Abstract
BACKGROUND: Simultaneous PET/MR imaging enables precise anatomical localization and PET quantification by reducing PET-to-MR misalignments. However, involuntary motion during scans may still cause misalignment and quantification imprecision. Current mutual information (MI)-based co-registration methods do not account for the tissue-specific uptake patterns of PET and therefore could result in suboptimal alignment. To address this, we proposed a novel image co-registration method, namely the tracer characteristic-based co-registration (TCBC) method, which takes advantage of specific PET uptake patterns within a selected anatomical region to improve the image alignment and PET quantification. RESULTS: TCBC was evaluated using simulation and in vivo (18)F-Florbetapir PET/MR data from the OASIS-3 dataset. In simulations, TCBC demonstrated superior alignment accuracy with lower root mean square error and higher R-squared values compared to the conventional MI-based co-registration from FreeSurfer in recovering the simulated patient motion. In the retrospective human study, we evaluated the detectability of age-related amyloid burden in healthy controls under different co-registration methods as a demonstrative use case. TCBC significantly enhanced the detectability of age-related amyloid burden with stronger correlations across all five regions of evaluation, such as the medial orbitofrontal cortex (p < 0.001), precuneus (p = 0.004), and early amyloid-β composite (p = 0.002), compared to FSMC (p = 0.004, 0.007, and 0.006, respectively) and uncorrected (p = 0.378, 0.023, and 0.039, respectively) methods. Bootstrap analyses also confirmed TCBC's robustness in smaller samples, yielding tighter confidence intervals and lower means of p-values, such as 0.032 (95% CI: 0.029-0.035) in the precuneus and 0.008 (CI: 0.007-0.010) in the medial orbitofrontal cortex, outperforming FSMC (p = 0.046 with CI: 0.042-0.049, and p = 0.040 with CI: 0.036-0.044, respectively). CONCLUSIONS: The TCBC method reduces image misalignment, improves PET quantification, and may have a good potential for being applied to both research and clinical studies with simultaneous brain PET/MR. CLINICAL TRIAL NUMBER: Not applicable.