<p>Noninvasive, three-dimensional, and longitudinal imaging of cerebral blood flow (CBF) in small animal models and ultimately in humans has implications for fundamental research and clinical applications. It enables the study of phenomena such as brain development and learning and the effects of pathologies, with a clear vision for translation to humans. Speckle contrast optical tomography (SCOT) is an emerging optical method that aims to achieve this goal by directly measuring three-dimensional blood flow maps in deep tissue with a relatively inexpensive and simple system. High-density SCOT is developed to follow CBF changes in response to somatosensory cortex stimulation. Measurements are carried out through the intact skull on the rat brain. SCOT is able to follow individual trials in each brain hemisphere, where signal averaging resulted in comparable, cortical images to those of functional magnetic resonance images in spatial extent, location, and depth. Sham stimuli are utilized to demonstrate that the observed response is indeed due to local changes in the brain induced by forepaw stimulation. In developing and demonstrating the method, algorithms and analysis methods are developed. The results pave the way for longitudinal, nondestructive imaging in preclinical rodent models that can readily be translated to the human brain.</p>
Neural activity is an important biomarker for the presence of neurodegenerative diseases, cerebrovascular alterations, and brain trauma; furthermore, it is a surrogate marker for treatment effects. These pathologies may occur and evolve in a long time-period, thus, noninvasive, transcutaneous techniques are necessary to allow a longitudinal follow-up. In the present work, we have customized noninvasive, transcutaneous, diffuse correlation spectroscopy (DCS) to localize changes in cerebral blood flow (CBF) induced by neural activity. We were able to detect changes in CBF in the somatosensory cortex by using a model of electrical forepaw stimulation in rats. The suitability of DCS measurements for longitudinal monitoring was demonstrated by performing multiple sessions with the same animals at different ages (from 6 to 18 months). In addition, functional DCS has been cross-validated by comparison with functional magnetic resonance imaging (fMRI) in the same animals in a subset of the time-points. The overall results obtained with transcutaneous DCS demonstrates that it can be utilized in longitudinal studies safely and reproducibly to locate changes in CBF induced by neural activity in the small animal brain.