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Vascular Risk Factors Influence Spatial Specificity of White Matter Hyperintensity

Key findings

  • This study was designed to investigate the burden of white matter hyperintensity (WMH) in distinct cerebral vascular territories of patients with acute ischemic stroke and how the burden is affected by common vascular risk factors
  • Older age, male sex, small-vessel stroke subtype, hypertension, hyperlipidemia and smoking had specific effects on WMH burden
  • The findings suggest the possibility of using new approaches to study the pathology of ischemic stroke and its risk factors

The total volume of white matter hyperintensity (WMH), a manifestation of cerebral ischemia on magnetic resonance imaging (MRI), has been linked to both the incidence and outcomes of stroke. However, little is known about the implications of the specific location of WMH in the brain.

Natalia S. Rost, MD, MPH, chief of the Stroke Division, and Markus D. Schirmer, PhD, research fellow in the Department of Neurology at Massachusetts General Hospital, and colleagues have established that the WMH burden in different cerebral vascular territories is influenced by well-established vascular risk factors. These observations, which may lead to a better understanding of stroke, are published in Frontiers in Neurology.

Study Design

The researchers retrospectively studied 882 adults who presented to the Mass General Emergency Department within 12 hours of acute ischemic stroke. Each patient underwent standard imaging within 48 hours of admission, including axial T2 fluid-attenuated inverse recovery (FLAIR) MRI.

A novel FLAIR-based vascular territory (age appropriate) template was built using 16 sets of images from four healthy controls and 12 stroke-free patients with the sporadic form of cerebral amyloid angiopathy. These individuals underwent T1, T2 and three-dimensional FLAIR MRI to create this template. Then, the researchers delineated four vascular territories in the supratentorial brain:

  • ACA — anterior cerebral artery
  • MCA — middle cerebral artery
  • PCA — posterior cerebral artery

In addition, a combined ACA and MCA territory (ANT) was investigated, named after the anterior circulation vs. posterior supratentorial circulation supplied by the PCA.

For each of the stroke patients, the researchers calculated the WMH volume globally and within each territory. In a regression model that included age, sex, common vascular risk factors and stroke subtypes, they assessed the spatial specificity of WMH volume.


There were significant differences in territory-specific WMH burden relative to global burden:

  • In the ACA, older age, small-vessel stroke, hypertension and smoking were all associated with a significantly increased burden of WMH
  • Hyperlipidemia was associated with significantly decreased WMH burden in the ACA
  • In the MCA, older age was associated with significantly decreased WMH burden
  • Older age and small-vessel stroke were associated with significantly decreased WMH burden in the PCA and significantly increased burden in the ANT
  • Male sex was associated with significantly increased WMH burden in the PCA and significantly decreased burden in the ANT

Toward the Future

The spatial specificity of WMH suggests the possibility of using new approaches to study the underlying vascular pathology of acute ischemic stroke and its risk factors. The study findings may also prove useful for studying connections between WMH burden in different vascular territories and the incidence of stroke.

Learn more about the Comprehensive Stroke Service at Mass General

Refer a patient to the Department of Neurology

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