Perspectives in Medicine (2012) 1, 8993

Bartels E, Bartels S, Poppert H (Editors):

New Trends in Neurosonology and Cerebral Hemodynamics an Update.
Perspectives in Medicine (2012) 1, 8993

journal homepage: www.elsevier.com/locate/permed

Clinical application of laser Doppler owmetry

in neurology
Zlatka Stoyneva

15 Acad. Ivan Geshov Str., St. Ivan Rilsky University Hospital, 1404 Soa, Bulgaria

KEYWORDS Summary Laser Doppler owmetry is a contemporary method for microcirculatory investiga-
Laser Doppler tion used in different medical elds including neurology.
owmetry; Aim: To present principles and clinical application of laser-Doppler method in neurology and
Clinical application; related pathologies.
Neurology Methods: The diagnostic value was studied by evaluating systematic literature and personal
experience. It is based on Doppler principle and uses a laser-generated monochromatic light
beam, a ber-optic probe and sensitive photodetectors. The tissue perfusion of a sample volume
is calculated by multiplying the number of moving blood cells and their velocity and is presented
in perfusion units.
Results: A high diagnostic value was established in studying microcirculation and its autoreg-
ulation using a battery of functional tests for evaluation of vasomotor response mediated by
sympathetic neural, axon-reex, receptor or endothelial mechanisms. It has clinical signi-
cance in assessment of Raynauds phenomenon, distal autonomic neuropathy of the small C
bers due to diabetes mellitus, peripheral arterial occlusive disease, systemic autoimmune
diseases, chronic venous insufciency, peripheral neuropathies, for medical expertise of occu-
pational diseases as hand-arm vibration syndrome, toxic neuropathies, etc. By iontophoretic
transducer different drugs or substances might be applied locally to test an effect, physiological
or pathophysiological mechanisms. Unlike the contemporary ultrasound investigations it studies
the blinded sphere for neurosonology microcirculation and its autoregulation.
Conclusions: Laser Doppler owmetry is a valuable and reliable method for diagnostics of
microcirculation and perfusion, for assessment of autoregulation and effect of treatment,
for experimental studies and research. In combination with ultrasound sonography it gives a
thorough information for both macro- and microcirculation.
2012 Elsevier GmbH. Open access under CC BY-NC-ND license.

Corresponding author. Tel.: +359 2 9525934.

E-mail address: zlatka stoyneva@yahoo.com

2211-968X 2012 Elsevier GmbH. Open access under CC BY-NC-ND license.

http://dx.doi.org/10.1016/j.permed.2012.03.009
90
Introduction
Laser Doppler owmetry (LDF) is a contemporary noninva-
sive method for microvascular investigation used in different
medical elds including neurology.
The Doppler shift of the laser beam is the carrier of the
information about microcirculatory blood ow.
Many studies have proved reliable correlations between
LDF and clearance of 133Xe [1], uorescence owmetry [2],
venous occlusion plethysmography and heat thermal clear-
ance [3] as methods for microcirculatory investigations.
Unlike plethysmography and isotope clearance techniques
LDF monitors and records sudden microcirculatory changes
and reex responses to sympathetic vasomotor stimuli [4]
giving a reproducible parameter of sympathetic vasomotor
control [5].
The aim of the study was to present the principles and
clinical application of laser-Doppler method in neurology
and related pathologies.
Methods
The diagnostic value of LDF was studied by evaluating the
systematic literature and our personal experience submit-
ting some data for illustration.
Results
The working of LDF is based on Doppler principle using a
laser-generated monochromatic light beam, a transducer
with optic bers and sensitive photodetectors. The light
beam is reected and scattered by the moving blood cells
undergoing a change of the wave length (Doppler shift),
dependent on the number and velocities of the cells in the
investigated sample volume but not on the direction of their
movement [6]. The scattered laser beam is perceived by
detectors with the help of optic bers. The signals are ana-
lyzed giving values to the number of the cells and their
velocities and perfusion is their product.
The depth of penetration of laser beam depends on the
tissue characteristics and its vascularisation, on the length
of the light wave, the distance between the optic bers.
So the penetration of light source with wave length 633 nm
is less than that with 780 nm. By investigation of the skin
the depth is from 0.5 to 1.5 mm, and the sample volume is
about 1 mm3 . Only the movement in microvessels but not in
the bigger blood vessels contributes to the perfusion value
because the vessel wall is enough to exclude the greatest
part of the laser beam.
Calibration of different apparatuses makes their values
equal.
LDF of the skin is easiest to access noninvasively and
thus global skin blood ow including both nutritious (cap-
illaries) and thermoregulatory (arterioles, venules and their
shunts) microvessels is investigated. The information about
thermoregulatory blood ow prevails because the blood ow
from the richly sympathetically innervated arterio-venular
anastomoses and subpapillary plexus contribute predomi-
nantly to the laser-doppler signal, especially of the volar site
of the hand and plantar site of the feet. About 9098% of the
Z. Stoyneva
Figure 1 Finger pulp perfusion during venoarteriolar test in
Raynauds phenomenon patients [16]. PU perfusion units at
a nger pulp; PUi initial perfusion; PUb basal perfusion
at 32 C; PUh perfusion at heart level; PUd perfusion in
the dependent hand; Controls group of healthy controls, Pri-
mary RP primary RP group; SSc RP secondary RP group due
to sclerodermy; Vibration RP secondary vibration-induced RP
group; *p < 0.05; **p < 0.0001 in relation to previous perfusion
value according to Wilcoxon matched pairs signed rank test.
nger pulp ow passes through arteriovenular anastomoses
[7].
Registration of initial skin perfusion in controlled stan-
dard laboratory conditions is measured at rst with the
natural supercial skin temperature of the patient and then
the perfusion is recommended to be measured at 3233
Celsius supercial skin temperature in order to make skin
perfusion at a denite site between different persons com-
parable.
The accuracy and sensitivity of LDF is improved by
applying standardized functional tests [8]. Monitoring of
microvascular responses to autonomic vasomotor stimuli is a
recognized method for functional diagnosis and assessment
of peripheral dysautonomy and function of small unmyeli-
nated autonomic bers [9].
Thus in orthostatic test constriction of skin precapil-
lary and arteriolar sphincters and microvessels due to the
increased sympathetic mediation induces a decrease of
skin blood ow. Posture changes of the limbs below heart
level activate sympathetic venoarteriolar axon-reex mech-
anisms and cause increased skin microvascular resistance
like in orthostatism with decrease of skin perfusion. Testing
of veno-arteriolar reex at the nger pulp by LDF is an indi-
cator of unmyelinated autonomic C ber function [8] and
pure postganglionic sympathetic nervous activity [10]. It is
more sensitive method for assessment of autonomic dysfunc-
tion than the sympathetic skin response [11].
Vasoconstrictor response is changed in the limbs of
patients with peripheral arterial occlusive disease [12], dia-
betic [13] or venous hypertensive microangiopathy [14]. In
diabetics type 2 and patients with chronic venous insuf-
ciency a primary defect of venoarteriolar axon-reex
is speculated [7]. Dysregulation of feedback mechanisms
between venules, identifying the transmural pressure and
arterioles, controlling precapillary resistance is found in sec-
ondary Raynauds phenomenon, too [15,16] (Fig. 1).
Inspiratory tests of Valsalva, deep breathing, deep
inspiration with abdominal arrest induce sympathetic vaso-
constriction activity with signicant decrease of skin
perfusion. Peripheral microvascular resistance is signi-
cantly decreased in diabetes mellitus.
By cold test a somatic afferent part consisted of pain
and temperature nerve bers in the skin and a sympathetic
Clinical application of laser Doppler owmetry 91

efferent vasoconstrictor part of the reex arch is evalu-

ated. The effectiveness of the response after cold stress
test with temperature below 15 Celsius might be an index
of a sympathetic vasoconstrictor activity [17,18].
Tests of isometric muscular constriction and emotional
stress also induce sympathetic skin vasoconstriction [19,20].
By heating test an axon-reex mediated thermoregu-
latory microvascular vasodilation is studied as a result of
activation of heat-induced nociceptors even at a lack of
conscious perception of heat-induced pain [21]. The release
of vasoactive peptides from primary nociceptor afferents
cause an initial local heat-induced vasodilation at temper-
atures above 40 Celsius followed by a sustained plateau
phase induced by nitric oxide. Thermoregulatory vasomotor
responses are abnormal in Raynauds phenomena (Fig. 2) and
diabetic foot (Fig. 3).
Reactive hyperemia test is mediated by local endothelial
dependent vasodilator factors with signicant decrease of
skin vascular resistance and sudden increase of skin perfu-
sion in healthy persons (Fig. 4). Microcirculatory vasodilator
reactivity in response to ischemia reects functional
integrity of terminal vessels and assesses microvascular
endothelial dependent dilator capacity in physiological and
pathological conditions. Figure 2 Perfusion at nger pulps during heating test in Ray-
Vascular responses to drugs or chemical substances as nauds phenomenon patients [22]. PU perfusion units at a
physiological or pathophysiological mechanisms in differ- nger pulp; PUi initial perfusion; PUb basal perfusion at
ent diseases can be studied experimentally by using an 32 C; PUh perfusion at 44 C; PUc perfusion back to 32 C;
iontophoresis system for delivering minute volumes of a sub- Controls group of healthy controls; Primary RP primary
stance non-invasively in a controlled fashion together with RP group; SSc RP secondary RP group due to sclerodermy;
LDF. Vibration RP secondary vibration-induced RP group.
Along with other spheres of application LDF is a valu-
able method in neurology to diagnose small ber neuropathy

Figure 3 Heating test applied to tiptoes in a healthy person (A) and diabetic patients (BD) with reduced or absent responses to
heating and/or cooling [23].
92
Figure 4 Reactive hyperemia test applied to tiptoes in healthy persons (A, B) and diabetic patients (C, D)[23].
and distal acral vasomotor dysautonomia as an idiopathic
or secondary manifestation of polyneuropathies, radicu-
lopathies, mononeuropathies, reex sympathetic dystrophy,
neurovascular syndromes caused by diabetes mellitus, thy-
roid dysfunction, rheumatic diseases, amyloidosis, lepra,
AIDS, venous limb insufciency, neuropathic pain or occu-
pationally induced by overstrain, vibration, micrortrauma,
toxic exposure, etc.
The method is valuable to follow up the effect of applied
therapy. It is reliable and with very good reproducibility.
A laser Doppler blood perfusion imager is created scan-
ning tissue with a low-power laser beam and colour-coded
images of the blood perfusion in the microvasculature.
Conclusions
Unlike the contemporary ultrasound investigations laser
Doppler owmetry studies the blinded sphere for neu-
rosonology, i.e. microcirculation and its autoregulation.
Laser Doppler owmetry is a valuable, easy to use, non-
expensive microcirculatory method of investigation which
in combination with ultrasound sonography gives thorough
information for both macro- and microcirculation.
Laser-generated monochromatic light beam is directed
towards the surface of the investigated tissue by a probe
with optic bers. The tissue perfusion of the investigated
sample volume monitored by the owmeter is calculated
automatically by multiplying the number of the moving
blood cells and their velocity and is presented in perfusion
units (PU).
Laser beam penetrates tissues, so monitoring of perfusion
is noninvasive. for assessment of the integrity of con-
strictor microcirculatory mechanisms. Afterwards with
Z. Stoyneva
increased skin ux, decreased venoarteriolar response
and increased skin ltration inducing edema
Using functional reex vasomotor tests contribute for
differentiation of primary from secondary Raynauds
phenomenon. diabetic distal sympathetic neuropathy
and microangiopathy; small ber neuropathy; polyneu-
ropathies or radiculopathies with autonomic dysfunction.,
distal sympathetic neuropathy, neurovascular syndromes,
toxic neuropathies and microvascular reex vasomotor
reactivity and evaluation of microcirculatory vasomotor
response mediated by sympathetic neural, axon-reex,
receptor or endothelial mechanisms;
It is reliable to follow up the effect of applied therapy.
Measurements are less dynamic than with the probe-based
single-point laser Doppler monitor but the microcircula-
tion can be studied over a larger area.
Laser Doppler owmetry not only measures and monitors
microvascular blood ow but also evaluates microcircula-
tion and its autoregulation.
References
[1] Tur E, Tur M, Maibach HI, Guy RH. Basal perfusion of
the cutaneous microcirculation: measurements as a function
of anatomic position. Journal of Investigative Dermatology
1983;81:4426.
[2] Proano E, Svensson L, Perbeck L. Correlation between the
uptake of sodium uorescein in the tissue and xenon-133 clear-
ance and laser Doppler uxmetry in measuring changes in skin
circulation. International Journal of Microcirculation: Clinical
and Experimental 1997;17:228.
[3] Saumet JL, Dittmar A, Leftheriotis G. Non-invasive measure-
ment of skin blood ow: comparison between plethysmog-
raphy, laser-doppler owmeter and heat thermal clearance
Clinical application of laser Doppler owmetry
method. International Journal of Microcirculation: Clinical and
Experimental 1986;5:7383.
[4] Oberg PA. Laser-Doppler owmetry. Biomedical Engineering
1990;18:12563.
[5] Hilz MJ, Hecht MJ, Berghoff M, Singer W, Neundoer-
fer B. Abnormal vasoreaction to arousal stimuli-an early
sign of diabetic sympathetic neuropathy demonstrated by
laser Doppler owmetry. Journal of Clinical Neurophysiology
2000;17:41925.
[6] Oberg PA. Blood ow measurements. Linkoping University: CRC
Press; 1999.
[7] Nuzzaci G, Evangelisti A, Righi D, Giannico G, Nuzzaci I. Is
there any relationship between cold-induced vasodilatation
and vasomotion? Microvascular Research 1999;57:17.
[8] Wahlberg E, Olofsson P, Swedenborg J, Fagrell B. Level of arte-
rial obstruction in patients with peripheral arterial occlusive
disease (PAOD) determined by laser Doppler uxmetry. Euro-
pean Journal of Vascular Surgery 1993;7:6849.
[9] Abbot NC, Beck JS, Mosto S, Weiss F. Sympathetic vasomotor
dysfunction in leprosy patients: comparison with electro-
physiological measurement and qualitative sensation testing.
Neuroscience Letters 1996;206:5760.
[10] Birklein F, Riedl B, Neundorfer B, Handwerker HO. Sympa-
thetic vasoconstrictor reex pattern in patients with complex
regional pain syndrome. Pain 1998;75:93100.
[11] Wilder-Smith A, Wilder-Smith E. Electrophysiological evalu-
ation of peripheral autonomic function in leprosy patients,
leprosy contacts and controls. International Journal of Leprosy
and Other Mycobacterial Diseases 1996;64:43340.
[12] Creutzig A, Caspary L, Alexander K. Disturbances of skin micro-
circulation in patients with chronic arterial occlusive disease
and venous incompetence. VASA 1988;17:7783.
[13] Rayman G, Hassan A, Tooke JE. Blood ow in the skin of the foot
related to posture in diabetes mellitus. British Medical Journal
1986;292:8790.
93
[14] Belcaro G, Laurora G, Cesarone MR, De Sanctis MT, Incandela
L. Microcirculation in high perfusion microangiopathy. Journal
of Cardiovascular Surgery 1995;36:3938.
[15] Edwards CM, Marshall JM, Pugh M. Cardiovascular responses
evoked by mild cool stimuli in primary Raynauds disease: the
role of endothelin. Clinical Science (London) 1999;96:57788.
[16] Stoyneva Z. Laser Doppler-recorded venoarteriolar reex
in Raynauds phenomenon. Autonomic Neuroscience
2004;116:628.
[17] Kurvers HA, Tangelder GJ, De-Mey JG, Slaaf DW, Beuk RJ, van-
den-Wildenberg FA, et al. Skin blood ow abnormalities in a
rat model of neuropathic pain: result of decreased sympathetic
vasoconstrictor outow? Journal of the Autonomic Nervous Sys-
tem 1997;63:1929.
[18] Hodges GJ, Traeger 3rd JA, Tang T, Kosiba WA, Zhao K, John-
son JM. Role of sensory nerves in the cutaneous vasoconstrictor
response to local cooling in humans. American Journal of Phys-
iology Heart and Circulatory Physiology 2007;293:H7849.
[19] Tuck RR, McLeod JG. Vasomotor function and dysfunction. In:
Asbury AK, McHaun GM, McDonald WI, editors. Diseases of the
Nervous System. Clinical Neurobiology, III, 2nd ed. London,
Toronto, Montreal, Sydney, Tokyo, Philadelphia: WB Saunders
Co.; 1992. p. 46888.
[20] Stanton AW, Levick JR, Mortimer PS. Assessment of noninvasive
tests of cutaneous vascular control in the forearm using a laser
Doppler meter and a Finapres blood pressure monitor. Clinical
Autonomic Research 1995;5:3747.
[21] Tew GA, Klonizakis M, Moss J, Ruddock AD, Saxton JM, Hodges
GJ. Role of sensory nerves in the rapid cutaneous vasodilator
response to local heating in young and older endurance-trained
and untrained men. Experimental Physiology 2011;96:16370.
[22] Stoyneva Z. Raynauds Phenomenon. Soa: AEM AMS Infopress;
2006. p. 252 (in Bulgarian).
[23] Stoyneva Z. Diabetic Peripheral Neuropathy. Soa: AEM AMS
Infopress; 2004. p. 260 (in Bulgarian).