MR-based spatial normalization improves [18F]MNI-659 PET regional quantification and detectability of disease effect in the Q175 mouse model of Huntington's disease

Daniele Bertoglio; Jeroen Verhaeghe; Lauren Kosten; David Thomae; Annemie Van der Linden; Sigrid Stroobants; John Wityak; Celia Dominguez; Ladislav Mrzljak; Steven Staelens

doi:10.1371/journal.pone.0206613

MR-based spatial normalization improves [18F]MNI-659 PET regional quantification and detectability of disease effect in the Q175 mouse model of Huntington's disease

PLoS One. 2018 Oct 26;13(10):e0206613. doi: 10.1371/journal.pone.0206613. eCollection 2018.

Authors

Affiliations

¹ Molecular Imaging Center Antwerp (MICA), University of Antwerp, Wilrijk, Belgium.
² Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
³ Bio-Imaging Lab, University of Antwerp, Wilrijk, Belgium.
⁴ CHDI Foundation, Princeton, NJ, United States of America.

Abstract

The positron emission tomography (PET) tracer [18F]MNI-659, selective for phosphodiesterase 10A (PDE10A), is a promising tool to assess an early biomarker for Huntington's disease (HD). In this study we investigated [18F]MNI-659 uptake in the Q175 mouse model of HD. Given the focal striatal distribution of PDE10A as well as the striatal atrophy occurring in HD, the spatial normalization approach applied during the processing could sensibly affect the accuracy of the regional quantification. We compared the use of a magnetic resonance images (MRI) template based on individual MRI over a PET and CT templates for regional quantification and spatial normalization of [18F]MNI-659 PET images. We performed [18F]MNI-659 PET imaging in six months old heterozygous (HET) Q175 mice and wild-type (WT) littermates, followed by X-ray computed tomography (CT) scan. In the same week, individual T2-weighted MRI were acquired. Spatial normalization and regional quantification of the PET/CT images was performed on MRI, [18F]MNI-659 PET, or CT template and compared to binding potential (BPND) using volumes manually delineated on the individual MR images. Striatal volume was significantly reduced in HET mice (-7.7%, p<0.0001) compared to WT littermates. [18F]MNI-659 BPND in striatum of HET animals was significantly reduced (p<0.0001) when compared to WT littermates using all three templates. However, BPND values were significantly higher for HET mice using the PET template compared to the MRI and CT ones (p<0.0001), with an overestimation at lower activities. On the other hand, the CT template spatial normalization introduced larger variability reducing the effect size. The PET and CT template-based approaches resulted in a lower accuracy in BPND quantification with consequent decrease in the detectability of disease effect. This study demonstrates that for [18F]MNI-659 brain PET imaging in mice the use of an MRI-based spatial normalization is recommended to achieve accurate quantification and fully exploit the detectability of disease effect.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / pathology
Disease Models, Animal
Fluorine Radioisotopes / administration & dosage
Humans
Huntington Disease / genetics
Huntington Disease / pathology*
Image Processing, Computer-Assisted / methods
Magnetic Resonance Imaging / methods
Male
Mice
Mice, Inbred C57BL
Phosphoric Diester Hydrolases / genetics

Substances

Fluorine Radioisotopes
Phosphoric Diester Hydrolases
Fluorine-18

Grants and funding

This work was funded by CHDI Foundation, Inc, a nonprofit biomedical research organization exclusively dedicated to developing therapeutics that will substantially improve the lives of HD-affected individuals. The funder had the following involvement with the study: study design and interpretation of the results. D. Bertoglio has a Ph.D. fellowship from the Research Foundation Flanders (FWO, 11W2516N/11W2518N).