title: Longitudinal in vivo MRI in a Huntington's disease mouse model: Global atrophy in the absence of white matter microstructural damage.
abstract: Huntington's disease (HD) is a genetically-determined neurodegenerative disease. Characterising neuropathology in mouse models of HD is commonly restricted to cross-sectional ex vivo analyses, beset by tissue fixation issues. In vivo longitudinal magnetic resonance imaging (MRI) allows for disease progression to be probed non-invasively. In the HdhQ150 mouse model of HD, in vivo MRI was employed at two time points, before and after the onset of motor signs, to assess brain macrostructure and white matter microstructure. Ex vivo MRI, immunohistochemistry, transmission electron microscopy and behavioural testing were also conducted. Global brain atrophy was found in HdhQ150 mice at both time points, with no neuropathological progression across time and a selective sparing of the cerebellum. In contrast, no white matter abnormalities were detected from the MRI images or electron microscopy images alike. The relationship between motor function and MR-based structural measurements was different for the HdhQ150 and wild-type mice, although there was no relationship between motor deficits and histopathology. Widespread neuropathology prior to symptom onset is consistent with patient studies, whereas the absence of white matter abnormalities conflicts with patient data. The myriad reasons for this inconsistency require further attention to improve the translatability from mouse models of disease.
authors: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.|Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.|Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff, CF24 4HQ, UK.|Experimental MRI Centre, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors: Jessica J
authors: JJ
authors: Steventon
authors: Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.|School of Life Sciences, Queen's Medical Centre, Nottingham University, Nottingham, NG7 2UH, UK.
authors: Rebecca C
authors: RC
authors: Trueman
authors: Centre for Medical Imaging Computing, University College London, London, UK.|Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, UK.
authors: Da
authors: D
authors: Ma
authors: Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.|Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff, CF24 4HQ, UK.
authors: Emma
authors: E
authors: Yhnell
authors: Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.|Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff, CF24 4HQ, UK.
authors: Zubeyde
authors: Z
authors: Bayram-Weston
authors: Centre for Medical Imaging Computing, University College London, London, UK.
authors: Marc
authors: M
authors: Modat
authors: Centre for Medical Imaging Computing, University College London, London, UK.
authors: Jorge
authors: J
authors: Cardoso
authors: Centre for Medical Imaging Computing, University College London, London, UK.
authors: Sebastian
authors: S
authors: Ourselin
authors: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, UK.
authors: Mark
authors: M
authors: Lythgoe
authors: Experimental MRI Centre, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors: Andrew
authors: A
authors: Stewart
authors: Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.|Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff, CF24 4HQ, UK.|Institute of Psychological Medicine and Neurology, School of Medicine, Hadyn Ellis Building, Maindy Road, Cathays, Cardiff CF24 4HQ, UK.
authors: Anne E
authors: AE
authors: Rosser
authors: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.|Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff, CF24 4HQ, UK.
authors: Derek K
authors: DK
authors: Jones
mesh_terms: D000818:Animals; D001284:Atrophy; D001835:Body Weight; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011596:Psychomotor Disorders / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011597:Psychomotor Performance; D013045:Species Specificity; D066127:White Matter / Q000000981:diagnostic imaging* / Q000378:metabolism
chemical_list: C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins