Assessing reproducibility of diffusion-weighted magnetic resonance imaging studies in a murine model of HER2+ breast cancer

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.

Keywords: Apparent diffusion coefficient; Diffusion-weighted MRI; Mouse; Reproducibility.

Fig. 1

Test–retest example of ADC parametric maps. Three regions of interest are indicated: tumor (denoted with a ‘T’), skeletal muscle (denoted with ‘M’), and a water phantom (denoted with a ‘W’). Take note of how the animal orientation is slightly different between repeat scans, which might affect ADC reproducibility as the same tissue sections from each scan might not be analyzed. This variation in positioning is somewhat noticeable in the tumor, as the location and size of higher ADC regions (white arrows) are different; however, the variability of regions with higher ADC values (red arrows) is much larger in the muscle. Units of ADC are in mm²/s.

Fig. 2

Bland–Altman plots displaying the difference in ADC between scans plotted against mean ADC for both tumor (left panel) and muscle (right panel) ROIs. The mean difference (solid line) is shown with 95% confidence intervals (dotted lines), which defines the significant threshold for the population. Repeatability is also shown (dashed lines), and represents the threshold required to guarantee a statistically significant change in an individual mouse.