Advanced MRI in cerebral small vessel disease

Abstract

Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. This review summarizes recent developments in advanced neuroimaging of cSVD with a focus on clinical and research applications. In the first section we highlight how advanced structural imaging techniques, including diffusion MRI, enable improved detection of tissue damage, including characterization of tissue appearing normal on conventional MRI. These techniques enable progression to be monitored and may be useful as surrogate endpoint in clinical trials. Quantitative MRI, including iron and myelin imaging, provides insights into tissue composition on the molecular level. In the second section, we cover how advanced MRI techniques can demonstrate functional or dynamic abnormalities of the blood vessels, which could be targeted in mechanistic research and early-stage intervention trials. Such techniques include the use of dynamic contrast enhanced MRI to measure blood-brain barrier permeability, and MRI methods to assess cerebrovascular reactivity. In the third section we discuss how the increased spatial resolution provided by ultra-high field MRI at 7T allows imaging of perforating arteries, and flow velocity and pulsatility within them. The advanced MRI techniques we describe are providing novel pathophysiological insights in cSVD and allow improved quantification of disease burden and progression. They have application in clinical trials, both in assessing novel therapeutic mechanisms, and as a sensitive endpoint to assess efficacy of interventions on parenchymal tissue damage. We also discuss challenges of these advanced techniques and suggest future directions for research.

Cerebral small vessel disease: Recent advances and future directions

“…In this issue, van den Brink et al. 16 review these advances. They cover how advanced structural imaging techniques, including diffusion MRI, enable improved detection of tissue damage, including characterization of white matter appearing normal on conventional MRI.…”

Mapping the current trends and hotspots of vascular cognitive impairment from 2000–2021: A bibliometric analysis

“… 49 Quantitative measures in imaging have been proposed as the markers of the SVD. 9 , 49 Future research on SVD can help explore the neuropathological correlates between small vessel diseases and cognitive impairment and develop new diagnostic and therapeutic interventions. 50 Meanwhile, the mouse model burst from 2017.…”

“…49 Quantitative measures in imaging have been proposed as the markers of the SVD. 9,49 Future research on SVD can help explore the neuropathological correlates between small vessel diseases and cognitive impairment and develop new diagnostic and therapeutic 51 The preclinical studies provided new mechanistic insight and discovered biomarkers and therapeutic strategies through genetic manipulation, pharmacological inhibition, and other methods, which could not be applied in clinical studies. 52 Drug discovery had little progress in VCI and VaD.…”

Association between white matter alterations and domain-specific cognitive impairment in cerebral small vessel disease: A meta-analysis of diffusion tensor imaging

“…Over the years, significant emphasis has been placed on biological markers for early identification and intervention in white matter damage. DTI can detect early tissue alterations, even in white matter appearing normal on conventional imaging (van den Brink et al, 2022 ). Some cognitive domains are affected during early cognitive impairment of CSVD, including executive function and attention (van der Flier et al, 2018 ; Peng, 2019 ).…”