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Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
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Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAβ Mouse Model of Cerebral

Giovanna D Ielacqua1, Felix Schlegel2, Martina Füchtemeier3

  • 1Institute for Biomedical Engineering, ETH and University of Zurich Zurich, Switzerland.

Frontiers in Aging Neuroscience
|February 3, 2016
PubMed
Summary

Magnetic resonance imaging (MRI) techniques, specifically Q mapping, effectively detect age-related cerebral microvascular changes in Alzheimer's disease mouse models. This method is more sensitive than hemodynamic measures for identifying amyloid-related vascular degeneration.

Keywords:
Alzheimer's diseasecerebral amyloid angiopathycerebral amyloidosisdynamic susceptibilty contrast MRImicrovessel densityrelaxation rate shift indexsuperparamagnetic iron oxide nanoparticles

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Area of Science:

  • Neuroimaging
  • Vascular Biology
  • Alzheimer's Disease Research

Background:

  • Cerebral microvascular alterations are hallmarks of Alzheimer's disease (AD).
  • Accurate detection of these changes is crucial for understanding AD pathogenesis.
  • Magnetic resonance imaging (MRI) offers potential for non-invasive assessment of cerebral vasculature.

Purpose of the Study:

  • To compare the efficacy of different MRI techniques in detecting age-dependent cerebral microvascular changes.
  • To evaluate dynamic susceptibility contrast (DSC)-MRI and Q mapping in the arcAβ mouse model of cerebral amyloidosis.
  • To assess the relationship between amyloid deposition and microvessel density.

Main Methods:

  • Dynamic susceptibility contrast (DSC)-MRI was used to estimate relative cerebral blood volume [rCBV(DSC)] and relative cerebral blood flow (rCBF).
  • Q mapping, derived from gradient echo and spin echo data before and after SPIO injection, estimated microvessel density.
  • Linear mixed effects modeling analyzed associations between MRI parameters, genotype, and age; CD31 immunohistochemistry validated microvessel density.

Main Results:

  • In 24-month-old arcAβ mice, Q values were significantly reduced (11–26%) in multiple brain regions compared to age-matched non-transgenic littermates (NTLs).
  • rCBV(DSC) and rCBV([Formula: see text]) showed significant associations with genotype in the cortex and cerebellum of older mice.
  • CD31 staining confirmed reduced microvessel density in aged arcAβ mice, correlating with parenchymal and vascular amyloid deposition.

Conclusions:

  • Q mapping is more sensitive than hemodynamic MRI measures (rCBV, rCBF) for detecting age-related microvascular degeneration in the arcAβ mouse model.
  • A region-specific association exists between amyloid deposition and decreased vascular density, independent of Aβ load.
  • MRI-based Q mapping shows promise for non-invasively assessing vascular pathology in Alzheimer's disease.