Water Exchange Rate Constant as a Biomarker of Treatment Efficacy in Patients With Brain Metastases Undergoing Stereotactic Radiosurgery

Purpose: This study was designed to evaluate whether changes in metastatic brain tumors after stereotactic radiosurgery (SRS) can be seen with quantitative MRI early after treatment. Methods and Materials: Using contrast-enhanced MRI, a 3-water-compartment tissue model consisting of intracellular (I), extracellular-extravascular (E), and vascular (V) compartments was used to assess the intra–extracellular water exchange rate constant (k_IE), efflux rate constant (k_ep), and water compartment volume fractions (M_0,I, M_0,E, M_0,V). In this prospective study, 19 patients were MRI-scanned before treatment and 1 week and 1 month after SRS. The change in model parameters between the pretreatment and 1-week posttreatment scans was correlated to the change in tumor volume between pretreatment and 1-month posttreatment scans. Results: At 1 week k_IE differentiated (P<.001) tumors that had partial response from tumors with stable and progressive disease, and a high correlation (R=−0.76, P<.001) was observed between early changes in the k_IE and tumor volume change 1 month after treatment. Other model parameters had lower correlation (M_0,E) or no correlation (k_ep, M_0,V). Conclusions: This is the first study that measured k_IE early after SRS, and it found that early changes in k_IE (1 week after treatment) highly correlated with long-term tumor response and could predict the extent of tumor shrinkage at 1 month after SRS.