Differential Pathlength Factor Research Articles

Differences in the hemodynamic response to event-related motor and visual paradigms as measured by near-infrared spectroscopy

Several current brain imaging techniques rest on the assumption of a tight coupling between neural activity and hemodynamic response. The nature of this neurovascular coupling, however, is not completely understood. There is some evidence for a decoupling of these processes at the onset of neural activity, which manifests itself as a momentary increase in the relative concentration of deoxyhemoglobin (HbR). The existence of this early component of the hemodynamic response function, however, is controversial, as it is inconsistently found. Near infrared spectroscopy (NIRS) allows quantification of levels of oxyhemoglobin (HbO 2) and HbR during task performance in humans. We acquired NIRS data during performance of simple motor and visual tasks, using rapid-presentation event-related paradigms. Our results demonstrate that rapid, event-related NIRS can provide robust estimates of the hemodynamic response without artifacts due to low-frequency signal components, unlike data from blocked designs. In both the motor and visual data the onset of the increase in HbO 2 occurs before HbR decreases, and there is a poststimulus undershoot. Our results also show that total blood volume (HbT) drops before HbO 2 and undershoots baseline, raising a new issue for neurovascular models. We did not find early deoxygenation in the motor data using physiologically plausible values for the differential pathlength factor, but did find one in the visual data. We suggest that this difference, which is consistent with functional magnetic resonance imaging (fMRI) data, may be attributable to different capillary transit times in these cortices.

Age dependency of the hemodynamic response as measured by functional near-infrared spectroscopy

Aging reduces cerebral blood flow in association cortices during rest. However, the influence of age on functional brain activation is still controversial. The aim of our study was to examine age dependency of brain activation in primary and association cortices. Therefore, changes in the concentration of oxy- and deoxyhemoglobin as well as changes in the redox state of cytochrome-c-oxidase (Cyt-Ox) were measured by functional near-infrared spectroscopy (fNIRS) in the lateral prefrontal and motor cortices during an event-related Stroop interference task. Fourteen young (23.9 ± 3.1 years old) and 14 elderly subjects (65.1 ± 3.1) participated in the study. Data revealed two effects of aging on brain activation: (1) Elderly and young subjects used the lateral prefrontal cortex to cope with interference during the Stroop task. In young subjects, the vascular response was higher during incongruent than neutral trials in the entire examined lateral prefrontal cortex. However, in the elderly, all lateral prefrontal regions showed a hemodynamic response but not necessarily a specific interference effect. (2) The hemodynamic response was reduced in elderly subjects in the lateral prefrontal association cortex, but obviously not in the motor cortex. We propose that calculating effect sizes is the only reliable approach to analyze age-related effects in fNIRS studies, because they are independent from the assumed differential pathlength factor. In summary, our findings suggest that aging decreases the hemodynamic response in the frontal association cortex during functional activation, omitting the primary motor cortex.

Maps of optical differential pathlength factor of human adult forehead, somatosensory motor and occipital regions at multi-wavelengths in NIR

The optical differential pathlength factor (DPF) is an important parameter for physiological measurement using near infrared spectroscopy, but for the human adult head it has been available only for the forehead. Here we report measured DPF results for the forehead, somatosensory motor and occipital regions from measurements on 11 adult volunteers using a time-resolved optical imaging system. The optode separation was about 30 mm and the wavelengths used were 759 nm, 799 nm and 834 nm. Measured DPFs were 7.25 for the central forehead and 6.25 for the temple region at 799 nm. For the central somatosensory and occipital areas (10 mm above the inion), DPFs at 799 nm are 7.5 and 8.75, respectively. Less than 10% decreases of DPF for all these regions were observed when the wavelength increased from 759 nm to 834 nm. To compare these DPF maps with the anatomical structure of the head, a Monte Carlo simulation was carried out to calculate DPF for these regions by using a two-layered semi-infinite model and assuming the thickness of the upper layer to be the sum of the thicknesses of scalp and skull, which was measured from MRI images of a subject's head. The DPF data will be useful for quantitative monitoring of the haemodynamic changes occurring in adult heads.

Utility and limitations of near-infrared spectroscopy during cardiopulmonary bypass in a piglet model.

Near-infrared spectroscopy assessment of cytochrome oxygenation could be a valuable technique to monitor cerebral intraneuronal oxygen delivery during cardiopulmonary bypass. However, the validity of the cytochrome signal has been questioned as it could easily be overwhelmed by the Hb signal. Five- to six-week-old control piglets (n = 5) underwent cardiopulmonary bypass at 37 degrees C. Study animals (n = 10) received 100 mg/kg of sodium cyanide to uncouple cytochrome from HB: Hematocrit was then decreased in steps of 5% from 35 to 5% with crystalloid hemodilution. In study piglets, the initiation of cardiopulmonary bypass was associated with oxygenated Hb increasing from 0 to 62.9 +/- 25.6 microM times the differential path-length factor, and oxidized cytochrome a,a3 increasing to 1.9 +/- 1.8 microM times the differential path-length factor. Cyanide caused oxygenated Hb to increase further to 132.3 +/- 48.9 microM times the differential path-length factor, and oxidized cytochrome c decreased to -7.0 +/- 2.6 microM times the differential path-length factor as anticipated, confirming uncoupling of electron transport. However, hemodilution subsequently resulted in linear decreases in oxidized cytochrome a,a3 (F = 8.57, p < 0.001) suggesting important cross-talk between the Hb and cytochrome signals as cytochrome is only intracellular. In control piglets, tissue oxygenation index showed a positive correlation with pump flow (r = 0.986, p = 0.013). The cytochrome signal as presently measured by near-infrared spectroscopy is highly dependent on hematocrit.

Utility of near-infrared spectroscopic measurements during deep hypothermic circulatory arrest

Background. Near-infrared spectroscopy (NIRS) is used to monitor cerebral oxygenation during cardiac surgery. However, interpretation of the signals is controversial. The aim of the study was to determine which NIRS variable best correlated with brain damage as assessed by animal behavior and neurohistologic score and to compare the accuracy of NIRS and magnetic resonance spectroscopy (MRS) in predicting brain injury.Methods. Forty 5-week-old piglets underwent 60 minutes of deep hypothermic circulatory arrest (DHCA) at 15°C. Changes in brain adenosine triphosphate (ATP), phosphocreatine (PCr), and intracellular pH (pHi) were determined by MRS and correlated to changes in oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and oxidized cytochrome a,a3 (CytOx) NIRS signals. Brains were fixed on day 4 and examined using a neurohistologic score.Results. Reductions in CytOx and HbO2 values were correlated closely with decreases in ATP, PCr, and pHi. The changes in CytOx and PCr showed the strongest correlation (r = 0.623). Maximal CytOx reduction during DHCA of more than −25 μM ∗ differential pathlength factor (DPF) predicted brain damage with a sensitivity of 100% and a specificity of 75%. The histologic score was also correlated with a decrease in ATP (r = −0.52 for CytOx; r = −0.32 for ATP); HbO2, PCr, and pHi showed no correlations.Conclusions. Reduction in CytOx correlates with decreased brain energy state and predicts histologic brain injury after DHCA with a high sensitivity. These data suggest that the level of CytOx could be a very important predictor of brain damage during DHCA.

Near Infrared Spectroscopy in Large Animals: Optical Pathlength and Influence of Hair Covering and Epidermal Pigmentation

The effects of epidermal pigmentation and hair covering on the relative transparency of various animal tissues to near infrared (NIR) light were examined, and the pathlengths of NIR light through tissues at four wavelengths in the NIR range were subsequently determined. Black hair covering and black or dark-coloured hooves prevented NIR light from penetration sufficient for conduction of pathlength or NIR spectroscopy measurements. Non-pigmented hair covering of the head did not appear to be a barrier to successful NIR light transmission. Tissues sufficiently transparent to NIR light had the differential pathlength factor (DPF, i.e. the ratio of the observed light pathlength and the geometric light source–detector separation) of NIR light determined by intensity modulated spectroscopy at the wavelengths 744, 806, 834 and 860 nm.Horse gluteal muscles had DPFs of 6.2, 6.2, 6.0, and 5.6, whereas forelimb muscles had DPF of 4.7, 4.4, 4.5 and 3.9 at the respective wavelengths. Sheep heads had DPF of 7.2 ± 0.3, 5.8 ± 0.5, 5.5 ± 0.4 and 4.4 ± 0.6 (± SEM) for the above respective wavelengths, of which the pathlengths all differed significantly from the other, except for between 806 and 834 nm, and 834 and 860 nm. The DPF of horse hooves were 4.8 ± 0.1, 4.8 ± 0.1, 4.7 ± 0.1 and 4.4 ± 0.1 (SEM) for the above noted wavelengths, of which the pathlength at 744 and 806 nm differed from the pathlength at 860 nm (P>0.05). These results show that NIRS is possible through lighter pigmented hair and epidermal tissues, and provide DPFs of horse feet and muscle and the sheep head that enables quantitative NIRS in these species

Non-invasive optical monitoring of the newborn piglet brain usingcontinuous-wave and frequency-domain spectroscopy

We have used continuous-wave (CW) and frequency-domain spectroscopy to investigate the optical properties of the newborn piglet brain in vivo and non-invasively. Three anaesthetized, intubated, ventilated and instrumented newborn piglets were placed into a stereotaxic instrument for optimal experimental stability, reproducible probe-to-scalp optical contact and 3D adjustment of the optical probe. By measuring the absolute values of the brain absorption and reduced scattering coefficients at two wavelengths (758 and 830 nm), frequency-domain spectroscopy provided absolute readings (in contrast to the relative readings of CW spectroscopy) of cerebral haemoglobin concentration and saturation during experimentally induced perturbations in cerebral haemodynamics and oxygenation. Such perturbations included a modulation of the inspired oxygen concentration, transient brain asphyxia, carotid artery occlusion and terminal brain asphyxia. The baseline cerebral haemoglobin saturation and concentration, measured with frequency-domain spectroscopy, were about 60% and 42 µM respectively. The cerebral saturation values ranged from a minimum of 17% (during transient brain asphyxia) to a maximum of 80% (during recovery from transient brain asphyxia). To analyse the CW optical data, we have (a) derived a mathematical relationship between the cerebral optical properties and the differential pathlength factor and (b) introduced a method based on the spatial dependence of the detected intensity (dc slope method). The analysis of the cerebral optical signals associated with the arterial pulse and with respiration demonstrates that motion artefacts can significantly affect the intensity recorded from a single optode pair. Motion artefacts can be strongly reduced by combining data from multiple optodes to provide relative readings in the dc slope method. We also report significant biphasic changes (initial decrease and successive increase) in the reduced scattering coefficient measured in the brain after the piglet had been sacrificed.

Determination of the wavelength dependence of the differential pathlength factor from near-infrared pulse signals

For the calculation of changes in oxyhaemoglobin, deoxyhaemoglobin and the redox state of cytochrome-c-oxidase from attenuation data via a modified Beer-Lambert equation the wavelength dependence of the differential pathlength factor (DPF) has to be taken into account. The DPF, i.e. the ratio of the mean optical pathlength and the physical light source-detector separation at each wavelength, determines the crosstalk between the different concentrations and is therefore essential for a sensitive detection of chromophore changes. Here a simple method is suggested to estimate the wavelength dependence of the DPF from pulse-induced attenuation changes measured on the head of adult humans. The essence is that the DPF is the ratio of the attenuation changes over absorption coefficient changes, and that the spectral form of the pulse correlated absorption coefficient change can be assumed to be proportional to the extinction coefficient of blood. Indicators for the validity of the DPF derived for wavelengths between 700 and 970 nm are the stability of the calculated haemoglobin and cytochrome signals with variations of the wavelength range included for their calculation and its overall agreement with the data available from the literature.

Separation of changes in light scattering and chromophore concentrations during cortical spreading depression in rats

We used near-infrared spectroscopy to separate tissue scattering changes from changes in cerebral oxyhemoglobin and deoxyhemoglobin and the redox state of cytochrome- c -oxidase. A separate term of the transport scattering coefficient (micro(s)(?)) was included in a modified Lambert-Beer equation. It is shown by diffusion equation analysis that there is a simple relationship between the differential path-length factor (D(a)) and its scattering equivalent (D(s)) . The method was applied to cortical spreading depression (CSD) data recorded through the skulls of rats. Biphasic changes in micro(s)(?)of +/-0.1mm(-1)were observed during CSD's that spread with a velocity of ~5mm/min . The method proposed has the promise to permit monitoring of scattering changes noninvasively in humans during cortical activation or pathophysiological conditions.

The effect of scalp ischaemia on measurement of cerebral blood volume by near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is a noninvasive method of quantifying changes in cerebral haemodynamics from changes in the absorption of near-infrared light by oxyhaemoglobin and deoxyhaemoglobin. Measurement of neonatal cerebral blood volume (CBV) by NIRS was described in 1990 but it has been suggested that, in adults, scalp and skull blood content contribute a significant amount to the cerebral haemodynamic variables quantifiable by NIRS. To investigate this, CBV was measured in nine adult subjects, in the frontal region of the head, before and after inflating a pneumatic tourniquet proximal to the measurement site. Because a change in scalp blood content could potentially alter the pathlength of light passing through the head and hence affect the measured CBV, the optical pathlength factor was therefore also measured before and after tourniquet inflation. Blood flow occlusion was confirmed by laser Doppler velocimetry. The results showed that tourniquet inflation had no effect on the estimated value of CBV or the differential pathlength factor. We conclude that, provided the distance between light entry and exit on the surface of the scalp is sufficiently large, changes in scalp blood flow have no effect on NIRS measurement of cerebral haemodynamics. Keywords: cerebral blood volume, near-infrared spectroscopy

Measurement of cranial optical path length as a function of age using phase resolved near infrared spectroscopy.

Near infrared spectroscopy (NIRS) has been used to measure concentration changes of cerebral hemoglobin and cytochrome in neonates, children, and adults, to study cerebral oxygenation and hemodynamics. To derive quantitative concentration changes from measurements of light attenuation, the optical path length must be known. This is obtained by multiplying the source/ detector separation by a laboratory measured differential path length factor (DPF) which accounts for the increased distance traveled by light due to scattering. DPF has been measured by time of flight techniques on small populations of adults and postmortem infants. The values for adults are greater than those for newborns, and it is not clear how to interpolate the present data for studies on children. Recent developments in instrumentation using phase resolved spectroscopy techniques have produced a bedside unit which can measure optical path length on any subject. We have developed an intensity modulated optical spectrometer which measures path length at four wavelengths. Two hundred and eighty three subjects from 1 d of age to 50 y were studied. Measurements were made at a fixed frequency of 200 MHz and a source detector separation of 4.5 cm. Results suggest a slowly varying age dependence of DPF, following the relation DPF690 = 5.38 + 0.049A0.877, DPF744 = 5.11 + 0.106A0.723, DPF807 = 4.99 + 0.067A0.814, and DPF832 = 4.67 + 0.062A0.819, where DPF690 is the DPF measured at 690 nm and A is age is expressed in years from full term. There was a wide scatter of values, however, implying that ideally DPF should be measured at the time of each study.

The noninvasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical path length in the neonatal brain by second derivative near infrared spectroscopy.

We have used second differential near infrared spectroscopy of water to determine the mean optical path length of the neonatal brain. By obtaining the ratio of the second differential features of deoxyhemoglobin to those of water, the absolute cerebral concentration of deoxyhemoglobin can be monitored continuously and noninvasively. Nineteen neonates were studied; the gestational age at birth varied from 23 to 38 wk, and the postconceptual age, when the spectra were recorded, ranged from 35 to 48 wk. The calculated mean deoxyhemoglobin concentration was 14.6 +/- 4.0 microM; the differential path length factor (mean optical path length/optode separation) calculated from the water peak at 730 nm was 4.66 +/- 1.01, and that calculated at the 830-nm peak was 3.91 +/- 0.75. These values are consistent with path length measurements using laser time-of-flight spectroscopy on postmortem neonates and phase-resolved spectroscopy on live neonates. Induced arterial oxygen saturation decreases from 98 to 93% showed no significant change in the mean optical path length, despite significant cerebral desaturation. Changes in the deoxyhemoglobin concentration after this procedure were identical, whether measured by second differential analysis at 760 nm or by multilinear regression over the wavelength range 740-900 nm. When combined with existing methods of measuring total cerebral hemoglobin concentration, second differential near infrared spectroscopy can be used to derive the mean cerebral oxygen saturation. A preliminary experiment outlined the feasibility of this approach and yielded a saturation value of 63%, consistent with near infrared sampling of a predominantly venous pool in the brain.

Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy

The authors have used an intensity modulated optical spectrometer, which measures the phase shift across tissue experienced by intensity modulated near-infrared light, to determine the absolute optical pathlength through tissue. The instrument is portable and takes only 5 s to record pathlength at four wavelengths (690 nm, 744 nm, 807 nm and 832 nm). The absolute pathlength divided by the known spacing between the light source and detector on the skin is the differential pathlength factor (DPF) which previous studies have shown is approximately constant for spacings greater than 2.5 cm. DPF results are presented for measurements on 100 adults and 35 newborn infants to determine the statistical variation on the DPF. All measurements were made at a frequency of 200 MHz with source-detector spacings of >4 cm. Results at 807 nm show a DPF of 4.16(+or-18.8%) for adult arm, 5.51(+or-18%) for adult leg, 6.26(+or-14.1%) for adult head and 4.99(+or-9%) for the head of a newborn infant. A wavelength dependence was obtained for DPF on all tissues and a difference in DPF between male and female was observed for both the adult arm and leg. The results can be used to improve the quantitation of chromophore concentration changes in adults and newborn infants.

Spectral dependence of temporal point spread functions in human tissues

We have determined the spectral dependence of the temporal point spread functions of human tissues experimentally between 740 and 840 nm in transmittance measurements on the adult head, forearm, and calf (in vivo) and the infant head (post mortem) by using picosecond laser pulses and a streak camera detector. Two parameters are extracted from the temporal point spread function; the differential path-length factor (DPF), calculated from the mean time, and the slope of the logarithmic intensity decay. In all tissues the DPF and the logarithmic slope show a reciprocal relationship and exhibit characteristics of the absorption spectra of hemoglobin. The DPF falls with increasing wavelength, the variation being typically 12%, while the logarithmic slope increases with wavelength. A quantitative analysis of the logarithmic slope spectrum significantly underestimated expected tissue chromophore concentrations. The absolute magnitudes of the DPF showed considerable intersubject variation, but the variation with wavelength was consistent and thus may be used in the correction of tissue attenuation spectra.

Wavelength dependence of the differential pathlength factor and the log slope in time-resolved tissue spectroscopy.

The monitoring of tissue oxygenation by the technique of near infrared spectroscopy (NIRS) was first described by Jobsis in 1977 (Jobsis, 1977). The technique relies upon the relative transparency of tissue to near infrared (NIR) light to enable measurements of changes in optical attenuation across many centimetres of tissue. Early NIRS measurements could only derive qualitative changes in tissue and blood oxygenation from the observed variations in tissue attenuation (Brazy et al., 1985). However, data on the optical pathlength of light in tissue, measured by time resolved techniques employing picosecond laser pulses, have now permitted a quantitative analysis of attenuation measurements to be made (Delpy et al., 1988; Wyatt et al., 1990a). By incorporating information on the optical pathlength into a modified Beer-Lambert law it is possible to quantify changes in chromophore concentration from the measured changes in tissue attenuation. The optical pathlength needed in this calculation, the Differential Pathlength (DP) is defined as the local gradient in a plot of the attenuation measured in a scattering medium versus the absorption coefficient of the medium (Cope et al., 1991a; Cope, 1991b). It has been shown in previous studies (Delpy et al., 1988) that the DP can be approximated by measuring the mean distance that a picosecond light pulse travels across the tissue. Furthermore, a dimensionless multiplying factor, the Differential Pathlength Factor (DPF), can be obtained when the DP is divided by the geometric distance between light source and detector on the tissue surface. This factor has been shown, both theoretically and experimentally, to be approximately constant for any tissue once the optode spacing is larger than about 25 mm (van der Zee et al., 1990; van der Zee et al, in press), enabling clinical NIRS measurements to be made with varying optode geometries.

Experimentally measured optical pathlengths for the adult head, calf and forearm and the head of the newborn infant as a function of inter optode spacing.

The Differential Pathlength Factor (DPF) has been measured for several different tissues. The results showed that the DPF varied with the type of tissue studied, and in the case of the adult calf with sex. However, the DPF for all tissues studied was constant once the inter optode spacing exceeded 2.5 cm. Thus, measurements can be made by NIR spectroscopy at a range of inter optode spacings, and a single DPF used in the calculation of chromophore concentration. The results also showed that the major source of error in the DPF lay in the measurement of the inter optode spacing. To improve accuracy, two options are possible. Firstly, some means of continuous measurement of inter optode spacing could be incorporated in the NIR instrumentation. The better alternative would be an instrument incorporating a method of directly measuring the optical pathlength at each wavelength. This could be done either by time of flight measurement, or if it can be validated, by phase shift measurement.

Differential pathlength factor for diffuse photon scattering through tissue by a pulse-response method

Although near-infrared (NIR) spectroscopy may one day provide a noninvasive measurement of oxidative metabolism in tissue, the method cannot be fully quantitative until the mean pathlength traveled by photons between reference and output detectors (i.e., optrodes) is known. In NIR spectroscopy, photons are transported primarily by diffuse scattering, and their mean pathlength can be expressed by a differential path factor (DPF) whose value is greater than the interoptrode distance. Beginning with a P 1 diffusion approximation of the Boltzmann equation, one-dimensional photon currents originating from plane, line, and point photon sources were analyzed. DPF was formulated from the attenuation of light intensity generated by constant sources, and an equation for the mean time of flight of photons between reference and output optrodes, Δτ, was derived for arbitrarily pulsed sources. The results indicate that (1) the attenuation of light in tissue does not, in general, vary with interoptrode distance in the manner predicted by Beer's law; (2) the relationship between DPF and interoptrode distance is nonlinear and geometry-dependent; and (3) in spite of these nonidealities, DPF is equal to the product of Δτ and the speed of light.

Measurement of Optical Path Length for Cerebral Near-Infrared Spectroscopy in Newborn Infants

The time taken for an extremely short pulse of near-infrared laser light to traverse the heads of 6 preterm infants was measured after death. The values obtained were used to calculate a differential path length factor (DPF), defined as the mean distance travelled by the photons divided by the distance between the points where light entered and left the head. The DPF was found to be 4.39 +/- 0.28. Knowledge of this factor will permit accurate quantitative measurements to be made by near-infrared spectroscopy of a range of indices of cerebral oxygenation and haemodynamics in live infants.