PROJECT SUMMARY The burden of mental illness continues to be a growing challenge in the United States. At the same time, the scientific community continues to study the brain and behavior, revealing relationships between brain structure and function and physiology and illness. The outer scope of brain and behavior research is governed by the imaging and analytical tools available to scientists. Magnetic resonance imaging (MRI) has greatly improved the study of the brain. However, even advanced forms of the technology have significant limitations. Specifically, all MRI techniques rely on a qualitative signal for semi-quantitative measurements. Moreover, standard MRI acquisition exhibit as much as 70% signal amplitude bias change with the orientation of the cerebral cortical (and hence the large pial vessels) relative to magnetic field. Quantitative Ultra-short Time-to-Echo Contrast-Enhanced (QUTE-CE, pronounced “cute-see”) MRI is a novel imaging modality that generates a quantitative signal directly representative of physiological information that can broaden the outer limit of what current technology makes possible. QUTE-CE advantages, thus far, include production of the highest quantitative measurement of CA concentration in mice; development of unprecedent non-invasive in vivo maps of brain vascular structure (CBV); mapping of neurofunctional response; biomarkers for cancer treatment efficacy; and, measurement of blood- brain barrier (BBB) leakage. This project strives to create a robust software suite to overcome current limitations unlocking the potential of phMRI and fMRI measurement with higher sampling time, increasing signal-to-noise by 1.67 compared to radial sampling and enabling sliding-window reconstruction for simultaneous high-spatial and temporal image reconstruction using the same data set. To achieve this, the project aims to develop and optimize a software prototype for use with industry-standard 7T small animal research scanners, implementing Imaginostics’ proprietary 3D UTE Radial Cones Pulse Sequence. Next, the project strives to test software prototypes and analytically characterize biomarkers. The goal of the project is to ultimately improve and standardize measurements to complement or replace existing options for a more precise approach that is uniquely quantitative at both the individual and group levels. This means potentially fewer animals would be needed to arrive at meaningful results. Moreover, structural, functional and BBB leakage metrics can be captured within one imaging session, greatly enriching the study of healthy and disordered brains. Overall, these efforts can help advance pre-clinical and related brain research efforts on small animals, by incorporating a novel MRI imaging technology into the repertoire of researchers.