Abstract
Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable information regarding the micro-anatomy of mammary/breast cancer. The use of ex vivo MRI to study mouse mammary cancer would be enhanced if there is a strong correlation between parameters derived from in vivo and ex vivo scans. Here, we report the correlation between apparent diffusion coefficient (ADC) and T2 values measured in vivo and ex vivo in mouse mammary glands with in situ cancers (mammary intraepithelial neoplasia (MIN)) and invasive cancers (those which spread outside the ducts into surrounding tissue). MRI experiments were performed on the Polyoma middle T oncoprotein breast cancer mouse model (n = 15) in a 9.4T scanner. For in vivo experiments, T2-weighted (T2W) images were acquired to identify abnormal regions, then ADC and T2 values were measured for nine selected slices. For ex vivo experiments, a midline incision was made along the spine, and then skin, glands, and tumors were gently peeled from the body. Tissue was fixed in formalin, placed around a mouse-sized sponge, and sutured together mimicking the geometry of the gland when attached to the mouse. The same pulse sequences used for in vivo experiments were repeated for ex vivo scans at room temperature. Regions of interest were manually traced on T2W images defining features that could be identified on in vivo and ex vivo images. The results demonstrate a strong positive correlations between in vivo and ex vivo invasive cancers for ADC (r = 0.89, p <0.0001) and T2 (r = 0.89, p <0.0001) values; and weak to moderate positive correlations between in vivo and ex vivo in situ cancers for ADC (r = 0.61, p <0.0001) and T2 (r = 0.79, p <0.0001) values. The average ex vivo ADC value was about 54% of the in vivo value; and the average ex vivo T2 was similar to the in vivo value for cancers. Although motion, fixation, and temperature differences affect ADC and T2, these results show a reliable relationship between ADC and T2 in vivo and ex vivo. As a result ex vivo images can provide valuable information with clinical and research applications.
Highlights
Ex vivo imaging of human breast cancer and murine mammary cancer has both clinical and research applications
In this study we evaluate whether there is a correlation between apparent diffusion coefficient (ADC) and T2 in vivo and ADC and T2 of formalin-fixed mammary cancers in polyoma middle T (PyMT) transgenic mice–a widely used model of human breast cancer [9]
Ex vivo T2 values were not significantly different between lymph nodes, in situ cancers, and invasive cancers. These results demonstrate strong positive correlations between in vivo and ex vivo mouse mammary invasive cancers for ADC (r = 0.89, p < 0.0001) and T2 (r = 0.89, p < 0.0001) values; and weak to moderate, but statistically significant positive correlations between in vivo and ex vivo mouse mammary in situ cancers for ADC (r = 0.61, p < 0.0001) and T2 (r = 0.79, p < 0.0001) values
Summary
Ex vivo imaging of human breast cancer and murine mammary cancer has both clinical and research applications. If the contrast in in vivo and ex vivo images is similar, this suggests MRI can aid intra-operative assessments of tumor margins in lumpectomy specimens. Intraoperative radiographs are currently used to identify tumor margins and this decreases re-excision rates [3,4], but X-ray imaging does not provide optimal soft tissue contrast. MRI has potential to improve intra-operative imaging by providing high resolution three-dimensional images with excellent soft tissue contrast. High resolution ex vivo imaging of breast/mammary cancers could provide new information concerning three-dimensional structure, and this may be useful for studies of in situ cancers [5]
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