Brain Amide Proton Transfer Imaging of Rat With Alzheimer’s Disease Using Saturation With Frequency Alternating RF Irradiation Method

Abstract

Amyloid-β (Aβ) deposits and some proteins play essential roles in the pathogenesis of Alzheimer's disease (AD). Amide proton transfer (APT) imaging, as an imaging modality to detect tissue protein, has shown promising features for the diagnosis of AD disease. In this study, we chose 10 AD model rats as the experimental group and 10 sham-operated rats as the control group. All the rats underwent a Y-maze test before APT image acquisition, using saturation with frequency alternating RF irradiation (APT SAFARI) method on a 7.0 T animal MRI scanner. Compared with the control group, APT (3.5 ppm) values of brain were significantly reduced in AD models (p < 0.002). The APT SAFARI imaging is more significant than APT imaging (p < 0.0001). AD model mice showed spatial learning and memory loss in the Y-maze experiment. In addition, there was significant neuronal loss in the hippocampal CA1 region and cortex compared with sham-operated rats. In conclusion, we demonstrated that APT imaging could potentially provide molecular biomarkers for the non-invasive diagnosis of AD. APT SAFARI MRI could be used as an effective tool to improve the accuracy of diagnosis of AD compared with conventional APT imaging.

Early detection of Alzheimer's disease using creatine chemical exchange saturation transfer magnetic resonance imaging

“…Chemical exchange saturation transfer (CEST) MRI is a versatile technique that can achieve enhanced sensitivity and spatial resolution on the standard clinical scanner by exploiting the exchange of protons between water and protein/metabolites ( Jones et al, 2017 ; Kogan et al, 2013 ; van Zijl and Yadav, 2011 ; Vinogradov et al, 2013 ; Zhou and van Zijl, 2006 ). Recently, CEST was used for measuring the protein aggregation involved in AD on both animal models ( Chen et al, 2018 ; Wang et al, 2019 ) and human patients ( Zhang et al, 2020 ). In this study, we aimed to investigate the feasibility of the creatine chemical exchange saturation transfer (CrCEST) MRI in detecting AD at an early stage.…”

Saturation Transfer MRI for Detection of Metabolic and Microstructural Impairments Underlying Neurodegeneration in Alzheimer’s Disease

“…The opposite findings come from animal studies, in which lower APT is observed in hippocampus and cortex at the stage of dense NFT deposition in tauopathy [ 130 , 131 ]. Such a decrease of APT is also observed in atrophic areas of hippocampus and cortex, independently of the model used [ 130 , 131 , 132 ]. The percentage change in APT negatively correlates with the severity of tau load [ 130 ], and in Aβ pathology APT and APT SAFARI in the hippocampus negatively correlate with GFAP-positive astrocyte density (astrogliosis assessed by glial fibrillary acidic protein, GFAP, immunostaining), and positively with short-term memory changes [ 132 ].…”

“…Such a decrease of APT is also observed in atrophic areas of hippocampus and cortex, independently of the model used [ 130 , 131 , 132 ]. The percentage change in APT negatively correlates with the severity of tau load [ 130 ], and in Aβ pathology APT and APT SAFARI in the hippocampus negatively correlate with GFAP-positive astrocyte density (astrogliosis assessed by glial fibrillary acidic protein, GFAP, immunostaining), and positively with short-term memory changes [ 132 ]. Wang et al also report that APT SAFARI signal is greater, and therefore easier to measure accurately, than conventional APT.…”

“…There are at least three studies applying APT imaging for studying patients with AD-related dementia [ 127 , 128 , 129 ] ( Table 4 ). Animal studies have been conducted in the transgenic rTg4510 mouse model of tauopathy [ 130 , 131 ], and a rat model of Aβ pathology [ 132 ] ( Table 4 ).…”

“…In the animal studies, the pulse characteristics were only provided in one study, in which a lower saturation power has been applied with a longer duration [ 132 ]. In normal tissue, the APT signal is negative at saturations powers below 2 μT [ 134 ] which may obscure any increase due to AD pathology.…”