Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26658298
DOI
10.1016/j.jneumeth.2015.11.017
PII: S0165-0270(15)00419-7
Knihovny.cz E-zdroje
- Klíčová slova
- Animal models, Brain atlas, MRI, Minipig, Preclinical research,
- MeSH
- geneticky modifikovaná zvířata MeSH
- Huntingtonova nemoc diagnostické zobrazování metabolismus MeSH
- magnetická rezonanční tomografie * přístrojové vybavení metody MeSH
- miniaturní prasata * MeSH
- modely nemocí na zvířatech * MeSH
- mozek diagnostické zobrazování metabolismus MeSH
- neurozobrazování přístrojové vybavení metody MeSH
- prasata MeSH
- protonová magnetická rezonanční spektroskopie * přístrojové vybavení metody MeSH
- velikost orgánu MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: As novel treatment approaches for Huntington's disease (HD) evolve, the use of transgenic (tg) large animal models has been considered for preclinical safety and efficacy assessments. It is hoped that large animal models may provide higher reliability in translating preclinical findings to humans, e.g., by using similar endpoints and biomarkers. NEW METHOD: We here investigated the feasibility to conduct MRI assessments in a recently developed tgHD model in the Libechov minipig. The model is characterized by high genetic homology to humans and a similar body mass and compartments. The minipig brain provides anatomical features that are attractive for imaging studies and could be used as endpoints for disease modifying preclinical studies similar to human HD. RESULTS: We demonstrate that complex MRI protocols can be successfully acquired with tgHD and wild type (wt) Libechov minipigs. We show that acquisition of anatomical images applicable for volumetric assessments is feasible and outline the development of a segmented MRI brain atlas. Similarly diffusion-weighted imaging (DWI) including fiber tractography is presented. We also demonstrate the feasibility to conduct in vivo metabolic assessments using MR spectroscopy. COMPARISON WITH EXISTING METHODS: In human HD, these MRI methods are already validated and used as reliable biomarker of disease progression even before the onset of a clinical motor phenotype. CONCLUSIONS: The results show that the minipig brain is well suited for MRI assessments in preclinical studies. We conclude that further characterization of phenotypical differences between tg and wt animals in sufficiently powered cross-sectional and longitudinal studies is warranted.
Department of Physics and Center for Nonlinear Science University of Muenster Germany
Dept of Psychiatry University of Iowa IowaCity IA USA
Dept of Radiology University of Muenster Albert Schweitzer Campus 1 48149 Muenster Germany
George Huntington Institute Technology Park Johann Krane Weg 27 48149 Muenster Germany
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