T1, diffusion tensor, and quantitative magnetization transfer imaging of the hippocampus in an Alzheimer's disease mouse model

Abstract

Alzheimer's disease (AD) pathology causes microstructural changes in the brain. These changes, if quantified with magnetic resonance imaging (MRI), could be studied for use as an early biomarker for AD. The aim of our study was to determine if T relaxation, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) metrics could reveal changes within the hippocampus and surrounding white matter structures in ex vivo transgenic mouse brains overexpressing human amyloid precursor protein with the Swedish mutation. Delineation of hippocampal cell layers using DTI color maps allows more detailed analysis of T-weighted imaging, DTI, and qMTI metrics, compared with segmentation of gross anatomy based on relaxation images, and with analysis of DTI or qMTI metrics alone. These alterations are observed in the absence of robust intracellular Aβ accumulation or plaque deposition as revealed by histology. This work demonstrates that multiparametric quantitative MRI methods are useful for characterizing changes within the hippocampal substructures and surrounding white matter tracts of mouse models of AD.

Characterization of Alzheimer’s Disease Using Ultra-high b-values Apparent Diffusion Coefficient and Diffusion Kurtosis Imaging

“…In the process of Aβ clearance, AQP4 plays an important role [21, 23]. Human amyloid precursor protein was overexpressed in HIP and the surrounding WM of transgenic AD mice [41]. This might be able to explain the changes in ADC_uh values in the white matter of bilateral TL in our study.…”

A literature review of MRI techniques used to detect amyloid-beta plaques in Alzheimer’s disease patients

“…So far, in order to improve diagnostic accuracy and specificity when assessing changes in WM in AD patients, a variety of DTI methods have been used (19). However, some studies have shown that DTI sequences do not detect significant changes in younger age groups because age-dependent Aβ plaque accumulation is related to WM abnormalities (10).…”

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

“…A number of studies have applied in vivo and ex vivo DTI for detecting the white matter impairment, which appears preceding the anatomical changes on structural MRI including the APPswe, APP/PS1, TgCRND8, APP NL-G-F , 3×Tg, CVN-AD and 5×FAD mice [81,93,97,175-183] (Table 3). In addition to DTI, diffusion kurtosis imaging (DKI) and quantitative magnetization transfer imaging (qMTI) have been applied in APP mouse models where hippocampal alterations were observed [178,184]. However the observed DTI scalars are not consistent across different studies, probably due to the dynamic microstructural changes various animal models model [193]: reduced FA, RD, and increased orientation dispersion and intracellular volume fraction were detected in the white matter and the hippocampus.…”

“…5×FAD mice [135] MRS TgF344 rats [132] J20 mice [109] APP/PS1 mice [121][122][123][124][125][126] 5×FAD mice [130] 3×Tg mice [129] APPswe mice [127,128]. APP/PS2/Tau mice [131] TASTPM mice [131,167] APP/PS1 mice [105,125,164,168,236] McGill-R-Thy1-APP rats [162] mice [250,251] APP-Au mice [252] 3×Tg mice [93,165,253] APPswe mice [244] APP/PS1KI mice [166] APP/TTA mice [254] DKI APP/PS1 mice [184] 3×Tg mice [188] qMTI APPswe mice [178] DTI TgF344 rats [183] APPswe mice [175,178,186,255] PDAPP mice [176] App NL-G-F knock-in mice [72] APP/PS1 mice [123,171,179,187,189,256] APP23 ...…”