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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.
Animal Model Exp Med. 2020 Jun; 3(2):117-129.AM

Abstract

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 17.6T were obtained from fixed, excised mouse brains, and spinal cords from ALS (G93A-SOD1) mice.

Results

Changes in fractional anisotropy (FA) and linear, planar, and spherical anisotropy ratios (CL, CP, and CS, 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, CL, and CP values decreased, whereas CS values increased. In GM structures (prefrontal cortex, hippocampus, and central spinal cord) FA and CP decreased, whereas the CL and CS values were unchanged or slightly smaller. Histological studies of a fluorescent mice model (YFP, G93A-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 CL, CP, and CS as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS.

Authors+Show Affiliations

Department of Bioengineering University of Illinois at Chicago Chicago IL USA.Instituto de Fisiología Biologia Molecular y Neurociencias-IFIBYNE-CONICET University of Buenos Aires Buenos Aires Argentina.Department of Biochemistry National High Magnetic Field Laboratory University of Florida Gainesville FL USA.Department of Pathology School of Medicine Northwestern University Chicago IL USA.Department of Pathology School of Medicine Northwestern University Chicago IL USA.Department of Biochemistry National High Magnetic Field Laboratory University of Florida Gainesville FL USA.Instituto de Fisiología Biologia Molecular y Neurociencias-IFIBYNE-CONICET University of Buenos Aires Buenos Aires Argentina.Department of Bioengineering University of Illinois at Chicago Chicago IL USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32613171

Citation

Gatto, Rodolfo G., et al. "Assessing Neuraxial Microstructural Changes in a Transgenic Mouse Model of Early Stage Amyotrophic Lateral Sclerosis By Ultra-high Field MRI and Diffusion Tensor Metrics." Animal Models and Experimental Medicine, vol. 3, no. 2, 2020, pp. 117-129.
Gatto RG, Weissmann C, Amin M, et al. Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra-high field MRI and diffusion tensor metrics. Animal Model Exp Med. 2020;3(2):117-129.
Gatto, R. G., Weissmann, C., Amin, M., Finkielsztein, A., Sumagin, R., Mareci, T. H., Uchitel, O. D., & Magin, R. L. (2020). Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra-high field MRI and diffusion tensor metrics. Animal Models and Experimental Medicine, 3(2), 117-129. https://doi.org/10.1002/ame2.12112
Gatto RG, et al. Assessing Neuraxial Microstructural Changes in a Transgenic Mouse Model of Early Stage Amyotrophic Lateral Sclerosis By Ultra-high Field MRI and Diffusion Tensor Metrics. Animal Model Exp Med. 2020;3(2):117-129. PubMed PMID: 32613171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra-high field MRI and diffusion tensor metrics. AU - Gatto,Rodolfo G, AU - Weissmann,Carina, AU - Amin,Manish, AU - Finkielsztein,Ariel, AU - Sumagin,Ronen, AU - Mareci,Thomas H, AU - Uchitel,Osvaldo D, AU - Magin,Richard L, Y1 - 2020/04/16/ PY - 2020/01/04/received PY - 2020/02/28/revised PY - 2020/03/22/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - G93A‐SOD1 mice KW - amyotrophic lateral sclerosis KW - animal models KW - diffusion tensor imaging KW - ultra‐high field MRI SP - 117 EP - 129 JF - Animal models and experimental medicine JO - Animal Model Exp Med VL - 3 IS - 2 N2 - 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 17.6T were obtained from fixed, excised mouse brains, and spinal cords from ALS (G93A-SOD1) mice. Results: Changes in fractional anisotropy (FA) and linear, planar, and spherical anisotropy ratios (CL, CP, and CS, 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, CL, and CP values decreased, whereas CS values increased. In GM structures (prefrontal cortex, hippocampus, and central spinal cord) FA and CP decreased, whereas the CL and CS values were unchanged or slightly smaller. Histological studies of a fluorescent mice model (YFP, G93A-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 CL, CP, and CS as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS. SN - 2576-2095 UR - https://www.unboundmedicine.com/medline/citation/32613171/Assessing_neuraxial_microstructural_changes_in_a_transgenic_mouse_model_of_early_stage_Amyotrophic_Lateral_Sclerosis_by_ultra-high_field_MRI_and_diffusion_tensor_metrics L2 - https://doi.org/10.1002/ame2.12112 DB - PRIME DP - Unbound Medicine ER -
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