Hybrid PET/MRI enables high-spatial resolution, quantitative imaging of amyloid plaques in an Alzheimer’s disease mouse model

• Published in: Scientific reports Vol. 10; no. 1; p. 10379
• Main Authors: Frost, Georgia R., Longo, Valerie, Li, Thomas, Jonas, Lauren A., Judenhofer, Martin, Cherry, Simon, Koutcher, Jason, Lekaye, Carl, Zanzonico, Pat, Li, Yue-Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.06.2020; Nature Publishing Group
• Subjects: 631/378; 631/378/1689; 631/378/1689/1283; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid; Animal models; Animals; Brain; Cerebellum; Computed tomography; Disease Models, Animal; Fluorine Radioisotopes - metabolism; Hippocampus - diagnostic imaging; Hippocampus - metabolism; Hippocampus - pathology; Humanities and Social Sciences; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mice; Mice, Inbred C57BL; multidisciplinary; Mutation; Neurodegenerative diseases; Neurofibrillary tangles; Neuroimaging; Pathology; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Positron emission tomography; Positron-Emission Tomography - methods; Radiopharmaceuticals - metabolism; Rodents; Science; Science (multidisciplinary); Senile plaques; Spatial discrimination; Thalamus; Thalamus - diagnostic imaging; Thalamus - metabolism; Thalamus - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-67284-z

The emergence of PET probes for amyloid plaques and neurofibrillary tangles, hallmarks of Alzheimer disease (AD), enables monitoring of pathology in AD mouse models. However, small-animal PET imaging is limited by coarse spatial resolution. We have installed a custom-fabricated PET insert into our small-animal MRI instrument and used PET/MRI hybrid imaging to define regions of amyloid vulnerability in 5xFAD mice. We compared fluorine-18 [ 18 F]-Florbetapir uptake in the 5xFAD brain by dedicated small-animal PET/MRI and PET/CT to validate the quantitative measurement of PET/MRI. Next, we used PET/MRI to define uptake in six brain regions. As expected, uptake was comparable to wild-type in the cerebellum and elevated in the cortex and hippocampus, regions implicated in AD. Interestingly, uptake was highest in the thalamus, a region often overlooked in AD studies. Development of small-animal PET/MRI enables tracking of brain region-specific pathology in mouse models, which may prove invaluable to understanding AD progression and therapeutic development.