Mamoru Tamura

Detection of dynamic changes in cerebral oxygenation coupled to neuronal function during mental work in man

Changes in the oxygenation state of brain hemoglobin during mental work were monitored in real time (time resolution: 1 s) using near-infrared spectrophotometry in 14 healthy volunteers. In a younger group (age range 22-30 years, n = 12), the subjects finding difficulty in solving a problem were accompanied by significant increases in both oxygenated hemoglobin and total hemoglobin, while the subjects making a correct answer without difficulty showed no significant changes in hemoglobin oxygenation. When compared with those younger subjects, observations on the older subject demonstrated a decrease in oxygenated hemoglobin and a reciprocal increase in deoxygenated hemoglobin, unaccompanied by changes in total hemoglobin.

NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo. A role for nitric oxide in the central regulation of sympathetic tone?

Continuous production of endothelium-derived nitric oxide (NO) in peripheral vessels has been shown to modulate vascular resistance and blood pressure. NO is also formed in the brain upon activation of glutamate receptors, which are thought to mediate central autonomic reflexes. In the present study we assessed whether NO plays a role in central autonomic regulation. For this, we have investigated the effects of NG-methyl-L-arginine (NMA), a selective inhibitor of NO synthesis from L-arginine, on sympathetic renal nerve activity (RNA), blood pressure, and heart rate in the anesthetized rat. NMA elicited a dose-dependent sustained increase in blood pressure (approximately 20 and 30 mm Hg, 5 minutes after 10 and 50 mumol/kg i.v., respectively). Heart rate and RNA decreased transiently (15 beats per minute and 40%, respectively); RNA subsequently increased (100%) while blood pressure remained elevated. Baroreceptor deafferentation markedly altered these responses to NMA; the transient decreases in heart rate and RNA were abolished, whereas the increases in RNA and blood pressure were significantly potentiated. After spinal C-1-C-2 transection, there was no increase in RNA, and blood pressure increased to a smaller extent. L-Arginine blocked the NMA-induced increases in blood pressure and RNA. Thus, in addition to modulating vascular resistance by a peripheral action, NO may also play a role in the central regulation of sympathetic tone.

Visuospatial imagery is a fruitful strategy for the digit span backward task: A study with near-infrared optical tomography.

Our newly developed 64-channel time-resolved optical tomographic imaging system using near-infrared light enables us to obtain a quantitative image of hemoglobin concentration changes associated with neuronal activation in the human brain ¿H. Eda, I. Oda, Y. Ito, Y. Wada, Y. Oikawa, Y. Tsunazawa, M. Takada, Y. Tsuchiya, Y. Yamashita, M. Oda, A. Sassaroll, Y. Yamada, M. Tamura, Multi-channel time-resolved optical tomographic imaging system, Rev. Sci. Instrum., 70 (1999) 3595-3602. Here, we used this optical imaging system to demonstrate that the backward digit span (DB) task activated the dorsolateral prefrontal cortex (DLPFC) of each hemisphere more than the forward digit span (DF) task in healthy adult volunteers, and higher performance of the DB task was closely related to the activation of the right DLPFC. These results suggest that visuospatial imagery is a useful strategy for the DB task. Optical tomography described here is a new modality of neuropsychological studies.

Optical measurements of intracellular oxygen concentration of rat heart in vitro.

Abstract The optical characteristics of hemoglobin-free perfused rat heart have been examined in detail. Ethyl hydrogen peroxide is found to convert myoglobin into “ferryl compound” in the perfused heart, as is also seen in vitro. After pretreatment with ethyl hydrogen peroxide, a typical mitochondrial absorption spectrum, similar to that of isolated rat heart mitochondria, is obtained in perfused heart. The overall absorption spectrum of the heart obtained by the aerobic to anaerobic transition is a superposition of the mitochondrial spectrum on that of myoglobin. By comparing these spectra, it is found that measurement of cytochrome a + a3 at 605–620 nm is possible in spite of the absorbance change due to the oxygenation-deoxygenation of myoglobin, whereas the wavelength pairs for cytochrome c at 550-540 nm, cytochrome b at 562–575 nm and cytochrome a + a3 at 445–450 nm can not be used in the heart because of interference from the absorption change of myoglobin. The partial pressure of O2 (P50) which is required for half maximal deoxygenation (or oxygenation) of myoglobin in perfused heart is found to be 2.4 mm Hg at room temperature and the Hill constant, n, is 1.1; these values are similar to those of myoglobin purified from rat heart. The steady-state O2 titration has been performed by using absorbancy changes of myoglobin and cytochrome a + a3 as intracellular O2 indicators. In the perfused heart, the percentage change of oxygenation-deoxygenation of myoglobin parallels the oxidation-reduction of cytochrome a + a3, while the mixture of purified myoglobin and isolated mitochondria shows a deviation, reflecting the difference of O2 affinities between myoglobin and cytochrome a + a3. The results indicate that there may be an O2 gradient between cytosolic and mitochondrial compartments in the hemoglobin-free perfused heart. The absorption changes of myoglobin and of cytochrome a + a3 can be measured in a single contraction-relaxation cycle. A triple beam method was introduced to eliminate the effect of light scattering changes in these measurements. The results demonstrated that myoglobin is more oxygenated during the systolic and diastolic periods and deoxygenated in the resting period, whereas cytochrome a + a3 is more reduced in systole and diastole and oxidized in the resting state. Changing the perfusion conditions greatly alters the time course of the events which occur during the contraction-relaxation cycle of the perfused heart.

Multichannel time-resolved optical tomographic imaging system

A time-resolved optical imaging system using near-infrared light has been developed. The system had three pulsed light sources and total 64 channels of detection, working simultaneously for acquisition of the time-resolved data of the pulsed light transmitted through scattering media like biological tissues. The light sources were provided by high power picosecond pulsed diode lasers, and optical switches directed one of the light sources to the object through an optical fiber. The light signals reemitted from the surface of the object were collected by optical fibers, and transmitted to a time-resolved detecting system. Each of the detecting channels consisted of an optical attenuator, a fast photomultiplier, and a time-correlated single photon counting circuit which contained a miniaturized constant fraction discriminator/time-to-amplitude converter module, and a signal acquisition unit with an A/D converter. The performance and potentiality of the imaging system have been examined by the image reconstr...

Non-synchronous behavior of neuronal activity, oxidative metabolism and blood supply during mental tasks in man.

In near-infrared spectroscopic studies during mental tasks such as problem solving and mental arithmetic, we found that 9 of 33 healthy volunteers showed decreases in both the regional cerebral blood flow (r-CBF) and oxygen consumption rate (CMRO2) in the frontal region of the dominant hemisphere. To confirm these unexpected observations, we performed simultaneous measurements by positron emission tomography (PET) and near-infrared spectroscopy (NIRS) in two such subjects. PET images also showed that CBF decreased within the presumptive area illuminated by near-infrared light during mental task. However, CBF decreased in almost all regions while the subject gave a correct answer. Thus, the questions arose: Are mental tasks always associated with increases in r-CBF and/or CMRO2?

In Vivo Noninvasive Measurement of Blood Glucose by Near-Infrared Diffuse-Reflectance Spectroscopy

This paper reports in situ noninvasive blood glucose monitoring by use of near-infrared (NIR) diffuse-reflectance spectroscopy. The NIR spectra of the human forearm were measured in vivo by using a pair of source and detector optical fibers separated by a distance of 0.65 mm on the skin surface. This optical geometry enables the selective measurement of dermis tissue spectra due to the skins optical properties and reduces the interference noise arising from the stratum corneum. Oral glucose intake experiments were performed with six subjects (including a single subject with type I diabetes) whose NIR skin spectra were measured at the forearm. Partial least-squares regression (PLSR) analysis was carried out and calibration equations were obtained with each subject individually. Without exception among the six subjects, the regression coefficient vectors of their calibration models were similar to each other and had a positive peak at around 1600 nm, corresponding to the characteristic absorption peak of glucose. This result indicates that there is every possibility of glucose detection in skin tissue using our measurement system. We also found that there was a good correlation between the optically predicted values and the directly measured values of blood samples with individual subjects. The potential of noninvasive blood glucose monitoring using our methodology was demonstrated by the present study.

Monte Carlo simulation of light transmission through living tissues

To analyze the fundamental characteristics of light transmitted through living tissues, we used the Monte Carlo method to trace the paths of the rays incident upon slabs of particles. The slabs contained either (i) two types of scattering particles in a solution or (ii) one type of particle with pigment added to the solution. Temporal analyses of the transmittance have illustrated that the differences in the optical density among the slabs having different absorption coefficients with the same scattering coefficient vary linearly with time. Also, their gradients have been shown to be proportional to the differences in the absorption coefficients, thus verifying the microscopic Beer-Lambert law in highly scattering media when temporally resolved measurement is used.

Noninvasive blood glucose assay using a newly developed near-infrared system

This paper reports in vivo near-infrared (NIR) noninvasive blood glucose assay using dermis tissue spectra. We assume that the glucose content in dermis tissue traces the variations in blood glucose. For dermis spectra measurements, epidermis, especially stratum corneum, acts as an interference in skin tissue. Thus, we have developed a method for the selective measurement of dermis tissue spectra, enabling us to obtain better quality spectra for an accurate blood glucose assay. The selective measurement of the dermis spectra realized by using a newly developed fiber-optic probe that consists of source and detector optical fibers separated by 0.65 mm on a skin surface. The light path in the skin tissue for this geometry has been simulated by a Monte Carlo method. The simulation results show that detected light mainly interrogates dermis tissue. As the absorbance signal of glucose in human tissue is extremely small, the quality of the measured spectra is critical for the reliable assay. The present method for blood glucose assay has been applied to one Type 1 diabetic. The correlation coefficient between the blood glucose content predicted by NIR spectra and those measured by finger-prick was 0.928 and the standard error of prediction was 32.2 mg/dL. These results demonstrate the potential of our methodology for noninvasive NIR blood glucose assay.

Near-infrared optical detection of sequential brain activation in the prefrontal cortex during mental tasks.

To examine the spatiotemporal differences of brain activation during mental tasks, changes in the oxygenation and hemodynamics in two regions of the prefrontal cortex were measured simultaneously by near-infrared spectroscopy (NIRS). Subjects were eight healthy adults who attempted to solve three different mathematical problems. The behavior of concentration changes in oxy-, deoxy-, and total hemoglobin in one brain region varied with the time course (more than 10 min). This suggested that regional brain activity varied during the performance of the mental task. In each single subject, the pattern of these changes varied with each problem, and this variation differed from subject to subject. When NIRS traces in two regions were compared, it was seen that activated regions moved alternatively: when in one region total hemoglobin that had first increased returned to the resting level, in the other it started to increase. These region-dependent temporal variations of brain activity might reflect mental processes. It is thus concluded that NIRS has the potential for imaging the sequence of brain activation.