Fellowship for Mehrana Mohtasebi: Mapping Brain Functional Connectivity Using Speckle Contrast Diffuse Correlation Tomography

Abstract: Stroke commonly results from the lack of blood supply to cerebral tissue, leading to cerebral ischemic/hypoxic stresses, neurological disorders, and impairments of functional brain networks involved in voluntary movements. When neurons are activated, the adjacent capillaries provide them energy with an increase in regional cerebral blood flow (CBF) and oxygen supply. CBF is therefore an indirect measure of neuronal activity. Although tissue death from ischemic stroke is often well localized, but focal brain lesions resulting from stroke produce widespread disruptions of brain function that often involve regions remote from the site of injury. Mapping resting-state functional connectivity (RSFC) is an emerging neuroimaging approach to identify low-frequency, spontaneous fluctuations in neural activity and their associated functional connections in the brain. RSFC measurements are able to detect more subtle injury that are not noticeable on anatomic imaging until far advanced. Since RSFC requires neither stimulation of the subject nor performance of a task during imaging, it can be performed easily on patients who are under anesthesia, unable to perform cognitive tasks, or with brain injury. Therefore, there is a need to develop robust technologies that can map CBF and RSFC to investigate complicated pathologies and develop innovative interventions for neurological disorders and cerebrovascular diseases. Recent development of an innovative speckle contrast diffuse correlation tomography (scDCT; US Patent #9861319, 2016- 2036) in the Biomedical Optics Laboratory (PI: Guoqiang Yu) at the University of Kentucky provides a noninvasive, noncontact, low-cost, and portable tool for high-density 3D imaging of CBF distributions in relatively deep brains (up to centimeters). The objective of this study is to optimize the scDCT system for repeated, longitudinal imaging of CBF distribution and mapping RSFC in a mouse model of stroke through two specific aims. Specific Aim 1: Optimize the scDCT for Imaging CBF and Mapping RSFC. The scDCT system will be optimized to achieve sufficient tempo-spatial resolution for CBF imaging and RSCF mapping. New algorithms will be developed to accomplish rapid data collection, fast image reconstruction, and high-density RSFC mapping. Specific Aim 2: Use RSFC to Assess Brain Injury in Mice with Ischemic Stroke. The optimized scDCT system will be used to map RSFC in a mouse model of stroke and results will be correlated with clinical outcomes including neurologic deficit score (NDS), behavior test, and histological examination. RVSD 04/15 (424249)