Jennifer G Whisenant1, Gregory D Ayers2, Mary E Loveless3, Stephanie L Barnes4, Daniel C Colvin4, Thomas E Yankeelov5. 1. Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Program in Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232-2675. 2. Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232-2675. 3. Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675. 4. Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232-2675. 5. Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Program in Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-2675. Electronic address: tom.yankeelov@vanderbilt.edu.
Abstract
BACKGROUND AND PURPOSE: The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a surrogate biomarker of response in preclinical studies is increasing. However, before a biomarker can be reliably employed to assess treatment response, the reproducibility of the technique must be established. There is a paucity of literature that quantifies the reproducibility of DW-MRI in preclinical studies; thus, the purpose of this study was to investigate DW-MRI reproducibility in a murine model of HER2+ breast cancer. MATERIALS AND METHODS: Test-Retest DW-MRI scans separated by approximately six hours were acquired from eleven athymic female mice with HER2+ xenografts using a pulsed gradient spin echo diffusion-weighted sequence with three b values [150, 500, and 800s/mm(2)]. Reproducibility was assessed for the mean apparent diffusion coefficient (ADC) from tumor and muscle tissue regions. RESULTS: The threshold to reflect a change in tumor physiology in a cohort of mice is defined by the 95% confidence interval (CI), which was±0.0972×10(-3)mm(2)/s (±11.8%) for mean tumor ADC. The repeatability coefficient defines this threshold for an individual mouse, which was±0.273×10(-3)mm(2)/s. The 95% CI and repeatability coefficient for mean ADC of muscle tissue were±0.0949×10(-3)mm(2)/s (±8.30%) and±0.266×10(-3)mm(2)/s, respectively. CONCLUSIONS: Mean ADC of tumors is reproducible and appropriate for detecting treatment-induced changes on both an individual and mouse cohort basis.
BACKGROUND AND PURPOSE: The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a surrogate biomarker of response in preclinical studies is increasing. However, before a biomarker can be reliably employed to assess treatment response, the reproducibility of the technique must be established. There is a paucity of literature that quantifies the reproducibility of DW-MRI in preclinical studies; thus, the purpose of this study was to investigate DW-MRI reproducibility in a murine model of HER2+ breast cancer. MATERIALS AND METHODS: Test-Retest DW-MRI scans separated by approximately six hours were acquired from eleven athymic female mice with HER2+ xenografts using a pulsed gradient spin echo diffusion-weighted sequence with three b values [150, 500, and 800s/mm(2)]. Reproducibility was assessed for the mean apparent diffusion coefficient (ADC) from tumor and muscle tissue regions. RESULTS: The threshold to reflect a change in tumor physiology in a cohort of mice is defined by the 95% confidence interval (CI), which was±0.0972×10(-3)mm(2)/s (±11.8%) for mean tumor ADC. The repeatability coefficient defines this threshold for an individual mouse, which was±0.273×10(-3)mm(2)/s. The 95% CI and repeatability coefficient for mean ADC of muscle tissue were±0.0949×10(-3)mm(2)/s (±8.30%) and±0.266×10(-3)mm(2)/s, respectively. CONCLUSIONS: Mean ADC of tumors is reproducible and appropriate for detecting treatment-induced changes on both an individual and mouse cohort basis.
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