Early Changes in Structural Brain Bioimaging Markers from a R6/1 Mouse Model of Huntington?s Disease Captured by Ultra High Field MRI Diffusion Imaging.

CARINA WEISSMANN; AMIN, MANISH; ANGELES-LÓPEZ, QUETZALLI D.; GARCÍA-LARA, LUCIA; CASTELLANOS, LIBIA C. SALINAS; DEYOUNG, DANIEL; SEGOVIA, JOSE; MARECI, THOMAS H.; OSVALDO D. UCHITEL; MAGIN, RICHARD L.; RODOLFO GATTO

Paris

Simposio; 2nd Biomarker Meeting of Paris: Proteomic and Therapeutic Targets.; 2020

Biomarker Meeting

Diffusion MRI (dMRI) has been able todetect early structural changes related toneurological symptoms present inHuntington?s disease (HD). However, thereis still a knowledge gap to interpret thebiological significance at earlyneuropathological stages. The purpose ofthis study is two fold: ( i ) Establish if thecombination of Ultra High Field DiffusionMRI (UHFD MRI) techniques can add amore comprehensive analysis of the earlymicrostructural changes observed in HD,and (ii) evaluate if early changes in dMRImicrostructural parameters can be linkedto cellular biomarkers ofneuroinflammation. Using an ultra highfield magnet (16.7T), diffusion tensorimaging (DTI), and neurite orientationdispersion and density imaging (NODDI)techniques were applied to fixed ex vivobrains of a preclinical model of HD (R6/1mice). Fractional anisotropy (FA) wasdecreased in deep and superficial greymatter (GM) as well as white matter (WM)brain regions with well known early HDmicrostructure and connectivity pathology.NODDI parameters associated with theintracellular and extracellularcompartment, such as intracellularventricular fraction (ICVF), orientationdispersion index (ODI), and isotropicvolume fractions (IsoVF) were altered inR6/1 mice GM. Further, histologicalstudies in these areas showed that glia cellmarkers associated withneuroinflammation (GFAP & Iba1) wereconsistent with the dMRI findings. MRIdiffusion can be used to extract noninvasive information of neuropathologicalevents present in the early stages of HD.The combination of multiple imagingtechniques represents a better approach tounderstand the neuropathological processallowing the early diagnosis andneuromonitoring of patients affected by HD