MR Elastography Derived Shear Stiffness-A New Imaging Biomarker for the Assessment of Early Tumor Response to Chemotherapy

Purpose: The overall goal is to develop magnetic resonance elastography derived shear stiffness as a biomarker for the early identification of chemotherapy response, allowing dose, agent type and treatment regimen to be tailored on a per patient basis, improving therapeutic outcome and minimizing normal tissue toxicity. The specific purpose of this study is to test the feasibility of this novel biomarker to measure the treatment response in a well-known chemotherapy model. Methods: Tumors were grown in the right flank of genetically modified mice by subcutaneous injection of DoHH2 (non-Hodgkin's lymphoma) cells. Magnetic resonance elastography was used to quantify tumor stiffness before and after injection of a chemotherapeutic agent or saline. Histological tests were also performed on the tumors. Results: A significant decrease (P < 0.0001) in magnetic resonance elastography-derived tumor shear stiffness was observed within 4 days of chemotherapy treatment, while no appreciable change was observed in saline-treated tumors. No significant change in volume occurred at this early stage, but there were decreased levels of cellular proliferation in chemotherapy-treated tumors. Conclusion: These results demonstrate that magnetic resonance elastography-derived estimates of shear stiffness reflect an initial response to cytotoxic therapy and suggest that this metric could be an early and sensitive biomarker of tumor response to chemotherapy. Magn Reson Med 71:1834-1840, 2014. (c) 2013 Wiley Periodicals, Inc.