7 Tesla MRI in cerebral small vessel disease Philip Benjamin 1 *†, Olivia Viessmann 2 †, Andrew MacKinnon 3 , Peter Jezzard 2 , and Hugh S. Markus 4 Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive decline. Magnetic resonance imaging (MRI) cur- rently plays a central role in diagnosis, and advanced MRI techniques are widely used in research but are limited by spatial resolution. Human 7 Tesla (7T) MRI has recently become available offering the ability to image at higher spatial reso- lution. This may provide additional insights into both the vas- cular pathology itself as well as parenchymal markers which could only previously be examined post mortem. In this review we cover the advantages and limitations of 7T MRI, review studies in SVD performed to date, and discuss potential future insights into SVD which 7T MRI may provide. Key words: 7T MRI, small vessel disease Introduction Cerebral small vessel disease (SVD) describes a group of patho- logical processes that affect the perforating cerebral arterioles and capillaries resulting in brain injury to the subcortical gray and white matter (1). It is associated with a number of brain paren- chymal pathologies including small deep infarcts, areas of diffuse gliosis, ischemic demyelination and axonal loss corresponding to regions of radiological leukoaraiosis, microbleeds, and diffuse brain atrophy (2). Clinically SVD presents with lacunar strokes, and is also the major cause of vascular cognitive impairment. In addition, it appears to interact with Alzheimer’s disease, exacer- bating the degree of cognitive impairment (3). Thus, SVD is an enormous health burden. Despite this, there is a limited under- standing of the disease and the mechanisms underlying it, which has hindered treatment approaches. As the disease is slowly progressive and lacunar stroke is asso- ciated with a low early mortality compared with other stroke subtypes, there is limited neuropathological data available, par- ticularly earlier in the disease process. Magnetic resonance imaging (MRI) at field strengths up to 3 Tesla is widely used for the clinical diagnosis in SVD and has provided many insights into disease pathogenesis. Recently, higher field strength imaging at 7 Tesla (7T) has become available on human MR systems offering the ability to image at higher signal to noise ratios (SNR) and therefore higher spatial resolution. This has the potential to improve our understanding of SVD by visualizing the vascular pathology itself as well as parenchymal markers which could only previously be examined post mortem. Disease pathogenesis Early pathological descriptions of SVD were made by C. Miller Fisher in the 1950s and 1960s who observed that occlusion of the small perforating arteries occurred by two main pathologies: a diffuse arteriopathy with hyaline deposition (which he termed lipohyalinosis) or atherosclerosis (4). He reported that while lipohyalinosis (characterized by loss of normal arterial architec- ture and mural foam cells) affected smaller arteries (200–800 μm diameter), atherosclerosis affected the larger perforating arteries near their origins and resulted in larger isolated lacunar infarcts (5). How the vascular lesions cause brain injury and in particular the diffuse ischemic changes seen as leukoaraiosis is not fully understood. The conventional hypothesis is that chronic ischemic changes occur in internal watershed regions, and both reduced blood flow (6) and impaired cerebral autoregulation (7) have been reported. However more recently a role for endothelial dys- function and increased blood brain barrier permeability, resulting in exudation of potentially toxic plasma constituents into the brain parenchyma, has been proposed (8). The current status of MRI in SVD MRI plays a crucial role in the diagnosis of SVD and is a key research technique in the field. Common features seen on con- ventional MRI include lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), perivascular spaces (PvS) and brain atrophy. WMHs are best seen on T2-weighted sequences, and contrast between WMHs and normal tissue is further increased on Fluid Attenuated Inversion Recovery (FLAIR) sequences in which signal from cerebrospinal fluid (CSF) is suppressed. Lacunar infarcts are seen acutely on diffusion-weighted images (9), while old lacunar infarcts with Correspondence: Philip Benjamin*, Neurosciences Research Centre, St Georges University of London, Cranmer Terrace, London SW17 0RE, UK. E-mail: philipbenjamin@doctors.net.uk 1 Neurosciences Research Centre, St George’s University of London, London, UK 2 Functional MRI of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK 3 Atkinson Morley Regional Neuroscience Centre, St George’s NHS Healthcare Trust, London, UK 4 Department of Clinical Neurosciences, University of Cambridge, Cam- bridge, UK Received: 19 November 2014; Accepted: 4 February 2015 †Authors contributed equally to the manuscript. Conflicts of interest: None declared. Funding: This work is supported by a Neurosciences Research Foundation (NRF) grant (PB) (Registered Charity No. 288438). Hugh Markus is sup- ported by an NIHR Senior Investigator award. His research is supported by the Cambridge University Hospitals NINR Comprehensive Biomedical Research Centre. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007–2013/under REA grant agreement n° [316716] (OV). We also thank the Dunhill Medical Trust for salary support (PJ). DOI: 10.1111/ijs.12490 Review © 2015 World Stroke Organization Vol ••, •• 2015, ••–•• 1