P2‐377: IMPAIRED GLUCOSE UPTAKE IN MOUSE BRAIN WITH ALZHEIMER'S DISEASE DETECTED BY DYNAMIC GLUCOSE ENHANCED (DGE) MRI AT 3T

Abstract

Altered cerebral glucose uptake is one of hallmarks of Alzheimer's disease (AD) (Alzheimer's Association, AD 2017, 13:325; Beglopoulos V, NC 2016, 7:11761). Chemical exchange saturation transfer (CEST) MRI (Ward K, JMR 2000, 143:79; van Zijl PC, MRM 2011, 65:927), especially glucose CEST (glucoCEST) (Chan KW, MRM 2012, 68:1764; Walker-Samuel S, NM 2013, 19:1067) and dynamic glucose enhanced (DGE) MRI (Xu X, MRM 2015, 74:1556), has been demonstrated to be capable of detecting natural D-glucose in in vivo bodies. Here, we utilized DGE MRI to monitor cerebral glucose uptake in AD mice at 3T. AD (APP/PS1) mice (n=5) and age-matched WT (C57) mice (n=5) at 18-month-old were imaged on a horizontal bore 3T animal scanner (Bruker BioSpec). DGE images were all acquired by setting the saturation frequency offset at 1.2 ppm. Saturation parameters for DGE MRI were optimized firstly. After DGE images acquisition, we applied a piecewise exponential to fit the DGE data, which can extract the time point that cerebral glucose level starts to increase (t0), the glucose uptake life time (Tu) and the amplitude of glucose uptake at equilibrium (Ae). Area-under-curve (AUC) maps were also calculated to evaluate the results (Xu X, MRM 2015; 74:1556.). A much lower glucose enhancement is observed in AD brain from the comparison results of visual image analysis (Fig. 1a, b) and DGE dynamic curves (Fig. 1c, d). Interestingly, both the Tu (8.0 ± 2.8) and Ae (1.1 ± 0.3%) of AD mice are significantly lower than Tu (15.3 ± 5.6) and Ae (1.8 ± 0.4%) of WT mice (Figs. 1f, g), While t0 is relatively synchronous between AD and WT mice (Fig. 1e). Regional results (Fig. 2b) show a significant lower glucose uptake in AD mice (thalamus: 1.1±0.5%; hippocampus: 0.9±0.3%; cortex: 1.6±0.4%) than in WT mice (thalamus: 1.6±0.4%; hippocampus: 1.7±0.5%; cortex: 2.3 ± 0.4%), with the largest reduction by 47% in hippocampus. Comparison of AUC maps and statistics (Fig. 3) confirmed these findings.