Chemical exchange saturation transfer MRI shows low cerebral 2-deoxy-D-glucose uptake in a model of Alzheimer’s Disease

Abstract

Glucose is the central nervous system’s only energy source. Imaging techniques capable to detect pathological alterations of the brain metabolism are useful in different diagnostic processes. Such techniques are also beneficial for assessing the evaluation efficacy of therapies in pre-clinical and clinical stages of diseases. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a possible alternative to positron emission tomography (PET) imaging that has been widely explored in cancer research in humans and animal models. We propose that pathological alterations in brain 2-deoxy-D-glucose (2DG) uptake, typical of neurodegenerative diseases, can be detected with CEST MRI. Transgenic mice overexpressing a mutated form of amyloid precusrsor protein (APP23), a model of Alzheimer’s disease, analyzed with CEST MRI showed a clear reduction of 2DG uptake in different brain regions. This was reminiscent of the cerebral condition observed in Alzheimer’s patients. The results indicate the feasibility of CEST for analyzing the brain metabolic state, with better image resolution than PET in experimental models.

Dynamic glucose‐enhanced (DGE) MRI in the human brain at 7 T with reduced motion‐induced artifacts based on quantitative R1ρ mapping

“…DGE-MRI after administration of glucose or glucose analogs (e.g., 2-deoxy-D-glucose or L-glucose) has been shown to provide valuable insights into tissue glucose concentration changes in small animal models of cancer [9][10][11]14,15 and Alzheimer's disease. 22 Whether glucose in blood vessels, extracellular glucose, or intracellular phosphorylated glucose derivatives are the driving source for the observed DGE contrast remains to be investigated in depth. 11,14,19 Furthermore, the applicability for examinations in humans has already been verified in independent pilot studies based on glucoCEST 12,13 and glucoCESL.…”

Sugar alcohol provides imaging contrast in cancer detection

“…Further, another study has shown the use of a non-caloric sweetener, sucralose, as a CEST contrast agent to detect glioma in a preclinical model 41 . There are several other studies involving another glucose analogue, 2-deoxy-D-glucose (2DG) as CEST agent to image cerebral glucose uptake 27 in cancer 35 and Alzheimer’s Disease 42 .…”

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

“…Glucose CEST MRI is a recently developed technique that detects unlabeled glucose at physiologically relevant concentrations using proton-only MRI scanners (Table 2). Tolomeo et al demonstrated glucose CEST detection of reduced cerebral 2deoxy-D-glucose uptake in APP23 mice compared to wild-type mice [133]. Using dynamic glucoseenhanced MRI, Huang et al demonstrated an altered level of D-glucose in brain parenchymal as well as in the cerebrospinal fluid (CSF) of aged APP/PS1 mice compared to wild-type mice [134].…”

“…The authors declare no completing interest relevant to the submitted manuscript. T2*w GE, T2w SE APP/PS1, APPV717I mice [32,49,225,226] CESL APP/PS1 mice [36] T1w, CE-MR APP/PS1, PDAPP mice [227] 3D GE T2*w APP/PS1, PS1 mice [228] MTC APP/PS1 mice T2*, Gd-DTPA-K6Aβ1-30 APP/PS1, APPswe mice [46] T1w, Cyanine-Gd(III) complex 5×FAD mice CEST APP23 mice [133] APP/PS1 mice [136,137].…”