Diffusion-weighted magnetic resonance imaging (DWI) analyzes water diffusion in tissues, indirectly reflecting cellular density and aiding tumor characterization. Our objective was to explore the utility of DWI in three topics: (i) differentiation of bone and soft tissue sarcomas with respect to tumor type/grade; (ii) correlation with chemotherapy response in Ewing's sarcoma and osteosarcoma; and (iii) differentiation of benign from malignant soft tissue and bone tumors. The aim of the review article was to assess the existing literature detailing the insight that can be provided by DWI when addressing bone and soft tissue tumors. A search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using Pubmed, Scopus, Embase, and CENTRAL databases from 1 January 2013 to 30 November 2023. Eligible studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) scoring system. In total, 22 studies met the inclusion criteria. DWI proved effective in select scenarios when distinguishing among bone and soft tissue sarcomas (sensitivity = 48%–89%, specificity = 75%–100%), correlating chemotherapy response with histopathology results (sensitivity = 25%–85%, specificity = 50%–100%), and differentiating between benign and malignant bone tumors (sensitivity = 54%–92%, specificity = 39%–92%) and soft tissue tumors (sensitivity = 68%–91%, specificity = 60%–81%). DWI is a valuable tool for the diagnosis and prognosis of bone and soft tissue sarcomas, treatment effect of primary bone tumors, and distinguishing benign from malignant bone/soft tissue tumors. Though promising, the technology has shown mixed results, warranting further research.
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