Diffuse Optics: Fundamentals & Tissue Applications

Diffuse Optics: Fundamentals
& Tissue Applications

Arjun G. Yodh
Department of Physics & Astronomy
University of Pennsylvania
Acknowledgement: NIH, ARMY

Outline
• Brief Introduction/Motivation
• Light Transport
• Single Scattering
• Multiple Scattering (Linear Transport & Diffusion Equations)
• Solutions (Homogeneous Turbid Media)
• Solutions (‘Simple’ Heterogeneous Turbid Media)
• Image Reconstruction
• Temporal Fluctuations: Diffuse Correlation Transport
• Biomedical Motivations Revisited
• Background on Hemodynamics
• Oxygen Metabolism
• Validation of the Techniques
• In-Vivo Biomedical Applications (recent)
• Breast
• Brain
• Cancer Therapy Monitoring
• Summary/Future/Acknowledgements
The Dream.
from: Star Trek

from: Minority Report
In-Vivo Optical Biopsy
• Near Infrared Light
Penetrates Tissue
• Sensitivity to Tissue
Physiology
• Unique Contrasts are
Complementary to Other
Medical Diagnostics
• Non-invasive, safe,
rapid, portable,
continuous,
inexpensive ...
Imaging & Monitoring
Clinical Scenarios
• Stroke detection and monitoring
• Cancer Imaging and Diagnosis
• Cancer Therapy monitoring
• Mitochondial diseases
• Epilepsy
• Brain Activation
• Muscle Activation
(Peripheral Vascular Disease)
Outline
• Light Transport
• Breast
• Brain
Light Transport
E0, I0 ?
• How are photons lost from the

incident light beam?
Absorption (linear response)
L
-μaL
I0 It = I 0 e
μa = Absorption Coefficient
μa = [Absorber Concentration] ε (λ)
Extinction Light
Coefficient Wavelength
Absorption Information
L
I0 It = I0 e -μaL
• What molecules are present?

(Hemoglobin, water, lipids, …)
• What are their concentrations?
• What is their local environment?
(spectral shifts & broadening)
Scattering (single scattering limit)
Is (θ )
θ
I0 -μsL
It = I 0 e
L
μs = Scattering Coefficient
μs = [Scatterer Concentration]σs (λ)
Scattering Light
Cross-section Wavelength
Scattering (single scattering limit)
Is (θ)
I0
θ
σd (θ) = Differential Scattering Cross-section
It = I0 e -μsL
L σs = σd (θ) dΩ
Is (θ) = σd (θ) I0
1
(g = anisotropy factor = σ σd (θ) cos (θ) dΩ) = 〈cos (θ)〉 )
s
μs’ = reduced scattering coefficient = μs (1-g)

(μs’)-1 = photon random walk step length
Scattering Information
Is (θ)
θ
I0
It = I0 e -μsL
L
• What are the scatterers?
(particles, organelles, cells, cell-networks)
• What are scatterer concentrations?
• What is their local environment?
(surrounding fluids)
Scattering: Temporal Fluctuations
time
• What is moving?
(organelles, red blood cells, …)
• How much is moving, how fast &
what is the manner of motion?
(Blood flow)
Traditional Optical Techniques
• Rigorous
• Tested
θ
I0 -(μs + μa ) L
It = I 0 e
L
Outline
• Light Transport
• Breast
• Brain
Problem of Tissue: Multiple Scattering
Linear Transport Theory
= Radiance [W/(cm2 sr)]
Power/Area-Angle at traveling in direction .
L ~ 〈E*(r,t) E(r,t)〉
Radiance is balanced in each

small volume of medium.
Transport
Transport Theory:
Theory: Convective
Convective Time
Time Derivative
Derivative
dr
Transport
Transport Theory:
Theory: Microscopic
Microscopic Sources
Sources &
& Sinks
Sinks
dr
Absorption & Radiance Sources

Scattering Losses Scattered into Ω
μt = μa + μs
Linear Transport Equation
dr
μt = μa + μs
Photon Fluence Rate & Flux
Fluence rate (W/cm2)
Flux (W/cm2)
PNN Approximation
Fluence & Flux in PNN Approximation
Radiance in the P11 Approximation (N=1)
Substitute P1 form of L into the linear transport equation.
Photon Diffusion Equation
Photon Diffusion Equation: Assumptions
• Scattering length much smaller

than absorption length
• Fluence rate much greater than
Flux (radiance is largely isotropic)
• Isotropic sources
(breaks down close to fiber sources)
•
•
(ω << υ μs’ )
Photon Diffusion Equation: Assumptions
(μs)-1 ~ 0.01 - 0.1 mm
• OK for Tissues (μs’)-1 ~ 1 mm
(μa)-1 ~ 2 - 10 cm
υ(μs’) ~ 300 MHz
• Scattering (on average)

Independent of Incident Direction.
• Tissue Measurements are NOT Precision
Measurements.
Outline
• Light Transport
• Breast
• Brain
Ideal Solutions
• Infinite
homogeneous
turbid media
• Point sources
Frequency Domain: Diffuse
Photon Density Waves*
*first suggested by Enrico Gratton

Frequency Domain: Point
Sources & Green’s Functions
If ,
= Green’s Function Solution.
for arbitrary source distribution

Frequency Domain: Point
Sources & Green’s Functions
• Point Source at the Origin in Infinite Homogeneous Media

• Diffuse Photon Density Waves
• Frequency Dispersion
Diffusive Wave Optics
Boas, Oleary, Chance, Yodh. Physical Review E, 47(5) 1993.

Oleary, Boas, Chance, Yodh. Physical Review Letters, 69 1992.
Time Domain Solution
Time Resolved Reflectance and Transmittance for The Noninvasive

Measurement of Tissue Optical-Properties, Patterson, MS, Chance, B,
Wilson, BC, Applied Optics 28, 1989
What has been gained?
• Can separate scattering from
absorption.
• Can measure absorption in turbid
media.
• Can measure scattering (photon
random walk step) in turbid media.
What about heterogeneous media?
Outline
• Light Transport
• Breast
• Brain
Boundary Conditions: Semi-infinite Media
• e.g. Air-Tissue Boundary

• Fiber Source Changed to Displaced Point Source
(lt ~ (μs’)-1 )
Boundary Conditions: Semi-infinite Media
• R(θ) is a Fresnel Coefficient

Semi-infinite
Semi-infinite Media:
Media: Partial-flux
Partial-flux Boundary
Boundary Condition
Condition
• Reff depends on indices of refraction (easily calculated)

• Ls approximately (μs’)-1
Extrapolated Zero-boundary Condition
≈
Solutions: Semi-infinite Medium
• Method of images
Solutions: Semi-infinite Medium
ρ2
Danen, R.M., Wang, Y., Li, X.D., Thayer, W.S., and Yodh, A.G., Photochemistry and Photobiology. 67, 33-40 (1998)
Solutions: Slab Medium
Spectroscopy:
Spectroscopy: Absorption
Absorption Coefficients vs. λλ
Coefficients vs.
Total Hemoglobin Concentration = [HbO2] + [Hb] = THC

THC =
Tissue Oxygen Saturation = [HbO2] / THC = StO2

Outline
• Light Transport
• Breast
• Brain
Image Reconstruction
Arridge SR, Optical tomography in medical imaging, Inverse Problems 15, R41-R93, 1999
Image Reconstruction
= D0 + ΔD
(Born)
(Rytov)
Basic Scattering Theory (Example)
ΔD = 0
Green’s Function
>> , Incident wave, Green’s function ~
Inverting the Data
Discretize the Integral
Inverting the Data (one-step)
[φ] = W [δμa] (Set of linear equations)
[δμa] = W [φ] -1
Principles of Computerized Tomographic Imaging by Avinash C. Kak, Malcolm Slaney

Inverting the Data (iteratively)
3D Image Reconstruction
Finite difference forward calculation, parallel processor implementation.
Culver, J.P., Choe, R., Holboke, M.J., Zubkov, L., Durduran, T., Slemp, A., Ntziachristos,
V., Pattanayak, D.N., Chance, B., and Yodh, A.G., Medical Physics 30, 235-247 (2003)
Outline
• Light Transport
• Breast
• Brain
(Single) Dynamic Light Scattering
Correlation Transport Equation
~ 〈E*(r,t+τ) E(r,t)〉
B. J. Ackerson, R. L. Dougherty, N. M. Reguigui, and U.Nobbman, "Correlation transfer: application of radiative transfer
solution methods to photon correlation problems," J. Thermophys. Heat Transfer 6, 577–588 (1992).
R. L. Dougherty, B. J. Ackerson, N. M. Reguigui, F. Dorri-Nowkoorani, and U. Nobbmann, "Correlation transfer:

development and application," J. Quant. Spectrosc. Radiat. Transfer. 52, 713–727 (1994).
P11 Approximation (Again)
α
Correlation Diffusion Equation

D. A. Boas, L. E. Campbell, and A. G. Yodh, Phys. Rev. Lett. 75, 1855–1858 (1995).
is Light Diffusion Coefficient. α = fraction of scatterers that move.
Differential Form of Diffusing-Wave Spectroscopy (DWS)

G. Maret and P. E. Wolf, Z. Phys. B 65, 409–413 (1987); D. J. Pine, D. A. Weitz,
P. M. Chaikin, and E. Herbolzheimer, Phys. Rev. Lett. 60, 1134–1137 (1988).
Remainder Analysis Formally Same
as Photon Diffusion Equation
• Solutions ~ ,
α
(k0 )2 3
• Diffuse Correlation Imaging &

Spectroscopy
Measurements of Blood Flow
Blood Flow Index (BFI)
Γ gives α〈Δr2 (τ)〉

〈Δr2 (τ)〉 ~ Db τ
αDb = BFI
α = fraction of scatterers moving
Db = effective diffusion constant
rBFI = relative blood flow change
Outline
• Light Transport
• Breast
• Brain
Sensitivity to Tissue Physiology
1. Absorption Variations [μa(λ)]
- Access to tissue chromophore concentrations
- Hemoglobin Concentration (Hb), Blood Volume
- Blood Oxygen Saturation (HbO2/[Hb + HbO2])
- Water, Lipids
2. Exogenous Contrast Agents
- Absorption Contrast, Drugs,… [μa(λ)]
- Fluorescence [c], τlifetime
- Uptake & Clearance [μa(λ)], [c(t)]
3. Scattering Variations [μs,(λ)]
- Organelle Concentrations (mitochondria,…)
- Background fluids, n(λ,t).
4. Motions of Scatterers [〈Δr2(τ)〉], Γ, BFI
- Average Blood Flow Density
- Brownian Dynamics
Circulatory
System
Images from Human

Physiology by Vander,
Sherman and Luciano,
Chapter 13.
Circulatory System
At any given time, some of the
Hemoglobin carried in the red
blood cells is oxygenated (HbO2)
and some is deoxygenated (Hb).
Images from Human

Physiology by Vander,
Sherman and Luciano,
Chapter 13.
Oxygen Exchange
• 98% of Oxygen in Blood is

bound reversibly to hemoglobin.
• O2 (dissolved gas) + Hb ↔ HbO2

• “Blood Volume/Concentration”: [Hb] + [HbO2]
• Blood Oxygen Saturation (SO2): [HbO2] / ([Hb] + [HbO2] )
Hypoxia:
Hypoxia: Deficiency
Deficiency of
of Oxygen
Oxygen at
at Tissue
Tissue Level
Level
O2 IN O2 OUT
Tissues
Arterioles Venules
O2 OUT
(Metabolism)
• Arterial Oxygen too low.
• Blood flow too slow (ischemic hypoxia).
• Local Tissue metabolism too large.
Clinical Scenarios (revisited)
• Stroke detection and monitoring
• Cancer Imaging and Diagnosis
• Cancer Therapy monitoring
• Mitochondial diseases
• Epilepsy
• Brain Activation
• Muscle Activation
(Peripheral Vascular Disease)
[Hb] , [HbO2] , THC, StO2 , BFI , rBFI
Cerebral Oxygen Metabolism: CMRO22
from DOS/NIRS from DCS

Outline
• Light Transport
• Breast
• Brain
DOS: Oxyhemoglobin Dissociation Curve
Mouse erythrocytes in tissue

phantom over the course of
phantom deoxygenation.
Wang, H.-W., Putt, M.E., Emanuele, M.J., Shin, D.E.,

Glatstein, E., Yodh, A.G., and Busch, T.M.,
Treatment-induced changes in tumor oxygenation
predict photodynamic therapy outcome. Cancer
Research 64, 7553-7561 (2004)
Diffuse optics get oxygen saturation (SO2).

Oxygen electrodes get pO2.
Validation of DCS
DCS has been validated:
• against ASL-MRI
• against Xenon-CT
• against Transcranial Doppler Ultrasound
• against Color Doppler Ultrasound
• against Fluorescent Microspheres
• against Laser Doppler
• by comparison to Literature
• in Phantoms
Validating DCS Across Spatial Scales in Brain
DCS vs Laser Doppler: Rat Brain (3cm)
Hypocapnia by
Hyperventilation.
(Flow decreases
during activation
period.)
Live vs Dead Piglet (25 cm)
Chao Zhou, Stephanie A. Eucker, Turgut Durduran, Guoqiang Yu, Jill Ralston, Stuart H.
Friess, Rebecca N. Ichord, Susan S. Margulies, and Arjun G. Yodh. Journal of Biomedical
Optics, 14(3):034015, 2009.
DCS vs Fluorescent Microspheres:
Neonatal Piglet Brain (25 cm)
Flow decrease
measured versus
time after ~200
Radian/sec
rotational head
injury to mimic
traumatic brain
injury in babies.
Hypercapnia (Whole Brain Response)
Two-layer model
Hypercapnia (Scalp Response)
Small (if any) scalp flow change detected during measurement!
DCS Validation with Xenon-CT
with Kofke, Levine, Grady, Detre, Greenberg

Example Patient
DCS vs Xenon-CT: Bed-Side Comparison
Good correlation, good agreement

with Kofke, Levine, Grady, Detre, Greenberg
Outline
• Light Transport
• Breast
• Brain
Diffuse Optical Tomography of Breast
Regine Choe, Soren D. Konecky, Alper Corlu, Kijoon Lee, Turgut Durduran, David R. Busch, Saurav Pathak, Brian J. Czerniecki,
Julia Tchou, Douglas L. Fraker, Angela DeMichele, Britton Chance, Simon R. Arridge, Martin Schweiger, Joseph P. Culver,
Mitchell D. Schnall, Mary E. Putt, Mark A. Rosen, and Arjun G. Yodh, Journal of Biomedical Optics, 14(2):024020, 2009.
Potential niches for DOT in Breast Cancer
Parallel-Plane DOT Instrument
Culver, Choe, Holboke, Zubkov, Durduran, Slemp, Ntziachristos, Chance, Yodh, Medical Physics 30 2003
3D Diffuse Optical Tomography
Invasive Ductal Carcinoma
• 53-year-old post-menopausal female, 2.2 cm invasive ductal carcinoma

Cyst & Invasive Ductal Carcinoma
• 47-year-old pre-menopausal female, 6 cm cyst & 1.3 cm invasive ductal carcinoma

Example: Malignant vs Benign
Malignant: Invasive Ductal Carcinoma

MRI axial slice rTHC rStO 2 Optical Index Region of Interest
Benign: Fibroadenoma
MRI axial slice rTHC rStO 2 Optical Index Region of Interest
Tumor/Normal Endogenous Contrast (N=51)
(A) Benign,
(B) Malignant measured before core biopsy, (C) Malignant measured after core biopsy
Outline
• Light Transport
• Breast
• Brain
Functional Activation In Brain
Functional Activation In Brain
THC = Total Hemoglobin Concentration

StO2 = Blood Oxygen Saturation
rBF = Relative Blood Flow
CMRO2 = Rate of Cerebral Oxygen Metabolism
Motor Stimulus: Optical
Motor Stimulus: Optical
Durduran, T., Yu, G., Burnett, M.G., Detre,

J.A., Greenberg, J.H., Wang, J., Zhou, C.,
and Yodh, A.G., Diffuse optical
measurement of blood flow, blood
oxygenation and metabolism in human
brain during sensorimotor cortex activation.
Optics Letters 29, 1766-1768 (2004).
Population Average (n=5)
Durduran, Yu, Burnett, Detre, Greenberg, Wang, Zhou, Yodh, Optics Letters, 2004
Clinic: Relevant Cerebral Physiology
MAP
ICP
CPP = MAP - ICP

Cerebral Blood Flow Autoregulation
CPP = MAP - ICP

Intracranial Pressure (ICP) Monitoring
Other CBF Monitoring Schemes
• Xenon – CT
• Arterial-Spin-Labeled MRI (ASL-MRI)
• Transcranial Doppler Ultrasound (TCD)
Opportunities for Optics
• Continuous CBF monitoring at the

bedside.
• Direct measurement of Tissue
Microvasculature.
• Combine with NIRS/DOS to get
cerebral metabolism.
Acute Ischemic Stroke Study Protocol
Turgut Durduran, Chao Zhou, Brian L. Edlow,

Guoqiang Yu, Regine Choe, Meeri N. Kim, Brett L.
Cucchiara, Mary E. Putt, Qaisar Shah, Scott E. Kasner,
Joel H. Greenberg, Arjun G. Yodh, and John A. Detre,
Opt. Express, 17(5):3884-3902, 2009.
Cerebral
Cerebral Blood
Blood Flow
Flow vs.
vs. Head
Head of
of Bed
Bed Angle:
Angle:
Healthy
Healthy Subjects
Subjects vs.
vs. Stroke
Stroke Patients
Patients
Common Response
Injured hemisphere doesn’t autoregulate.

Cerebral
Cerebral Blood
Blood Flow
Flow vs.
vs. Head
Head of
of Bed
Bed Angle:
Angle:
Healthy
Healthy Subjects
Subjects vs.
vs. Stroke
Stroke Patients
Patients
Paradoxical Response
Injured hemisphere doesn’t autoregulate.

Results
• HOB position was found to be a significant factor in both

hemispheres (healthy and stroke groups).
• HOB was a stronger factor in the infarcted area which also

showed a larger variation (stroke group).
• “Paradoxical Response” (25% of stroke group): the maximal

CBF occurred at an elevated angle. Therefore, standard clinical
practice of “HOB flat” might not be optimal for all stroke
patients.
Turgut Durduran, Chao Zhou, Brian L. Edlow, Guoqiang Yu, Regine Choe, Meeri N. Kim, Brett L. Cucchiara, Mary E. Putt,
Qaisar Shah, Scott E. Kasner, Joel H. Greenberg, Arjun G. Yodh, and John A. Detre, Opt. Express, 17(5):3884-3902, 2009.
Outline
• Light Transport
• Breast
• Brain
Tumor Therapy Monitoring
Neoadjuvant chemotherapy
Choe, Corlu, Lee, Durduran, Konecky, Grosicka-Koptyra, Arridge, Czerniecki,

Fraker, DeMichele, Chance, Rosen, Yodh, Medical Physics, 32, 2005.
Photodynamic Therapy
Tumor Injection of Illuminated
photosensi tizer by light
Laser
Single t
S1 Intersystem
Crossing Excited Type I Photo-
Trip let O2 -
activa ted
T1 drug
e
1O
2
c
n
e
n
tio
o
rp
induced
s
b
A
Type I I single t
oxygen
c
s
re
o
lu
F
destroys
3O
2 tum or
Diffuse
Diffuse Optical
Optical Measurements
Measurements ofof Tumor
Tumor
Response
Response Before,
Before, During
During &
& After
After PDT
PDT
Measurement Protocol
Radiation-Induced Fibrosarcoma (RIF) mice tumors

Control group = light (135J/cm2 at 75 mW/cm2)
Treated group = light + Photofrin (5 mg/Kg)
Treatment efficacy
Days after PDT for tumor growth to a volume of 400 mm3
(starting volume ~100 mm3)
Before/After PDT
Significant decreases in blood flow and oxygen saturation

Responses During PDT
Large slope → Poor treatment efficacy
Yu, Durduran, Zhou, Wang, Putt, Saunders, Sehgal, Glatstein, Yodh, Busch,
Clinical Cancer Research 11, (2005)
Oxygenation Response Just After PDT
(n = 12)
Low relative - SO2 immediately after PDT → Poor treatment efficacy
Wang, Putt, Emanuele, Shin, Glatstein, Yodh, Busch, Cancer Research 64, (2004)
Summary/Future
• Diffuse Optics Probes Physiology of

Deep Tissues.
• Breast Tumors, Brain, Head & Neck
Tumors, Muscle ...
• Animal Model Research (Pre-clinical)
Summary/Future
• Image Reconstruction (large data sets)
• Image/Data Processing
(composite indices, automated segmentation)
• Flow plus Oxygen gives Metabolism
• Contrast Agents (fluorescence)
• Multi-modal Imaging & Diagnosis
• Near Surface (skin)
• Dosimetry
• Microscopic Origins of Signals
(molecular, tissue level)
• Identify New Applications
Collaborators
PhD Students & Post-docs
Baker, Wes Boas, David Holboke, Monica Ripoll, Jorge
Ban, Han Yong Cheung, Cecil Intes, Xavier Slemp, Alison
Buckley, Erin Cheung,Rex Konecky, Sore Solonenko, Michael
Busch, David Corlu, Alper Lee, Kijoon Sunar, Ulas
Kim, Meeri Culver, Joseph Li, Xingde Vulcan, Teodor
Xing, Xiaoman Danen, Robert Liu, Hanli Wang, Hsing-Wen
Choe, Regine Fisher, Jonathan A. N. Meglinsky, Igor Yu, Guoqiang
Durduran, Turgut Giammarco, Joe Ntziachristos, Vasilis Zhou, Chao
Patak, Saurav Gonatas, Dinos O'Leary, Maureen Zubkov, Leonid
Senior Collaborators
Simon Arridge, University College London, UK Chandrakala (Kala) Menon, University of Pennsylvania
Larry Campbell, Hobart & Williams College Emile Mohler III, University of Pennsylvania
Mark Burnett, University of Pennsylvania Shoko Nioka, Johnson Foundation, Penn/HUP
Theresa Busch, University of Pennsylvania Deva Pattanayak, Vishay Intertechnology Inc.
Britton Chance, University of Pennsylvania Mary Putt, University of Pennsylvania
Brian Czerniecki, University of Pennsylvania Harry Quon, University of Pennsylvania
Angela DeMichele, University of Pennsylvania Nimi Ramanujam, Duke University
John Detre, University of Pennsylvania Robert (Bob) Rogers, University of Delaware
Jared Finlay, University of Pennsylvania (HUP) Mark Rosen, University of Pennsylvania
Tom Floyd, University of Pennsylvania Mitch Schnall, University of Pennsylvania
Doug Fraker, University of Pennsylvania Martin Schwieger, University College London, UK
Joe Friedberg, University of Pennsylvania Chandra (Sandy) Sehgal, University of Pennsylvania
Eli Glatstein, University of Pennsylvania Bruce Tromberg, University of California at Irvine
Joel Greenberg, University of Pennsylvania Qing Zhu, University of Connecticut
Steve Hahn, University of Pennsylvania Tim Zhu, University of Pennsylvania
Daniel Licht, Children's Hospital of Philadelphia (CHOP)

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Diffuse Optics: Fundamentals

& Tissue Applications

Acknowledgement: NIH, ARMY

from: Star Trek

• How are photons lost from the

• What molecules are present?

μs’ = reduced scattering coefficient = μs (1-g)

= Radiance [W/(cm2 sr)]

Power/Area-Angle at traveling in direction .

Radiance is balanced in each

Absorption & Radiance Sources

Fluence rate (W/cm2)

Substitute P1 form of L into the linear transport equation.

• Scattering length much smaller

(μs)-1 ~ 0.01 - 0.1 mm

• OK for Tissues (μs’)-1 ~ 1 mm

υ(μs’) ~ 300 MHz

• Scattering (on average)

*first suggested by Enrico Gratton

= Green’s Function Solution.

for arbitrary source distribution

• Point Source at the Origin in Infinite Homogeneous Media

Boas, Oleary, Chance, Yodh. Physical Review E, 47(5) 1993.

Time Resolved Reflectance and Transmittance for The Noninvasive

What about heterogeneous media?

• e.g. Air-Tissue Boundary

• R(θ) is a Fresnel Coefficient

• Reff depends on indices of refraction (easily calculated)

Total Hemoglobin Concentration = [HbO2] + [Hb] = THC

Tissue Oxygen Saturation = [HbO2] / THC = StO2

>> , Incident wave, Green’s function ~

[φ] = W [δμa] (Set of linear equations)

Principles of Computerized Tomographic Imaging by Avinash C. Kak, Malcolm Slaney

R. L. Dougherty, B. J. Ackerson, N. M. Reguigui, F. Dorri-Nowkoorani, and U. Nobbmann, "Correlation transfer:

Correlation Diffusion Equation

is Light Diffusion Coefficient. α = fraction of scatterers that move.

Differential Form of Diffusing-Wave Spectroscopy (DWS)

• Diffuse Correlation Imaging &

Γ gives α〈Δr2 (τ)〉

Images from Human

Images from Human

• 98% of Oxygen in Blood is

• O2 (dissolved gas) + Hb ↔ HbO2

• Blood Oxygen Saturation (SO2): [HbO2] / ([Hb] + [HbO2] )

[Hb] , [HbO2] , THC, StO2 , BFI , rBFI

from DOS/NIRS from DCS

Mouse erythrocytes in tissue

Wang, H.-W., Putt, M.E., Emanuele, M.J., Shin, D.E.,

Diffuse optics get oxygen saturation (SO2).

Small (if any) scalp flow change detected during measurement!

with Kofke, Levine, Grady, Detre, Greenberg

Good correlation, good agreement

• 53-year-old post-menopausal female, 2.2 cm invasive ductal carcinoma

• 47-year-old pre-menopausal female, 6 cm cyst & 1.3 cm invasive ductal carcinoma

Malignant: Invasive Ductal Carcinoma

THC = Total Hemoglobin Concentration

Durduran, T., Yu, G., Burnett, M.G., Detre,

CPP = MAP - ICP

CPP = MAP - ICP

• Arterial-Spin-Labeled MRI (ASL-MRI)

• Transcranial Doppler Ultrasound (TCD)

• Continuous CBF monitoring at the

Turgut Durduran, Chao Zhou, Brian L. Edlow,