Abstract

Purpose:To develop magnetic resonance elastography (MRE) as a noninvasive imaging biomarker of treatment response in cancer and to evaluate its prognostic potential for assessing chemotherapy response in non‐Hodgkin's lymphoma (NHL).Methods:A small animal cancer MRE methodology was developed which included a custom‐built 4 cm, 8‐channel receive‐only coil and an electromechanical driver capable of producing shear waves at a frequency of 800 Hz attached to an MRI‐compatible needle inserted in tissue. MRE reproducibility was evaluated in tumor phantoms and in vivo mouse experiments. Tumor shear stiffness was monitored following a single chemotherapy treatment in a murine xenograft of NHL to determine the biomechanical effect of an initial therapy response followed by tumor regrowth. The effect of an increased chemotherapy dose on the resulting decrease in tumor shear stiffness was quantified. In vivo evaluation of the feasibility of this potential biomarker was performed on three patients with NHL prior to and 2 weeks after chemotherapy treatment.Results:Tumor phantom models and in vivo measurements demonstrated excellent shear stiffness reproducibility with a standard deviation of ±3%. In the murine model, tumor shear stiffness and volume changes following chemotherapy treatment corresponded to periods of response and subsequent tumor regrowth. Shear stiffness alterations demonstrated a dose dependency with a decrease of 15% and 25% for the low and high dose group respectively compared to an increase of 7% in an untreated control group. In three patients with NHL, tumor shear stiffness decreased by an average of 38% within 2 weeks of chemotherapy treatment.Conclusion:These data demonstrate that MRE is a potentially sensitive biomarker of disease stage and response to therapy in cancer. The results demonstrate that MRE‐derived shear stiffness measurements are sensitive to chemotherapy response and disease progression in vivo, and are the first human application of MRE as a noninvasive assessment of therapy response.Funding provided by the Mayo Clinic Center for Individualized Medicine, Imaging Biomarker Discovery Program and the Mayo Graduate School.

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