Advanced Dual-Nuclei MRI for Differentiation of Recurrent Brain Metastases and Radiation Necrosis - PROJECT SUMMARY Brain metastases (BM) are the most common intracranial tumors in adults, affecting 10–40% of cancer patients. Stereotactic radiosurgery (SRS) is a standard treatment for BM, but assessing treatment response is challenging due to the difficulty in distinguishing recurrent brain metastasis (rBM) from radiation-induced necrosis (RN) using conventional imaging methods. Both conditions can appear similar on conventional magnetic resonance imaging (MRI) but require markedly different management strategies: rBM may necessitate aggressive interventions, while RN is often managed conservatively. Accurate, non-invasive differentiation between rBM and RN is critical for effective patient care but remains an unmet clinical need. This project aims to investigate the use of advanced dual-nuclei MRI techniques, proton-based diffusion- relaxation correlation spectrum imaging (DR-CSI) and sodium imaging, to non-invasively differentiate between rBM and RN and to monitor microstructural changes in BM patients undergoing SRS. DR-CSI enables sub-voxel characterization of tissue microstructure by quantifying components with different diffusion and T2 relaxation properties, while sodium imaging measures total sodium concentration (TSC), which increases with cell death and changes in membrane permeability, providing complementary information to proton-based MRI. Aim 1 will develop and validate DR-CSI and sodium imaging biomarkers in BM patients with radiographic progression scheduled for surgical resection or biopsy. Pre-operative imaging will be acquired to identify biopsy targets with distinct microstructural features. We will obtain stereotactic image-guided biopsies from these regions and determine pathological diagnosis of rBM or RN. We will use statistical models, including logistic regression and ROC analysis, to assess the predictive value of imaging biomarkers to differentiate between rBM and RN, validated against histopathological diagnosis. Aim 2 will investigate longitudinal microstructural changes following SRS in BM patients. Dual-nuclei MRI will be performed at baseline (pre-SRS) and at 2 weeks, 3 months, and 6 months post-SRS. We hypothesize that early changes in DR-CSI and sodium imaging at 2 weeks and 3 months will predict treatment response at 6 months, as determined lesion-by-lesion using the RANO-BM criteria. Successful completion of this project will establish advanced dual-nuclei MRI techniques as non-invasive imaging biomarkers for differentiating rBM from RN and for monitoring treatment response in BM patients. This advancement has the potential to significantly impact clinical practice by improving diagnostic accuracy, guiding patient management, reducing unnecessary invasive procedures, and enabling timely interventions. Moreover, these imaging approaches may have broader applications in other cancers where distinguishing between progressive disease and treatment effects is crucial.
