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Its manifestations on magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) include white matter hyperintensities, lacunes, microbleeds, perivascular spaces, small subcortical infarcts, and brain atrophy. Many studies focus only on one of these manifestations. A protocol for the differential assessment of all these features is, therefore, needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To identify ways of quantifying imaging markers in research of patients with <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content> and operationalize the recommendations from the <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>andards for ReportIng Vascular changes on <jats:styled-content style=\"fixed-case\">nE<\/jats:styled-content>uroimaging guidelines. Here, we report the rationale, design, and methodology of a brain image analysis protocol based on our experience from observational longitudinal studies of patients with nondisabling stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> analysis protocol is designed to provide quantitative and qualitative measures of disease evolution including: acute and old stroke lesions, lacunes, tissue loss due to stroke, perivascular spaces, microbleeds, macrohemorrhages, iron deposition in basal ganglia, substantia nigra and brain stem, brain atrophy, and white matter hyperintensities, with the latter separated into intense and less intense. Quantitative measures of tissue integrity such as diffusion fractional anisotropy, mean diffusivity, and the longitudinal relaxation time are assessed in regions of interest manually placed in anatomically and functionally relevant locations, and in others derived from feature extraction pipelines and tissue segmentation methods. Morphological changes that relate to cognitive deficits after stroke, analyzed through shape models of subcortical structures, complete the multiparametric image analysis protocol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Outcomes<\/jats:title><jats:p>Final outcomes include guidance for identifying ways to minimize bias and confounds in the assessment of <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content> and stroke imaging biomarkers. It is intended that this information will inform the design of studies to examine the underlying pathophysiology of <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content> and stroke, and to provide reliable, quantitative outcomes in trials of new therapies and preventative strategies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.415","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T02:02:38Z","timestamp":1448589758000},"source":"Crossref","is-referenced-by-count":77,"title":["Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2771-6546","authenticated-orcid":false,"given":"Maria del C.","family":"Vald\u00e9s Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Department of Neuroimaging Sciences Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Armitage","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Thrippleton","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Sciences Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Chappell","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Sciences Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Sandeman","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Sciences Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Mu\u00f1oz Maniega","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Sciences Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Shuler","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Sciences Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna M.","family":"Wardlaw","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Sciences Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2003.10.012"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93206-O"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200207190-00024"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.295095034"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl387"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.526996"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002227"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.21130"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-008-1119-2"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.19.10.1285"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.06.013"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2014.10.001"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn265"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-010-1718-6"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.64"},{"key":"e_1_2_6_17_1","unstructured":"Hoban K. 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