Can radiomics signatures and machine learning methods reinforce the revived role of 18F-NaF in metastatic bone disease?

Document Type : Original Article

Authors

1 Nuclear Medicine unit, National cancer Institute (NCI), Cairo University, Egypt

2 Radiodiagnosis department, Faculty of Medicine, Cairo University, Egypt

3 Clinical oncology and Nuclear Medicine department, Faculty of Medicine, Zagazig University, Egypt

4 Physics department, Faculty of Science, Zagazig University, Egypt

5 School of information Technology, New Giza University, Egypt

6 Nuclear medicine department, Children’s Cancer Hospital, Egypt

Abstract

Objective(s): To evaluate whether radiomic features extracted from 18F-NaF PET/CT scans, analyzed using machine learning (ML) methods, can improve the differentiation between true metastatic bone lesions (TP) and false-positive benign uptake (FP), thereby enhancing the diagnostic utility of 18F-NaF PET/CT.
Methods: This retrospective study included 62 patients with known primary malignancies who underwent 18F-NaF PET/CT. Lesions were classified as TP or FP based on consensus interpretation including follow-up. Patients were randomly split into training (n=41) and validation (n=21) groups. Radiomic features were extracted from PET images using LIFEx software. Feature selection (ANOVA, RFE) and ML model training (SVM, Random Forest, XGBoost) were performed. Model performance was evaluated using accuracy, specificity, sensitivity, and AUC, initially with a train/validation split and subsequently with 5-fold cross-validation incorporating feature engineering and hyperparameter tuning. Feature importance was assessed using SHAP.
Results: Significant differences in SUVmax (p=0.006) and SUVmean (p=0.034) were observed between TP and FP lesions. Initial validation showed XGBoost performed best (AUC=0.78). After optimization and 5-fold cross-validation on the combined dataset (n=62), the tuned XGBoost model achieved the highest performance (Mean Accuracy: 85.7% ±2.9%, Mean AUC: 0.86), outperforming Random Forest (AUC: 0.79) and SVM (AUC: 0.74). SHAP analysis identified SUVmax, SUVmean, Voxel Volume Num, GLRLM RLNU, and Skew.
Conclusion: Radiomics-based machine learning classifiers, particularly XGBoost, demonstrated strong performance in distinguishing true metastatic from false-positive benign lesions on 18F-NaF PET/CT. Integrating radiomics and ML can potentially improve the diagnostic accuracy and robustness of 18F-NaF PET/CT for assessing bone metastases. Further validation in larger cohorts is warranted.

Keywords

Main Subjects


  1. Blau M, Ganatra R, Bender MA. Bender. 18F-Fluoride for bone imaging. Seminars in Nuclear Medicine.1972; 2(1):31–37.
  2. Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Loidl W, et al. Detection of bone metastases in patients with prostate cancer by 18F Fluorocholine and 18F Fluoride PET/CT: a comparative study. European Journal of Nuclear Medicine and Molecular Imaging. 2008; 35(10): 1766-74.
  3. Even-Sapir E, Metser U, Flusser G, Zuriel L, Kollender Y, Lerman H, et al. Assessment of malignant skeletal disease: initial experience with 18F-Fluoride PET/CT and comparison between 18F-fluoride PET and 18F-Fluoride PET/CT. Journal of Nuclear Medicine. 2004; 45(2): 272-8.
  4. Grant FD, Fahey FH, Packard AB, Davis RT, Alavi A, Treves ST. Skeletal PET with 18F-Fluoride: applying new technology to an old tracer. Journal of Nuclear Medicine. 2008; 49(1):68-78.
  5. Gillies RJ, Kinahan PE, Hricak H. Radiomics: images are more than pictures, they are data. Radiology. 2016; 278(2): 563-77.
  6. Lambin P, Leijenaar RT, Deist TM, Peerlings J, De Jong EE, Van Timmeren J, et al. Radiomics: the bridge between medical imaging and personalized medicine. Nature Reviews Clinical Oncology. 2017; 14(12): 749-62.
  7. Aerts HJ, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Carvalho S, et al. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nature communications. 2014; 5(1): 4006.
  8. Zhou Y, Ma XL, Zhang T, Wang J, Zhang T, Tian R. Use of radiomics based on 18F-FDG PET/CT and machine learning methods to aid clinical decision-making in the classification of solitary pulmonary lesions: an innovative approach. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(9): 2904-13.
  9. Mayerhoefer ME, Materka A, Langs G, Häggström I, Szczypiński P, Gibbs P, et al. Introduction to radiomics. Journal of Nuclear Medicine. 2020; 61(4): 488-95.
  10. Zhou Y, Ma XL, Zhang T, Wang J, Zhang T, Tian R. Use of radiomics based on 18F-FDG PET/CT and machine learning methods to aid clinical decision-making in the classification of solitary pulmonary lesions: an innovative approach. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(9): 2904-13.
  11. Huang RH, Hong YK, Du H, Ke WQ, Lin BB, Li YL. A machine learning framework develops a DNA replication stress model for predicting clinical outcomes and therapeutic vulnerability in primary prostate cancer. Journal of Translational Medicine. 2023; 21(1): 20.
  12. Ji GW, Zhu FP, Xu Q, Wang K, Wu MY, Tang WW, et al. Machine-learning analysis of contrast-enhanced CT radiomics predicts recurrence of hepatocellular carcinoma after resection: A multi-institutional study. EBio Medicine. 2019; 50: 156-65.
  13. Nioche C, Orlhac F, Boughdad S, Reuzé S, Goya-Outi J, Robert C, et al. LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Research. 2018; 78(16): 4786-9.
  14. Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, Blondel M, Prettenhofer P, Weiss R, Dubourg V, Vanderplas J. Scikit-learn: Machine learning in Python. Journal of Machine Learning Research. 2011; 12: 2825-30.
  15. Chan YH. Biostatistics 102: quantitative data–parametric & non-parametric tests. Blood Press. 2003; 140(24.08): 79.
  16. Kulshrestha RK, Vinjamuri S, England A, Nightingale J, Hogg P. The role of 18F-Sodium Fluoride PET/CT bone scans in the diagnosis of metastatic bone disease from breast and prostate cancer. Journal of Nuclear Medicine Technology. 2016; 44(4): 217-22.
  17. Withofs N, Grayet B, Tancredi T, Rorive A, Mella C, Giacomelli F, et al. 18F-fluoride PET/CT for assessing bone involvement in prostate and breast Nuclear Medicine Communications. 2011; 32(3): 168-76.
  18. Damle NA, Bal C, Bandopadhyaya GP, Kumar L, Kumar P, Malhotra A, et al. The role of 18F-Fluoride PET-CT in the detection of bone metastases in patients with breast, lung and prostate carcinoma: a comparison with FDG PET/CT and 99mTc-MDP bone scan. Japanese Journal of Radiology. 2013; 31(4):262-9.
  19. Wang H, Qiu J, Lu W, Xie J, Ma J. Radiomics based on multiple machine learning methods for diagnosing early bone metastases not visible on CT images. Skeletal Radiology. 2025; 54(2): 335-43.
  20. Lin C, Bradshaw T, Perk T, Harmon S, Eickhoff J, Jallow N, et al. Repeatability of quantitative 18F-NaF PET: a multicenter study. Journal of Nuclear Medicine. 2016; 57(12): 1872-9.