Klinische Neurophysiologie 2011; 42 - P315
DOI: 10.1055/s-0031-1272762

PET/MRI-based phenotyping of a transgenic rat model for Huntington's disease – a 16 months follow-up study

E. Hölzner 1, V. Lippross 1, S. Hermann 1, N. Nagelmann 1, J. Heselhaus 1, S. Bohlen 1, H. Kugel 1, M. Deppe 1, J. Sommer 1, C. Bremer 1, H. Nguyen 1, O. Riess 1, S. von Hörsten 1, M. Schäfers 1, A.H. Jacobs 1, R. Reilmann 1
  • 1Münster, Tübingen, Erlangen

Background: The tgHD rat (von Horsten et al. 2003) carries 51 CAG repeats, which is within ranges observed in human genotypes. It was previously reported that small animal FDG-PET is able to detect hypometabolism in the whole brain of tgHD rats at 18–24 months of age. However, this initial imaging study was limited by its cross-sectional nature, the resolution of the small animal PET employed and the lack of a regional analysis. Due to the late-onset development of phenotype in tgHD rats compared to, e.g., the juvenile onset in R6/2 mouse, in-vivo imaging may facilitate phenotype assessment in therapeutic studies.

Objective: To study striatal and cortical glucose uptake in individual tgHD rats over time with high spatial resolution using PET (FWHM: 0.7mm) and MRI in a larger cohort.

Methods: 20 tgHD and 20 wt rats, mixed gender, were included into this study. Repeated small animal FDG-PET (50 MBq, 15min acquisition 1h p.i., quadHIDAC, Oxford, UK) and MRI were performed at 4, 8, 12, and 16 months of age. ROIs encompassing striatum, amygdala, thalamus, cortex, cerebellum, whole brain and control ROIs in non-neuronal tissue were placed manually on the MRI and transferred to the co-registered PET data set (MPI-Tool, ATV, Germany). Mean FDG-PET activity in the striatum was calculated and normalized to mean cerebellar and whole brain uptake.

Results: Although FDG uptake showed variations in the rats over time in all regions assessed, we found no significant difference in glucose uptake between similar age and sex matched tgHD and wt rats in all ROIs at any time point.

Conclusions: In this study employing high-resolution small animal PET, we did not reproduce the typical clinical finding of reduced striatal or cortical glucose uptake in the tgHD rat animal model in an intra-individual follow-up of 16 months. These data indicate that in the age period studied ROI-based FDG-PET do not depict possible subtle differences of glucose uptake in brains of tgHD rats. Future studies concentrate on SPM analysis and other tracers for image-based phenotyping in vivo.

Acknowledgment: RR was supported by grant #RE-120524 from the Innovative Medical Research Fund (IMF) of the University of Münster. OR and SvH were supported by a grant from CHDI.