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J Neurosci Methods. 2016 May 30;265:46-55. doi: 10.1016/j.jneumeth.2015.11.017. Epub 2015 Dec 1.

Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments.

Author information

1
George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, Germany.
2
George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, Germany; Dept of Radiology, University of Muenster, Albert-Schweitzer Campus 1, 48149 Muenster, Germany.
3
Dept of Radiology, University of Muenster, Albert-Schweitzer Campus 1, 48149 Muenster, Germany.
4
George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, Germany; Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany.
5
Dept of Psychiatry, University of Iowa, IowaCity, IA, USA; Electrical and Computer Engineering, University of Iowa, IowaCity, IA, USA.
6
Dept of Psychiatry, University of Iowa, IowaCity, IA, USA.
7
Department of Physics and Center for Nonlinear Science, University of Muenster, Germany.
8
Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, v.v.i., AS CR, Libechov, Czech Republic.
9
George-Huntington-Institute, Technology Park, Johann-Krane-Weg 27, 48149 Muenster, Germany; Dept of Radiology, University of Muenster, Albert-Schweitzer Campus 1, 48149 Muenster, Germany; Department of Neurology, University of Munster, Germany; Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler Str. 3, 72076 Tuebingen, Germany. Electronic address: ralf.reilmann@ghi-muenster.de.

Abstract

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.

KEYWORDS:

Animal models; Brain atlas; MRI; Minipig; Preclinical research

PMID:
26658298
DOI:
10.1016/j.jneumeth.2015.11.017
[Indexed for MEDLINE]

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