Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI

Rodolfo G. Gatto; Manish Amin; Ariel Finkielsztein; Carina Weissmann; Thomas Barrett; Caroline Lamoutte; Osvaldo Uchitel; Ronen Sumagin; Thomas H. Mareci; Richard L. Magin

doi:10.1080/21678421.2019.1620285

Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI

Rodolfo G. Gatto^*, Manish Amin, Ariel Finkielsztein, Carina Weissmann, Thomas Barrett, Caroline Lamoutte, Osvaldo Uchitel, Ronen Sumagin, Thomas H. Mareci, Richard L. Magin

^*Corresponding author for this work

Pathology

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Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterized by the progressive impairment of motor functions. However, a significant portion of affected patients develops severe cognitive dysfunction, developing a widespread white (WM) and gray matter (GM) microstructural impairment. The objective of this study is to determine if Gaussian and non-Gaussian diffusion models gathered by ultra-high field diffusion MRI (UHFD-MRI) are an appropriate tool to detect early structural changes in brain white and gray matter in a preclinical model of ALS. ALS brains (G93A-SOD1mice) were scanned in a 16.7 T magnet. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) have shown presymptomatic decrease in axonal organization by Fractional Anisotropy (FA) and neurite content by Intracellular Volume Fraction (ICVF) across deep WM (corpus callosum) as well as superficial (cortex) and deep (hippocampus) GM. Additional diffusion kurtosis imaging (DKI) analysis demonstrated broader and earlier GM reductions in mean kurtosis (MK), possibly related to the decrease in neuronal complexity. Histological validation was obtained by an ALS fluorescent mice reporter (YFP, G93A-SOD1 mice). The combination of DTI, NODDI, and DKI models have proved to provide a more complete assessment of the early microstructural changes in the ALS brain, particularly in areas associated with high cognitive functions. This comprehensive approach should be considered as a valuable tool for the early detection of neuroimaging markers.

Original language	English (US)
Pages (from-to)	549-561
Number of pages	13
Journal	Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume	20
Issue number	7-8
DOIs	https://doi.org/10.1080/21678421.2019.1620285
State	Published - Oct 2 2019

Funding

This study was supported by the High Magnetic Field Laboratory (NHMFL) and Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) under Magnetic Laboratory Visiting Scientist Program [Award VSP #278] to RG. The McKnight Brain Institute at the National High Magnetic Field Laboratory’s AMRIS Facility is supported by National Science Foundation Cooperative Agreement No. DMR-1157490* and the State of Florida. A portion of the work was performed in the Department of Anatomy and Cell Biology at the University of Illinois at Chicago (UIC), the Department of Pathology, Feinberg School of Medicine from Northwestern University and the Instituto de Fisiología Biologia Molecular y Neurociencias-IFIBYNE-CONICET, University of Buenos Aires, Argentina. MRI studies were conducted at the University of Florida in Gainesville, McKnight Brain Institute. We would like to acknowledge Dr. Gerardo Morfini at UIC for providing some chemicals and materials used in particular histological preparations.

Keywords

Amyotrophic lateral sclerosis
G93A-SOD1 mice
diffusion kurtosis imaging
diffusion tensor imaging
neurite orientation dispersion and density imaging
neuronal degeneration
transgenic animals
yellow fluorescence protein

ASJC Scopus subject areas

Clinical Neurology
Neurology

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10.1080/21678421.2019.1620285

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Gatto, R. G., Amin, M., Finkielsztein, A., Weissmann, C., Barrett, T., Lamoutte, C., Uchitel, O., Sumagin, R., Mareci, T. H., & Magin, R. L. (2019). Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 20(7-8), 549-561. https://doi.org/10.1080/21678421.2019.1620285

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title = "Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI",

abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterized by the progressive impairment of motor functions. However, a significant portion of affected patients develops severe cognitive dysfunction, developing a widespread white (WM) and gray matter (GM) microstructural impairment. The objective of this study is to determine if Gaussian and non-Gaussian diffusion models gathered by ultra-high field diffusion MRI (UHFD-MRI) are an appropriate tool to detect early structural changes in brain white and gray matter in a preclinical model of ALS. ALS brains (G93A-SOD1mice) were scanned in a 16.7 T magnet. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) have shown presymptomatic decrease in axonal organization by Fractional Anisotropy (FA) and neurite content by Intracellular Volume Fraction (ICVF) across deep WM (corpus callosum) as well as superficial (cortex) and deep (hippocampus) GM. Additional diffusion kurtosis imaging (DKI) analysis demonstrated broader and earlier GM reductions in mean kurtosis (MK), possibly related to the decrease in neuronal complexity. Histological validation was obtained by an ALS fluorescent mice reporter (YFP, G93A-SOD1 mice). The combination of DTI, NODDI, and DKI models have proved to provide a more complete assessment of the early microstructural changes in the ALS brain, particularly in areas associated with high cognitive functions. This comprehensive approach should be considered as a valuable tool for the early detection of neuroimaging markers.",

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note = "Publisher Copyright: {\textcopyright} 2019, {\textcopyright} 2019 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases.",

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doi = "10.1080/21678421.2019.1620285",

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Gatto, RG, Amin, M, Finkielsztein, A, Weissmann, C, Barrett, T, Lamoutte, C, Uchitel, O, Sumagin, R, Mareci, TH & Magin, RL 2019, 'Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI', Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol. 20, no. 7-8, pp. 549-561. https://doi.org/10.1080/21678421.2019.1620285

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T1 - Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI

AU - Gatto, Rodolfo G.

AU - Amin, Manish

AU - Finkielsztein, Ariel

AU - Weissmann, Carina

AU - Barrett, Thomas

AU - Lamoutte, Caroline

AU - Uchitel, Osvaldo

AU - Sumagin, Ronen

AU - Mareci, Thomas H.

AU - Magin, Richard L.

PY - 2019/10/2

Y1 - 2019/10/2

N2 - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterized by the progressive impairment of motor functions. However, a significant portion of affected patients develops severe cognitive dysfunction, developing a widespread white (WM) and gray matter (GM) microstructural impairment. The objective of this study is to determine if Gaussian and non-Gaussian diffusion models gathered by ultra-high field diffusion MRI (UHFD-MRI) are an appropriate tool to detect early structural changes in brain white and gray matter in a preclinical model of ALS. ALS brains (G93A-SOD1mice) were scanned in a 16.7 T magnet. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) have shown presymptomatic decrease in axonal organization by Fractional Anisotropy (FA) and neurite content by Intracellular Volume Fraction (ICVF) across deep WM (corpus callosum) as well as superficial (cortex) and deep (hippocampus) GM. Additional diffusion kurtosis imaging (DKI) analysis demonstrated broader and earlier GM reductions in mean kurtosis (MK), possibly related to the decrease in neuronal complexity. Histological validation was obtained by an ALS fluorescent mice reporter (YFP, G93A-SOD1 mice). The combination of DTI, NODDI, and DKI models have proved to provide a more complete assessment of the early microstructural changes in the ALS brain, particularly in areas associated with high cognitive functions. This comprehensive approach should be considered as a valuable tool for the early detection of neuroimaging markers.

AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterized by the progressive impairment of motor functions. However, a significant portion of affected patients develops severe cognitive dysfunction, developing a widespread white (WM) and gray matter (GM) microstructural impairment. The objective of this study is to determine if Gaussian and non-Gaussian diffusion models gathered by ultra-high field diffusion MRI (UHFD-MRI) are an appropriate tool to detect early structural changes in brain white and gray matter in a preclinical model of ALS. ALS brains (G93A-SOD1mice) were scanned in a 16.7 T magnet. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) have shown presymptomatic decrease in axonal organization by Fractional Anisotropy (FA) and neurite content by Intracellular Volume Fraction (ICVF) across deep WM (corpus callosum) as well as superficial (cortex) and deep (hippocampus) GM. Additional diffusion kurtosis imaging (DKI) analysis demonstrated broader and earlier GM reductions in mean kurtosis (MK), possibly related to the decrease in neuronal complexity. Histological validation was obtained by an ALS fluorescent mice reporter (YFP, G93A-SOD1 mice). The combination of DTI, NODDI, and DKI models have proved to provide a more complete assessment of the early microstructural changes in the ALS brain, particularly in areas associated with high cognitive functions. This comprehensive approach should be considered as a valuable tool for the early detection of neuroimaging markers.

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KW - G93A-SOD1 mice

KW - diffusion kurtosis imaging

KW - diffusion tensor imaging

KW - neurite orientation dispersion and density imaging

KW - neuronal degeneration

KW - transgenic animals

KW - yellow fluorescence protein

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ER -

Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI

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