A unified deep learning framework for cross-platform harmonization of multi-tracer PET quantification in neurodegenerative disease.

Wang, Jing; Zhong, Aocheng; Xu, Qian; Huang, Haolin; Zhu, Yuhua; Lu, Jiaying; Wang, Min; Jiang, Jiehui et al. · NPJ Digit Med · 2026

basic_science · Level V

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Abstract

Quantitative PET underpins diagnosis and treatment monitoring in neurodegenerative disease, yet systematic biases between PET-MRI and PET-CT preclude threshold transfer and cross-site comparability. We developed and validated the first unified, anatomically guided deep-learning framework to harmonize PET-MRI quantification to PET-CT standards across multiple tracers and scanner manufacturers. The model learns CT-anchored attenuation representations using a vision transformer autoencoder, aligns MRI features to the CT space via contrastive objectives, and performs attention-guided residual correction. In paired same-day scans (N = 70; <sup>18</sup>F-FDG, <sup>18</sup>F-florbetaben, and <sup>18</sup>F-florzolotau), cross-platform bias fell by >80% while preserving inter-regional biological topology. The framework generalized zero-shot to held-out tracers (<sup>18</sup>F-florbetapir and <sup>18</sup>F-FP-CIT) without retraining. Multicenter validation (N = 420; three sites, four vendors) reduced amyloid Centiloid discrepancies from 23.6 to 4.1 (close to, though slightly above, PET-CT test-retest variability) and aligned tau SUVR thresholds. These results support more consistent cross-platform diagnostic cut-offs and reliable longitudinal monitoring when patients transition between modalities, establishing a practical route to scalable, radiation-sparing quantitative PET in therapeutic workflows.