Quantitative diffusion imaging and genotype-by-sex interactions in a rat model of Alexander disease.

Autor: Stowe NA; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA., Singh AP; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Barnett BR; Neuroscience Training Program, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, Madison, Wisconsin, USA., Yi SY; Neuroscience Training Program, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, Madison, Wisconsin, USA., Frautschi PC; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA., Messing A; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Hagemann TL; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Yu JJ; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Neuroscience Training Program, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Jazyk: angličtina
Zdroj: Magnetic resonance in medicine [Magn Reson Med] 2024 Mar; Vol. 91 (3), pp. 1087-1098. Date of Electronic Publication: 2023 Nov 09.
DOI: 10.1002/mrm.29917
Abstrakt: Purpose: The clinical diagnosis and classification of Alexander disease (AxD) relies in part on qualitative neuroimaging biomarkers; however, these biomarkers fail to distinguish and discriminate different subtypes of AxD, especially in the presence of overlap in clinical symptoms. To address this gap in knowledge, we applied neurite orientation dispersion and density imaging (NODDI) to an innovative CRISPR-Cas9 rat genetic model of AxD to gain quantitative insights into the neural substrates and brain microstructural changes seen in AxD and to potentially identify novel quantitative NODDI biomarkers of AxD.
Methods: Multi-shell DWI of age- and sex-matched AxD and wild-type Sprague Dawley rats (n = 6 per sex per genotype) was performed and DTI and NODDI measures calculated. A 3 × 2 × 2 analysis of variance model was used to determine the effect of genotype, biological sex, and laterality on quantitative measures of DTI and NODDI across regions of interest implicated in AxD.
Results: There is a significant effect of genotype in the amygdala, hippocampus, neocortex, and thalamus in measures of both DTI and NODDI brain microstructure. A genotype by biological sex interaction was identified in DTI and NODDI measures in the corpus callosum, hippocampus, and neocortex.
Conclusion: We present the first application of NODDI to the study of AxD using a rat genetic model of AxD. Our analysis identifies alterations in NODDI and DTI measures to large white matter tracts and subcortical gray nuclei. We further identified genotype by sex interactions, suggesting a possible role for biological sex in the neuropathogenesis of AxD.
(© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)
Databáze: MEDLINE
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