Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology

Radiation necrosis is a serious potential adverse event of stereotactic radiosurgery that cannot be reliably differentiated from recurrent tumor using conventional imaging techniques. Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) based method that uses a diffusion-weighted sequence to estimate quantitative perfusion and diffusion parameters. This study evaluated the IVIM-derived apparent diffusion coefficient (ADC) and perfusion fraction (f), and compared the results to the gold standard histopathological-defined outcomes of radiation necrosis or recurrent tumor. Nine patients with ten lesions were included in this study; all lesions exhibited radiographic progression after stereotactic radiosurgery for brain metastases that subsequently underwent surgical resection due to uncertainty regarding the presence of radiation necrosis versus recurrent tumor. Pre-surgical IVIM was performed to obtain f and ADC values and the results were compared to histopathology. Five lesions exhibited pathological radiation necrosis and five had predominantly recurrent tumor. The IVIM perfusion fraction reliably differentiated tumor recurrence from radiation necrosis (f(mean) = 10.1 +/- 0.7 vs. 8.3 +/- 1.2, p = 0.02; cutoff value of 9.0 yielding a sensitivity/specificity of 100%/80%) while the ADC did not distinguish between the two (ADC(mean) = 1.1 +/- 0.2 vs. 1.2 +/- 0.4, p = 0.6). IVIM shows promise in differentiating recurrent tumor from radiation necrosis for brain metastases treated with radiosurgery, but needs to be validated in a larger cohort.