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Stroke Novel Noninvasive Magnetic Resonance Imaging Methods in Cerebrovascular Disease Manus J Donahue, PhD 1 and Megan K Strother, MD 2 1. Assistant Professor, Departments of Radiology, Neurology, Psychiatry, and Physics and Astronomy; 2. Associate Professor, Department of Radiology, School of Medicine, Vanderbilt University, Nashville, Tennessee, US Abstract Neuroimaging is a critical component of patient care in multiple stages of cerebrovascular disease. Most imaging focuses on measurements of tissue or vascular structure, with comparatively less emphasis on function. Furthermore, imaging approaches that rely on exogenous contrast agents or ionizing radiation are common and provide crucial information regarding treatment decisions; however, they are suboptimal for monitoring patients longitudinally or in response to therapy due to dose restrictions and related health concerns. We review the state of noninvasive magnetic resonance imaging (MRI) approaches that have demonstrated clinical potential in patients with cerebrovascular disease, yet have not been incorporated into routine radiologic protocols at most hospitals. These approaches include blood oxygenation level-dependent (BOLD) for cerebrovascular reactivity, arterial spin labeling (ASL) for cerebral blood flow quantification, chemical exchange saturation transfer (CEST) for macromolecule, and pH determination and arterial vessel wall imaging for plaque visualization. The strengths and limitations of these approaches are presented, as well as a summary of their implementation in stroke. Keywords Stroke, BOLD, ASL, CEST, reactivity, neurovascular imaging Disclosure: The authors have no conflicts of interest to declare. Acknowledgments: This work was supported in part by the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) (5R01NS078828-02). Received: August 16, 2013 Accepted: October 30, 2013 Citation: US Neurology, 2014;10(1):23–9 Correspondence: Manus J Donahue, PhD, Vanderbilt University Institute of Imaging Science, 1161 21st Ave N, MCN, AAA-3115, Nashville, TN 37232–2310, US. E: mj.donahue@vanderbilt.edu Stroke is the leading cause of adult disability and the second leading cause of death in developed countries. 1 Despite progress in stroke treatment, 20–30  % of strokes result in death within 1 month and 70–80  % result in significant long-term disability. 2–4 Improved preventative and acute management of cerebrovascular disease has reduced stroke-related mortality; 5 however, many stroke survivors remain impaired with nearly 33 % institutionalized after stroke. 6–9 Neuroimaging is a critical component of patient care in all stages of cerebrovascular disease: from identification of stroke risk factors to stratifying acute and chronic stroke patients to the most effective revascularization and rehabilitation treatments. Evaluation of management decisions and post-stroke therapy strategies would be accelerated with an improved understanding of the complex interplay between vascular, neurochemical, and tissue-level hemodynamic impairment. Characterization of soft-tissue structure using fluid attenuated inversion recovery (FLAIR) and T1-weighted magnetic resonance imaging (MRI) © TO U CH MED ICA L MEDIA 2014 is central to most standard MRI protocols and extensive work has documented the relevance of these techniques. 10–12 In more specialized protocols, diffusion weighted imaging (DWI) or diffusion tensor imaging (DTI) can be applied to characterize membrane integrity and fiber tract directionality, respectively, 13 and neurochemical tissue signatures can be assessed using principles of magnetic resonance spectroscopy. 14 These relatively well-known approaches have been implemented in patients with cerebrovascular disease for more than 2 decades. However, newer approaches are continuously being developed that hold potential for further expanding our understanding of the functional and structural sequela of tissue changes during and following ischemia. Here, we review the state of novel, noninvasive MRI approaches capable of complementing the existing stroke imaging infrastructure for more comprehensive evaluation of cerebrovascular disease. As each method is in a different stage of development, with varying timelines for routine clinical implementation, the purpose of this article is to review these emerging methods in the context of their strengths and limitations for 23