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

Abstract

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. 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. 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). 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.