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

• Published in: PloS one Vol. 16; no. 8; p. e0256749
• Main Authors: Leaston, Joshua, Ferris, Craig F, Kulkarni, Praveen, Chandramohan, Dharshan, van de Ven, Anne L, Qiao, Ju, Timms, Liam, Sepulcre, Jorge, El Fakhri, Georges, Ma, Chao, Normandin, Marc D, Gharagouzloo, Codi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.08.2021; Public Library of Science (PLoS)
• Subjects: Abnormalities; Alzheimer's disease; Amygdala; Animal models; Animals; Apolipoprotein E; Apolipoprotein E4; Apolipoprotein E4 - genetics; Biology and Life Sciences; Blood; Blood circulation disorders; Blood vessels; Blood-Brain Barrier - diagnostic imaging; Blood-Brain Barrier - pathology; Brain; Brain - abnormalities; Brain - blood supply; Brain - diagnostic imaging; Brain research; Cerebellum; Circuits; Comparative analysis; Dementia; Diagnosis; Disease Models, Animal; Evaluation; Feasibility studies; Gene Knock-In Techniques; Genetic aspects; Hospitals; Humans; Magnetic resonance; Magnetic Resonance Imaging; Medical imaging; Medical schools; Medicine and Health Sciences; Neurodegenerative diseases; Neuroimaging; Pathology; Rats; Rattus; Research and Analysis Methods; Vascularization; Wages & salaries; United States; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0256749

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.