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

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.     

Earlier detection of tumor treatment response using magnetic resonance diffusion imaging with oscillating gradients

An improved method for detecting early changes in tumors in response to treatment, based on a modification of diffusion-weighted magnetic resonance imaging, has been demonstrated in an animal model. Early detection of therapeutic response in tumors is important both clinically and in pre-clinical assessments of novel treatments. Noninvasive imaging methods that can detect and assess tumor response early in the course of treatment, and before frank changes in tumor morphology are evident, are of considerable interest as potential biomarkers of treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to changes in water diffusion rates in tissues that result from structural variations in the local cellular environment, but conventional methods mainly reflect changes in tissue cellularity and do not convey information specific to microstructural variations at sub-cellular scales. We implemented a modified imaging technique using oscillating gradients of the magnetic field for evaluating water diffusion rates over very short spatial scales that are more specific for detecting changes in intracellular structure that may precede changes in cellularity. Results from a study of orthotopic 9L gliomas in rat brains indicate that this method can detect changes as early as 24 h following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea, when conventional approaches do not find significant effects. These studies suggest that diffusion imaging using oscillating gradients may be used to obtain an earlier indication of treatment efficacy than previous magnetic resonance imaging methods.     

A compositeness test that never fails for Carmichael numbers

Paper withdrawn by author after original electronic posting date of September 19, 2006 and prior to preparation of the printed issue.

     

New limits on D0 (1.865) production in proton-nucleus collisions at 400 GeV/c

We present final results of a sensitive search for new particles in π^±K^? effective mass spectra observed in proton-nucleus collisions at 400 GeV/c. We establish a limit for D⁰ (1.865) production B_π⁺π^? dσ/dy < 360 nb/nucleon at y_cm^≈ ?0.4. For D?⁰ → π^?K⁺ the limit is 290 nb/nucleon.