Velocity profiles in the rat cerebral microvessels measured by optical coherence tomography.

In order to analyze cerebral hemodynamics and its change following neural activation, the cross-sectional profiles of blood flow velocity in the rat pial microvessels and their temporal changes were measured in vivo using Doppler OCT technique (Doppler optical coherence tomography). The OCT system used in this study has axial resolution of 11 microm and lateral resolution about 14 microm in the cortical tissue. The velocity distributions along the vertical diameter of pial microvessels in a cranial window of the rats were measured at short time intervals by scanning the OCT sampling point repeatedly. The velocity profiles obtained in the pial arterioles were parabolic at any phase, although the centerline velocity pulsated following heart beats with amplitude as large as 50% of the temporal mean velocity. It indicates that the blood flow in the pial microvessels is a quasi-steady laminar flow, which is consistent with the flow expected for the case of a small Reynolds number and a small frequency parameter. The stimulus-induced increase in velocity pulsation was much larger than the increase in the mean velocity, which places a restriction on the mechanism of regulating the regional cerebral blood flow and blood volume. The results obtained in this study showed that the Doppler OCT has a potential of measuring velocity profiles and their temporal changes with both high temporal and spatial resolutions for the pial microvessels with diameter up to 200 microm.

Optical coherence tomography reveals in vivo cortical plasticity of adult mice in response to peripheral neuropathic pain.

We examined neural plasticity in mice in vivo using optical coherence tomography (OCT) of primary somatosensory (S1) and motor (M1) cortices of mice under the influence of sciatic nerve chronic constriction injury (CCI), a model of neuropathic pain widely utilized in rats. The OCT system used in this study provided cross-sectional images of the cortical tissue of mice up to a depth of about 1mm with longitudinal resolution up to 11 microm. This is the first study to evaluate neural plasticity in vivo using OCT. CCI mice exhibited cold allodynia and spontaneous pain behaviors, which are signs of neuropathic pain, 30 days after sciatic nerve ligation, when OCT observation of S1 and M1 cortices was carried out. The scattering intensity of near-infrared light within the hind paw area of S1 and M1 regions in the contralateral hemisphere was significantly higher than in the ipsilateral hemisphere. These CCI-induced increases in scattering intensity within cortical regions associated with the hind paw probably reflect elevated neural activity associated with neuropathic pain. Synapses and mitochondria are believed to have high light scattering coefficients, since they contain remarkably high concentrations of proteins and complicated membrane structure. Number densities of mitochondria and synapses are known to increase in parallel with increases in neural activity. Our findings thus suggest that neuropathic pain gives rise to neural plasticity within the hind paw area of S1 and M1 contralateral to the ligated sciatic nerve.

In vivo imaging of the rat cerebral microvessels with optical coherence tomography.

A technique called optical coherence tomography (OCT) was applied to in vivo observation of microcirculation in the rat cerebral cortex. The OCT system used in this study provided cross-sectional images of the cerebral cortical tissue up to about 1 mm depth with longitudinal resolution up to 8 microm. It could visualize cross-sectional structure of the dura, arachnoid membrane, cortical tissue, and pial microvessels through the cranial window. Pial microvessels with diameter larger than several 10 microm could be detected to observe their cross-sectional shape, while the microvessels within the cortical tissue with smaller diameter were not discernible. The OCT observation revealed that the pial microvessels showed different spatial configurations depending on the cerebral preparations with intact dura and without dura. Stimulus responses of the somatosensory cortices were also different among the preparation methods; Delayed swelling of the cortical surface appeared in the somatosensory cortex following the electrical stimulation of the hind paw in the case of dura removal, which was restricted to a thin surface layer with less than several 10 microm. It is considered to reflect the reactive hyperemia accompanying the neuronal activation. Doppler frequency shift due to the blood flow was detected in pial arterioles. This phenomenon is promising to provide the velocity profile within microvessels and may be applicable to the functional imaging of the brain.

Regulation of oxygen transport during brain activation: stimulus-induced hemodynamic responses in human and animal cortices.

BACKGROUND: The correlation between regional changes in neuronal activity and changes in hemodynamics is a major issue for noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared optical imaging (NIOI). A tight coupling of these changes has been assumed to elucidate brain function from data obtained with those techniques. In the present study, we investigated the relationship between neuronal activity and hemodynamic responses in the occipital cortex of humans during visual stimulation and in the somatosensory cortex of rats during peripheral nerve stimulation. METHODS: The temporal frequency dependence of macroscopic hemodynamic responses on visual stimuli was investigated in the occipital cortex of humans by simultaneous measurements made using fMRI and NIOI. The stimulus-intensity dependence of both microscopic hemodynamic changes and changes in neuronal activity in response to peripheral nerve stimulation was investigated in animal models by analyzing membrane potential (fluorescence), hemodynamic parameters (visible spectra and laser-Doppler flowmetry), and vessel diameter (image analyzer). RESULTS: Above a certain level of stimulus-intensity, increases in regional cerebral blood flow (rCBF) were accompanied by a decrease in regional cerebral blood volume (rCBV), i.e., dissociation of rCBF and rCBV responses occurred in both the human and animal experiments. Furthermore, the animal experiments revealed that the distribution of increased rCBF and O2 spread well beyond the area of neuronal activation, and that the increases showed saturation in the activated area. CONCLUSIONS: These results suggest that above a certain level of neuronal activity, a regulatory mechanism between regional cerebral blood flow (rCBF) and rCBV acts to prevent excess O2 inflow into the focally activated area.