Exploring the nigrostriatal and digestive interplays in Parkinson's disease using dynamic total-body [11C]CFT PET/CT

Abstract

Purpose: Dynamic total-body imaging enables new perspectives to investigate the potential relationship between the central and peripheral regions. Employing uEXPLORER dynamic [¹¹C]CFT PET/CT imaging with voxel-wise simplified reference tissue model (SRTM) kinetic modeling and semi-quantitative measures, we explored how the correlation pattern between nigrostriatal and digestive regions differed between the healthy participants as controls (HC) and patients with Parkinson's disease (PD).

Methods: Eleven participants (six HCs and five PDs) underwent 75-min dynamic [¹¹C]CFT scans on a total-body PET/CT scanner (uEXPLORER, United Imaging Healthcare) were retrospectively enrolled. Time activity curves for four nigrostriatal nuclei (caudate, putamen, pallidum, and substantia nigra) and three digestive organs (pancreas, stomach, and duodenum) were obtained. Total-body parametric images of relative transporter rate constant (R₁) and distribution volume ratio (DVR) were generated using the SRTM with occipital lobe as the reference tissue and a linear regression with spatial-constraint algorithm. Standardized uptake value ratio (SUVR) at early (1-3 min, SUVR_EP) and late (60-75 min, SUVR_LP) phases were calculated as the semi-quantitative substitutes for R₁ and DVR, respectively.

Results: Significant differences in estimates between the HC and PD groups were identified in DVR and SUVR_LP of putamen (DVR: 4.82 ± 1.58 vs. 2.58 ± 0.53; SUVR_LP: 4.65 ± 1.36 vs. 2.84 ± 0.67; for HC and PD, respectively, both p < 0.05) and SUVR_EP of stomach (1.12 ± 0.27 vs. 2.27 ± 0.65 for HC and PD, respectively; p < 0.01). In the HC group, negative correlations were observed between stomach and substantia nigra in both the R₁ and SUVR_EP values (r=-0.83, p < 0.05 for R₁; r=-0.94, p < 0.01 for SUVR_EP). Positive correlations were identified between pancreas and putamen in both DVR and SUVR_LP values (r = 0.94, p < 0.01 for DVR; r = 1.00, p < 0.001 for SUVR_LP). By contrast, in the PD group, no correlations were found between the aforementioned target nigrostriatal and digestive areas.

Conclusions: The parametric images of R₁ and DVR generated from the SRTM model, along with SUVR_EP and SUVR_LP, were proposed to quantify dynamic total-body [¹¹C]CFT PET/CT in HC and PD groups. The distinction in correlation patterns of nigrostriatal and digestive regions between HC and PD groups identified by R₁ and DVR, or SUVRs, may provide new insights into the disease mechanism.

Keywords: Nigrostriatal-digestive interplays; Parametric imaging; Parkinson’s disease; Total-body PET/CT; [11C]CFT.