Peter J. Rolfe

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.

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.

Definition and Measurement of Quantities Pertaining to Oxygen in Blood

Since the introduction of more dedicated methods in blood gas analysis a lot of confusion started about definition and notation on oxygen related quantities in blood. The (US) National Committee for Clinical Laboratory Standards (NCCLS) has published a proposed guideline in which these problems are thoroughly discussed18. In the present paper a consistent set of definitions is given of the principal quantities pertaining to oxygen in blood in relation to the methods employed in the measurement of the quantities. Its core is the correct definition of oxygen saturation of hemoglobin as given in equations [3], [6], and [12a], which is in agreement with that given by NCCLS19. This system at least is consistent and the arguments are presented in this paper in a number of statements. The core of it is the correct definition on oxygen saturation of hemoglobin as given in and around equation [3].

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.

Improved performance of intravascular pO2 sensor incorporating poly(MPC-co-BMA) membrane

The first in vivo evaluation of a pO2 sensor constructed with a novel copolymer is described. The performance of the sensor is assessed under dynamic conditions in vitro and in vivo. This sensor is more stable and reliable than the control sensor with a heparintreated polyethylene membrane.

In vivo assessment of catheter-tip PO2 sensor: sampling lumen fabrication

Fabrication of the sampling lumen of an intra-arterial PO2 sensor is performed in standard catheters mechanically or by laser. Clinical evaluation is performed with respect to catheter insertion, complications, accuracy of oxygen sensor data and fibrin deposition on the catheter surface. The success rate for catheter insertion is 57% for 138 standard and 50% for 74 laser-cut catheters studied. The proportion of catheter failures (blocked or non-reading) is 14% in laser-cut compared with 30% in standard. These differences are not statistically significant at the 5% level. There is no clinically significant difference in sensor accuracy, with 37·5% of results within ±0·0.5 kPa and 80% within ±2·0 kPa of simultaneous blood gas values. Drift is within ±0·3 kPa h−1 for 78% of monitoring time. Significant errors of recalibration occur in 6% of calibrations. Scanning electron micrographs demonstrate a much smaller sampling lumen in the laser-cut group, but no reduction in fibrin deposition at the site of the sampling hole. The low success rate for catheter insertion is a problem because of cost implications. The accuracy of the system is usually sufficient for clinical purposes, provided the calibration is checked every 4 h.

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.

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.

Novel algorithm to determine absorption and scattering coefficients from time-resolved measurements

A novel algorithm is demonstrated to determine the reduced scattering and absorption coefficients from time-resolved reflectance measurements at two positions on the surface of biotissue. The algorithm is very straightforward and fast, in which only some simple mathematical operations are involved, avoiding complicated iterative non-linear fitting to the time- resolved curve. The derived reduced scattering coefficient is not affected by whatever boundary condition is applied. The algorithm was verified using the time-resolved data from the Monte-Carlo model. Both the semi-infinite medium and the turbid slab medium were tested. In contrast to the non-linear fitting method, it is found using this algorithm that both the scattering and absorption coefficients can be determined to a high accuracy.