Ductal Carcinoma in Situ: X-ray Fluorescence Microscopy and Dynamic Contrast-enhanced MR Imaging Reveals Gadolinium Uptake within Neoplastic Mammary Ducts in a Murine Model

Abstract

Purpose:To combine dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue samples from mice to identify the spatial distribution of gadolinium after intravenous injection. Materials and Methods:C3(1) Sv-40 large T antigen transgenic mice (n ϭ 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentrationtime curves were fit to a two-compartment pharmacokinetic model with the following parameters: transfer constant (K trans ) and volume of extravascular extracellular space per unit volume of tissue (v e ). Eleven mice received gadodiamide before XFM. These mice were sacrificed 2 minutes after injection, and frozen slices containing ducts distended with murine ductal carcinoma in situ (DCIS) were prepared for XFM. One mouse received saline and served as the control animal. Elemental gadolinium concentrations were measured in and around the ducts with DCIS. Hematoxylin-eosin-stained slices of mammary tissues were obtained after DCE MR imaging and XFM. Results:Ducts containing DCIS were unambiguously identified on MR images. DCE MR imaging revealed gadolinium uptake along the length of ducts with DCIS, with an average K trans of 0.21 min Ϫ1 Ϯ 0.14 (standard deviation) and an average v e of 0.40 Ϯ 0.16. XFM revealed gadolinium uptake inside ducts with DCIS, with an average concentration of 0.475 mmol/L Ϯ 0.380; the corresponding value for DCE MR imaging was 0.30 mmol/L Ϯ 0.13. Conclusion:These results provide insight into the physiologic basis of contrast enhancement of DCIS lesions on DCE MR images: Gadolinium penetrates and collects inside neoplastic ducts. RSNA, 2009 Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, use the Radiology Reprints form at the end of this article.T he sensitivity and specificity of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging in the early detection of invasive cancers have been shown to be equal or superior to those of x-ray mammography (1). However, this has not been consistently demonstrated for ductal carcinoma in situ (DCIS), which is a nonobligate precursor to invasive breast cancer, in which cancer cells are still confined by the basement membrane of mammary ducts. Because DCIS is the earliest stage of breast cancer and has the best prognosis, it is likely that further improvements in the detection of breast cancers at a preinvasive stage may improve patient outcomes. Some reports have shown decreased diagnostic accuracy of DCE MR imaging for DCIS (2,3), while others have shown comparable or even higher performance compared with that of x-ray mammography (4,5). The sensitivity of DCE MR imaging for detection of DCIS may be compromised if the lesion does not exhibit sufficient gadolinium uptake or if it is obscured by strongly enhancing parenchyma (6,7). Even when D...

Alterations in Low-Z Elements Distribution in Heart Tissue after Treatments to Breast Cancer Using LEXRF Technique

“…major importance in the tissue physiology. Figure 5, Figure 6 and Figure 7(d) and Figure 7(e) show absorption and phase contrast images, also in 1600 µm 2 , respectively, corresponding to the analysed areas. All maps were fitted and analysed first with Pymca, normalized by the acquisition time and the scattering intensities to correct the effect of coherent and incoherent scattering.…”

“…Heart tissue sections that were mounted on Ultralene foil fixed in teflon support were carefully examined with light microscope to select regions of interest (ROIs) with a 1.4 keV of effective energy. LEXRF images were acquired with a 1.4 keV of incident energy and with 25 seconds of exposure time per pixel with a field of view of at least 1600 μm 2 and spatial resolution of 1 μm.…”

“…A combination of compositional and morphological information can be used to make a semiquantitative investigation able to identify reliable marker elements and to better understand some aspects of healthy tissues and tissues treated with chemotherapy and/or radiotherapy [2] [3].…”

Calcified and Non-Calcified Ductal Carcinoma <i>in Situ</i>: Contrast-Enhanced MRI Features and Pathological Correlation

“…The periductal stroma associated with DCIS has a higher microvessel density than normal breast tissue [21]. Jansen et al postulated that ductal basement membrane permeability is elevated in the presence of DCIS, due to protease secretion from cancer cells, leading to an accumulation of gadolinium within the duct at the site of DCIS [22]. Consequently, MRI can detect DCIS more accurately than mammography, since it may be able to demonstrate mammographically occult or non-calcified DCIS.…”

Normal parenchymal enhancement patterns in women undergoing MR screening of the breast

“…This is a plausible link as estrogen is known to cause vascular changes such as hyperemia, vasodilatation and capillary permeability, as well as parenchymal enhancement pattern differences [2]. Another possibility is motivated by recent work suggesting that gadodiamide penetrates and accumulates within ducts with DCIS [39]; it could be that contrast agents penetrate into 'leaky' normal mammary ducts, accumulating in the lumen and resulting in nodular enhancement with persistent curve shapes. Clearly, further work is needed to rigorously evaluate these and other hypotheses.…”