Journal article
Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments
Journal of neuroscience methods, Vol.265, pp.46-55
05/30/2016
DOI: 10.1016/j.jneumeth.2015.11.017
PMID: 26658298
Abstract
•Large animal models such as minipigs provide new options for research in HD.•Their long lifespan resembles human HD calling for sensitive phenotype assessments.•Imaging detects changes in the brain of premanifest and symptomatic human HD.•We assessed feasibility to perform these imaging assessments in tgHD minipigs.•We established volumetric, diffusion-weighted and spectroscopic MR imaging protocols.
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.
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.
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.
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.
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.
Details
- Title: Subtitle
- Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments
- Creators
- Robin Schubert - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, GermanyFrauke Frank - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, GermanyNina Nagelmann - Dept of Radiology, University of Muenster, Albert-Schweitzer Campus 1, 48149 Muenster, GermanyLennart Liebsch - Dept of Radiology, University of Muenster, Albert-Schweitzer Campus 1, 48149 Muenster, GermanyVerena Schuldenzucker - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, GermanySarah Schramke - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, GermanyMaike Wirsig - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, GermanyHans Johnson - Dept of Psychiatry, University of Iowa, IowaCity, IA, USAEun Young Kim - Dept of Psychiatry, University of Iowa, IowaCity, IA, USAStefanie Ott - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, GermanyEva Hölzner - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, GermanySergej O Demokritov - Department of Physics and Center for Nonlinear Science, University of Muenster, GermanyJan Motlik - Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, v.v.i., AS CR, Libechov, Czech RepublicCornelius Faber - Dept of Radiology, University of Muenster, Albert-Schweitzer Campus 1, 48149 Muenster, GermanyRalf Reilmann - George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, Germany
- Resource Type
- Journal article
- Publication Details
- Journal of neuroscience methods, Vol.265, pp.46-55
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jneumeth.2015.11.017
- PMID
- 26658298
- ISSN
- 0165-0270
- eISSN
- 1872-678X
- Grant note
- DOI: 10.13039/100005725, name: CHDI Foundation
- Language
- English
- Date published
- 05/30/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Psychiatry; The Iowa Institute for Biomedical Imaging; The Iowa Initiative for Artificial Intelligence; Iowa Informatics Initiative
- Record Identifier
- 9984221628602771
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