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

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. C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentration-time 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. 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(-1) +/- 0.14 (standard deviation) and an average v(e) of 0.40 +/- 0.16. XFM revealed gadolinium uptake inside ducts with DCIS, with an average concentration of 0.475 mmol/L +/- 0.380; the corresponding value for DCE MR imaging was 0.30 mmol/L +/- 0.13. 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.