Yappa A.B.D. Wickramasinghe

The Non-Invasive Monitoring of Cerebral Tissue Oxygenation

The instrument drift was found to be less than 0.004 OD/hour and from measurements on glass filters of 8 optical density units, a coefficient of variation of 0.01 over the 30 second averaging time was observed. The instrument is sufficiently sensitive to enable monitoring of changes in the cerebral oxygen saturation level of haemoglobin and to enable changes in the concentration of cyt aa3 (oxidised form), to be measured with reasonable confidence. It is of the utmost importance in NIRS investigations to be certain of the specificity of the technique, and it is vital that reliable determinations of the amount of cytochrome aa3 in brain are made in addition to measurements of the extinction coefficients. This is still a matter of considerable debate, not only in the isolation and properties of the multisubunit structured membrane bound protein, which many enzymologists have been investigating for the last 50 years, (Keilin and Hartree, 1939; Brunori et al, 1981) but also in relating to in-vivo versus in vitro comparisons. An additional point for consideration is the validity of employing multiplier coefficients derived from the rat brain, as several groups have done (Wyatt et al 1986, Ferrari et al 1985,) and applying them to the human brain and to the infant brain. There may be significant differences in the activity of the enzyme, and the profound physiological effects which will arise during the end point fluorocarbon studies: the presence of fetal haemoglobin must also be considered (Carta et al., 1987). The clinical determination of the optical path length is a considerable problem (Cope etal., 1988,) and once again estimates of the pathlength correction factor made in animals and dead fetuses may not be valid for living human tissue. Results from our animal studies indicate that NIRS can be used to monitor changes in the oxygenation level of Hb and, in extreme hypoxia, changes in the level of the redox state of cyt aa3 can be reliably measured and are well within the sensitivity of the instrument. The results indicate that under small change in saturation the redox state of cyt aa3 appears to be unaltered. It may be that under normal physiological conditions the redox state of aa3 appears to be apparently unchanged under episodes of mild hypoxia of short duration.

Measurement of peripheral oxygen utilisation in neonates using near infrared spectroscopy: comparison between arterial and venous occlusion methods.

The aim of this study was to develop an arterial occlusion method and compare it with the venous occlusion method for measurement of peripheral oxygen utilisation in neonates using near infrared spectroscopy (NIRS). Twenty healthy neonates were studied. Arterial occlusion was produced by inflating a neonatal blood pressure cuff to 100 mmHg for 30-40 s and oxygen utilisation (VO(2)) was calculated using the HbO(2) decrement slope following occlusion. Venous occlusion was produced by inflating the cuff to 30 mmHg for 15-20 s and VO(2) was calculated by: VO(2)=HbTx4x(SaO(2)-SvO(2)), where SaO(2) is the arterial oxygen saturation measured by pulse oximetry and SvO(2) is the venous oxygen saturation measured by NIRS. Each baby had a minimum of three arterial and three venous occlusions. Criteria were developed for acceptance/rejection of an occlusion. Using the arterial method, the mean VO(2) was 1.12 mM cm(-1) O(2)/min (S.D.=0.25), (95% CI=1.00-1.24 mM cm(-1) O(2)/min). The coefficient of variation was 6.6+/-4.1%. Using the venous method, the mean VO(2) was 1.60 mM cm(-1) O(2)/min (S.D.=0.48), (95% CI=1. 38-1.82 mM cm(-1) O(2)/min). The coefficient of variation was 12. 6+/-5.7%. The correlation between the two methods was weak (r=0.28 and r(2) was 0.08). The mean difference between the two methods was 0. 47 mM cm(-1) O(2)/min (S.D.=0.51). The limits of agreement were -0. 53 to 1.47 mM cm(-1) O(2)/min. The arterial method gives more consistent results.

Non-invasive optical monitoring of cerebral blood oxygenation in the foetus and newborn: preliminary investigation

Near infra-red spectroscopy was applied as a non-invasive and continuous technique for the in vivo monitoring of blood and tissue oxygenation in human neonates. Monitoring of cerebral blood oxygenation in the wavelength range 775-904 nm was carried out on preterm infants after inducing a transient mild hypoxic change; the measurements were performed either by the transmission or reflection (backscattering) mode of monitoring. The results of these investigations were used to assess the application of the technique to foetal monitoring. A series of foetal monitoring studies was performed to investigate the influence of maternal contractions on foetal cerebral blood oxygenation. Although only changes in haemoglobin concentration can be monitored at present, the results suggest that near infra-red monitoring could provide a non-invasive, real-time monitoring method in intensive neonatal and intrapartum care.

Experimental study of spatial resolution for time-resolved near-infrared imaging

A preliminary study into the spatial resolution that may be achieved for time resolved near infrared imaging through highly scattering media has been performed. The spatial resolution, for time gated images, has been investigated quantitatively by measuring the edge-spread function for scattering media of different properties and at different depths. Transmission scans of two absorbing rods, spaced by different distances, were used to qualitatively study the contrast obtained at different integration periods or using the measured mean time-of-flight. Both spatial resolution and contrast are improved as the time gating interval is reduced. However, for thick tissue sections it may not be possible to reduce the spatial resolution below about 10 mm, because of the small amount of light arriving at these early times.

Development and clinical evaluation of noninvasive near-infrared monitoring of cerebral oxygenation

Near infrared spectroscopy (NIRS) is a relatively new method which is suitable for monitoring oxygenation in blood and tissue in the brain of the fetus and the neonate. The technique involves in-vivo determination of the absorption of light in the wavelength range 775 to 900 nm through such tissue and converting such changes in absorbance to provide information about the changes in the concentration of oxygenated and de-oxygenated haemoglobin (HbO2 and Hb). Recent developments of the methodology now enable the calculation of changes in cerebral blood volume (CBV) as well as absolute CBV and cerebral blood flow (CBF). The attraction of this method is its applicability to monitor cerebral function in a wide variety of patient groups. Although primarily developed for neonatal use it is today applied on the fetus to investigate fetal hypoxia and on adults undergoing surgery.

Optical pH sensor for physiological pH measurement

A miniature optical sensor based on the fluorescent indicator, 8-hydroxyl-1,3,6-pyrene trisulfonic Acid Trisodium Salt (HOPSA), was developed for physiological pH measurement. Dowex-1 strongly basic anion exchange resin was used as a medium to immobilize the indicator on the end of an optical fiber to form a pH sensing layer. Polyetherurethane was dip- coated onto the sensing layer as the permeable membrane for H+. The properties of the sensor were assessed and found to be suitable for monitoring physiological pH values.

Near Infrared Spectroscopy: In-vivo Measurements Of Effective Penetration Depths And Absorption Coefficients

Non-invasive near infra-red spectroscopy was used to determine the apparent effective absorption coefficient and penetration depths at four wavelengths. The measurements were done on 10 preterm infants. The penetration depths were found to depend on the position of the measurements on the head and the wavelength of light. Maximum pene-tration depths were found at 805-845nm.

Intensity modulated near infrared spectroscopy : instrument design issues

Tissue oxygenation instruments which rely on phase sensitive detection suffer form phase-amplitude crosstalk, i.e. the phase of the detected signal with respect to a reference signal is dependent on the average intensity of the light entering the photomultiplier tube (PMT). If an instrument that detects the phase of the scattered signal is to yield the phase accuracy required in order to provide useful clinical parameters, quantitative haemoglobin and oxy- haemoglobin concentrations (Hb), and (HbO2) and mixed arterial-venous saturation all sources of phase-amplitude effects must be understood. The phase-amplitude effect has in the past been attributed to the fact that the rise time of the detector decreases with increasing light intensity. In this work an additional phase-amplitude effect in intensity modulated near IR spectroscopy (IMNIRS) instrumentation is studied. The presence of a coherent interfering signal due to low level RF coupling at the detector output will corrupt the phase of the signal of interest and cause a phase-amplitude effect. Under certain conditions a relatively low level interfering RF signal can introduce a significant error in the slope of the phase per unit distance plot. A comparison between measured and modeled phase distortion is presented and ways to reduce the effect discussed. In addition to phase-amplitude effects, the final accuracy of the quantitative measurements made by an IMNIRS instrument depends heavily on the calibration. Calibration of the measured phase and the AC and DC components of the detected light must take into account distortions due to, (a) phase-amplitude crosstalk and system phase offset, (b) detector non-linearities, (c) variation in laser source intensity and phase with time and temperature, (d) optical probe light loss and (e) variations in detector sensitivity. Current instrument performance will be presented and discussed.

Development of near-infrared spectroscopy for monitoring cerebral regional blood oxygenation and volume in the human newborn

Human newborns can suffer from neuro-developmental abnormalities, when they are born as preterms. With near infrared spectroscopy (NIRS) it is possible to investigate any brain disease occurring together with these neuro- abnormalities. The specific absorption properties of haemoglobin and oxygenated haemoglobin in the near infrared region allow to measure the oxygenation status and several other variables. Local variations in cerebral blood volume (CBV) and blood oxygenation is important for a better understanding of these abnormalities.

Quantitation of brain oxygenation and blood volume using a new intensity modulated NIR instrument

During the past decade, instruments that can non-invasively monitor the oxygenation state of tissues have become increasingly common. This has primarily been accomplished by measuring the attenuation of the near infrared (NIR) light that has passed through the tissue. Instruments based on light attenuation alone can provide trend information but not quantitative information. A new intensity modulated near infrared spectrophotometry (IMNIRS) instrument has been developed, measuring the attenuation, phase shift and modulation depth of light that has passed through blood perfused tissue. This technique opens up the possibility of providing quantitative data for chromophore (Hb, HbO/sub 2/, and Cytaa/sub 3/) concentrations and hence the calculation of cerebral blood volume. The design of the instrument and preliminary results will be discussed.