Comparison of MEMRI and diffusion MRI evaluation of a feeding/fasting paradigm in glioblastoma bearing rats

Trabajo presentado en el 37th Annual Meeting European Society for Magnetic Resonance In Medicine and Biology, celebrado en Rotterdam del 3 al 5 de octubre de 2019.[Purpose/Introduction]: Magnetic resonance imaging (MRI) allows carrying out studies of neuronal activity in response to certain stimuli, such as the regulation of appetite, which is involved in numerous disorders of the global energy balance. Manganese-enhanced MRI (MEMRI) [1] and diffusion tensor imaging (DTI) [2], are approaches that enable the study of the brain functionality. On the other hand, HRMAS ex vivo analysis can identify metabolites as surrogate markers of healthy and pathological brain conditions [2]. [Subjects and Methods]: Wistar adult male rats were distributed in three groups (n = 12): i) controls without Mn2?; ii) healthy animals with Mn2?and iii) orthotopic glioma bearing rats [3] with Mn2?. Animals were studied in two experimental conditions: fed ad libitum and fasted. MnCl2 was injected intraperitoneally 24 h before the MRI evaluation in a 7T system. T1 parametric maps were generated for MEMRI evaluation (7TR/TE = 150–6000/12 ms). DTI studies were acquired by applying diffusion gradients in 6 directions (TR/TE = 3000/40 ms; D/d = 16/4 ms; 3b (0–1000 s/mm2). Images were computed with homemade software and ROIS were manually selected and statically analyzed. Animals were sacrificed with a high-power microwave, brain excised and regionalized. 1H HRMAS CPMG spectra of the different regions were acquired in a 11.7T system and processed with LCModel. [Results]: The accumulation of manganese in brain yielded to a significant decrease of T1 in all groups (healthy and glioma bearing), experimental condition (fed and fasted) and brain areas evaluated (fig. 1a, 3a). In healthy and tumor rats the T1 decreased due to the fasting status reaching statistical significance in several regions (fig. 1b, 3a). Regarding on diffusion studies, mean diffusivity (MD) values were sensitive to fasting in healthy animals with a significant decrease (Figs. 2a, 3b); but the ability to detect this metabolic status was lost in the presence of Mn2? (Figs. 2b, 3b). Data from HRMAS spectra also identified changes in metabolites linked to alterations in the global energy metabolism (GABA, glutamate, glutamine), and/or the presence of inflammatory processes (myo-inositol). [Discussion/Conclusion]: MEMRI allows to study the brain functionality associated to voltage dependent channels because of the Guadilla, IreneMn2? competition with Ca2?. In our study, there was a higher neuronal activation (lower T1) in fasted condition. DTI corroborated this by detecting the astrocyte swelling [4], but the presence of Mn2? affects the diffusion parameters avoiding this functional detection. The obtained results evidence the contraindication of performing diffusion MRI evaluation when manganese has been used as contrast agent