From Radiomics to Generative Models: Evaluating Early Radiation Effects in Metastatic Brain Lesions

Brain metastases (BM), along with primary central nervous system lymphomas and glioblastomas, represent the majority of malignant brain tumors encountered in clinical neuro-oncology, driving a need for advanced imaging techniques and post-processing methods to improve their characterization and treatment monitoring. In particular, stereotactic radiosurgery (SRS), a cornerstone treatment for BM, delivers high-dose, focused radiation (>20 Gy) to target lesions with minimal impact on surrounding tissues. Despite its efficacy, radiation-induced effects such as early radiation effects (ERE) and adverse radiation effects (ARE) complicate diagnosis and management, with ARE occurring in up to 30% of patients, often presenting as ring-enhancing T2/FLAIR hyperintensities. To address these challenges, we aimed to compare standard radiomics-based machine learning approaches with pretrained generative models for assessing ERE in BM lesions. A cohort of 21 patients for a total of 35 lesions (17 treatment-naïve and 18 post-SRS +/- combination therapy) who underwent multiparametric ¹⁸F-FPIA PET/MRI was analyzed. The study investigated: 1) Multiparametric analysis of PET and MRI diffusion/perfusion parameters (ADC, K^trans, CBF, K₁, v_t); 2) MRI-based radiomics; 3) static PET radiomics; 4) Dynomics; 5) a combination of PET and MRI radiomics; and 6) low-level embeddings from a pretrained generative diffusion model applied to full T1, static PET, and their combination. Using manually contoured lesion masks for analyses 1-5 and lesion-free embeddings for analysis 6, multiple classifiers (SVM, XGBoost, Linear regressor) were applied after feature standardization and principal component analysis (retaining 90% variance). Fivefold cross-validation demonstrated comparable performances across radiomic approaches (Accuracy: 71.95±0.05%, AUC: 0.72±0.05%), while the pretrained generative model achieved significantly higher performance (Accuracy: 83.82±0.01%, AUC: 0.83±0.01%) without requiring lesion segmentation in assessing ERE in BM lesions.Clinical Relevance-This study shows the potential of generative models to streamline and enhance the assessment of early radiation effects in parenchymal metastatic lesions without need of lesion segmentation.