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 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.

Assessing the accuracy and reproducibility of modality independent elastography in a murine model of breast cancer

“…71 Similarly, Whisenant et al reported a wCV of 12.0% and 95% CI of 11.8% for a metric extracted from repeated diffusion weighted MRI (DW-MRI) scans. 65 As our animal model is similar to these studies, the MIE elasticity biomarker is shown to exhibit a precision similar to DCE-MRI and DW-MRI analyses.…”

“…70 Our results are also in agreement with reproducibility analysis for other types of quantitative MRI data previously reported. 65,[71][72][73] In a similar mouse model of breast cancer, Barnes et al reported wCVs from 8.3 to 15.6% and 95% CIs from 7.5 to 14.3% for metrics extracted from standard pharmacokinetic analysis of dynamic contrast enhanced MRI (DCE-MRI) data over the tumor region of interest for repeat scans. 71 Similarly, Whisenant et al reported a wCV of 12.0% and 95% CI of 11.8% for a metric extracted from repeated diffusion weighted MRI (DW-MRI) scans.…”

“…Reproducibility statistics were calculated as previously described, 64,65 following the methods described by Bland and Altman. 63 The root mean square deviation (rMSD) was calculated from the differences between repeated measurements, d, as…”

Magnetic single-walled carbon nanotubes as efficient drug delivery nanocarriers in breast cancer murine model: noninvasive monitoring using diffusion-weighted magnetic resonance imaging as sensitive imaging biomarker

“…An increase in ADC was reported as a reproducible good index for efficient cancer therapy, which is directly related to the number of killed tumor cells and thought to be due to the liberation of water into the extracellular space as a result of cell necrosis. 17 Interestingly, the iron oxide nanoparticles presented in SWCNT⋅ + CD105 + DOX samples, which were found to express an attenuation in T2* once reaching the tumor site, produced a transient decrease in ADC at 2 hours post-administration, due to the disturbance of …”

“…MRI has the superiority of simultaneously offering both anatomical (ie, using standard spin-echo sequence) and early quantitative assessments of disease responses (ie, using diffusion-weighted MRI [DW-MRI]) by characterizing the treatment-induced changes in tumor cell density. 17 Water-stable and homogeneously dispersed polyvinylpyrrolidone (PVP)-functionalized short SWCNTs that were further tagged with iron nanoparticles and conjugated with Endoglin/CD105 monoclonal antibody for specific targeting to tumor sites, were recently developed. 15 Coupling antibodyactive targeting with magnetic targeting by applying an external high-energy flexible magnet was found to improve the delivery of the magnetic SWCNTs to the tumor site in a murine breast cancer model.…”