The enormous economic and social burden of stroke demands better tools to assess the cerebrovascular system. Magnetic Resonance Imaging (MRI) is widely used in the evaluation and management of patients presenting with symptoms of stroke and is standard of care for most diagnostic neurological imaging. In the case of intact aneurysms and atherosclerotic plaques, MRI offers unique contrast mechanisms unavailable from competing technologies. In both these diseases, an interaction of the endothelial wall with hemodynamic forces exerted by blood has been established. The exact relationship between forces and subsequent vascular pathogenesis is uncertain; however, flow conditions that predispose subjects to stenosis and aneurysm formation have been identified. MRI with flow encoding (4D flow), holds potential to non-invasively probe potentially hostile hemodynamic conditions. Furthermore, endothelial status can be probed with MRI utilizing black blood imaging to visualize the uptake of exogenous contrasts. Recent MRI studies suggest a link between post-contrast arterial wall enhancement (AWE) and lesion instability, potentially indicating AWE as a measure of active inflammation and remodeling. The simultaneous depiction of hemodynamics and inflammation holds tremendous potential to improve the in-vivo characterization of diseases involving vessel wall dysfunction or active remodeling. Unfortunately, current MRI methods often suffer from signal loss due complex and turbulent flow, inadequate coverage, and limitations in spatial resolution. Furthermore, many unique MRI contrast mechanisms, such as 4D flow, are not practical for clinical imaging due to extended scan times with required resolutions for accurate quantification. This proposal suggests a next generation of accelerated imaging technology for the comprehensive evaluation of intracranial stenoses and aneurysms that will rival and surpass computed tomography (CT) through the symbiotic development of new image acquisition and constrained reconstruction methods. In particular, we aim to develop methods for robust quantitative MRA (qMRA), a multi-contrast high resolution vascular imaging paradigm. In order to achieve the required combinations of artifact reduction, spatial resolution and signal-to-noise ratio, we harness acquisition strategies utilizin novel ultra-short echo time acquisition techniques in combination with robust model based reconstruction techniques. By acquiring data more rapidly and in a more efficient manor, these strategies allow improved spatial resolution while mitigating diagnostic obscuring artifacts from the complex flow.
We aim to harness these advances to into a synergistic combination of angiographic MRI with highly accelerated 4D-flow and vessel wall imaging to investigate the interactions between vascular remodeling, inflammation, and hemodynamics in intact intracranial aneurysms and atherosclerotic lesions. The ultimate goal is to observed correlations between hostile hemodynamic conditions and arterial wall enhancement utilizing non-invasive imaging, which may provide new clinical treatment paradigms and improve the management of a broad array of neurovascular diseases.

Public Health Relevance

This project provides several highly innovative strategies to dramatically improve the visualization of the structure and hemodynamics of vascular lesions of the brain using Magnetic Resonance Imaging (MRI). Techniques are of minimal risk compared to conventional catheter based X-ray angiography while provide unique markers of disease and are thus better suited for the evaluation of atherosclerotic disease in elderly patients or in case of surveillance imaging. Studies outlined in this project will provide initial validation of non- invasive MRA methods to evaluate patients with atherosclerotic disease and brain aneurysms, leading causes of ischemic and hemorrhagic stroke in the US. he

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Babcock, Debra J
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University of Wisconsin Madison
Schools of Medicine
United States
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Rivera-Rivera, Leonardo A; Schubert, Tilman; Knobloch, Gesine et al. (2018) Comparison of ferumoxytol-based cerebral blood volume estimates using quantitative R1 and R2* relaxometry. Magn Reson Med 79:3072-3081
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Bannas, Peter; Bell, Laura C; Johnson, Kevin M et al. (2016) Pulmonary Embolism Detection with Three-dimensional Ultrashort Echo Time MR Imaging: Experimental Study in Canines. Radiology 278:413-21
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Chang, W; Wu, Y; Johnson, K et al. (2015) Fast contrast-enhanced 4D MRA and 4D flow MRI using constrained reconstruction (HYPRFlow): potential applications for brain arteriovenous malformations. AJNR Am J Neuroradiol 36:1049-55
Velikina, Julia V; Samsonov, Alexey A (2015) Reconstruction of dynamic image series from undersampled MRI data using data-driven model consistency condition (MOCCO). Magn Reson Med 74:1279-90
Bauman, Grzegorz; Johnson, Kevin M; Bell, Laura C et al. (2015) Three-dimensional pulmonary perfusion MRI with radial ultrashort echo time and spatial-temporal constrained reconstruction. Magn Reson Med 73:555-64

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