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.
Highlights
Alzheimer’s disease (AD) is characterized by amyloid deposition in the brain parenchyma, intracellular fibrillary tangles formed by hyperphosphorylated tau and diffuse cerebral atrophy
Cerebral blood flow (CBF) and functional Magnetic Resonance Imaging (MRI) techniques have been implemented to obtain functional biomarkers helping in early AD diagnosis[10,11]
Our aim was to show that pathological deficits in the brain metabolism of amyloid precursor protein (APP) transgenic mice can be highlighted by detecting differences in 2DG uptake
Summary
Alzheimer’s disease (AD) is characterized by amyloid deposition in the brain parenchyma, intracellular fibrillary tangles formed by hyperphosphorylated tau and diffuse cerebral atrophy. The metabolic status measured by [18F]FDG-PET is combined with the use of different PET tracers (e.g. Pittsburgh compound B [11C]PIB, [18F]florbetapir or [18F]florbetaben) to identify the deposition of amyloid plaques. These have boosted the accuracy in the prediction of the conversion to AD in subjects with mild cognitive impairment (MCI)[2,5,6]. In anticipation of large screening tests for risk assessment of the population at pre-clinical stages of the pathology, or long follow-up studies, PET imaging suffers certain drawbacks It has low spatial resolution and needs special infrastructures to synthesize, distribute and dispose of radioactive tracers, making it expensive. Cerebral blood flow (CBF) and functional MRI (fMRI) techniques have been implemented to obtain functional biomarkers helping in early AD diagnosis[10,11]
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