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Assessing reproducibility of diffusion-weighted magnetic resonance imaging studies in a murine model of HER2 + breast cancer
Authors:Jennifer G Whisenant  Gregory D Ayers  Mary E Loveless  Stephanie L Barnes  Daniel C Colvin  Thomas E Yankeelov
Institution:1. Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232–2675;2. Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232–2675;3. Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232–2675;4. Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232–2675;5. Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee 37232–2675;6. Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232–2675;g Department of Program in Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232–2675;h Department of Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232–2675
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 800 s/mm2]. 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 mm2/s (± 11.8%) for mean tumor ADC. The repeatability coefficient defines this threshold for an individual mouse, which was ± 0.273 × 10- 3 mm2/s. The 95% CI and repeatability coefficient for mean ADC of muscle tissue were ± 0.0949 × 10- 3 mm2/s (± 8.30%) and ± 0.266 × 10- 3 mm2/s, respectively.

Conclusions

Mean ADC of tumors is reproducible and appropriate for detecting treatment-induced changes on both an individual and mouse cohort basis.
Keywords:Reproducibility  Diffusion-weighted MRI  Apparent diffusion coefficient  Mouse
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