High-density speckle contrast optical tomography of cerebral blood flow response to functional stimuli in the rodent brain

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.

Dissecting the microvascular contributions to diffuse correlation spectroscopy measurements of cerebral hemodynamics using optical coherence tomography angiography

“…Although we were careful to minimize trauma and animals recovered well with no apparent behavioral side effects, residual bleeding, or bruising, it is possible that there was some level of trauma and compromise of the microvasculature due to the craniotomy itself. 50 Regarding the biphasic nature of the evoked responses and the presence of a prominent undershoot, our findings match those empirically observed in the other DCS studies as well as evoked responses measured by other modalities, such as laser speckle, 51 , 52 laser Doppler, 53 , 54 and arterial spin labeling. 55 …”

Speckle contrast diffuse correlation tomography of cerebral blood flow in perinatal disease model of neonatal piglets

“…While decreasing the number of source positions and number of images at each source position would improve the temporal resolution, this would reduce the sampling density and SNR. Alternatively, we may implement a new reconstruction scheme based on a moving window, where a tomographic image is obtained as data from a new source position becomes available [76]. As a result, the sampling time can be shortened tens of folds (e.g., 1.6 seconds = 40 seconds/25 sources).…”

Synthetic exposure with a CMOS camera for multiple exposure speckle imaging of blood flow

“…Another issue, not specific to synthetic acquisition, is the importance of homogeneous illumination for speckle contrast calculation, as inhomogeneous illumination leads to biased flow maps due to inhomogeneous shot noise contributions within the field of view 19 , 20 . Although calculating speckle contrast in the temporal dimension solves this issue 21 , 22 , in the current implementation of the synthetic exposure mode, the speckle contrast is calculated using spatial kernels and the non-uniformity of field illumination should be minimized or corrected as differences add with the sum of frames.…”