TRD 1: Quantitative Imaging of Physiological Markers Lead Principal investigator: Hanzhang Lu, Professor of Radiology Co-investigators: Jim Pekar, Qin Qin, Jun Hua, Peiying Liu, Wenbo Li This TRD will develop physiological MRI techniques that provide quantitative and biologically interpretable measures of the brain. We will develop methods to probe basal physiological parameters including cerebral blood flow (CBF), bolus arrival time (BAT), oxygen extraction fraction (OEF), and blood-brain barrier (BBB) permeability. We will also develop techniques to assess dynamic physiological parameters including cerebrovascular reactivity (CVR), arterial pulsatility, and vascular compliance (VC). We will achieve these goals through systematic development of novel pulse sequences, models, and data processing methods. To allow these sophisticated measures to be obtained with clinically practical time, fast acquisition methods will be integrated into our techniques such as compressed sensing, multi-band/simultaneous-multi-slice, parallel imaging, variable-density spiral sampling, and stack-of-stars 3D acquisition. Multi- contrast imaging (e.g. combining physiological with anatomic imaging) will be achieved by MR Fingerprinting (MRF). To improve the speed and reliability of parametric estimations, especially for MRF-type of acquisitions, deep learning methods will also be applied. To ensure readiness of these techniques for biomarker testing, small-scale standardization and compatibility assessments will be performed which include intra- session, inter-session, inter-vendor, inter-rater test-retest, and cloud-based MRI data processing. The development of the techniques will be conducted with close interactions (so-called “push-pull relationship”) with the Collaborative Projects (CPs) and in collaboration with other TRDs. Additionally, these tools, once fully tested, will be disseminated to the Service Projects (SPs) and other interested researchers.