Hiroshi Kawaguchi

Voxel-based analysis of the diffusion tensor

IntroductionDiffusion tensor imaging (DTI) has provided important insights into the neurobiological basis for normal development and aging and various disease processes in the central nervous system. The aim of this article is to review the current protocols for DTI acquisition and preprocessing and statistical testing for a voxelwise analysis of DTI, focused on statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS).MethodsWe tested the effects of distortion correction induced by gradient nonlinearity on fractional anisotropy (FA) maps or FA skeletons processed via two SPM-based methods (coregistration and FA template methods), or TBSS-based method, respectively.ResultsWith two SPM-based methods, we found similar results in some points (e.g., significant FA elevation for uncorrected images in anterior-dominant white matter and for corrected images in bilateral middle cerebellar peduncles) and different results in other points (e.g., significantly larger FA for corrected images with coregistration method, but significantly smaller with FA template method in bilateral internal capsules, extending to corona radiata, and semioval centers). In contrast, there was no area with significant difference between uncorrected and corrected FA skeletons with TBSS-based method.ConclusionThe discrepancy among these results was not explained in full, but possible explanations were misregistration and smoothing for the SPM-based methods and insensitivity to FA changes outside the local centers of white matter bundles for TBSS-based method.

Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.

To study distribution and patterns of nerve hypertrophy in chronic inflammatory demyelinating polyneuropathy (CIDP), magnetic resonance neurography with 3‐dimensional reconstruction of short tau inversion recovery images was performed in 33 patients. This technique clearly showed longitudinal morphological changes from the cervical roots to the nerve trunks in the proximal arm. Nerve enlargement was detected in 88% of the patients. According to the clinical subtype of CIDP, typical CIDP patients showed symmetric and root‐dominant hypertrophy, whereas Lewis–Sumner syndrome patients had multifocal fusiform hypertrophy in the nerve trunks. The patterns of nerve hypertrophy presumably reflect the different pathophysiology of each CIDP subtype. Ann Neurol 2014.

Effect of probe arrangement on reproducibility of images by near-infrared topography evaluated by a virtual head phantom

The effect of the probe arrangement on the reproducibility of topographic images of the concentration changes in oxygenated hemoglobin and deoxygenated hemoglobin is evaluated by a virtual head phantom. A virtual head phantom consists of five types of tissue the 3D structure of which is based on a magnetic resonance imaging scan of an adult head. Localized and broadened brain activation is assumed in a virtual head phantom. The topographic images are obtained from the reflectance detected by the standard probe arrangement and the double-density probe arrangement. The uneven thickness of the superficial layer, which cannot be evaluated by the previous slab model, affects the distribution of measured activation in the topographic image, and this reduces the position reproducibility of near-infrared (NIR) topography with the standard probe arrangement. The overlapping measurements by the double-density probe arrangement can improve the reproducibility of the image obtained by NIR topography.

Theoretical evaluation of accuracy in position and size of brain activity obtained by near-infrared topography.

Near-infrared (NIR) topography can obtain a topographical distribution of the activated region in the brain cortex. Near-infrared light is strongly scattered in the head, and the volume of tissue sampled by a source-detector pair on the head surface is broadly distributed in the brain. This scattering effect results in poor resolution and contrast in the topographic image of the brain activity. In this study, a one-dimensional distribution of absorption change in a head model is calculated by mapping and reconstruction methods to evaluate the effect of the image reconstruction algorithm and the interval of measurement points for topographic imaging on the accuracy of the topographic image. The light propagation in the head model is predicted by Monte Carlo simulation to obtain the spatial sensitivity profile for a source-detector pair. The measurement points are one-dimensionally arranged on the surface of the model, and the distance between adjacent measurement points is varied from 4 mm to 28 mm. Small intervals of the measurement points improve the topographic image calculated by both the mapping and reconstruction methods. In the conventional mapping method, the limit of the spatial resolution depends upon the interval of the measurement points and spatial sensitivity profile for source-detector pairs. The reconstruction method has advantages over the mapping method which improve the results of one-dimensional analysis when the interval of measurement points is less than 12 mm. The effect of overlapping of spatial sensitivity profiles indicates that the reconstruction method may be effective to improve the spatial resolution of a two-dimensional reconstruction of topographic image obtained with larger interval of measurement points. Near-infrared topography with the reconstruction method potentially obtains an accurate distribution of absorption change in the brain even if the size of absorption change is less than 10 mm.

Long-Term Adaptation of Cerebral Hemodynamic Response to Somatosensory Stimulation during Chronic Hypoxia in Awake Mice

Effects of chronic hypoxia on hemodynamic response to sensory stimulation were investigated. Using laser-Doppler flowmetry, change in cerebral blood flow (CBF) was measured in awake mice, which were housed in a hypoxic chamber (8% O2) for 1 month. The degree of increase in CBF evoked by sensory stimulation was gradually decreased over 1 month of chronic hypoxia. No significant reduction of increase in CBF induced by hypercapnia was observed during 1 month. Voltage-sensitive dye (VSD) imaging of the somatosensory cortex showed no significant decrease in neural activation over 1 month, indicating that the reduction of increase in CBF to sensory stimulation was not caused by cerebrovascular or neural dysfunction. The simulation study showed that, when effective diffusivity for oxygen in the capillary bed (D) value increases by chronic hypoxia due to an increase in capillary blood volume, an increase in the cerebral metabolic rate of oxygen utilization during neural activation can occur without any increase in CBF. Although previous study showed no direct effects of acute hypoxia on CBF response, our finding showed that hemodynamic response to neural activation could be modified in response to a change in their balance to energy demand using chronic hypoxia experiments.

Microvascular sprouting, extension, and creation of new capillary connections with adaptation of the neighboring astrocytes in adult mouse cortex under chronic hypoxia

The present study aimed to determine the spatiotemporal dynamics of microvascular and astrocytic adaptation during hypoxia-induced cerebral angiogenesis. Adult C57BL/6J and Tie2-green fluorescent protein (GFP) mice with vascular endothelial cells expressing GFP were exposed to normobaric hypoxia for 3 weeks, whereas the three-dimensional microvessels and astrocytes were imaged repeatedly using two-photon microscopy. After 7 to14 days of hypoxia, a vessel sprout appeared from the capillaries with a bump-like head shape (mean diameter 14u2009μm), and stagnant blood cells were seen inside the sprout. However, no detectable changes in the astrocyte morphology were observed for this early phase of the hypoxia adaptation. More than 50% of the sprouts emerged from capillaries 60u2009μm away from the center penetrating arteries, which indicates that the capillary distant from the penetrating arteries is a favored site for sprouting. After 14 to 21 days of hypoxia, the sprouting vessels created a new connection with an existing capillary. In this phase, the shape of the new vessel and its blood flow were normalized, and the outside of the vessels were wrapped with numerous processes from the neighboring astrocytes. The findings indicate that hypoxia-induced cerebral angiogenesis provokes the adaptation of neighboring astrocytes, which may stabilize the blood–brain barrier in immature vessels.

Hemodynamic changes during somatosensory stimulation in awake and isoflurane-anesthetized mice measured by laser-Doppler flowmetry.

Elucidating the mechanisms underlying the regulation of cerebral blood flow (CBF) is important to understanding the hemodynamic changes measured by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) signals. The purpose of this study was to explore changes in hemodynamic characteristics during resting and sensory stimulation in awake animals as compared with those in anesthetized animals. Changes in CBF, red blood cell (RBC) velocity and concentration in the somatosensory cortex to whisker stimulation were measured using laser-Doppler flowmetry in awake and anesthetized mice. The increase in the rate of RBC velocity change observed during whisker stimulation was far greater than the increase in the rate of RBC concentration change under the awake condition. During the resting condition, significant differences in baseline CBF, RBC velocity and concentration between awake and anesthesia mice were not observed. Isoflurane-induced anesthesia attenuated the increase in RBC velocity and concentration during stimulation, with the attenuation of the RBC velocity increase being greater than that of RBC concentration. The RBC measurement techniques in awake animals should lead to much better understanding of the hemodynamic system evoked by neural activity.

Unveiling astrocytic control of cerebral blood flow with optogenetics

Cortical neural activities lead to changes in the cerebral blood flow (CBF), which involves astrocytic control of cerebrovascular tone. However, the manner in which astrocytic activity specifically leads to vasodilation or vasoconstriction is difficult to determine. Here, cortical astrocytes genetically expressing a light-sensitive cation channel, channelrhodopsin-2 (ChR2), were transcranially activated with a blue laser while the spatiotemporal changes in CBF were noninvasively monitored with laser speckle flowgraphy in the anesthetised mouse cortex. A brief photostimulation induced a fast transient increase in CBF. The average response onset time was 0.7u2009±u20090.7u2009sec at the activation foci, and this CBF increase spread widely from the irradiation spot with an apparent propagation speed of 0.8–1.1u2009mm/sec. The broad increase in the CBF could be due to a propagation of diffusible vasoactive signals derived from the stimulated astrocytes. Pharmacological manipulation showed that topical administration of a K+ channel inhibitor (BaCl2; 0.1–0.5u2009mM) significantly reduced the photostimulation-induced CBF responses, which indicates that the ChR2-evoked astrocytic activity involves K+ signalling to the vascular smooth muscle cells. These findings demonstrate a unique model for exploring the role of the astrocytes in gliovascular coupling using non-invasive, time-controlled, cell-type specific perturbations.

The influence of frontal sinus in brain activation measurements by near-infrared spectroscopy analyzed by realistic head models

Adequate modeling of light propagation in the head is important to predict the sensitivity of NIRS signal and the spatial sensitivity profile of source-detector pairs. The 3D realistic head models of which the geometry is based upon the anatomical images acquired by magnetic resonance imaging and x-ray computed tomography are constructed to investigate the influence of the frontal sinus on the NIRS signal and spatial sensitivity. Light propagation in the head is strongly affected by the presence of the frontal sinus. The light tends to propagate around the frontal sinus. The influence of the frontal sinus on the sensitivity of the NIRS signal to the brain activation is not consistent and depends on the depth of the frontal sinus, the optical properties of the superficial tissues and the relative position between the source-detector pair and the frontal sinus. The frontal sinus located in the shallow region of the skull tends to reduce the sensitivity of the NIRS signal while the deep frontal sinus can increase the sensitivity of the NIRS signal.

Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy

This study aimed to examine the cortical microvessel diameter response to hypercapnia in misery perfusion using two-photon laser scanning microscopy (TPLSM). We evaluated whether the vascular response to hypercapnia could represent the cerebrovascular reserve. Cerebral blood flow (CBF) during normocapnia and hypercapnia was measured by laser-Doppler flowmetry through cranial windows in awake C57/BL6 mice before and at 1,7, 14, and 28 days after unilateral common carotid artery occlusion (UCCAO). Diameters of the cortical microvessels during normocapnia and hypercapnia were also measured by TPLSM. Cerebral blood flow and the vascular response to hypercapnia were decreased after UCCAO. Before UCCAO, vasodilation during hypercapnia was found primarily in arterioles (22.9% ± 3.5%). At 14 days after UCCAO, arterioles, capillaries, and venules were autoregulatorily dilated by 79.5% ± 19.7%, 57.2% ±32.3%, and 32.0% ± 10.8%, respectively. At the same time, the diameter response to hypercapnia in arterioles was significantly decreased to 1.9% ± 1.5%. A significant negative correlation was observed between autoregulatory vasodilation and the diameter response to hypercapnia in arterioles. Our findings indicate that arterioles play main roles in both autoregulatory vasodilation and hypercapnic vasodilation, and that the vascular response to hypercapnia can be used to estimate the cerebrovascular reserve.