Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Abstract

Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating the Aβ pathology, such as transgenic, knock-in mouse and rat models, have facilitated the understanding of disease mechanisms and the development of therapeutics targeting Aβ. There is a rapid advance in high-field MRI in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences, such as diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MRI, and MR spectroscopy, as well as contrast agents, have been developed for preclinical imaging in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole-brain field of view. MRI has been used to visualize non-invasively the Aβ deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, and cerebrovascular and glymphatic system in animal models of Alzheimer’s disease amyloidosis. Many of the readouts are translational toward clinical MRI applications in patients with Alzheimer’s disease. In this review, we summarize the recent advances in MRI for visualizing the pathophysiology in amyloidosis animal models. We discuss the outstanding challenges in brain imaging using MRI in small animals and propose future outlook in visualizing Aβ-related alterations in the brains of animal models.

Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease

“…On the other hand, biomarkers based on diagnostic imaging methods provide information about histological abnormalities compatible with AD. Among these markers are positron tomography (PET) and high-resolution magnetic resonance imaging (MRI) [ 85 , 86 , 87 , 88 ]. PET is a diagnostic method that elucidates the processes involved in cellular metabolism and can map the specific proteins involved in the disease.…”

Magnetic Resonance Imaging in Tauopathy Animal Models

“…For clinical application in humans, 7 and 10.5T MRIs have been reported ( Ehman et al, 2017 ; Ladd et al, 2018 ). For small animal imaging, 7, 9.4, 11.7, 16, and up to 21.1 T high-field MRI has been utilized in the laboratory ( Schepkin et al, 2010 ; Miyaoka and Lehnert, 2020 ; Ni, 2021 ), providing insights into the function and pathophysiology of the brain. Higher magnetic fields substantially increase the sensitivity and signal-to-noise ratio for MRI, although the tissue heating and non-uniformity of the radio-frequency field might affect the image quality.…”

Diagnostic accuracy study of automated stratification of Alzheimer’s disease and mild cognitive impairment via deep learning based on MRI

“…To train supervised models, features are generally extracted from task-based images; however, such models require human specialists, as well as ample effort, time, and funding (14). This presents an enormous challenge for the continuation of this mode of disease diagnosis (15,16). With the emergence of deep-learning (DL) models, it is feasible to retrieve features directly from imaging data without human intervention.…”

“…The relative ease of this approach is compelling more research into DL models to enable the precise diagnosis of various diseases (17,18). Compared to the challenges of other image analysis programs [e.g., computed tomography (CT), MRI, X-rays, ultrasounds, and sentiment analysis], DL models have achieved considerable success (16,19). Notably, they have been reported to produce reliable results in terms of disease diagnosis and stratification, especially in the lungs, abdomen, brain, cardiovascular, and retina.…”