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| 1 | Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice显示文摘Background:Amyotrophic lateral sclerosis(ALS)is a disease characterized by a progressive degeneration of motor neurons leading to paralysis.Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation.Here,we extend those studies using ultra-high field MRI(17.6 T)and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice.Methods:The spinal cords from presymptomatic and symptomatic mice(80 to 120 days of age)were scanned(ex-vivo)using diffusion-weighted MRI.The fractional anisotropy(FA),axial(AD)and radial(RD)diffusivities were calculated for axial slices from the thoracic,cervical and lumbar regions of the spinal cords.The diffusion parameters were compared with fluorescence microscopy and membrane cellular markers from the same tissue regions.Results:At early stages of the disease(day 80)in the lumbar region,we found,a 19% decrease in FA,a 9% decrease in AD and a 35% increase in RD.Similar changes were observed in cervical and thoracic spinal cord regions.Differences between control and ALS mice groups at the symptomatic stages(day 120)were larger.Quantitative fluorescence microscopy at 80 days,demonstrated a 22% reduction in axonal area and a 22% increase in axonal density.Tractography and quantitative connectome analyses measured by edge weights showed a 52%decrease in the lumbar regions of the spinal cords of this ALS mice group.A significant increase in ADC(23.3%)in the ALS mice group was related to an increase in aquaporin markers.Conclusions:These findings suggest that the combination of ultra-high field diffusion MRI with fluorescent ALS mice reporters is a useful approach to detect and characterize presymptomatic white matter micro-ultrastructural changes and axonal connectivity anomalies in ALS. | Rodolfo G.Gatto Manish Y.Amin Daniel Deyoung Matthew Hey Thomas H.Mareci Richard L.Magin | 2018 | Translational Neurodegeneration2018，7，1： | 2 |
| 2 | Preliminary examination of early neuroconnectivity features in the R6/1 mouse model of Huntington's disease by ultra-high field diffusion MRI显示文摘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 illness.However,events related to early neuropathological events,neuroinflammation,deterioration of neuronal connectivity and compensatory mechanisms still remain vastly unknown.Ultra-high field diffusion MRI(UHFD-MRI)techniques can contribute to a more comprehensive analysis of the early microstructural changes observed in HD.In addition,it is possible to evaluate if early imaging microstructural parameters might be linked to histological biomarkers.Moreover,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 regeneration.The 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 disease.Although 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 matter.Thus,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. | Rodolfo G.Gatto Carina Weissmann | 2022 | Neural Regeneration Research2022，17，5： | 0 |
| 3 | Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra-high field MRI and diffusion tensor metrics显示文摘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 ALS.Methods: 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) mice.Results: 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 DTI.Conclusions: 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. | Rodolfo G.Gatto Carina Weissmann Manish Amin Ariel Finkielsztein Ronen Sumagin Thomas H.Mareci Osvaldo D.Uchitel Richard L.Magin | 2020 | Animal Models and Experimental Medicine2020，3，2： | 0 |
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