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Investigating Brain Vascular Disease In Vivo: Challenges and Opportunities

  • Gwenn S. Smith
    Correspondence
    Send correspondence and reprint requests to Gwenn S. Smith, Ph.D., Department of Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, 5300 Alpha Commons Drive, 4th Floor, Baltimore, MD 21224.
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Baltimore, MD
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Published:August 16, 2022DOI:https://doi.org/10.1016/j.jagp.2022.08.001
      Brain vascular disease is a major contributor to mood disorders and to cognitive decline in late-life. The role of brain vascular disease has been studied mainly by using structural magnetic resonance imaging (MRI) methods to measure white matter hyperintensities (reflecting both vascular and neurodegenerative processes) and strokes. A major advance to understanding the underlying cerebral hemodynamic mechanisms has been the development of arterial spin labelling (ASL) perfusion MRI that provides a noninvasive, quantitative measure of regional cerebral blood flow (rCBF) by using magnetically labeled blood as an endogenous CBF tracer.
      • Williams DS
      • Detre JA
      • Leigh JS
      • et al.
      Magnetic resonance imaging of perfusion using spin inversion of arterial water.
      Prior to the introduction of ASL, the primary methods for imaging rCBF in the brain involved administration of radiotracers (e.g., 133Xe, [15O]-water, [123I]-iodoamphetamine and [99TC]-HMPAO) that are more challenging logistically than ASL imaging studies. As shown in the study by Gyanwali et al., ASL was implemented on a relatively large scale in a memory clinic sample to address fundamental questions about the role of rCBF and other aspects of vascular function in predicting cognitive decline and incident vascular events (e.g., stroke, transient ischemic attack, heart disease).
      • Gyanwali B
      • Mutsaerts HJ
      • Tan CS
      • et al.
      Association of arterial spin labeling parameters with cognitive decline, vascular events and mortality in a memory-clinic sample.
      The study sample included individuals without cognitive impairment, as well as those who met criteria for cognitive impairment over a range of severities and pathophysiologies (cognitively impaired without dementia, vascular dementia, Alzheimer dementia, or mixed dementia). One of the ASL outcome measures used was a proxy measure of brain cerebrovascular insufficiency, the gray matter spatial coefficient of variation of ASL (GM-sCoV). This is a measure of the spatial heterogeneity of rCBF in the brain that reflects the delayed arterial transit time (ATT) of labelled blood to the tissue. Delayed ATT is a major confounding factor in the quantification of rCBF by ASL, especially in older adults who have a greater burden of brain vascular disease than young adults.
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