Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments
R Schubert, F Frank, N Nagelmann, L Liebsch… - Journal of neuroscience …, 2016 - Elsevier
R Schubert, F Frank, N Nagelmann, L Liebsch, V Schuldenzucker, S Schramke, M Wirsig…
Journal of neuroscience methods, 2016•ElsevierBackground 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, eg, 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 …
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, eg, 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 …
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.
Elsevier