Inflammation-driven glial alterations in the cuprizone mouse model probed with diffusion-weighted magnetic resonance spectroscopy at 11.7 T.

Inflammation of brain tissue is a complex response of the immune system to the presence of toxic compounds or to cell injury, leading to a cascade of pathological processes that include glial cell activation. Noninvasive MRI markers of glial reactivity would be very useful for in vivo detection and monitoring of inflammation processes in the brain, as well as for evaluating the efficacy of personalized treatments. Due to their specific location in glial cells, myo-inositol (mIns) and choline compounds (tCho) seem to be the best candidates for probing glial-specific intra-cellular compartments. However, their concentrations quantified using conventional proton MRS are not specific for inflammation. In contrast, it has been recently suggested that mIns intra-cellular diffusion, measured using diffusion-weighted MRS (DW-MRS) in a mouse model of reactive astrocytes, could be a specific marker of astrocytic hypertrophy. In order to evaluate the specificity of both mIns and tCho diffusion to inflammation-driven glial alterations, we performed DW-MRS in a volume of interest containing the corpus callosum and surrounding tissue of cuprizone-fed mice after 6 weeks of intoxication, and evaluated the extent of astrocytic and microglial alterations using immunohistochemistry. Both mIns and tCho apparent diffusion coefficients were significantly elevated in cuprizone-fed mice compared with control mice, and histologic evaluation confirmed the presence of severe inflammation. Additionally, mIns and tCho diffusion showed, respectively, strong and moderate correlations with histological measures of astrocytic and microglial area fractions, confirming DW-MRS as a promising tool for specific detection of glial changes under pathological conditions.

Choline-containing compounds quantification by 1H NMR spectroscopy using external reference and noise measurements.

Proton magnetic resonance spectroscopy ((1)H-MRS) is largely exploited in clinical settings to non-invasively investigate chemical compounds in human tissues. Applications of (1)H-MRS in oncology field are connected to the detection of abnormal levels of choline compounds in more active tumours, providing useful information for cancer diagnosis and treatment monitoring. Since benign lesions may also show presence of a choline peak, implementing absolute evaluation will help differentiating benign from malignant tumours. An external reference procedure was described to provide choline quantification in standard unit of measurements. Spectra were acquired on a 1.5 T scanner using both phantoms and healthy volunteers with a PRESS sequence. The implemented quantification procedure used metabolite and noise measurements on the spectrum to remove large part of scanner settings contributing to metabolites of interest. A standard quantification was also used to compare performances of the noise-based method. In vitro quantification had accuracy and precision in the range (95-99)% and (5-13)%, respectively. When applied to in vivo studies on healthy volunteers, the method provided very close values of choline concentration, more exactly (1.73 ± 0.24) mmol/l. The method proposed can quantify the proper choline content in phantoms as well as in human structures, as brain. The method is ease of use, computational costless and it can be rapidly calibrated and implemented in any centre.