Background: Cerebral small vessel diseases (SVDs) are a major cause of stroke and dementia. Yet, specific treatment strategies are lacking in part because of a limited understanding of the underlying disease processes. There is therefore an urgent need to study SVDs at their core, the small vessels themselves.
Objective: This paper presents the rationale and design of the ZOOM@SVDs study, which aims to establish measures of cerebral small vessel dysfunction on 7T MRI as novel disease markers of SVDs.
Methods: ZOOM@SVDs is a prospective observational cohort study with two years follow-up. ZOOM@SVDs recruits participants with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL, N = 20), sporadic SVDs (N = 60), and healthy controls (N = 40). Participants undergo 7T brain MRI to assess different aspects of small vessel function including small vessel reactivity, cerebral perforating artery flow, and pulsatility. Extensive work-up at baseline and follow-up further includes clinical and neuropsychological assessment as well as 3T brain MRI to assess conventional SVD imaging markers. Measures of small vessel dysfunction are compared between patients and controls, and related to the severity of clinical and conventional MRI manifestations of SVDs.
Discussion: ZOOM@SVDs will deliver novel markers of cerebral small vessel function in patients with monogenic and sporadic forms of SVDs, and establish their relation with disease burden and progression. These small vessel markers can support etiological studies in SVDs and may serve as surrogate outcome measures in future clinical trials to show target engagement of drugs directed at the small vessels.
Keywords: ASL, Arterial Spin Labeling; BOLD, Blood Oxygenation Level-Dependent; CADASIL; CADASIL, Cerebral Autosomal Dominant Arteriopathy with Leukoencephalopathy and Subcortical Infarcts; CDR, Clinical Dementia Rating scale; CERAD+, Consortium to Establish a Disease Registry for Alzheimer's Disease Plus battery; CES-D, Center for Epidemiologic Studies Depression Scale; CO2, Carbon Dioxide; CSF, Cerebrospinal Fluid; Cerebral small vessel disease; DTI, Diffusion Tensor Imaging; EPIC, European Prospective Investigation into Cancer and Nutrition; EtCO2, End-tidal Carbon Dioxide; FLAIR, Fluid Attenuated Inversion Recovery; FOV, Field Of View; FWHM, Full-Width-at-Half-Maximum; GE, Gradient Echo; GM, Grey Matter; GPRS, General Packet Radio Service; HRF, Hemodynamic Response Function; High field strength MRI; LMU, Ludwig-Maximilians-Universität; MMSE, Mini-Mental State Examination; NAWM, Normal Appearing White Matter; NIHSS, National Institute for Health Stroke Scale; PI, Pulsatility Index; ROI, Region Of Interest; SPPB, Short Physical Performance Battery; SVDs, Small Vessel Diseases; SWI, Susceptibility Weighted Imaging; Small vessel function; Sporadic SVD; Stroke; TE, Echo Time; TI, Inversion Time; TR, Repetition Time; TSE, Turbo Spin Echo; UMCU, University Medical Center Utrecht; Vmax, Maximum velocity; Vmean, Mean velocity; Vmin, Minimum velocity; WM, White Matter; WMH, White Matter Hyperintensity; fMRI, Functional Magnetic Resonance Imaging.
© 2021 The Author(s). Published by Elsevier B.V.