Aspects of determination
of skin oxygenation by near-infrared spectroscopy (overview)
Igor V. Meglinsky1, 2, Stephen J. Matcher1
1- Department
of Physics, University of Exeter,
Exeter, UK
2- Optics Department, Saratov
State University, Saratov,
Russia
E-mail: I.V.Meglinsky@exeter.ac.uk
ABSTRACT
The near-infrared spectroscopy technique is being used
for non-invasive in vivo measurements and quantifying of oxygenation
of hemoglobin in skin blood microcirculations. The method utilizes a simple
model for studying of skin oxygenation. The aim of this lecture is to show
young researches and students some perspectives of near-infrared spectroscopy
as a technique with great promise and a new medical tool for non-invasive
diagnostics and monitoring of blood oxygenation in vivo.
NEAR INFRARED SPECTROSCOPY (NIRS)
For many years different methods have been used to measure and quantify
the level of tissue oxygenation, oxyhemoglobin (HbO2) saturation,
blood volume changes and related topics1-3. In recent years
there has been a growing interest in the non-invasive study and quantitative
in vivo measurements of blood volume and tissue oxygenation changes
during exercise, post-exercise recovery and at rest by using the near-infrared
spectroscopy (NIRS) technique3.
NIRS is a spectral analysis of transmitted of reflected light in
the near-infrared spectral range (600-1000 nm) which is much less absorbed
in biotissues than visible light (400-700 nm). The first publication on
NIRS in biomedicine appeared in 19774 and was orientated toward
fundamental physiologycal studies with laboratory animals. This technique
is based on different absorption of near-infrared light by the oxy- and
deoxygenated forms of heme components (as hemoglobin (Hb), myoglobin (Mb),
and cytochromes)5. The average optical power in NIRS clinical
measurements is about 5-10 mW, i.e. the value of irradiation on the skin
surface is less than 50 mW cm-2 which is similar to the intensity
of the sun on a sunny day6. That is the radiation which is used
by NIRS prevents skin and other tissues from thermal damage. Besides, the
results of NIRS measurements are in qualitatively good agreement with the
physiological behavior of vascular system, which means that this method
gives a possibility for accurate observation of mitochondrial metabolism
changes and for some other physiological studies7. However,
the best applications of these studies are clinical where they may use
as a non-invasive tool for measurements of oxy- and deoxygemoglobin changes
in capillary loops, large and small blood vessels of skin in vivo8-10,
as well as study of cerebral haemodynamics in newborn babies11-13,
children14, adults15-17, and study of the oxygenation
changes in muscles3, 17-20 and other biological tissues21-24.
The near-infrared light can penetrate even in muscles as deep as 10 cm
and more25, that also promotes a clinical application of this
technique.
SKIN AS OBJECT OF INVESTIGATIONS
As an object of investigation by NIRS technique skin represents a
complex heterogeneous medium consisting of different layers with different
optical properties. In the figure 1 we represent the simplest model for
description of human skin26-27. The first layer - epidermis
is about 80-100 mm thick without
blood vessels. The next layer is the papillary dermis (thickness about
100 mm) which includes capillary loops generally
oriented perpendicularly to the surface of the skin capillary loops29.
These superficial capillary loops with the inner diameter about 2-40 mm
are perfused by slow-speed red blood cells that supply the tissue with
oxygen and nutritive substances and remove waste metabolites29-33.
Deeper in upper blood plexus lie arterioles, venules and arteriovenous
anastomosises with inner diameter of 10-40 mm34
which take an active part in body temperature regulation35.
Therefore the non-invasive conditions for blood microcirculations measurements
(i.e. measuring device should not be in physical contact with the tissue)
should be satisfied, because any probe-tissue contacts may disturb the
microcirculation flows conditions in the capillary network36.
Fig.1. Skin tissue model. Optical properties of the different
skin layers model as well as for other biotissues defined in Ref.26 (and
references therein, see also ref.27-28).
Reticular dermis (about 1500 mm
thick) also includs small arteries and veins (20-60 mm
inner diameter) which are orientated almost perpendicularly to skin surface.
These small vessels constitute routes for blood supply and drainage to
veins and arteries (50-100 mm inner diameter)
from deep blood plexus (220 mm thick) and subcutaneous
fat (can be as much as 5 mm thick). Behavior of blood in skin capillaries
of less than 100m m in diameter is non-Newtonian37,
38, which present difficulties for a phantom modeling and computer
simulation.
MONTE CARLO
The application of Monte Carlo technique for simulation of light
propagation started from determination of optical properties of photographic
emulsions39. However the first use of Monte Carlo model in the
biomedical area was reported only in 198340. The method is based
on the simulation of individual statistical pathways of the photons in
tissue and requires information about anisotropy and absorption and scattering
coefficients of tissue as input data. Nowadays Monte Carlo applications
in biomedicine are innumerable27, 28, 41-50 (and other).
As mentioned above, the Monte Carlo method is approach for description
of photon migration through highly scattering media. During their travel
from laser source (area of light input) to detector area or output boundaries
photons do not penetrate ballistically through turbid media including biotissues.
They undergo approximately 100 more scattering events than absorption ones,
or in other words, for many biotissues the light scattering coefficient
m s is much bigger
than the absorption coefficient m a.
It should be noted, that a Monte Carlo model of light
propagation through high scattering turbid media is based on the follow
assumptions:
-
photons are neutral ballistic particles and thus wave phenomena
(coherence and interference) can be disregarded;
-
photons experience only elastic scattering events, i.e. the
energy of photons doesn’t change during a scattering event (but in practice,
in computer simulation packets of photons are being used, that is not similar
to photons), inelastic scattering events, polarization and fluorescence
effects are ignored;
-
the absorbed energy doesn’t change the optical properties
of the tissue;
-
optical properties for each layer of tissue are described
solely by:
-
n – refractive index;
-
the scattering coefficient m s
– which is probability of scatter per unit42;
-
the absorption coefficient m a
– which is probability of photon absorption per unit42;
-
factor of anisotropy g – which characterizes the average
amount of scattering in a medium, specifies the shape of scattering function43,
and is the first moment of the
probability
density function42, termed the "scattering phase function".
g - equal to average cosine of scattering angle q
- which is angle between
and
(0<q
<p ):
.
Scattering of incident beam is symetrical relative to axis of incident
beam (asymetrical scattering is ignored). In this case the phase function
depends only on q 26, 43:
.
The scattering phase function gives the probability of photon scatter from
initial propagation direction
to
a final direction
. Often
this phase function is taken to the Henyey-Greenstein scattering function51:
,
which is originally used for Mie approximation of galactic
light scattering upon particles with size comparable to wavelength of incident
light.
In spite of the fact that it takes large amounts of computer
time, this method is very flexible because it can describe light propagation
in objects with complex boundaries and heterogeneous properties. Moreover,
in skin oxygenation measurements and microcirculation investigations when
source-detector separations is small, diffusion theory becomes invalid
and only the Monte Carlo technique can provide a realistic model. Also,
in determination of tissue oxygenation by NIRS Monte Carlo modeling may
be used to predict the depth sensitivity in various layers of skin. Monte
Carlo technique can give us the fluence rate distribution within the tissue,
which is often required where direct measurements are difficult. Knowledge
of it this may allow optimization of the wavelength region for accurate
measurements of hemoglobin saturation primarily in the papillary dermis.
SUMMARY
The results of NIRS measurements including new microvasculature data
of the skin are of interest to dermatologists, physiologists and some other
physicians for many years, because these data provide a lot of useful information
about physiological and pathological processes in tissues52,53.
Nowadays it is significant for monitoring problems and radiotherapy of
deep-seated tumors, and monitoring of the cerebral oxygenation of newborn
infants, that is not only academic interest.
ACKNOWLEDGEMENTS
IVM acknowledges financial supports under EPSRC
grant GR/L89433, and U.C.CRDF
grant RB1-230. The authors also would like to thank personally to Prof.Valery
V. Tuchin for the possibility of present this lecture at the Internet session
of the "Saratov
Fall Meeting’98".
REFERENCES
-
E.M.Kreps, "Oxyhemometry, Engineering. Application in physiology and
medicine", Leningrad, Medgiz, 1959 (in Russian)
-
A.P.Shepherd, P.A.Oberg, "Laser doppler blood flowmetry", Khuwer Academic
Publishers, 1990.
-
T.Hamaoka, C.Albani, B.Chance, H.Iwane, "A new method for the evaluation
of muscle aerobic capacity in relation to physical activity measured by
near-infrared spectroscopy", Medicine and Sport science, vol.37, pp.421-429,
1992.
-
F.F.Jobsis, "Noninvasive, infrared monitoring of cerebral and myocardial
oxygen sufficiency and circulatory parameters", Science, vol.198, pp.1264-1267,
1977.
-
W.Bank and B.Chance, "Diagnosis of mitochondrial diseases by near infrared
spectroscopy (NIRS)", Proc SPIE, vol.2389, pp.829-834, 1995.
-
M.Cope, "The development of a near infrared spectroscopy system and
its application for non invasive monitoring of cerebral blood and tissue
oxygenation in the newborn infant", PhD thesis, Department of Medical Physics
and Bioengineering, University College London, 1991.
-
N.Hampson, C.Piantadosi, "Near infrared monitoring of human skeletal
muscle oxygenation during forearm ischemia", J.Appl. Physiol., vol.64,
pp.2449-2457, 1988.
-
G.B.Hanna, D.J.Newton, D.K.Harrison, J.J.F.Belch, and P.T.McCollum,
"Use of lightguide spectrophotometry to quantify skin oxygenation in a
variable model of venous hypertension", Br,J.Surg., vol.82, pp.1352-1356,
1995.
-
G.B.Hanna, D.J.Newton, D.K.Harrison, and P.T.McCollum, "Use of lightguide
spectrophotometry to investigate the effect of postural changes on skin
oxygenation in deep venous insufficiency", Br,J.Surg., vol.84, pp.520-523,
1997.
-
D.K.Harrison, S.D.Evans, N.C.Abbort, J.Swanson Beck, and P.T.McCollum,
"Spectrophotometric measurements of haemoglobin saturation and concentration
in skin during the tuberculin reaction in normal human subjects", Clin.Phys.Physiol.Meas.,
vol.13, No.4, pp.349-363, 1992.
-
J.E.Brazy, D.V.Lewis, M.H.Mitnick, and F.F. Jobsis vander Viliet, "Noninvasive
monitoring of cerebral oxygenation in preterm infants: Preliminary observations",
Paediatrics, vol.75, No.2, pp.217-225. 1985.
-
A.E.Edwards, J.Wyatt, C.Richardson, D.T.Delpy, M.Cope, and E.O.R.Reynolds,
"Cotside measurement of cerebral blood flow in ill newborn infants by near
infrared spectroscopy", Lancet, ii, pp.770-771, 1988.
-
J.S.Wyatt, M.Cope, D.T.Delpy, C.Richardson, A.D.Edwards, S.Wray and
E.O.R.Reynolds, "Quantitation of cerebral blood volume in human infants
by near-infrared spectroscopy" J.Appl.Physiol., vol.68, No.3, pp.1086-1091,
1990.],
-
C.W.Yoxall, A.M.Weindling, N.Dawani, and I.Peart, "Measurement of cerebral
venous oxyhaemoglobin saturation in children with near infrared spectroscopy
and partial jugular venous occlusion", Pediatr.res., vol.38, pp.319-323,
1995.
-
P.W.McCormick, M.Stewart, M.G.Goetting and G.Balakrishnan, "Regional
cerebrovascular oxygen saturation measured by optical spectroscopy in humans",
Stroke, vol.22, pp.596-602, 1991.
-
C.Elwell, M.Cope, A.D.Edwards, J.S.Wyatt, E.O.R.Reynolds, and D.T.Delpy,
"Measurement of cerebral blood flow in adult humans using near-infrared
spectroscopy - methodology and possible errors" Adv.Exp.Med.Biol., vol.317,
pp.235-245, 1992.
-
C.A.Paintadosi, T.M.Hemstreet, and J.J.Jobis van der Vliet, "Near infrared
spectroscopy of oxygen distribution in intact brain and skeletal muscle",
Crit.Care Med., vol.14, pp.698-706, 1986.
-
J.R.Wilson, D.M.Mancini, K.McCully, N.Ferraro, F.Lanoce, and B.Chance,
"Noninvasive detection of skeletal muscle underperfusion with near infrared
spectroscopy in patients with heart failure", Circulation, vol.80, pp.1668-1674,
1989.
-
A.D.Edwards, C.Richardson, P. van der Zee, C.Elwell, J.S.Wyatt, M.Cope,
D.T.Delpy, and E.O.R.Reynolds, "Measurement of hemoglobim flow and blood
flow by near-infrared spectroscopy" J.Appl.Physiol., vol.75, No.4, pp.1884-1889,
1993.
-
R.A.de Blasi, M.Ferrari, A.Natali, G.Conti, A.Mega, and A.Gasparetto,
"Noninvasive measurement of forearm blood flow and oxygen consumption by
near infrared spectroscopy", J.Apply. Physiol., vol.76, pp.1388-1393, 1994.
-
V.Quaresima, S.J.Matcher, and M.Ferrary, "Identification and quantification
of intrinsic optical constant for near-infrared mammography", Photochemistry
and Photobiology, vol.67, No.1, pp.4-14, 1998.
-
M.H.Smith, K.R.Denninghoff, L.W.Hillman, and R.A.Chipman, "Oxygen saturation
measurements of blood in retinal vessels during blood loss", Journal of
Biomedical Optics, vol.3. No.3, pp.296-303, 1998.
-
O. Hazeki and M.Tamura, "Quantitative analysis of hemoglobin oxygenation
state of rat brain in situ by near-infrared spectrophotometry",
J.Appl.Physiol., vol.64, pp.796-802, 1988.
-
T.Tamura, H.Eda, M.Takada, and T.Kubodera, "New instrument for monitoring
hemoglobin oxygenation", Adv.Exp.Med.Biol., vol.248, pp.103-107, 1988.
-
P. van der Zee, M.Cope, S.Rarridge, M.Essenpreis, L.A.Potter, A.D.Edwards,
J.S.Wyatt, D.C.McCormick, S.C.Roth, E.O.R.Reynolds, and D.T.Delpy, "Experimentally
measured optical pathlengths for the adult’s head, calf and forearm and
the head of the newborn infant as a function of interoptode spacing", Adv.Exp.Biol.,
vol.316, pp.143-153, 1992.
-
V.V.Tuchin, "Laser and fiber optics in biomedical investigations", Saratov,
Saratov State University Press, 1998 (in Russian).
-
I.V.Meglinsky, Yu.P.Sinichkin, S.R.Utz, H.A.Pilipenko, "Simulation of
fluorescence measurements in the human skin", Proc. SPIE, vol.2389, pp.621-631,
1995.
-
S.P.Treweek, J.C.Barbenel, "Direct measurement of the optical properties
of human breast skin", Medical & Biological Engineering & Computing,
vol.34, pp.285-289, 1996.
-
R.J.Gush, T.A.King, and M.I.V.Jayson, "Aspects of laser light scattering
from skin tissue with application to laser Doppler blood flow measurement",
Phys.Med.Biol., vol.29., No.12, pp.1463-1476, 1984.
-
R.L. Whitmore, "Rheology of the circulation", London, Pergamon Press,
1968.
-
V.V.Kupryyanov, "Ways of microcirculation", Kishinev, Kartya Moldovenske,
1969 (in Russian).
-
V.V.Kupryyanov, Ya.L.Karaganov, V.I.Kozlov, "Microcirculate channel",
Moscow, Medicine, 1975 (in Russia).
-
K.A.Shoshenko, "Blood capillaries", Novosibirsk, Nauka, Sibiryan department,
1975 (in Russian).
-
V.A.Levtov, S.A.Rigirer, N.Kh.Shadrina, "Blood rheology", Moscow, Medicine,
1982 (in Russia).
-
G.I.Mchedlashvilli, "Capillar circulation of the blood", Tbilisi, Izv.
AN Gruzinskoi SSR, 1958 (in Russian).
-
G.I.Mchedlashvilli, Microcirculation of blood: General conformity to
natural laws of the regulation and violation", Leningrad, Nauka, 1989 (in
Russian).
-
T.J.Pedley, "The fluid mechanics of large blood vessels", Cambridge
Univ. Press. 1980.
-
S.Chen, "Biophysical behavior of red blood cells in suspensions"./ "The
red blood cell", Edited by D. MacN. Sargenor, Vol. II, NY, Academic Press,
1975, pp.1031-1133.
-
J.K.Bowker, "Optical diffusion and the inherent resolution of photographic
materials", JOSA A, vol.52, p.1317, 1983.
-
B.C.Wilson, G.Adam, "A Monte Carlo model for the absorption and flux
distributions of light in tissue", Medical Physics, vol.10, pp.824-830,
1983.
-
R.L.Barbour, H.Graber, J.Lubowsky, and R.Anderson, "Monte Carlo modeling
of photon transport in tissue" // Biophys. J. vol.57. pp.381a-382a, 1990.
-
S.T.Flock, B.C.Wilson, D.R.Wyman, and M.S.Paterson, "Monte Carlo modeling
of light propagation in highly scattering tissues I: model predictions
and comparison with diffusion theory", // IEEE Trans.Biomed.Eng. vol.36.
No.10, pp.1162-1168, 1989.
-
S.L.Jacques and L.Wang, "Monte Carlo modeling of light transport in
tissues", / "Optical-Thermal Response of Laser-Irradiated Tissues", edited
by A.J.Welch and M.J.C. van Gemert, New York, Plenum Press, pp.73-100,
1995.
-
V.P.Kandidov, "Monte Carlo technique in nonlinear statistical optics",
UFN, vol.166, No.12, pp.1309-1338, 1996.
-
R. Graaf, M.H.Koelink, F.F.M. de Mul, W.G.Zijlstra, A.C.M.Dassel., and
J.G.Aarnoudse, "Condensed Monte Carlo simulations for the description of
light transport" // Applied Optics, vol.32, No.4, pp.426-434, 1993.
-
M.Keijzer, "Light transport for medical laser treatments" / PhD thesis,
Proefschrift Tecnische Universiteit Delff, 1993.
-
G.Soelkner, G.Mitic, and R.Lohwasser, "Monte Carlo simulations and laser
Doppler flow measurements with high penetration depth in biological tissuelike
head phantoms", / Applied Optics, vol.36, No.22, pp.56475654, 1997.
-
A.Kienle, L.Lilge, I.A.Vitkin, M.S.Patterson, B.C.Wilson, R.Hibst, and
R.Steiner, "Why do veins appear blue? A new look at an old question", Applied
Optics, vol.35, No.7, pp.1151-1160, 1996.
-
I.V.Yaroslavsky, A.N.Yaroslavsky, T.Goldbach, and H.-J.Schwarzmaier.
Inverse hybrid technique for determining the optical properties of turbid
media from integrating-sphere measurements, Appl. Opt., v.35, 1996, pp.6797-6809.
-
H.Nilsson and G.E.Nilsson, "Monte Carlo Simulations of the Light Interaction
with Blood Vessels in Human Skin in the Red Wavelength Region" / Proc.
SPIE, vol. 3252, 1998.
-
L.G.Heneye and J.L.Greenstein, "Diffuse radiation in the galaxy", Astrophys.J.,
vol.93, pp.70-83, 1941.
-
B.I.Tkachenko, "Venule circulation of the blood", Leningrad, Meditzna,
1979 (in Russian).
-
E.K.Zhukov, "Respiratory function of blood", Leningrad, Leningrad State
University Press, 1937 (in Russia).