Optimized reference region and the effect on test-retest reliability and detection of Parkinson's disease with UCB-J.

Khattar, N.; Matuskey, D.; Gallezot, J.-D.; Naganawa, M.; Holmes, S. E.; Sadabad, F. E.; Esterlis, I.; van Dyck, C. H.; Mecca, A. P.; D'Souza, D. C.; Nabulsi, N. B.; Finnema, S. J.; Huang, Y.; Carson, R. E.; Toyonaga, T.

doi:10.1101/2025.10.15.682460

bioRxiv · 10.1101/2025.10.15.682460

Optimized reference region and the effect on test-retest reliability and detection of Parkinson's disease with UCB-J.

Khattar, N.·Matuskey, D.·Gallezot, J.-D.·Naganawa, M.·Holmes, S. E.·Sadabad, F. E.·Esterlis, I.·van Dyck, C. H.·Mecca, A. P.·D'Souza, D. C.·Nabulsi, N. B.·Finnema, S. J.·Huang, Y.·Carson, R. E.·Toyonaga, T.

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Abstract

[11C]UCB-J is a radioligand targeting synaptic vesicle glycoprotein 2A, used to image synaptic density. For quantification, a small-volume centrum semiovale area was previously optimized as a [11C]UCB-J reference region (CS2mL); however, its high variability resulted in reduced reliability. Herin, we evaluated an alternative reference region method to assess longitudinal test-retest reliability and detection of Parkinsons disease (PD). For estimating distribution volume ratio (DVR), CS2mL and eleven white matter (WM) reference regions (range: 0.5-200 mL) were generated using the Freesurfer WM map. Same-day and longitudinal test-retest variability (TRV) were assessed (24 healthy subjects (HS); n=10 same-day and n=20 longitudinal HRRT scans, range: 7-1028 days). Each reference region was used to evaluate the substantia nigra (SN) and caudate DVRs in HS (n=25) and PD (n=20). The 10mL WM reference region yielded [11C]UCB-J DVR measurements with reduced variability in TRV (same-day: 10mL: 1.2{+/-}5.7%, same-day: CS2mL: -0.9{+/-}9.2% longitudinal: 10mL: 1.5{+/-}7.0%, CS2mL: 1.6{+/-}11.9%,) while maintaining <10% volume of distribution difference, compared to CS2mL. Further, a significant difference between PD and HS groups in SN and caudate DVRs was found using 10mL, with greater effect size (Cohens d 0.61 for SN and 0.66 for caudate) compared to CS2mL (0.38 for SN and 0.43 for caudate).

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Khattar, N., Matuskey, D., Gallezot, J.-D., Naganawa, M., Holmes, S. E., Sadabad, F. E., Esterlis, I., van Dyck, C. H., Mecca, A. P., D'Souza, D. C., Nabulsi, N. B., Finnema, S. J., Huang, Y., Carson, R. E., Toyonaga, T.. 2025-10-15. Optimized reference region and the effect on test-retest reliability and detection of Parkinson's disease with UCB-J.. https://doi.org/10.1101/2025.10.15.682460

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