R44MH129278

Summary This project will develop MRI physiological imaging with higher spatial and temporal resolution, larger brain coverage, and faster accelerated pulse sequences. The physiologic images have contrasts of microvascular- weighted blood oxygen level dependent (BOLD), cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the techniques to be developed are largely insensitive to venous blood contributions to signal, unlike traditional BOLD echo planar imaging (EPI) sequences, and thus they are extremely useful for precision imaging of physiological markers in neurological disorders and for higher specificity in cortical layer fMRI, enabling higher granularity in human neurocircuitry imaging. Novel acceleration techniques for each pulse sequence will be incorporated to increase slice-volume coverage and improve signal to noise ratio (SNR) and point spread function (PSF) in signal localization. Sequence development and evaluations will be performed at several 3T and 7T imaging sites. We will develop a software package with advanced variants of several pulse sequences: zoomed 3D gradient-and-spin-echo (GRASE), arterial spin labeling (ASL) for CBF imaging, slice- saturation slab- inversion vascular space occupancy (SS-SI-VASO) for CBV imaging, and the novel VASO technique with “multiple acquisitions with global excitation cycling” (MAGEC)-VASO to achieve whole brain coverage. The software package will also include a modular analysis pipeline for use by neuroscientists and physicians without the need for extensive MR-physics or coding expertise. Achieving non-invasive imaging of neuronal circuits in the human brain will allow neuroscientists to study normal brain processes and allow medical scientists to study neurocircuitry changes and neurological diseases. Currently, high-resolution fMRI technology could be used to identify fMRI of neural activity at different cortical depths, but is severely limited by poorly localized signal from venous drainage in the cortex. This project innovates new, robust 3D fMRI imaging sequences that eliminate venous contamination, thus affording high fidelity mapping of fine-scale neuronal circuitry compared to current gradient echo EPI BOLD imaging.Narrative This project innovates high resolution and high speed MRI to enable robust measuring of several physiological parameters important to determine normal and abnormal brain states. The new high resolution imaging techniques will be able to evaluate neuronal activity at different depths through the neocortex to better define both normal and abnormal circuitry in the brain. These novel physiological imaging techniques can potentially be used to improve medical diagnosis of several neurological diseases as well as to elucidate neurocircuitry mechanisms behind several different neuropsychological and neurological disorders.