title: Assessing reproducibility of diffusion-weighted magnetic resonance imaging studies in a murine model of HER2+ breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Program in Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232-2675.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Whisenant
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232-2675.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ayers
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Loveless
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232-2675.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Barnes
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232-2675; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232-2675.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Colvin
authors.affiliation: 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.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Yankeelov
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Apparent diffusion coefficient; Diffusion-weighted MRI; Mouse; Reproducibility