Advanced Neuroimaging to Unravel Mechanisms of Cerebral Small Vessel Diseases

M. Edip Gurol, MD, MSc; Geert J. Biessels, MD; Jonathan R. Polimeni, PhD


Stroke. 2020;51(1):29-37. 

In This Article

Abstract and Introduction


Cerebral small vessel disease (cSVD) is the umbrella term used to describe pathologies of the vascular structures (small arteries, arterioles, capillaries, small veins, and venules) that are located in the brain parenchyma or the subarachnoid space.[1] Despite the fact that some pathological processes can damage both large and small vessels, there is ample evidence suggesting that these conditions have distinct mechanisms and clinical consequences. Even common risk factors, such as hypertension, have discernible effects on the cerebral large vessels (intracranial atherosclerosis) and small vessels (white matter disease, lacunar infarcts as well as intracerebral hemorrhages [ICHs] and microbleeds).[2] Research into the causes and consequences of cSVD have blossomed over the past 2 decades, improving our understanding of the relevance of these microangiopathies as causes of ischemic strokes, ICHs as well as contributors to cognitive impairment, gait disorders and behavioral changes in older adults.[3,4] Appropriate diagnosis of cSVDs is clinically relevant to select appropriate stroke prevention methods, and research into their mechanisms is key to decrease the burden of age-related dementia and motor impairments, major causes of disability and death.[5–7]

Until recently, the only way to estimate microstructural and molecular alterations in the human brains was to perform detailed histopathologic studies. Such studies are possible only in the context of a postmortem examination, at the tail end of the pathological evolution. The role of histopathologic evaluation is, therefore, limited in identifying the initial changes in the brain and their progression, processes that might take decades before strokes and microstructural changes culminate into motor and cognitive impairments. Understanding the early phases of such progression is key to stopping the pathological cascade before severe damage occurs. Understanding changes in cerebral vessel function and their pathological consequences constitute another major target in cSVD research.

Early physiological studies of the vessels in humans included mainly transcranial doppler based approaches that are typically limited to large intracranial vessels. Contrast-based perfusion studies depict hemodynamics at tissue level, but they had relatively low resolution and lacked the capacity to show dynamic changes in vessel function. Most of the research in the field of cerebrovascular physiology came from animal studies that do not always translate into successful diagnostic and therapeutic efforts in humans. For all these reasons, developing neuroimaging methods that can detect microstructural, molecular, and physiological alterations in living humans has been an important goal in cSVD research.[6,7]

The current article will review the contributions of advanced neuroimaging in studies evaluating the mechanisms of common sporadic cSVDs in living humans. The focus will be on studies that used cohorts of patients with relatively severe cerebral microangiopathies, such as primary ICH, where a distinction of the cSVD cause can be made. The aim is to discuss the novel imaging techniques and their applications to cSVD research and showcase results that currently guide our understanding of brain microangiopathies. We will specifically review advanced structural imaging, molecular neuroimaging, novel physiological imaging methods and their contributions to the cSVD field.