Etsuko Ohmae

Cerebral hemodynamics evaluation by near-infrared time-resolved spectroscopy: Correlation with simultaneous positron emission tomography measurements

We compared pharmacologically-perturbed hemodynamic parameters (cerebral blood volume; CBV, and flow; CBF) by acetazolamide administration in six healthy human subjects studied with positron emission tomography (PET) and near-infrared (NIR) time-resolved spectroscopy (TRS) simultaneously to investigate whether NIR-TRS could measure in vivo hemodynamics in the brain tissue quantitatively. Simultaneously with the PET measurements, TRS measurements were performed at the forehead with four different optode spacing from 2 cm to 5 cm. Total hemoglobin and oxygen saturation (SO2) measured by TRS significantly increased after administration of acetazolamide at any optode spacing in all subjects. In PET study, CBV and CBF were estimated in the following three volumes of interest (VOIs) determined on magnetic resonance images, VOI1: scalp and skull, VOI2: gray matter region, VOI3: gray and white matter regions. Acetazolamide treatment elevated CBF and CBV significantly in VOI2 and VOI3 but VOI1. TRS-derived CBV was more strongly correlated with PET-derived counterpart in VOI2 and VOI3 when the optode spacing was above 4 cm, although optical signal from cerebral tissue could be caught with any optode spacing. As to increase of the CBV, 4 cm of optode spacing correlated best with VOI2. To support the result of TRS-PET experiment, we also estimated the contribution ratios of intracerebral tissue to observed absorption change based on diffusion theory. The contribution ratios at 4 cm were estimated as follows: 761 nm: 50%, 791 nm: 72%, 836 nm: 70%. These results demonstrated that NIR-TRS with 4 cm of optode spacing could measure cerebral hemodynamic responses optimally and quantitatively.

Near-infrared time-resolved spectroscopy system for tissue oxygenation monitor

We have developed a three-wavelength (759,797, and 833 nm) time-resolved spectroscopy (TRS) system as a tissue oxygenation monitor employing a time-correlated single photon counting method. This system achieved a high data acquisition rate and system miniaturization maintaining a high sensitivity and time resolution. Our system succeeded in accurately measuring concentrations of oxy-(HbO2) and deoxyhemoglobin (Hb) by means of TRS data observation through studies using a phantom model and living tissue.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Methodological validation of the dynamic heterogeneity of muscle deoxygenation within the quadriceps during cycle exercise

The conventional continuous wave near-infrared spectroscopy (CW-NIRS) has enabled identification of regional differences in muscle deoxygenation following onset of exercise. However, assumptions of constant optical factors (e.g., path length) used to convert the relative changes in CW-NIRS signal intensity to values of relative concentration, bring the validity of such measurements into question. Furthermore, to justify comparisons among sites and subjects, it is essential to correct the amplitude of deoxygenated hemoglobin plus myoglobin [deoxy(Hb+Mb)] for the adipose tissue thickness (ATT). We used two time-resolved NIRS systems to measure the distribution of the optical factors directly, thereby enabling the determination of the absolute concentrations of deoxy(Hb+Mb) simultaneously at the distal and proximal sites within the vastus lateralis (VL) and the rectus femoris muscles. Eight subjects performed cycle exercise transitions from unloaded to heavy work rates (>gas exchange threshold). Following exercise onset, the ATT-corrected amplitudes (A(p)), time delay (TD(p)), and time constant (τ(p)) of the primary component kinetics in muscle deoxy(Hb + Mb) were spatially heterogeneous (intersite coefficient of variation range for the subjects: 10-50 for A(p), 16-58 for TD(p), 14-108% for τ(p)). The absolute and relative amplitudes of the deoxy(Hb+Mb) responses were highly dependent on ATT, both within subjects and between measurement sites. The present results suggest that regional heterogeneity in the magnitude and temporal profile of muscle deoxygenation is a consequence of differential matching of O(2) delivery and O(2) utilization, not an artifact caused by changes in optical properties of the tissue during exercise or variability in the overlying adipose tissue.

Kinetics of muscle deoxygenation and microvascular Po2 during contractions in rat: comparison of optical spectroscopy and phosphorescence-quenching techniques

The overarching presumption with near-infrared spectroscopy measurement of muscle deoxygenation is that the signal reflects predominantly the intramuscular microcirculatory compartment rather than intramyocyte myoglobin (Mb). To test this hypothesis, we compared the kinetics profile of muscle deoxygenation using visible light spectroscopy (suitable for the superficial fiber layers) with that for microvascular O(2) partial pressure (i.e., Pmv(O(2)), phosphorescence quenching) within the same muscle region (0.5∼1 mm depth) during transitions from rest to electrically stimulated contractions in the gastrocnemius of male Wistar rats (n = 14). Both responses could be modeled by a time delay (TD), followed by a close-to-exponential change to the new steady level. However, the TD for the muscle deoxygenation profile was significantly longer compared with that for the phosphorescence-quenching Pmv(O(2)) [8.6 ± 1.4 and 2.7 ± 0.6 s (means ± SE) for the deoxygenation and Pmv(O(2)), respectively; P < 0.05]. The time constants (τ) of the responses were not different (8.8 ± 4.7 and 11.2 ± 1.8 s for the deoxygenation and Pmv(O(2)), respectively). These disparate (TD) responses suggest that the deoxygenation characteristics of Mb extend the TD, thereby increasing the duration (number of contractions) before the onset of muscle deoxygenation. However, this effect was insufficient to increase the mean response time. Somewhat differently, the muscle deoxygenation response measured using near-infrared spectroscopy in the deeper regions (∼5 mm depth) (∼50% type I Mb-rich, highly oxidative fibers) was slower (τ = 42.3 ± 6.6 s; P < 0.05) than the corresponding value for superficial muscle measured using visible light spectroscopy or Pmv(O(2)) and can be explained on the basis of known fiber-type differences in Pmv(O(2)) kinetics. These data suggest that, within the superficial and also deeper muscle regions, the τ of the deoxygenation signal may represent a useful index of local O(2) extraction kinetics during exercise transients.

Clinical evaluation of time-resolved spectroscopy by measuring cerebral hemodynamics during cardiopulmonary bypass surgery

We developed a three-wavelength time-resolved spectroscopy (TRS) system, which allows quantitative measurement of hemodynamics within relatively large living tissue. We clinically evaluated this TRS system by monitoring cerebral circulation during cardiopulmonary bypass surgery. Oxyhemoglobin, deoxyhemoglobin, total hemoglobin and oxygen saturation (SO(2)) were determined by TRS on the left forehead attached with an optode spacing of 4 cm. We also simultaneously monitored jugular venous oxygen saturation (SjvO(2)) and arterial blood hematocrit (Hct) using conventional methods. The validity and usefulness of the TRS system were assessed by comparing parameters obtained with the TRS and conventional methods. Although the changes in SO(2) were lower than those in SjvO(2), SO(2) obtained by TRS paralleled the fluctuations in SjvO(2), and a good correlation between these values was observed. The only exceptions occurred during the perfusion period. Moreover, there was a good correlation between tHb and Hct values (r(2)=0.63). We concluded that time-resolved spectroscopy reflected the conditions of cerebral hemodynamics of patients during surgical operations.

Validation of a high-power time resolved near-infrared spectroscopy system for measurement of superficial and deep muscle deoxygenation during exercise

Near-infrared assessment of skeletal muscle is restricted to superficial tissues due to power limitations of spectroscopic systems. We reasoned that understanding of muscle deoxygenation may be improved by simultaneously interrogating deeper tissues. To achieve this, we modified a high-power (∼8 mW), time-resolved, near-infrared spectroscopy system to increase depth penetration. Precision was first validated using a homogenous optical phantom over a range of inter-optode spacings (OS). Coefficients of variation from 10 measurements were minimal (0.5-1.9%) for absorption (μa), reduced scattering, simulated total hemoglobin, and simulated O2 saturation. Second, a dual-layer phantom was constructed to assess depth sensitivity, and the thickness of the superficial layer was varied. With a superficial layer thickness of 1, 2, 3, and 4 cm (μa = 0.149 cm(-1)), the proportional contribution of the deep layer (μa = 0.250 cm(-1)) to total μa was 80.1, 26.9, 3.7, and 0.0%, respectively (at 6-cm OS), validating penetration to ∼3 cm. Implementation of an additional superficial phantom to simulate adipose tissue further reduced depth sensitivity. Finally, superficial and deep muscle spectroscopy was performed in six participants during heavy-intensity cycle exercise. Compared with the superficial rectus femoris, peak deoxygenation of the deep rectus femoris (including the superficial intermedius in some) was not significantly different (deoxyhemoglobin and deoxymyoglobin concentration: 81.3 ± 20.8 vs. 78.3 ± 13.6 μM, P > 0.05), but deoxygenation kinetics were significantly slower (mean response time: 37 ± 10 vs. 65 ± 9 s, P ≤ 0.05). These data validate a high-power, time-resolved, near-infrared spectroscopy system with large OS for measuring the deoxygenation of deep tissues and reveal temporal and spatial disparities in muscle deoxygenation responses to exercise.

Muscle deoxygenation in the quadriceps during ramp incremental cycling: Deep vs. superficial heterogeneity

Muscle deoxygenation (i.e., deoxy[Hb + Mb]) during exercise assesses the matching of oxygen delivery (Q̇O2) to oxygen utilization (V̇O2). Until now limitations in near-infrared spectroscopy (NIRS) technology did not permit discrimination of deoxy[Hb + Mb] between superficial and deep muscles. In humans, the deep quadriceps is more highly vascularized and oxidative than the superficial quadriceps. Using high-power time-resolved NIRS, we tested the hypothesis that deoxygenation of the deep quadriceps would be less than in superficial muscle during incremental cycling exercise in eight males. Pulmonary V̇O2 was measured and muscle deoxy[Hb + Mb] was determined in the superficial vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF-s) and the deep rectus femoris (RF-d). deoxy[Hb + Mb] in RF-d was significantly less than VL at 70% (67.2 ± 7.0 vs. 75.5 ± 10.7 μM) and 80% (71.4 ± 11.0 vs. 79.0 ± 15.4 μM) of peak work rate (WR(peak)), but greater than VL and VM at WR(peak) (87.7 ± 32.5 vs. 76.6 ± 17.5 and 75.1 ± 19.9 μM). RF-s was intermediate at WR(peak) (82.6 ± 18.7 μM). Total hemoglobin and myoglobin concentration and tissue oxygen saturation were significantly greater in RF-d than RF-s throughout exercise. The slope of deoxy[Hb + Mb] increase (proportional to Q̇O2/V̇O2) in VL and VM slowed markedly above 70% WR(peak), whereas it became greater in RF-d. This divergent deoxygenation pattern may be due to a greater population of slow-twitch muscle fibers in the RF-d muscle and the differential recruitment profiles and vascular and metabolic control properties of specific fiber populations within superficial and deeper muscle regions.

Reflectance Diffuse Optical Tomography: Its Application to Human Brain Mapping

We report the successful application of reflectance diffuse optical tomography (DOT) using near-infrared light with the new reconstruction algorithm that we developed to the observation of regional hemodynamic changes in the brain under specific mental tasks. Our results reveal the heterogeneous distribution of oxyhemoglobin and deoxyhemoglobin in the brain, showing complementary images of oxyhemoglobin and deoxyhemoglobin changes in certain regions. We conclude that our reflectance DOT has practical potential for human brain mapping, as well as in the diagnostic imaging of brain diseases.

Time-resolved optical mammography and its preliminary clinical results.

We have been developing an optical mammography prototype consisting of a multi-channel time-resolved spectroscopy system for breast cancer screening. The system utilizes the time-correlated single photon counting method, and the detector modules and the signal processing circuits were custom-made to obtain a high signal to noise ratio and high temperature stability with a high temporal resolution. Pulsed light generated by a Ti: Sapphire laser was irradiated to the breast, and the transmitted light was collected by optical fibers placed on the surface of a hemispherical gantry filled with an optical matching fluid. To reconstruct a 3D image of the breast, we employed a method using a time-resolved photon path distribution based on the assumption that scattering and absorption are independent of each other. We verified the possibility of human breast imaging by using a three-dimensional phantom model, which provides a simulation of human breast cancer, in the gantry. The clinical study was also started in January 2007. In a comparative study with conventional modalities, the breast cancers were detected as regions of optically higher absorption. Moreover, the results suggest that optical mammography is useful in monitoring the effects of chemotherapy.

Bedside Assessment of Cerebral Vasospasms After Subarachnoid Hemorrhage by Near Infrared Time-Resolved Spectroscopy

We examined the usefulness of near infrared time-resolved spectroscopy (TRS) for detection of vasospasm in subarachnoid hemorrhage (SAH). We investigated seven aneurysmal SAH patients with poor clinical conditions (WFNS grade V) who underwent endovascular coil embolization. Employing TRS, we measured the oxygen saturation (SO(2)) and baseline hemoglobin concentrations in the cortices. Measurements of TRS and transcranial Doppler sonography (TCD) were performed repeatedly for 14 days after SAH. In four of the seven patients, the SO(2) and hemoglobin concentrations measured in the brain tissue of the middle cerebral artery territory remained stable after SAH. However, in three patients, TRS revealed abrupt decreases in SO(2) and total hemoglobin between 5 and 9 days after SAH. Cerebral angiography performed on the same day revealed severe vasospasms in these patients. Although TCD detected the vasospasm in two of three cases, it failed to do so in one case. TRS could detect vasospasms after SAH by evaluating the cortical blood oxygenation.