T₂* relaxation times of intraductal murine mammary cancer, invasive mammary cancer, and normal mammary gland

Abstract

Purpose: This study investigates the feasibility of T 2 * to be a diagnostic indicator of early breast cancer in a mouse model. T 2 * is sensitive to susceptibility effects due to local inhomogeneity of the magnetic field, e.g., caused by hemosiderin or deoxyhemoglobin. In these mouse models, unlike in patients, the characteristics of single mammary ducts containing pure intraductal cancer can be evaluated. Methods: The C3(1)SV40Tag mouse model of breast cancer (n ¼ 11) and normal FVB=N mice (n ¼ 6) were used to measure T 2 * of normal mammary gland tissue, intraepithelial neoplasia, invasive cancers, mammary lymph nodes, and muscle. MRI experiments were performed on a 9.4T animal scanner. High resolution (117 microns) axial 2D multislice gradient echo images with fat suppression were acquired first to identify inguinal mammary gland. Then a multislice multigradient echo pulse sequence with and without fat suppression were performed over the inguinal mammary gland. The modulus of a complex double exponential decay detected by the multigradient echo sequence was used to fit the absolute proton free induction decay averaged over a region of interest to determine the T 2 * of water and fat signals. Results: The measured T 2 * values of tumor and muscle are similar ($15 ms), and almost twice that of lymph nodes ($8 ms). There was a statistically significant difference (p < 0.03) between T 2 * in normal mammary tissue (13.7 6 2.9 ms) and intraductal cancers (11 6 2.0 ms) when a fat suppression pulse was applied. Conclusions: These are the first reported T 2 * measurements from single mammary ducts. The results demonstrated that T 2 * measurements may have utility for identifying early pre-invasive cancers in mouse models. This may inspire similar research for patients using T 2 * for diagnostic imaging of early breast cancer.

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

“…On the other hand, MRI provides excellent soft tissue contrast, can detect early cancer in vivo much more reliably than other imaging modalities, allows evaluation of the surrounding parenchyma, and allows accurate tumor volume measurements over time. Previous work from our laboratory demonstrated that in vivo T 2 ‐weighted MRI reliably detects very early in situ mammary tumors in SV40TAg mice with high sensitivity and specificity, and differentiates in situ from invasive cancer . Precise correlations between in vivo MR and histology images have also been demonstrated .…”

“…Previous work from our laboratory demonstrated that in vivo T 2 -weighted MRI reliably detects very early in situ mammary tumors in SV40TAg mice with high sensitivity and specificity, and differentiates in situ from invasive cancer. [17][18][19][20] Precise correlations between in vivo MR and histology images have also been demonstrated. 20 Furthermore, serial MRI directly demonstrated great heterogeneity in initiation time, growth rate, and time at which in situ cancers became invasive.…”

Magnetic resonance angiography reveals increased arterial blood supply and tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

“…MRI has been proven to sensitively and specifically detect and differentiate DCIS and invasive cancers in vivo. [18][19][20][21] A past study from our laboratory has also shown the efficacy of non-invasive time-of-flight (TOF) MR angiography for detecting neoangiogenesis and demonstrated increased arterial recruitment to cancerous mammary glands in the same mouse model as used here. 22 However, in that study, mice were imaged at one time point and fed with regular chow.…”

MRI accurately identifies early murine mammary cancers and reliably differentiates between in situ and invasive cancer: correlation of MRI with histology

“…In addition, we tested whether lesions identified on MRI with a largest diameter greater than 0.4 mm, and a signal intensity relative to muscle of at least 2.08 : 1, could reliably be identified as invasive cancer. Lymph nodes could be identified and excluded from this analysis on the basis of morphology , signal intensity and location. Based on these criteria, for in situ cancer, there were 50 true positives (TPs), i.e.…”

“…In situ cancers were reliably identified in the present study in part because the SNR of normal parenchyma was very low (Table ). Normal mammary ducts in the mice used in this study are 20–50 µm in diameter, have a relatively short T 2 / T 2 * and are not easily detected on T 2 ‐weighted images. As a result, small in situ cancers of 150–400 µm in diameter were easily detected against a relatively dark background.…”