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Preliminary examination of early neuroconnectivity features in the R6/1 mouse model of Huntington's disease by ultra-high field diffusion MRI

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Neural Regeneration Research 2022年第5期17卷 983-986页

作者： Rodolfo G.Gatto carina weissmann Department of Bioengineering the University of Illinois at ChicagoChicagoILUSA Instituto de Fisiología Biología Molecular y Neurociencias-IFIBYNECONICET Universidad de Buenos AiresBuenos AiresArgentina

During the last decades,advances in the understanding of genetic,cellular,and microstructural alterations associated to Huntington's disease(HD)have improved the understanding of this progressive and fatal ***,events related to early neuropathological events,neuroinflammation,deterioration of neuronal connectivity and compensatory mechanisms still remain vastly ***-high field diffusion MRI(UHFD-MRI)techniques can contribute to a more comprehensive analysis of the early microstructural changes observed in *** addition,it is possible to evaluate if early imaging microstructural parameters might be linked to histological ***,qualitative studies analyzing histological complexity in brain areas susceptible to neurodegeneration could provide information on inflammatory events,compensatory increase of neuroconnectivity and mechanisms of brain repair and *** application of ultra-high field diffusion-MRI technology in animal models,particularly the R6/1 mice(a common preclinical mammalian model of HD),provide the opportunity to analyze alterations in a physiologically intact model of the *** some disparities in volumetric changes across different brain structures between preclinical and clinical models has been documented,further application of different diffusion MRI techniques used in combination like diffusion tensor imaging,and neurite orientation dispersion and density imaging have proved effective in characterizing early parameters associated to alteration in water diffusion exchange within intracellular and extracellular compartments in brain white and grey ***,the combination of diffusion MRI imaging techniques and more complex neuropathological analysis could accelerate the discovery of new imaging biomarkers and the early diagnosis and neuromonitoring of patients affected with HD.

关键词： brain repair diffusion tensor imaging Huntington's disease neurite orientation dispersion and density imaging neuroconnectivity neuroinflammation neuroplasticity neuroregeneration R6/1 mice ultra-high field diffusion MRI

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Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra-high field MRI and diffusion tensor metrics

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Animal Models and Experimental Medicine 2020年第2期3卷 117-129页

作者： Rodolfo G.Gatto carina weissmann Manish Amin Ariel Finkielsztein Ronen Sumagin Thomas H.Mareci Osvaldo D.Uchitel Richard L.Magin Department of Bioengineering University of Illinois at ChicagoChicagoILUSA Instituto de Fisiología Biologia Molecular y Neurociencias-IFIBYNE-CONICET University of Buenos AiresBuenos AiresArgentina Department of Biochemistry National High Magnetic Field LaboratoryUniversity of FloridaGainesvilleFLUSA Department of Pathology School of MedicineNorthwestern UniversityChicagoILUSA

Objective: Cell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis(ALS). In this work, we propose the use of diffusion tensor imaging(DTI) metrics to assess specific ultrastructural changes in the central nervous system during the early neurodegenerative stages of ***: Ultra-high field MRI and DTI data at 17.6 T were obtained from fixed, excised mouse brains, and spinal cords from ALS(G93 A-SOD1) ***: Changes in fractional anisotropy(FA) and linear, planar, and spherical anisotropy ratios(C_L, C_P, and C_S, respectively) of the diffusion eigenvalues were measured in white matter(WM) and gray matter(GM) areas associated with early axonal degenerative processes(in both the brain and the spinal cord). Specifically, in WM structures(corpus callosum, corticospinal tract, and spinal cord funiculi) as the disease progressed, FA, C_L, and C_P values decreased, whereas C_S values increased. In GM structures(prefrontal cortex, hippocampus, and central spinal cord) FA and C_P decreased, whereas the C_L and C_S values were unchanged or slightly smaller. Histological studies of a fluorescent mice model(YFP, G93 A-SOD1 mouse) corroborated the early alterations in neuronal morphology and axonal connectivity measured by ***: Changes in diffusion tensor shape were observed in this animal model at the early, nonsymptomatic stages of ALS. Further studies of C_L, C_P, and C_S as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS.

关键词： amyotrophic lateral sclerosis animal models diffusion tensor imaging G93A-SOD1 mice ultra-high field MRI

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