Abstract
.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.
Highlights
Microvascular cerebral blood flow (CBF) dynamics is an important biomarker of healthy brain development, pathology, and injury since it is a measure of the delivery of nutrients necessary for tissue metabolism and of the clearance of the by-products
The coupling between the neuronal activity and regional CBF is regarded as fundamental in the study of functional brain activity and is the basis of many functional neuroimaging techniques.[1,2]. It is responsible for the blood oxygen level-dependent (BOLD) signal that is commonly employed in functional magnetic resonance imaging
Most common optical techniques for blood flow monitoring are based on the dynamic scattering of light and include laser Doppler flowmetry,[12,13] laser speckle contrast imaging,[9,11] and diffuse correlation spectroscopy (DCS).[14]
Summary
Microvascular cerebral blood flow (CBF) dynamics is an important biomarker of healthy brain development, pathology, and injury since it is a measure of the delivery of nutrients necessary for tissue metabolism and of the clearance of the by-products. We highlight speckle contrast optical tomography (SCOT) which, by taking advantage of the scalability of SCOS detection, achieves tomographic measurements using scanning sources and array detectors.[27,28] Our recent developments in mice revealed comparable results to magnetic resonance imaging in following the infarct induced by CBF reduction.[27] A similar development[29] has been successfully used in the intraoperative room, where the three-dimensional (3-D) distribution of blood flow from a mastectomy skin flap was resolved. In order to increase the temporal resolution, we have introduced a technique based on a moving window scheme, which effectively improves the sampling efficiency
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