Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities

PLoS One. 2021 Aug 27;16(8):e0256749. doi: 10.1371/journal.pone.0256749. eCollection 2021.

Abstract

Cerebrovascular abnormality is linked to Alzheimer's disease and related dementias (ADRDs). ApoE-Ɛ4 (APOE4) is known to play a critical role in neurovascular dysfunction, however current medical imaging technologies are limited in quantification. This cross-sectional study tested the feasibility of a recently established imaging modality, quantitative ultra-short time-to-echo contrast-enhanced magnetic resonance imaging (QUTE-CE MRI), to identify small vessel abnormality early in development of human APOE4 knock-in female rat (TGRA8960) animal model. At 8 months, 48.3% of the brain volume was found to have significant signal increase (75/173 anatomically segmented regions; q<0.05 for multiple comparisons). Notably, vascular abnormality was detected in the tri-synaptic circuit, cerebellum, and amygdala, all of which are known to functionally decline throughout AD pathology and have implications in learning and memory. The detected abnormality quantified with QUTE-CE MRI is likely a result of hyper-vascularization, but may also be partly, or wholly, due to contributions from blood-brain-barrier leakage. Further exploration with histological validation is warranted to verify the pathological cause. Regardless, these results indicate that QUTE-CE MRI can detect neurovascular dysfunction with high sensitivity with APOE4 and may be helpful to provide new insights into health and disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein E4 / genetics*
  • Blood-Brain Barrier / diagnostic imaging*
  • Blood-Brain Barrier / pathology
  • Brain / abnormalities*
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Disease Models, Animal
  • Gene Knock-In Techniques
  • Humans
  • Magnetic Resonance Imaging
  • Rats

Substances

  • Apolipoprotein E4