Chie Sato

Analysis of Optical Signals Evoked by Peripheral Nerve Stimulation in Rat Somatosensory Cortex: Dynamic Changes in Hemoglobin Concentration and Oxygenation

The origins of reflected light changes associated with neuronal activity (optical signals) were investigated in rat somatosensory cortex with optical imaging, microspectrophotometry, and laser-Doppler flowmetry, and dynamic changes in local hemoglobin concentration and oxygenation were focused on. Functional activation was carried out by 2-second, 5-Hz electrical stimulation of the hind limb under chloralose anesthesia. These measurements were performed at the contralateral parietal cortex through a thinned skull. Regional cortical blood flow (rCBF) started to rise 1.5 seconds after the stimulus onset, peaked at 3.5 seconds (26.7% ± 9.7% increase over baseline), and returned to near baseline by 10 seconds. Optical signal responses at 577, 586, and 805 nm showed a monophasic increase in absorbance coincident with the increase in rCBF; however, the signal responses at 605 and 760 nm were biphasic (an early increase and late decrease in absorbance) and microanatomically heterogeneous. The spectral changes of absorbance indicated that the concentrations of both total hemoglobin and oxyhemoglobin increased together with rCBF; deoxyhemoglobin, increased slightly but distinctly (P = 0.016 at 1.0 seconds, P = 0.00038 at 1.5 seconds) just before rCBF increases, then decreased. The authors conclude that activity-related optical signals are greatly associated with a moment-to-moment adjustment of rCBF and metabolism to neuronal activity.

Resting hypofrontality in schizophrenia: A study using near-infrared time-resolved spectroscopy

Hypofrontality has been a major finding obtained from functional neuroimaging studies on schizophrenia, although there have also been contradictory results that have questioned the reality of hypofrontality. In our previous study, we confirmed the existence of activation hypofrontality by using a 2-channel continuous-wave-type (CW-type) near-infrared spectroscopy (NIRS) instrument. In this study, we employed a single-channel time-resolved spectroscopy (TRS) instrument, which can quantify hemoglobin (Hb) concentrations based on the photon diffusion theory, to investigate resting hypofrontality. A pair of incident and detecting light guides was placed on either side of the forehead at approximately Fp2-F8 or Fp1-F7 alternately in 14 male schizophrenic patients and 16 age-matched male control subjects to measure Hb concentrations at rest. The patients were also measured with a 2-channel CW-type NIRS instrument during the performance of a random number generation (RNG) task. A reduced total hemoglobin concentration (t-Hb) less than 60 microM (the mean value of the control subjects-1.5 SD) was observed bilaterally in 4 patients and only in the left side in 3 patients. Activation hypofrontality was more manifest in these patients than in the remaining 7 patients despite the same task performance. This decreased t-Hb was related to the duration of illness, and it was not observed in patients whose duration of illness was less than 10 years. These results indicate that resting hypofrontality is a chronically developed feature of schizophrenia. This does not necessarily represent frontal dysfunction, but may reflect anatomical and/or functional changes in frontal microcirculation.

Optical Imaging and Measuring of Local Hemoglobin Concentration and Oxygenation Changes During Somatosensory Stimulation in Rat Cerebral Cortex

The dynamic changes in local hemoglobin concentration and oxygenation in the cerebral cortex closely correlate with neuronal activity through the changes of cerebral metabolism and blood flow, but their mechanisms are not understood in detail. The purpose of this study is to reveal the changes in local hemoglobin concentration and oxygenation associated with neuronal activity using the techniques of charge-coupled device (CCD) imaging and microspectrophotometry, and to investigate the origin of the intensity changes of reflected light (intrinsic signals) in the activated cortex from the viewpoint of hemoglobin concentration and oxygenation changes.

Intraoperative monitoring of depth-dependent hemoglobin concentration changes during carotid endarterectomy by time-resolved spectroscopy

By measuring the adult human head during carotid endarterectomy, we investigate the depth sensitivity of two methods for deriving the absorption coefficient changes (Dmu(a)) from time-resolved reflectance data to absorption changes in inhomogeneous media: (1) the curve-fitting method based on the diffusion equation (DE-fit method) and (2) the time-independent calculation based on the modified Lambert-Beer law (MLB method). Remarkable differences in the determined values of Dmu(a) caused by clamping the external carotid artery and subsequently clamping the common carotid artery were observed between the methods. The DE-fit method was more sensitive to mu(a) changes in cerebral tissues, whereas the MLB method was rather sensitive to mu(a) changes in the extracerebral tissues. Our results indicated that the DE-fit was useful for monitoring the cerebral blood circulation and oxygenation during neurosurgical operations. In addition, the combined evaluation of mu(a) changes with the DE-fit and MLB methods will provide us with more available information about the hemodynamic changes in the depth direction.

Effect of stimulus frequency on human cerebral hemodynamic responses to electric median nerve stimulation: a near-infrared spectroscopic study.

We examined the effect of stimulus frequency on optically recorded hemodynamic responses to electric median nerve stimulation. Electric stimuli were delivered to the right median nerve with an intensity of 90% of motor threshold. Four different stimulus frequencies (2, 5, 10, and 20 Hz) were administered in each subject. By means of a multi-channel near-infrared spectroscopic instrument, changes in concentration of oxygenated hemoglobin were continuously measured over the left scalp. After 20 Hz stimulation, we found two spatially and temporally distinct hemodynamic responses. One lasted beyond 60 s, and the center of this response was located over the secondary somatosensory area. The other had a transient duration starting immediately after the stimulus onset and was located in the primary somatosensory hand area. Both responses were linearly augmented as a function of the stimulus frequency. Since temporal activation patterns are different in two somatosensory areas, real-time optical monitoring is necessary in evaluation of hemodynamic responses to electric nerve stimulation.

Diversity of neural-hemodynamic relationships associated with differences in cortical processing during bilateral somatosensory activation in rats.

The neural-hemodynamic relationships may vary depending on cortical processing patterns. To investigate how cortical hemodynamics reflects neural activity involving different cortical processing patterns, we delivered electrical stimulation pulses to rat hindpaws, unilaterally or bilaterally, and simultaneously measured electrophysiological (local field potential, LFP < 100 Hz; multiunit activity, MUA>300 Hz) and optical intrinsic signals associated with changes in cerebral blood volume (CBV). Unilateral stimulation evoked neural and optical signals in bilateral primary somatosensory cortices. Ipsilateral optical responses indicating an increased CBV exhibited a peak magnitude of ~30% and mediocaudal shifts relative to contralateral responses. Correlation analyses revealed different scale factors between contralateral and ipsilateral responses in LFP-MUA and LFP-CBV relationships. Bilateral stimulation at varying time intervals evoked hemodynamic responses that were strongly suppressed at 40-ms intervals. This suppression quantitatively reflected suppressed LFP responses to contralateral testing stimulation and not linear summation, with slowly fluctuating LFP responses to ipsilateral conditioning stimulation. Consequently, in the overall responses to bilateral stimulation, CBV-related responses were more linearly correlated with MUA than with LFPs. When extracting high-frequency components (>30 Hz) from LFPs, we found similar scale factors between contralateral and ipsilateral responses in LFP-MUA and LFP-CBV relationships, resulting in significant linear relationships among these components, MUA, and cortical hemodynamics in overall responses to bilateral stimulation. The dependence of LFP-MUA-hemodynamic relationships on cortical processing patterns and the LFP temporal/spectral structure is important for interpreting hemodynamic signals in complex functional paradigms driving diverse cortical processing.

Estimation of the absorption coefficients of two-layered media by a simple method using spatially and time-resolved reflectances.

Our newly developed method using spatially and time-resolved reflectances can easily estimate the absorption coefficients of each layer in a two-layered medium if the thickness of the upper layer and the reduced scattering coefficients of the two layers are known a priori. We experimentally validated this method using phantoms and examined its possibility of estimating the absorption coefficients of the tissues in human heads. In the case of a homogeneous plastic phantom (polyacetal block), the absorption coefficient estimated by our method agreed well with that obtained by a conventional method. Also, in the case of two-layered phantoms, our method successfully estimated the absorption coefficients of the two layers. Furthermore, the absorption coefficients of the extracerebral and cerebral tissue inside human foreheads were estimated under the assumption that the human heads were two-layered media. It was found that the absorption coefficients of the cerebral tissues were larger than those of the extracerebral tissues.

Estimating the absorption coefficient of the bottom layer in four-layered turbid mediums based on the time-domain depth sensitivity of near-infrared light reflectance

Abstract. Expanding our previously proposed “time segment analysis” for a two-layered turbid medium, this study attempted to selectively determine the absorption coefficient (μa) of the bottom layer in a four-layered human head model with time-domain near-infrared measurements. The difference curve in the temporal profiles of the light attenuation between an object and a reference medium, which are obtained from Monte Carlo simulations, is divided into segments along the time axis, and a slope for each segment is calculated to obtain the depth-dependent μa(μaseg). The reduced scattering coefficient (μs′) of the reference is determined by curve fitting with the temporal point spread function derived from the analytical solution of the diffusion equation to the time-resolved reflectance of the object. The deviation of μaseg from the actual μa is expressed by a function of the ratio of μaseg in an earlier time segment to that in a later segment for mediums with different optical properties and thicknesses of the upper layers. Using this function, it is possible to determine the μa of the bottom layer in a four-layered epoxy resin-based phantom. These results suggest that the method reported here has potential for determining the μa of the cerebral tissue in humans.

Quantitative optical imaging of brain activity—human and animal studies

Abstract In order to overcome the problems associated with near-infrared optical imaging (NIR-imaging) such as the lack of the quantification and poor spatial resolution, we developed a 64-channel time-resolved optical imaging system, by which we could obtain quantitative functional images of human brain activity. Reflectance tomographic images of the changes in oxy-hemoglobin [oxy-Hb], deoxy-hemoglobin [deoxy-Hb], and total-hemoglobin [t-Hb] associated with neural activation were obtained, and given as absolute concentration changes. Then, the obtained optical functional images were superimposed on 3-D images of the subjects brain reconstructed from MRI, on which fMRI images were also superimposed. Very interestingly, but curiously, we found that the activation maps of [oxy-Hb] rather than [deoxy-Hb] were very reasonable and similar to those of the fMRI. The maximum increase in [oxy-Hb] due to finger tapping was about 1 μM, whereas in several cognitive tasks such as the digit span task, the increase was much larger, at 3–8 μM. The optical imaging system employed here can be applied to the subjects of all ages and be used at the bedside as well. By simplifying and miniaturizing the imaging system, we could construct a conventional single channel oxygen monitor for clinical use, by which we could quantify the changes of [oxy-, deoxy- and total Hb] during neuronal activation in each subject and, therefore, statistical analysis became possible.

Estimation of absorption coefficient in bottom regions in multi-layered turbid media based on the time-domain depth sensitivity : a Monte Carlo investigation

We attempted to selectively determine the absorption coefficient (μa) of bottom regions in two- and four-layered models with time-domain near infrared measurement. The difference curve in the time-resolved reflectance between a target and a reference medium was divided into segments, and a slope of each segment was calculated to determine depth-dependent μa (μaseg). The deviation of μaseg in later time segments from the real μa of the bottom layer was μaseg in an earlier time segment to that in a later one. Using this function, we could determine μa in the bottom layer for various target media with different conditions.