The present disclosure includes methods, apparatuses, and systems for three-dimensional phenotyping and physiologic characterization of brain lesions and tissue encompassing one or more enlarged boundaries surrounding the brain lesion to study the metabolic and physiologic profiles from tissue within and around lesions and their impacts on lesion shape and surface texture. The non-invasive biomarker blood-oxygen their impacts on lesion shape and surface texture. The non-invasive biomarker blood-oxygen-level-dependent (BOLD) slope was used to metabolically characterize lesions. Metabolically active lesions with more intact tissue and myelin architecture have more symmetrical shapes and more complex surface textures compared to metabolically inactive lesions with less intact tissue and myelin architecture. The association of lesions' shapes and surface features with their metabolic signatures aid in the translation of MRI data to clinical management by providing information related to metabolic activity, lesion age, and risk for disease reactivation and self-repair.