Monitoring response to chemotherapy of non-Hodgkin's lymphoma xenografts by T(2)-weighted and diffusion-weighted MRI

Abstract

An effective method for in vivo detection of early therapeutic response of patients with non-Hodgkin's lymphoma would enable personalized clinical management of cancer therapy and facilitate the design of optimal treatment regimens. This study evaluates the feasibility of T(2)-weighted MRI (T2WI) and diffusion-weighted MRI (DWI) for in vivo detection of response of human diffuse large B-cell lymphoma xenografts in severe combined immunodeficient mice to chemotherapy. Each cycle of combination chemotherapy with cyclophosphamide, hydroxydoxorubicin, Oncovin, prednisone, and bryostatin 1 (CHOPB) was administered to tumor-carrying mice weekly for up to four cycles. T2WI and DWI were performed before the initiation of CHOPB and after each cycle of CHOPB. In order to corroborate the MRI results, histological analyses were carried out on control tumors and treated tumors after completion of all MRI studies. DWI revealed a significant (P < 0.03) increase in the mean apparent diffusion coefficient in CHOPB-treated tumors as early as 1 week after initiation of CHOPB. However, a significant (P < 0.03) decrease in mean T(2) was observed only after two cycles of CHOPB. Both MRI methods produced high-resolution (0.1 x 0.1 x 1.0 mm(3)) maps of regional therapeutic response in the treated tumors based on local apparent diffusion coefficient and T(2). Only a specific region of the tumors (in 3 of the 5 tumors) corresponding to about one third of the tumor volume exhibited a response-associate increase in ADC and decrease in T(2). An adjacent region exhibited an increase in T(2) and no change in ADC. The rest of the tumor was indistinguishable from sham-treated controls by MRI criteria. The therapeutic response of the treated tumors detected by MRI was accompanied by changes in tumor cell density, proliferation and apoptosis revealed by histological studies performed upon completion of the longitudinal study. The mechanism producing the regional response of the tumor remains to be elucidated.