Increasing evidence suggests that alterations in cerebral microvasculature play a critical role in the pathogenesis of Alzheimer's disease (AD). The objective of this study was to characterize and evaluate the cerebral microvascular architecture of AD transgenic (Tg) mice and compare it with that of non-Tg mice using brain microvascular indices obtained by MRI. Seven non-Tg mice and 10 5xFAD Tg mice were scanned using a 7-T animal MRI system to measure the transverse relaxation rates of R2 and R2* before and after the injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculating ΔR2* and ΔR2, the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density, mean vessel-weighted image (MvWI) and blood volume fraction (BVf) were mapped. Voxel-based analyses and region of interest (ROI)-based analyses were performed to compare the indices of the non-Tg and Tg groups. Voxel comparisons showed that BVf, mVD, VSI and MvWI were greater in the Tg group than in the non-Tg group. Additionally, the ROI-based analysis showed that ΔR2*, BVf, mVD, MvWI and VSI increased in several brain regions of the Tg group compared with those in the non-Tg group. VSI and mVD increased in Tg mice; these findings indicated microvascular disruption in the brain that could be related to damage to the neurovascular unit in AD caused by cerebral amyloid angiopathy.

The objective of this study was to differentiate the neuronal responses, which was related or unrelated, to pain associated with acupuncture stimulation, and to localize the brain regions with response to stimulation that is unrelated to pain by using Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). BOLD fMRI was performed in six normal healthy beagle dogs, during placebo and verum acupuncture stimulations, at the right side of BL60 (KunLun) acupoint before and after local anesthesia of the acupoint. The order of the four sessions was placebo; verum acupuncture stimulation; before local anesthesia; and followed by the same stimulation after local anesthesia. One-sample t-test analysis was performed to localize the activated or deactivated areas, during both pre-anesthesia and post-anesthesia. In order to compare the pre-anesthesia to post-anesthetic responses, and placebo to verum acupuncture stimulation, within-subject analysis was performed. The post-anesthetic verum acupuncture stimulation resulted in increased activations in the left somatic afferent area I and II, right visual and auditory association area, and the descending reticular activating system of the brainstem. In addition, differential areas during post-anesthesia compared to that of the pre-anesthesia were in the left olfactory peduncle and descending reticular activating system of the brainstem. These results indicate that the areas of specific neural pathway are considered to be unrelated to the pain response during acupuncture stimulation.

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Purpose Growing evidence suggests that alterations of the cerebral microvasculature play a critical role in the pathogenesis of Alzheimer’s disease (AD). The objective of this study was to characterize and evaluate the cerebral microvascular architecture in the AD transgenic (Tg) mice model compared with non-Tg mice using brain microvascular indices obtained by MRI.Methods Seven non-Tg mice and ten 5xFAD Tg mice were scanned using a 7-T animal MRI system to measure the transverse relaxation rates of R2 and R2* before and after injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculation of the relaxation rate difference of ΔR2* and ΔR2, the microvascular indices of the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density (Q), mean vessel-weighted image (MvWI), and blood volume fraction (BVf) were mapped. The voxel-based analyses and regions-of-interest (ROIs)-based analyses were performed to compare the indices between the non-Tg and Tg groups.Results The BVf, mVD, VSI, and MvWI were greater in the Tg group than in the non-Tg group based on voxel comparisons. Additionally, the ROIs-based analysis showed that ΔR2*, BVf, mVD, MvWI, and VSI were increased in the Tg group compared to the non-Tg group in several brain regions. Most ROIs defined by the mouse brain atlas were not significantly different between the two groups.Conclusion We found increased microvascular indices of VSI and mVD in the Tg mice, reflecting microvascular disruption in the brain, which may be related to damages of the neurovascular unit in AD caused by cerebral amyloid angiopathy.Clinical Relevance / Application: To date, few studies have investigated the microvascular injuries of the AD brain using MRI. We suggest that investigation of cerebral microvasculature using a high-field MRI in AD would be worthwhile to elucidate the pathophysiology of cerebral amyloid angiopathy in this disease. Indeed, microvascular MRI can be a promising imaging tool for investigating early diagnosis and monitoring treatment in AD.