UC Davis

Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia and increasing in prevalence as lifespans increase. Clinical MRI traditionally relies on structural abnormalities to identify this vascular dysfunction but lacks microstructure and functional information that could be critical for early identification and assessment of disease. Cerebrovascular dysfunction is one of the only contributors to dementia that can currently be treated, and therefore, earlier identification and subsequent intervention could prevent irreversible structural changes that lead to cognitive decline.Magnetic resonance fingerprinting (MRF) is a novel approach to MRI acquisition and reconstruction using biophysical modeling in parallel to image acquisition for the simultaneous collection of quantitative, multiparametric brain maps. MRF can be adapted to specifically measure cerebrovascular parameters via MR vascular fingerprinting (MRvF), which produces quantitative cerebral blood volume (CBV), microvascular vessel radius (R), and tissue oxygen saturation (SO2) maps of the whole brain. This dissertation aims to advance MRvF for contrast-free, dynamic mapping of cerebrovascular function. First, we compare MRvF to another quantitative MRI method, quantitative blood oxygen level dependent (BOLD) imaging, and show consistency between the techniques, reliable oxygen extraction fraction (OEF) measurements, and expected changes in OEF in response to hypoxia and hyperoxia. Next, we describe a new MRvF pattern-matching algorithm developed for improved mapping without contrast agents, investigate the tradeoffs between SNR, sensitivity, and temporal resolution, and optimize an accelerated spin- and gradient-echo (SAGE) sequence for dynamic MRvF. We show adequate SNR with the SAGE sequence from just one repetition for robust whole-brain vascular parameter mapping every 4.5 seconds. Following this, we demonstrate a novel protocol in which this optimized SAGE sequence allows for dynamic and simultaneous acquisition of MRvF and BOLD measures. By combining this with a tailored hypercapnic (5% CO2) breathing paradigm, we show parameter consistency over time and regional changes in BOLD, CBV, R, and SO2 in response to this stimulus, enabling the calculation of cerebrovascular reactivity (CVR). Finally, we use this newly developed imaging paradigm to compare differences in MRvF-derived CVR measurements in healthy young and healthy old adults. We juxtapose these CVR results against more commonly utilized techniques of measuring CVR to compare and validate our MRvF metrics. Collectively, we demonstrate the development of dynamic MRvF in an ongoing effort toward new quantitative functional imaging biomarkers of cerebrovascular dysfunction with the potential to enable better understanding and earlier diagnoses of diseases like VCID.