Impact of dose reduction and multi‐parametric harmonization on multi‐organ radiomics robustness in total‐body PET imaging: Methodological implications for quantitative theranostics
Mohammad Saber Azimi, Maryam Cheraghi, Habib ZaidiAbstract
Background
Radiomic features derived from positron emission tomography (PET) are sensitive to count statistics and acquisition protocol variability, thereby limiting quantitative reliability in low‐dose and multi‐center total‐body PET imaging.
Purpose
This study evaluated dose robustness of PET radiomics and assessed the impact of multi‐parameter ComBat harmonization on feature reproducibility.
Methods
A multi‐center total‐body PET dataset comprising 550 patients from two institutions was retrospectively analyzed. Seven dose levels were simulated from list‐mode data (Standard; dose reduction factors (DRF) of 2, 4, 10, 20, 50, and 100). Automatic deep learning–based segmentation was applied. A total of 107 Image Biomarker Standardization Initiative (IBSI)‐compliant radiomic features were extracted from standardized uptake value (SUV)‐normalized images. Feature‐level ComBat harmonization was performed under five configurations (scanner manufacturer, pixel spacing, radiopharmaceutical, scatter correction, and non‐harmonized baseline). Reproducibility was quantified using intraclass correlation coefficient (ICC (2,1)) across dose levels, organs, and harmonization settings.
Results
Dose reduction produced organ‐ and feature‐dependent effects. Overall, 32.7% of the features achieved good or excellent reproducibility (ICC ≥ 0.75) in at least one anatomical region. Selected first‐order and intensity‐associated features retained good reproducibility in several anatomical regions under moderate dose reduction (DRF ≤ 20), whereas severe count reduction (DRF 50–100) was associated with greater organ‐ and feature‐dependent instability, particularly among higher‐order texture features in vascular and lower‐contrast soft‐tissue regions. Harmonization produced organ and feature‐dependent changes but did not uniformly improve cross‐dose reproducibility or compensate for noise‐induced instability.
Conclusion
Radiomics robustness in total‐body PET is strongly influenced by dose level, anatomy, and acquisition variability. Moderate dose reduction preserves selected intensity‐based features, while extreme count reduction compromises higher‐order textures. Harmonization altered reproducibility patterns but did not uniformly improve cross‐dose agreement or fully offset noise‐induced instability, underscoring the need for dose‐aware feature selection in multi‐center PET radiomics.