Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3

Abstract

Background Cerebral small vessel disease is a major cause of dementia and stroke, visible on brain magnetic resonance imaging. Recent data suggest that small vessel disease lesions may be dynamic, damage extends into normal-appearing brain and microvascular dysfunctions include abnormal blood–brain barrier leakage, vasoreactivity and pulsatility, but much remains unknown regarding underlying pathophysiology, symptoms, clinical features and risk factors of small vessel disease. Patients and Methods: The Mild Stroke Study 3 is a prospective observational cohort study to identify risk factors for and clinical implications of small vessel disease progression and regression among up to 300 adults with non-disabling stroke. We perform detailed serial clinical, cognitive, lifestyle, physiological, retinal and brain magnetic resonance imaging assessments over one year; we assess cerebrovascular reactivity, blood flow, pulsatility and blood–brain barrier leakage on magnetic resonance imaging at baseline; we follow up to four years by post and phone. The study is registered ISRCTN 12113543. Summary Factors which influence direction and rate of change of small vessel disease lesions are poorly understood. We investigate the role of small vessel dysfunction using advanced serial neuroimaging in a deeply phenotyped cohort to increase understanding of the natural history of small vessel disease, identify those at highest risk of early disease progression or regression and uncover novel targets for small vessel disease prevention and therapy.

Tracer kinetic assessment of blood–brain barrier leakage and blood volume in cerebral small vessel disease: Associations with disease burden and vascular risk factors

“…Lastly, regional analyses may mask local differences, WMH may vary in their constituent tissue characteristics and underlying vascular (dys)function depending on their age and stage of evolution. Longitudinal studies at higher magnetic field strengths may allow systematic comparisons with structural neuroimaging data to investigate how local BBB permeability relates to visible pathologies ( Clancy et al, 2021 ).…”

Sources of systematic error in DCE‐MRI estimation of low‐level blood‐brain barrier leakage

“…We used data from the first 50 patients with recent non‐disabling ischaemic stroke recruited into an ongoing prospective longitudinal study of cerebral SVDs, as per published protocol 25 . MRI was performed ≥1 month post‐stroke to minimize acute effects of stroke on regional BBB integrity.…”

“…Structural imaging, T 1 measurement and DCE-MRI were acquired using a MAGNETOM Prisma 3T clinical MRI scanner (Siemens Healthcare GmbH, Erlangen, Germany) with a 32-channel receive head coil (acquisition parameters are provided as supplementary material of Ref. 25).…”

Super-Resolution of Magnetic Resonance Images Acquired Under Clinical Protocols using Deep Attention-based Method

“…The data used in this study is part of an ongoing observational clinical study of sporadic SVD, a disease of the small blood vessels that, if progresses, can result in stroke and/or dementia, and is currently diagnosed by the presence of specific pathological features in brain MRI scans. The primary study that provided the data (Trial registration ISRCTN 12113543) includes a comprehensive set of assessments such as blood tests, blood pressure, retinal imaging, electrocardiograms, cognitive tests, and more to elucidate which factors determine the progression and rate of changes of the disease [11]. The present study only uses low-resolution and high-resolution paired brain MRI sets from 61 patients (mean age [std.…”

“…We use a dataset of paired low-and high-resolution scans of the same patients, who had an MRI head scan as part of a routine clinical examination, and, within 3 months, were re-scanned at a field strength of 3 Tesla using a research protocol, after consenting to participate on a study of sporadic small vessel disease (SVD) [11]. Thus, instead of using down-sampled scans X, we use true low-resolution scans X acquired in routine clinical settings, for our framework to approximate the quality difference between low-and high-resolution scans directly g(X) ≈ Y independent from any choice of down-sampling function.…”