18F-FDG PET / CT is used clinically for the detection of extramedullary lesions in patients with relapsed acute leukemia (AL). However, the visual analysis of 18F-FDG diffuse bone marrow uptake in detecting bone marrow involvement (BMI) in routine clinical practice is still challenging. This study aims to improve the diagnostic performance of 18F-FDG PET/CT in detecting BMI for patients with suspected relapsed AL. Methods: Forty-one patients (35 in training group and 6 in independent validation group) with suspected relapsed AL were retrospectively included in this study. All patients underwent both bone marrow biopsy (BMB) and 18F-FDG PET/CT within one week. The BMB results were used as the gold standard or real "truth" for BMI. The bone marrow 18F-FDG uptake was visually diagnosed as positive and negative by three nuclear medicine physicians. The skeletal volumes of interest were manually drawn on PET/CT images. A total of 781 PET and 1045 CT radiomic features were automatically extracted to provide a more comprehensive understanding of the embedded pattern. To select the most important and predictive features, an unsupervised consensus clustering method was first performed to analyze the feature correlations and then used to guide a random forest supervised machine learning model for feature importance analysis. Cross-validation and independent validation were conducted to justify the performance of our model. Results: The training group involved 16 BMB positive and 19 BMB negative patients. Based on the visual analysis of 18F-FDG PET, 3 patients had focal uptake, 8 patients had normal uptake, and 24 patients had diffuse uptake. The sensitivity, specificity, and accuracy of visual analysis for BMI diagnosis were 62.5%, 73.7%, and 68.6%, respectively. With the cross-validation on the training group, the machine learning model correctly predicted 31 patients in BMI. The sensitivity, specificity, and accuracy of the machine learning model in BMI detection were 87.5%, 89.5%, and 88.6%, respectively, significantly higher than the ones in visual analysis (P < 0.05). The evaluation on the independent validation group showed that the machine learning model could achieve 83.3% accuracy. Conclusions:18F-FDG PET/CT radiomic analysis with machine learning model provided a quantitative, objective and efficient mechanism for identifying BMI in the patients with suspected relapsed AL. It is suggested in particular for the diagnosis of BMI in the patients with 18F-FDG diffuse uptake patterns.
Keywords: 18F-FDG PET/CT; bone marrow involvement; machine learning; radiomics; relapsed leukemia.