FDG μPET Fails to Detect a Disease-Specific Phenotype in Rats Transgenic for Huntington's Disease – A 15 Months Follow-up Study.
BACKGROUND
FDG-PET detects hypometabolism in premanifest and symptomatic Huntington's disease (HD). A cross-sectional study suggested that whole-brain FDG-PET is capable to detect a phenotype in transgenic (tg) HD rats. Recently, a longitudinal follow-up study showed no FDG-PET changes in tgHD rats. Both studies applied small sample sizes and analysis was limited to whole-brain or striatum.


OBJECTIVE
We therefore performed a follow-up study in a larger cohort of tgHD and wild-type (wt) rats encompassing several pre-defined regions of interest (ROIs) and hypothesis free voxel-by-voxel SPM analysis to clarify whether FDG-PET can detect a phenotype in tgHD rats and to determine onset …and effect sizes of changes over time.


METHODS
N = 19 tgHD- and n = 20 wt-rats, mixed gender, were included. Repeated small animal FDG-μPET and MRI were performed at 5,10,15, and 20 months of age. ROIs encompassing entire brain, cortex, striatum, thalamus, subventricular-zone, and cerebellum were placed manually on the MRI and transferred to the co-registered μPET. Mean and maximal FDG-PET activities within ROIs were calculated and normalized to cerebellar FDG uptake. Activity and spatially normalized FDG-μPET were compared between groups on a hypothesis-free voxel-by-voxel basis using SPM.


RESULTS
FDG uptake showed changes over time in both tgHD- and wt-rats, however, there was no consistent difference between tgHD- and wt-rats in both the manual ROI and SPM analysis.


CONCLUSIONS
In this transgenic rat model of HD FDG-μPET imaging does not detect significant alterations at the ages investigated. Further investigations are warranted employing other age groups and alternative imaging biomarkers for neuronal degeneration, respectively.
George-Huntington-Institute, Muenster, Germany. ralf.reilmann@ghi-muenster.de
Ralf
R
Reilmann
Veronika
V
Lippross
Eva
E
Hölzner
Fabian
F
Gigengack
Stefan
S
Bohlen
Harald
H
Kugel
Michael
M
Deppe
Nani
N
Osada
M
M
Lücke
Olaf
O
Riess
Huu Phuc
HP
Nguyen
Stephan
S
Von Hörsten
Klaus
K
Schäfers
Michael
M
Schäfers
Andreas H
AH
Jacobs
Sven
S
Hermann
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18