This study investigates the comparative changes in the sodium MRI signal and proton diffusion following treatment using a 9L rat glioma model to develop markers of earliest response to cancer therapy. Sodium MRI and proton diffusion mapping were performed on untreated (n = 5) and chemotherapy 1,3-bis(2-chloroethyl)-1-nitrosourea-treated rats (n = 5). Animals were scanned serially at 2- to 3-day intervals for up to 30 days following therapy. The time course of Na concentration in a tumor showed a dramatic increase in the treated brain tumor compared to the untreated tumor, which correlates in time with an increase in tumor water diffusion. The largest posttreatment increase in sodium signal occurred 7-9 days following treatment and correlated to the period of the greatest chemotherapy-induced cellular necrosis based on diffusion and histopathology. Both Na MRI and proton ADC mapping revealed early changes in tumor sodium content and cellularity. This study demonstrates the possibility of Na MRI to function as a biomarker for monitoring early tumor treatment and validates the use of monitoring changes in diffusion MRI values for assessing tumor cellularity.
Copyright 2004 Wiley-Liss, Inc.