the A-scans obtained in a ultra-high-resolution OCT system. The latter method allows the spectrum of backscattered light to be measured over the entire available optical bandwidth simultaneously in a single measurement. Specic spectral features can be extracted by use of digital signal The future of ophthalmic imaging lies in the integration of different forms of information produced by combinations of techniques. A multi-modal functional imaging concept is of high value for an accurate and early diagnosis of retinal pathologies and pathogenesis. Three parameters have been used in this review to assess comparatively different combinations: (i) the number of Mv/s, (ii) the time to produce a C-scan image, Tenface and (iii) the number of different types of information provided simultaneously, I. So far, research efforts have placed emphasis on the increase of the number of voxels, i.e. on acquiring as much possible volume data in minimum time. In the last 5 years, progress in SD-OCT has lead to an order of magnitude increase in the number of Mv/s acquired and progress is still expected in this direction. The other parameter, Tenface, is connected to the minimum time to generate a C-scan image, or in case of A-scanbased OCT systems, to the time to generate a synthesized SLO image. When the natural scanning orientation is B-scan, a C-scan can be obtained only after the whole volume has been acquired and progress in the increase of number of Mv/s lead to a signicant reduction of the Tenface as well. For the moment, this parameter may not seem as essential as the number of Mv/s. However, as the technology progresses and combinations of techniques evolve to include more functional aspects, such as oximetry, the need for fast C-scan imaging will become paramount. How this goal will be achieved will become an area of increasing interest.
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Table 2 The imaging content units, I, for SLO, OCT, OCT/SLO and OCT/SLO/uorescence in combination with other techniques Initial value Polarization non correlated channels Polarization, correlated channels and Mueller polarimetry Up to16 316 632 733 Flow Physiology Spectroscopic (oximetry)
SLO OCT OCT/SLO OCT/SLO/uorescence
1 1 2 3
2 24 48 59
2 2 3 4
2 2 3 4
2 2 3 4
Table 3 Comparison of performances for different OCT methods and their potential to be combined with SLO, AO and multiplexed OCT method Performance C-scan in real time B-scan in real time TD, A-scan based TD, T-scan based, ying spot Full eld (TD, T-scan based) O Almost real time, slightly delayed by the time to produce the rst image O, Focus change at frame rate (Hz) (ideal for dynamic focus) Ideal FD-OCT (A-scan based) n.a. Almost real time, slightly delayed by the time to produce the rst image n.a. SS-OCT (A-scan based) n.a. Almost real time, slightly delayed by the time to produce the rst image n.a. LF-SD-OCT (A-scan based) n.a. Almost real time, slightly delayed by the time to produce the rst image n.a.
n.a. (nonapplicable) O
O O
Dynamic focus
Potential for combination with AO Guidance of OCT investigation via a pixel to pixel correspondence SLO image Minimum time to produce (infer) a C-scan Multiplexing
O, Focus change at frame rate O, Possible, but needs focus change (Hz) (ideal for dynamic focus) at the line rate (kHz) Unsuitable if AO Suitable correction is ideal O, Post acquisition O, Real time only
Unsuitable if AO correction is ideal O, Post acquisition only
Unsuitable if AO correction is ideal O, Post acquisition only
Unsuitable if AO correction is ideal Quasi-simultaneously
In principle possible, but no report
Sub-second Sub-second, in principle, the same with the time required to produce an SLO image at video rate, i.e. 20 ms Requires division of Potential, as it requires division Potential, as it requires division of the beam towards of the reference beam only the reference beam the retina, so only impractical Very long, over tens of seconds
Over 1 s
Over 1 s
Over 1 s
Requires division of Requires division of Requires division of the beam towards the the beam towards the the beam towards the retina, so impractical retina, so impractical retina, so impractical
The multidimensional space of information provided by a combined instrument can be assessed by the three parameters. Table 2 concludes the number of dimensions, I, added by other techniques to an SLO, OCT, OCT/SLO and OCT/SLO/uorescence instrument. AO and tracking are not included because they only improve the resolution and stability of the other imaging modalities and do not add dimensions to the information space. Having reviewed a whole diversity of congurations combining high-resolution imaging modalities of the retina, with the knowledge we have today, we can state the following in respect to the potential of different such imaging technologies.
11.1. Potential of existing technologies and trends Table 3 presents comparatively the OCT methods and their characteristics as well as their potential to be combined with other imaging techniques considered in the review. Longitudinal TD-OCT: Historically, this was the rst method used, and is considered to have reached maturity. TD-en-face OCT: This has an untapped potential in improving the time to collect a whole volume and increase the number of
Mv/s, if the problem of acquiring simultaneous C-scans at several depth is addressed. This is equivalent to depth multiplexing. A possible avenue is based on the development of integrated multiple delay optical modulators. A 10-delay modulator will allow acquisition of 10 C-scans at the same time. This will be sufcient to offset the advantage of FD-OCT in comparison with TD-OCT. With the continuous improvement in AO correction, the en-face display in the OCT channel will gain in popularity as commented in the Section 8.2.2, fueled by the capability to perform dynamic focus and conserve the transversal resolution at any depth in the retina within a depth range of several mm. Also, en-face OCT with adjustable coherence length has an untapped potential in producing an SLO-like image in one frame not realized as yet. The success of such avenue has been hampered by the noise in the optical sources so far, progress in the development of adjustable coherence length optical sources may allow instantaneous change from OCT to SLO using an OCT instrument only. FF-OCT: This is the method that provided the highest transversal resolution reported in histology and anterior chamber, also characterized by a large value of Mv/s exceeding 100.
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Development of the smart sensor array, with its potential mentioned for spectroscopic OCT analysis (with possible applications in oximetry) in Section 10.4 seems to have stopped before being tested to the eye imaging. FD-OCT: Currently, this is the preferred method due to its high acquisition speed and low cost of equipment. Work is underway to improve the sensitivity decay with depth and the spectrometer reading, such as direct linearization of data in the frequency space. SS-OCT: This method allowed the highest acquisition rate achieved so far. Work is underway on improving the optical source to achieve similar spectrum behavior irrespective of the direction of tuning and lower the cost. The development of buffered FD mode-locked SS for microscopy achieved 370 kHz line rate (Huang et al., 2007) while the principle of SS-OCT was demonstrated up to MHz (Moon and Kim, 2006). It is expected that both FD-OCT and SS-OCT methods will continue to play an important role in imaging the retina. Several companies now produce and distribute FD-OCT systems for the retina, while 3 years ago there were none.
transferred to axial tracking. This will allow longer collection time of weak signals, such as in autouorescence and better distinction of patterns in small size images. The cumulative effect of AO correction and tracking will raise supplementary problems of safety. Several safety calculations take into consideration the micro-saccades and consider an average large area of the spot projected on the retina due to movement. AO leads to a reduction of the spot size and tracking ensures irradiation of the same place in the retina. Safety standards consider the optical power at the cornea and requires adaptation and interpretation when scanning is concerned. Sometime, a supplementary optical source is used, which launches a second beam to the eye in addition to the imaging beam. This may also be the case in combining different imaging modalities with uorescence. OCT+ICG angiography can be performed with the same source, but OCT+FA requires a visible source in addition to the IR OCT source. All these examples show that safety calculations have to be improved to include particular scenarios of scanning, as already approached by several authors (Delori et al., 2007; Rosa et al., 2007). Acknowledgments The authors acknowledge all those who kindly accepted to have their published gures included in this review, as indicated in the corresponding gure caption. A. Podoleanu acknowledges support from Engineering and Physical Sciences Research Council of the UK, European Commission, New York Eye and Ear Inrmary, Ophthalmic Technology Inc., Toronto, Canada. R. Rosen acknowledges support from Ophthalmic Technology Inc., Toronto, Canada, the Bendheim-Lowenstein Family Foundation, the Leon Lane Foundation and the Ophthalmology Chairmans Research Fund of the New York Eye and Ear Inrmary. The authors also thank Patricia Garcia from New York Eye and Ear Inrmary, Ejaz Ansari, from Maidstone and Tunbridge Wells NHS Trust and Jim Brown in the School of Physical Sciences, University of Kent for valuable comments. References
Al-Chalabi, S.A., Culshaw, B., Davies, D.E.N., 1983. Partially coherent sources in interferometric sensors. First International Conference on Optical Fibre Sensors, 2628 April 1983, I.E.E. London, pp. 132135. Arathorn, D.W., Yang, Q., Vogel, C.R., Zhang, Y., Tiruveedhula, P., Eoorda, A., 2007. Retinally stabilized cone-targeted stimulus delivery. Opt. Express 15, 1373113744. Barton, J.K., Guzman, F., Tumlinson, A., 2004. Dual modality instrument for simultaneous optical coherence tomography imaging and uorescence spectroscopy. J. Biomed. Opt. 9, 618623. Bartsch, D.U., Freeman, W.R., 1994. Axial intensity distribution analysis of the human retina with a confocal scanning laser tomograph. Exp. Eye Res. 58, 161173. Bartsch, D.U., Intaglietta, M., Bille, J.F., Dreher, A.W., Gharib, M., Freeman, W.R., 1989. Confocal laser tomographic analysis of the retina in eyes with macular hole formation and other focal macular diseases. Am. J. Ophthalmol. 108, 277287. tzinger, E., Pircher, M., Hitzenberger, C.K., 2007. Single camera Baumann, B., Go based spectral domain polarization sensitive optical coherence tomography. Opt. Express 15, 10541063. Bindewald, A., Stuhrmann, O., Roth, F., Schmitz-Valckenberg, S., Helb, H.M., Wegener, A., Eter, N., Holz, F.G., 2005. Lower limits of uorescein and indocyanine green dye for digital cSLO uorescence angiography. Br. J. Ophthalmol. 89, 16091615. Bizheva, K., Pug, R., Hermann, B., Povazay, B., Sattmann, H., Qiu, P., Anger, E., Reitsamer, H., Popov, S., Taylor, J.R., Unterhuber, A., Ahnelt, P., Drexler, W., 2006. Optophysiology: depth resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography. Proc. Natl. Acad. Sci. USA 103 (13), 50665071. Cense, C., Chen, T.C., Park, B.H., Pierce, M.C., de Boer, J.F., 2002. In vivo depthresolved birefringence measurements of the human retinal nerve ber layer by polarization-sensitive optical coherence tomography. Opt. Lett. 27, 16101612. Cense, B., Nassif, N., Chen, T., Pierce, M., Yun, S.H., Park, B., Bouma, B., Tearney, G., de Boer, J.F., 2004. Ultrahigh-resolution high-speed retinal imaging
11.2. Synergies provided by the combination of techniques Several examples have been given in the review on the synergy between different imaging technologies implemented within a unique instrument, such as: (i) guidance of the OCT C-scan provided by the SLO image; (ii) depth location, provided by OCT Bscans for patterns seen in the SLO images, such as the regular pattern of photoreceptors enhanced in the AO adapted SLO; (iii) elimination of lateral movement disturbance in B-scan OCT images using the lateral shifts in the SLO image in a simultaneous OCT/SLO system operating in the B-scan regime; (iv) using the SLO image in a simultaneous OCT/SLO system to track the eye movements between frames and for subsequent transversal alignment of the OCT image stacks; (v) using SLOs to precisely excite regions of the retina in ERG; (vi) improving the diffusive imaging model using OCT; (vii) Doppler OCT for no-dye angiography, etc. It is expected that the synergy of effects will continue to drive our imagination to invent other combined congurations to transfer the information provided by one technology to a different one, or to combine technologies to obtain a better picture of morphology and functionality. Combination of techniques also require addressing conicting hardware needs. Trade-off between the large band demand in OCT and the increase in the tasks for AO corrections, raised the problem of polychromatic aberrations (Section 8.2.1). Chromatic aberration is also a problem in combining OCT with uorescence imaging, due to the wide band required for the interface optics between the eye and the interferometer, respectively the uorescence channels. In terms of OCT/AO, SD-OCT is still expected to play a major role. However, optimum combination of AO with SD-OCT may not require 0.8 mm depth in the B-scan OCT image (Section 8.2.2). As the confocal prole is expected to be improved under better AO correction, a range in depth of 200 mm may sufce, in which case an increase in the acquisition speed of four times is achievable. This shows how progress in one technology, AO, will impact the imaging strategy and performance of another technology, the A-scan-based OCT in respect to its depth range. Tracking is expected to play an important role in enhancing the quality of high-resolution images, where OCT will be employed to implement axial tracking in SLO imaging as well as in OCT imaging. A 3D axes tracker is expected soon, given the work on lateral tracking and the work on OCT, which could be easily
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using spectral-domain optical coherence tomography. Opt. Express 12, 24352447. Chen, D.C., Jones, S.M., Silva, D.A., Olivier, S.S., 2007. High-resolution adaptive optics scanning laser ophthalmoscope with dual deformable mirrors. J. Opt. Soc. Am. A 24, 13051312. Choma, M.A., Sarunic, M.V., Yang, C., Izatt, J.A., 2003. Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Opt. Express 11, 21832189. Choplin, N.T., Zhou, Q., Knighton, R.W., 2003. Effect of individualized compensation for anterior segment birefringence on retinal nerve ber layer assessments as determined by scanning laser polarimetry. Ophthalmology 110, 719725. Costa, R.A., Skaf, M., Melo Jr., L.A.S., Calucci, D., Cardillo, J.A., Castro, J.C., Huang, D., Wojtkowski, M., 2006. Retinal assessment using optical coherence tomography. Prog. Retinal Eye Res. 25, 325353. Cucu, R.G., Pedro, J., Rosen, R.B., Podoleanu, A.Gh., 2004. Polarization-sensitive OCT system using single-mode ber. SPIE Proc. 5579, 170177. Cucu, R.G., Podoleanu, A.Gh., Rogers, J.A., Pedro, J., Rosen, R.B., 2006. Combined confocal/en face T-scan-based ultrahigh-resolution optical coherence tomography in vivo retinal imaging. Opt. Lett. 31, 16841686. Delori, F.C., Webb, R.H., Sliney, D.H., 2007. Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices. J. Opt. Soc. Am. A 24, 12501265. Dobre, G.M., Podoleanu, A.G., Rosen, R.B., 2005. Simultaneous optical coherence tomographyindocyanine green dye uorescence imaging system for investigations of the eyes fundus. Opt. Lett. 30, 5860. Dreher, A.W., Bille, J.F., Weinreb, R.N., 1989. Active optical depth resolution improvement of the laser tomographic scanner. Appl. Opt. 28, 804808. Dresel, T., Hausler, G., Venzke, H., 1992. Three-dimensional sensing of rough surfaces by Coherence Radar. Appl. Opt. 31, 919925. Drexler, W., 2004. Ultrahigh-resolution optical coherence tomography. J. Biomed. Opt. 9, 4774. Drexler, W., Fujimoto, J.G., 2008. State-of-the-art retinal optical coherence tomography. Prog. Retinal Eye Res. 27, 4588. Drexler, W., Morgner, U., Ghanta, R.K., Kartner, F.X., Schuman, J.S., Fujimoto, J.G., 2001. Ultrahigh-resolution ophthalmic optical coherence tomography. Nat. Med. 7, 502507. Drexler, W., Sattmann, H., Hermann, B., Ko, T.H., Stur, M., Unterhuber, A., Scholda, C., Findl, O., Wirtitsch, M., Fujimoto, J.G., Fercher, A.F., 2003. Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. Arch. Ophthalmol. 121, 695706. Dubois, A., Vabre, L., Boccara, A.C., Beaurepaire, E., 2002. High resolution full-eld optical coherence tomography with a Linnik microscope. Appl. Opt. 41, 805812. , R.P., 2002. Ducros, M., Laubscher, M., Karamata, B., Bourquin, S., Lasser, T., Salathe Parallel optical coherence tomography in scattering samples using a twodimensional smart-pixel detector array. Opt. Commun. 202, 2935. Dudgeon, S.M., Keating, D., Parks, S., 2007. Simultaneous structural and functional imaging of the macula using combined optical coherence tomography ophthalmoscope and multifocal electroretinogram. J. Opt. Soc. Am. A 24, 13941401. Elsner, A.E., Burns, S.A., Weiter, J.J., Delori, F.C., 1996. Infrared imaging of sub-retinal structures in the human ocular fundus. Vision Res. 36, 191205. Fercher, A.F., Mengedoht, K., Werner, W., 1988. Eye length measurement by interferometry with partially coherent light. Opt. Lett. 13, 186189. ndez, E., Drexler, W., 2005. Inuence of ocular chromatic aberration and pupil Ferna size on transverse resolution in ophthalmic adaptive optics optical coherence tomography. Opt. Express 13, 81848197. Ferguson, R.D., Hammer, D.X., Elsner, A.E., Burns, S.A., Webb, R.H., Weiter, J.J., 2004. Wide-eld stabilized Doppler owmetry with the tracking scanning laser ophthalmoscope (TSLO). SPIE Proc. 5314, 170178. Gotzinger, E., Pircher, M., Hitzenberger, C.K., 2005. High speed spectral domain polarization sensitive optical coherence tomography of the human retina. Opt. Express 13, 1021710229. Gray, D.C., Merigan, W., Wolng, J.I., Gee, B.P., Porter, J., Dubra, A., Twietmeyer, T.H., Ahamd, K., Tumbar, R., Reinholz, F., Williams, D.R., 2006. In vivo uorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells. Opt. Express 14, 71447158. Grieve, K., Paques, M., Dubois, A., Sahel, J., Boccara, C., Le Gargasson, J.F., 2004. Ocular tissue imaging using ultrahigh-resolution, full-eld optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 45, 41264131. ques, M., Sahel, J., Le Gargasson, J.F., Grieve, K., Dubois, A., Simonutti, M., Pa Boccara, C., 2005. In vivo anterior segment imaging in the rat eye with high speed white light full-eld optical coherence tomography. Opt. Express 13, 62866295. Grieve, K., Tiruveedhula, P., Zhang, Y., Roorda, A., 2006. Multi-wavelength imaging with the adaptive optics scanning laser Ophthalmoscope. Opt. Express 14, 1223012242. Hammer, D.X., Ferguson, R.D., Iftimia, N., Ustun, T.E., Wollstein, V., Ishikawa, H., Gabriele, M., Dilworth, W., Kagemann, L., Schuman, J., 2005. Advanced scanning methods with tracking optical coherence tomography. Opt. Express 13, 79377947. Hammer, D.X., Ferguson, R.D., Bigelow, C.E., Iftimia, N.V., Ustun, T.E., Burns, S.A., 2006. Adaptive optics scanning laser ophthalmoscope for stabilized retinal imaging. Opt. Express 14, 33543367. Hausler, G., Lindner, M.W., 1998. Coherence radar and spectral radarnew tools for dermatological diagnosis. J. Biomed. Opt. D 3, 2131.
Hermann, B., Fernandez, E.J., Unterhuber, A., Sattmann, H., Fercher, A.F., Drexler, W., Prieto, M., Artal, P., 2004. Adaptive-optics ultrahigh-resolution optical coherence tomography. Opt. Lett. 29, 21422144. Hitzenberger, C.K., Trost, P., Lo, P., Zhou, Q., 2003. Three-dimensional imaging of the human retina by high-speed optical coherence tomography. Opt. Express 11, 27532761. Holz, F.G., Bellmann, C., Dithmar, S., Vocker, H.E., 1997. Confocal scanning laser uorescein and indocyanine green angiography. Ophthalmologe 94, 348353. Hong, Y., Makita, S., Yamanari, M., Miura, M., Kim, S., Yatagai, T., Yasuno, Y., 2007. Three-dimensional visualization of choroidal vessels by using standard and ultra-high resolution scattering optical coherence angiography. Opt. Express 15, 75387550. Huang, D., Swanson, E.A., Lin, C.P., Schuman, J.S., Stinson, W.G., Chang, W., Hee, M.R., Flotte, T., Gregory, K., Puliato, C.A., 1991. Optical coherence tomography. Science 254, 11781181. Huang, S.W., Aguirre, A.D., Huber, R.A., Adler, D.C., Fujimoto, J.G., 2007. Swept source optical coherence microscopy using a Fourier domain mode-locked laser. Opt. Express 15 (10), 62106217. Huber, R., Adler, D.C., Srinivasan, V.J., Fujimoto, J.G., 2007. Fourier domain mode locking at 1050 nm for ultra-high-speed optical coherence tomography of the human retina at 236,000 axial scans per second. Opt. Lett. 32, 20492051. Iftimia, N.V., Hammer, D.X., Bigelow, C.E., Ustun, T., de Boer, J.F., Ferguson, R.D., 2006. Hybrid retinal imager using line-scanning laser ophthalmoscopy and spectral domain optical coherence tomography. Opt. Express 14, 1290912914. Izatt, J.A., Kulkarni, M.D., Wang, H.W., Kobayashi, K., Sivak, M.V., 1996. Optical coherence tomography and microscopy in gastrointestinal tissues. IEEE J. Sel. Top. Quantum Electron. 2 (4), 10171028. Jenkins, F.A., White, H.E., 1957. Fundamentals of Optics. McGraw-Hill, New York, 284pp. Jiao, S.L., Knighton, R.W., Huang, X.R., Gregori, G., Puliato, C.A., 2005. Simultaneous acquisition of sectional and fundus ophthalmic images with spectraldomain optical coherence tomography. Opt. Express 13, 444452. Jiao, S.L., Wu, C.Y., Knighton, R.W., Gregori, G., Puliato, C.A., 2006. Registration of high-density cross sectional images to the fundus image in spectral-domain ophthalmic optical coherence tomography. Opt. Express 14, 33683376. Johnson, W.R., Wilson, D.W., Fink, W., Humayun, M., Bearman, G., 2007. J. Biomed. Opt. 12 (1), 014036. Jorzik, J.J., Bindewald, A., Dithmar, S., Holz, F.G., 2005. Digital simultaneous uorescein and indocyanine green angiography, autouorescence, and red-free imaging with a solid-state laser-based confocal scanning laser ophthalmoscope. Retina-J. Ret. Vit. Dis. 25 (4), 405416. Kimura, S., Wilson, T., 1991. Confocal scanning optical microscope using singlemode ber for signal detection. Appl. Opt. 30, 21432150. Lara, D., Dainty, C., 2006. Axially resolved complete Mueller matrix confocal microscopy. Appl. Opt. 45 (9), 19171930. Laubscher, M., Bourquin, S., Froehly, L., Karamata, B., Lasser, T., 2004. Spectroscopic optical coherence tomography based on wavelength de-multiplexing and smart pixel array detection. Opt. Commun. 237 (46), 275283. Leitgeb, R.A., Schmetterer, L., Drexler, W., Fercher, A.F., Zawadzki, R.J., Bajraszewski, T., 2003. Real-time assessment of retinal blood ow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. Opt. Express 11 (23), 31163121. Leitgeb, R.A., Bachmann, A.H., Villiger, M., Michaely, R., Blatter, C., Lasser, T., Pache, C., Pircher, M., 2007. Measurement of retinal physiology using functional fourier domain OCT concepts. Proc. SPIE 6426-art. no. 642609, 42609. Liang, J., Williams, D.R., Miller, D.T., 1997. Supernormal vision and high-resolution retinal imaging through adaptive optics. J. Opt. Soc. Am. A 14, 28842892. Lim, H., Mujat, M., Kerbage, C., Lee, E.C., Chen, Y., Chen, T.C., de Boer, J.F., 2006. High-speed imaging of human retina in vivo with swept-source optical coherence tomography. Opt. Express 14, 1290212908. Lompado, A., Smith, M.H., Hillman, L.W., Denninghoff, K.R., 2000. Multi-spectral confocal scanning laser ophthalmoscope for retinal vessel oximetry. Proc. SPIE 1 (14), 6773. Makita, S., Hong, Y., Yamanari, M., Yatagai, T., Yasuno, Y., 2006. Optical coherence angiography. Opt. Express 14, 78217840. Martin, J.A., Roorda, A., 2005. Direct and noninvasive assessment of parafoveal capillary leukocyte velocity. Ophthalmology 112 (12), 22192224. Masters, B.R., 1998. Three-dimensional confocal microscopy of the human optic nerve in vivo. Opt. Express 3, 356359. Merino, D., Dainty, C., Bradu, A., Podoleanu, A.Gh., 2006. Adaptive optics enhanced simultaneous en-face optical coherence tomography and scanning laser ophthalmoscopy. Opt. Express 14 (8), 33453353. Mikelberg, F.S., Partt, C.M., Swindale, N.V., Graham, S.L., Drance, S.M., Gosine, R., 1995. Ability of the Heidelberg Retina Tomograph to detect early glaucomatous visual eld loss. J. Glaucoma 4, 242247. Miller, D.T., Qu, J., Jonnal, R.S., Thorn, K.E., 2003. Coherence gating and adaptive optics in the eye. Proc. SPIE 4956, 6572. Moon, S., Kim, D.Y., 2006. Ultra-high-speed optical coherence tomography with a stretched pulse supercontinuum source. Opt. Express 14, 1157511584. Morgner, U., Drexler, W., Kartner, F.X., Li, X.D., Pitris, C., Ippen, E.P., Fujimoto, J.G., 2000. Spectroscopic optical coherence tomography. Opt. Lett. 25 (2), 111113. Nakamura, Y., Makita, S., Yamanari, M., Itoh, M., Yatagai, T., Yasuno, Y., 2007. Highspeed three-dimensional human retinal imaging by line-eld spectral domain optical coherence tomography. Opt. Express 15, 71037116. Nassif, N.A., Cense, B., Park, B.H., Pierce, M.C., Pierce, M.C., Yun, S.H., Bouma, B.E., Tearney, G.J., Chen, T.C., de Boer, J.F., 2004. In vivo high-resolution video-rate
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spectral-domain optical coherence tomography of the human retina and optic nerve. Opt. Express 12, 367376. Pircher, M., Gotzinger, E., Leitgeb, R., Sattmann, H., Findl, O., Hitzenberger, C.K., 2004. Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT. Opt. Express 12, 59405951. tzinger, E., Hitzenberger, C.K., 2006a. Retinal cone Pircher, M., Baumann, B., Go mosaic imaged with transverse scanning optical coherence tomography. Opt. Lett. 31, 18211823. Pircher, M., Gotzinger, E., Hitzenberger, C.K., 2006b. Dynamic focus in optical coherence tomography for retinal imaging. J. Biomed. Opt. 11 (5), 054013054016. Podoleanu, A., Woods, D., 2007. Power-efcient Fourier domain optical coherence tomography setup for selection in the optical path difference sign using Talbot bands. Opt. Lett. 32, 23002302. Podoleanu, A.G., Jackson, D.A., 1998. Combined optical coherence tomograph and scanning laser ophthalmoscope. Electron. Lett. 34 (11), 10881090. Podoleanu, A.G., Jackson, D.A., 1999. Noise analysis of a combined optical coherence tomograph and a confocal scanning ophthalmoscope. Appl. Opt. 38, 21162127. Podoleanu, A.G., Dobre, G.M., Webb, D.J., Jackson, D.A., 1996. Coherence imaging by use of a Newton rings sampling function. Opt. Lett. 21, 17891791. Podoleanu, A.G., Dobre, G.M., Webb, D.J., Jackson, D.A., 1997. Simultaneous en-face imaging of two layers in the human retina by low-coherence reectometry. Opt. Lett. 22, 10391041. Podoleanu, A.G., Dobre, G.M., Webb, D.J., Jackson, D.A., 1998a. En-face coherence imaging using galvanometer scanner modulation. Opt. Lett. 23, 147149. Podoleanu, A.G., Seeger, M., Dobre, G.M., Webb, D.J., Jackson, D.A., Fitzke, F.W., 1998b. Transversal and longitudinal images from the retina of the living eye using low coherence reectometry. J. Biomed. Opt. 3, 1220. Podoleanu, A.G., Rogers, J.A., Jackson, D.A., 1999. OCT en-face images from the retina with adjustable depth resolution in real time. IEEE J. Sel. Top. Quantum Electron. 5, 11761184. Podoleanu, A.Gh., Rogers, J.A., Cucu, R.C., Jackson, D.A., Wacogne, B., Porte, H., Gharbi, T., 2001. Simultaneous low coherence interferometry imaging at two depths using an integrated optic modulator. Opt. Commun. 191, 2130. Podoleanu, A.Gh., Cucu, R.G., Rosen, R.B., Dobre, G.M., Rogers, J.A., Jackson, D.A., 2003. Quasi-simultaneous OCT en-face imaging with two different depth resolutions. J. Phys. D: Appl. Phys. 36, 16961702. Podoleanu, A.G., Dobre, G.M., Cucu, R.G., Rosen, R., Garcia, P., Nieto, J., Will, D., Gentile, R., Muldoon, T., Walsh, J., Yannuzzi, L.A., Fisher, Y., Orlock, D., Weitz, R., Rogers, J.A., Dunne, S., Boxer, A., 2004a. Combined multiplanar optical coherence tomography and confocal scanning ophthalmoscopy. J. Biomed. Opt. 9, 8693. Podoleanu, A.Gh., Cucu, R.G., Pedro, J., Weitz, R., Jackson, D.A., Rosen, R.B., 2004b. Hybrid conguration for simultaneous en-face OCT imaging at different depths. SPIE Conf. Proc. 5634, 160165. Podoleanu, A.Gh., Dobre, G.M., Cucu, R.G., Rosen, R.B., 2004c. Sequential OCT and confocal imaging. Opt. Lett. 29 (4), 364366. Podoleanu, A.Gh., Jackson, D.A., Dobre, G.M., Cucu, R.G., 2005. Optical mapping apparatus with optimized OCT conguration. US Patent 6927860. Podoleanu, A.G., Dobre, G.M., Cernat, R., Pedro, J., Rosen, R.B., Garcia, P., 2007. Investigations of the eye fundus using a simultaneous Optical Coherence Tomography /Indocyanine Green uorescence imaging system. J. Biomed. Opt., 12/1/014019, 014019-1014019-8. Qu, J.L., Jonnal, R.S., Miller, D.T., 2003. Ultrafast parallel coherence gating for an adaptive optics retina camera. SPIE Proc. 4956, 352359. Qu, J.L., Jonnal, R.S., Miller, D.T., 2004. Parallel optical coherence tomography using a CCD camera. Chin. Opt. Lett. 2, 475476. Rha, J., Jonnal, R.S., Thorn, K.E., Qu, J., Zhang, Y., Miller, D.T., 2006. Adaptive optics ood-illumination camera for high speed retinal imaging. Opt. Express 14 (10), 45524569. Rollins, A., Yazdanfar, S., Kulkarni, M., Ung-Arunyawee, R., Izatt, J., 1998. In vivo video rate optical coherence tomography. Opt. Express 3, 219229. Roorda, A., Romero-Borja, F., Donnelly, W., Queener III, H., Hebert, T., Campbell, M., 2002. Adaptive optics scanning laser ophthalmoscopy. Opt. Express 10, 405412. Rosa, C.C., Rogers, J., Pedro, J., Rosen, R.B., Podoleanu, A.Gh., 2007. Multi-scan time domain OCT for retina imaging. Appl. Opt. 46, 17951807. Rosen, R.B., Podoleanu, A.G., Dunne, S., Garcia, P.M.T., 2003. Optical coherence tomography ophthalmoscopy. In: Ciulla, T.A., Regillo, C.D., Harris, A. (Eds.), Retina and Optic Nerve Imaging, rst ed. Lippincott Williams & Wilkins, Philadelphia, pp. 119136. Rosen, R.B., Podoleanu, A.Gh. Rogers, J.A., Garcia, P., Lydon, C., Dunne, S., Dobre, G., Gentile, R., Rosenthal, J., Muldoon, J.T., Orlock, D.A., Fisher, Y., Yannuzzi, L.A., 2004. Challenges and recognizable patterns in the en-face OCT of the retina. In: Tuchin, V.V., Izatt, J.A., Fujimoto, J.G. (Eds.), Coherence Domain Optical Methods and Optical Coherence Tomography, Conference in Biomedicine VIII. Proc. SPIE 5316, 1622. Rosen, R.B., Hathaway, M., Rogers, J., Pedro, J., Garcia, P., Dobre, G.M., Weitz, R., Podoleanu, A.Gh., 2006. Simultaneous OCT/SLO/ICG System, Biomedical Optics Conference, San Jose, 2126 January 2006, Proc. SPIE 6079, 60790A-160790A6. Rudolph, G., Kalpadakis, P., Bechmann, M., Haritoglou, C., Kampik, A., 2003. Scanning laser ophthalmoscope-evoked multifocal ERG (SLO-mfERG) in patients with macular holes and normal individuals. Eye 17 (7), 801808.
Saito, W., Yamamoto, S., Hayashi, M., Ogata, K., 2003. Morphological and functional analyses of adult onset vitelliform macular dystrophy. Br. J. Ophthalmol. 87, 758762. Sawatari, T., 1973. Optical heterodyne scanning microscope. Appl. Opt. 12 (11), 27682772. Schweitzer, D., Hammer, M., Schweitzer, F., 2005. Limits of the confocal laserscanning technique in measurements of time-resolved autouorescence of the eye-ground. Biomed. Technol. 50, 263267. Smith, L.M., Dobson, C.C., 1981. Absolute displacement measurements using modulation of the spectrum of white light in a Michelson interferometer. Appl. Opt. 28 (15), 33393342. Srinivasan, V.J., Wojtkowski, M., Fujimoto, J.G., Duker, J.S., 2006. In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography. Opt. Lett. 31, 23082310. Srinivasan, V.J., Huber, R., Gorczynska, I., Fujimoto, J.G., Jiang, J.Y., Reisen, P., Cable, A.E., 2007. High-speed, high-resolution optical coherence tomography retinal imaging with a frequency-swept laser at 850 nm. Opt. Lett. 32 (4), 361363. Swanson, E.A., Izatt, J.A., Hee, M.R., Huang, D., Lin, C.P., Schuman, J.S., Puliato, C.A., Fujimoto, J.G., 1993. In vivo retina imaging by optical coherence tomography. Opt. Lett. 18, 18641866. Takada, K., Himeno, A., Yukimatsu, K., 1991. Phase-noise and shot-noise operations of low coherence optical time domain reectometry. Appl. Phys. Lett. 59, 24832485. Targowski, P., Wojtkowski, M., Kowalczyk, A., Bajraszewski, T., Szkulmowski, M., Gorczynska, W., 2004. Complex spectral OCT in human eye imaging in vivo. Opt. Commun. 229, 7984. Trifanov, I., Hughes, M., Podoleanu, A.Gh., 2008. J. Biomed. Opt., in press. Tuohy, S., Bradu, A., Podoleanu, A.Gh., Chateau, N., Dainty, C., 2007. Correcting ocular aberrations in optical coherence tomography. In: Sixth International Workshop on Adaptive Optics in Industry and Medicine, Galway Ireland, 1215 June, Imperial College Press (World Scientic), 359365. van Velthoven, M.E.J., Verbraak, F.D., Yannuzzi, L.A., Rosen, R.B., Podoleanu, A.Gh., De Smet, M.D., 2006. Imaging the retina by en face optical coherence tomography. Retina-J. Ret. Vit. Dis. 26, 129136. van Velthoven, M.E.J., Faber, D.J., Verbraak, F.D., van Leeuwen, T.G., de Smet, M.D., 2007. Recent developments in optical coherence tomography for imaging the retina. Prog. Retinal Eye Res. 26, 5777. Venkateswaran, K., Roorda, A.M., Romero-Borja, F., 2004. Theoretical modeling and evaluation of the axial resolution of the adaptive optics scanning laser ophthalmoscope. J. Biomed. Opt. 9 (1), 132138. Vogel, C.R., Arathorn, D.W., Roorda, A., Parker, A., 2006. Retinal motion estimation in adaptive optics scanning laser ophthalmoscopy. Opt. Express 14, 487497. Webb, R.H., 1990. Scanning laser ophthalmoscope. In: Masters, B.R. (Ed.), Noninvasive Diagnostic Techniques in Ophthalmology. Springer, New York, pp. 438450. White, B.R., Pierce, M.C., Nassif, N., Cense, B., Park, B.H., Tearney, G.J., Bouma, B.E., Chen, T.C., de Boer, J.F., 2003. In vivo dynamic human retinal blood ow imaging using ultra-high-speed spectral domain optical Doppler tomography. Opt. Express 11 (25), 34903497. Wojtkowski, M., Srinivasan, V.J., Ko, T.H., Fujimoto, J.G., Kowalczyk, A., Duker, J.S., 2004. Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation. Opt. Express 12 (11), 24042422. Wojtkowski, M., Srinivasan, V., Fujimoto, J.G., Ko, T., Schuman, J.S., Kowalczyk, A., Duker, J.S., 2005. Three dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology 112, 17341746. Woon, W.H., Fitzke, F.W., Bird, A.C., Marshall, J., 1992. Confocal imaging of the fundus using a scanning laser ophthalmoscope. Br. J. Ophthalmol. 76, 470474. Xu, R., Qiang, B., Roberts, C., 2006. Retinal tissue oxygen imaging by near infrared light and white light interferometry. Proc. SPIE 6138, L1381. Yazdanfar, S., Rollins, A.M., Izatt, J.A., 2003. In vivo imaging of human retinal ow dynamics by color Doppler optical coherence tomography. Arch. Ophthalmol. (Chicago) 121 (2), 235239. Youngquist, R.C., Carr, S., Davies, D.E.N., 1987. Optical coherence-domain reectometry: a new optical evaluation technique. Opt. Lett. 12 (3), 158160. Yasuno, Y., Sutoh, Y., Makita, S., Itoh, M., Yatagai, T., 2003. Polarization sensitive spectral interferometric optical coherence tomography for biological samples. Opt. Rev. 10 (5), 498500. Yasuno, Y., Hong, Y.J., Makita, M., Yamanari, M., Akiba, M., Miura, M., Yatagai, T., 2007. In vivo high-contrast imaging of deep posterior eye by 1-mm swept source optical coherence tomography and scattering optical coherence angiography. Opt. Express 15, 61216139. Zawadzki, R.J., Jones, S.M., Olivier, S.S., Zhao, M.T., Bower, B.A., Izatt, J.A., Choi, S., Laut, S., Werner, J.S., 2005. Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging. Opt. Express 13, 85328546. Zawadzki, R.J., Choi, S.S., Jones, S.M., Oliver, S.S., Werner, J.S., 2007. Adaptive opticsoptical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions. J. Opt. Soc. Am. A 24, 13731383. Zhang, Y., Roorda, A., 2006. Evaluating the lateral resolution of the adaptive optics scanning laser ophthalmoscope. J. Biomed. Opt. 11, 014002014015. Zhang, Y., Rha, J.T., Jonnal, R.S., et al., 2005. Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina. Opt. Express 13, 47924811.

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Progress in Retinal and Eye Research 27 (2008) 464 499

Contents lists available at ScienceDirect

Progress in Retinal and Eye Research

Combinations of techniques in imaging the retina with high resolution

150 118b 100 285

Not contemplated 6095

16 (8)c 0.85 0.5 0.019 38.2c(or 8.25) 8.83c 12.8d 17

1.27 3j 0.56c 0.0026d

SLOWEST SLOW FAST X

Image Depth 1 PC Low coherence source Image Depth 2 Control of depth 2

TD-OCT Resonant scanner

0.019 0 1998 2000 2002 Year 2004 2006

SLO/OCT Aperture OPD control Interferometer

OCT Aperture OPD control Interferometer

OCT Optical source

SLO Optical source

Fig. 7. Generic congurations used in the combination of OCT with SLO.

Fig. 9. Illustration of synergy between C-scans and B-scans.

Signal processing unit

Reference path adjustment

Fluorescence emission filter ICG Optical Receiver

SLO Optical Receiver

Variable scan frame grabber

3 mm Pupil 4 mm Pupil 5 mm Pupil 6 mm Pupil

1.2 1 0.8 0.6 0.4 0.2 0 0.5

3 mm Pupil 4 mm Pupil 5 mm Pupil 6 mm Pupil

1.2 1 0.8 0.6 0.4 0.2

0 -5 -10 -15 -20 -25 -30 -35 -40 -45 -50

SLO OCT OCT/SLO OCT/SLO/uorescence

Unsuitable if AO correction is ideal O, Post acquisition only

Unsuitable if AO correction is ideal O, Post acquisition only

Unsuitable if AO correction is ideal Quasi-simultaneously

In principle possible, but no report

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