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Determination of the blood

oxygenation in the brain by time-

resolved reflectance spectroscopy:

contribution of vascular absorption

and tissue background absorption

Andreas H. Hielscher, Hanli Liu, Lihong V. Wang, Frank K.

Tittel, Britton Chance, et al.

Andreas H. Hielscher, Hanli Liu, Lihong V. Wang, Frank K. Tittel, Britton

Chance, Steven L. Jacques, "Determination of the blood oxygenation in the

brain by time-resolved reflectance spectroscopy: contribution of vascular

absorption and tissue background absorption," Proc. SPIE 2136, Biochemical

Diagnostic Instrumentation, (21 July 1994); doi: 10.1117/12.180773

Event: OE/LASE '94, 1994, Los Angeles, CA, United States

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Determination of blood oxygenation in the brain

by time resolved reflectance spectroscopy (I):

Influence of the skin, skull, and meninges

A.H. Hielscher1'2, H. Liu3, L. Wang1, F.K. Tittel2, B. Chance3 and S.L. Jacques1

1University of Texas M.D. Anderson Cancer Center,

Laser Biology Research Laboratory, Houston, Texas 77030

2Rice University, Dept. of Electrical and Computer Engineering,

Houston, Texas 7725 1 -1892

3University of Pennsylvania, Dept. of Biochemistry and Biophysics,

Philadelphia, Pennsylvania 19104-6089

ABSTRACT

In recent years the possibility of measuring the blood oxygenation in the brain with near

infrared light has been studied by several authors. However the fact that the brain is encapsulated

by different layers of tissues (skin, skull, meninges) has attracted little attention. The goal of this

study was to quantify the influence of these different layers on brain blood oxygenation

measurements. Experimental results obtained from time resolved reflectance measurements on

layered tissue phantoms were compared to Monte Carlo simulations of layered models, diffusion

theory, and in vivo measurements on the human head.

Both, the experimental results and simulations show that the absorption coefficient p.s,

which is closely related to the blood oxygenation, of deeper layers can be accessed in the time

domain. The early parts (t 1 .0 ns) of the impulse response are influenced by the outer layers of

the head (skin, skull, meninges), which leads to a shift of the peak position of the impulse

response. However the later parts (t 1 .0 ns) are clearly dominated by the optical properties of the

underlying tissue. Thus by fitting analytical expressions found from diffusion theory only to the

late part of the time resolved reflectance allows to determine p.a and subsequently the blood

oxygenation of the deepest medium (e.g. brain tissue).

1. INTRODUCTION

Two major areas, where continuously monitoring the blood oxygenation in the brain is of

major interest are newborn and cardiac surgery intensive care. Cerebral injuries due to hypoxia as

well as hyperoxia are considered to be the cause of about one third of all deaths in the full term

infants1. In the preterm infant it is estimated to be the cause of neuro-developmental abnormality

in up to two thirds of the survivors2. Of the 340,000 patients who undergo cardiac surgery each

year in the US, roughly 100,000 suffer at least a minor neurological deficit because of cerebral

ischemia, during or after surgery. Therefore objective measurement techniques are needed which

allow for an oxygen support that is sufficient yet minimal toxic.

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The clinical symptoms of hypoxia (e.g. tachypnea, tachycardia or cyanosis) and hyperoxia

(e.g. worsening lung disease from direct oxygen toxicity or retinopathy) are unreliable indicators

and may even be completely absent until irreversible damage has occurred3 .

The

same critique

holds for conventional imaging methods like ultrasound, X-ray, CT or NMR, which can only

detect irreversible tissue damages4. The "gold standard" assays, arterial blood gas measurement or

estimation of oxygen consumption, are invasive, expensive, often painful, and risky. In addition,

these standard methods only reveal static information about oxygenation at one point in time,

rather than continuous measurements over time. What is needed is a technique for non invasively

and continuously monitoring the oxygenation status of the blood in the brain. This would allow to

intervene in time to prevent irreversible damage.

This.paper first discusses briefly the possibilities and limitations of a current state of the art

method of non invasively measuring the blood oxygenation with light. This will be followed by a

proposal how to overcome these limitations with time resolved reflectance measurements. After an

introduction to the principles of these techniques, the problem of layered tissue structures will be

addressed in detail. The brain is knowingly encapsulated by different layers with varying optical

properties (skin, skull and meninges). How this layers effect the determination of the blood

oxygenation of the underlying brain tissue, the brain, is of substantial interest and has up to know

not been studied systematically.

2. STATE OF THE ART TECHNIQUE

Jöbsis first demonstrated the possibility of detecting near infrared light of only 48jiWcm2

in a 6.6nm wide band around 800nm, after it traveled through a brain of 13.3cm diameter5. In the

wavelength region between 700-900 am, known as the therapeutical window, the major absorbing

chromophores in the brain are the two blood constituents hemoglobin (Hb) and oxygenated

hemolobin (Hb02). These two absorbers display well known different absorption character-

isticsb. Therefore, with the use of at least 2 wavelength it is in principle possible to determine the

two unknowns, the concentration of hemoglobin [HbI and deoxygenated hemoglobin {Hb02],

with a set of linear equations:

AX1 =

[Hb]

8HbO2

[Hb02] }

(la)

A2 =

[Hb]

EHbO2

[Hb02] I

(ib)

where

A :=

Absorbance

at wavelength X.

c :=

Extinction

coefficient [mMlcml]

L :=

Optical

path length at wavelength .

Several

studies have shown the possibility of monitoring changes in the blood oxygenation

based on the equations (la,b) 49. However in order to quantify [Hb] and [HbO2] from the

measurements of the absorbance (A), the path length (L) traveled by the photons before they reach

the detector must be known. Usually L is assumed to be a constant, independent of wavelength,

blood concentration, or individuals. However Benaron et. al found that the path lengths measured

among infants of even similar weight and age differ substantially 10 Since blood itself is a highly

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