Ductography is an important clinical tool for imaging the breast and finding small lesions (1). Mouse models of breast cancer can provide useful information about the development of breast/mammary cancers (2). Here we report 3D in vivo MRI ductography of FVB/N mice and the SV40 mammary cancer model to evaluate contrast media distribution and to evaluate the permeability of normal mammary ducts and ducts with in situ cancer (3). The results suggest that increased ductal permeability may be a biomarker for early in situ breast/mammary cancer (4).Five 19-week old female FVB/N mice and eight 15-week old female SV40Tag mice were studied. After mice were anesthetized, a 34G, 45° tip Hamilton needle attached to a 25uL Hamilton syringe was inserted into the tip of an inguinal gland nipple. Approximately 15uL of a Gadodiamide and Trypan blue solution was slowly injected over one minute. Immediately post injection the animal was placed into a 30 mm quadrature coil inside a 9.4 T Bruker scanner. 3D T1W FLASH images with fat suppression were acquired (TR/TE = 22.2/4.4 ms, flip angle = 15°, FOV = 25.6×19.2×38.4 mm, matrix size = 256×192×192, partial Fourier factor = 1.5, NEX = 1) repeatedly for ~90 min to follow the contrast washout with temporal resolution of 9.13 min. Acquisition of the first T1W image began approximately 10 min after intra-ductal injections. Axial multi-slice RARE T2W images with fat suppression (TR/TEeffective = 4000/20.3 ms, FOV = 25.6×19.2 mm, matrix size = 256×192, slice thickness = 0.5 mm, number of slice = 41, RARE factor = 4, NEX = 2) were acquired at the end to provide anatomic information. The non-parametric Mann-Whitney U-Test was used to determine whether there was a statistically significant difference between FVB/N mice and SV40 mice for calculated parameters. A p-value less than 0.05 was considered significant.Figure 1 shows (a) FVB/N and (b) SV40 mouse 3D volume rendered T1W image of the mammary duct and aorta acquired between 10 and 20 minutes post intra-ductal injection. The FVB/N has a larger enhanced ductal volume (yellow circle) than the SV40 mouse. Signal enhancement in the aorta (red box) is greater in the SV40 mouse than in the FVB/N mouse, probably due to increased leakage of contrast media from the ducts in the SV40 mouse. Figure 2 shows a box plot of the total volume of signal enhancement in the first post-injection scan for the FVB/N and SV40 mammary gland. On average the total volume of significant enhancement was 5 times higher (p <0.005) in FVB/N mice than SV40 mice. Figure 3 shows a box plot of the average contrast agent washout rate in (a) the mammary gland and (b) aorta for the FVB/N and SV40 mice. The washout rate in the mammary gland was 20% faster (p <0.05) in SV40 mice than the FVB/N mice. The rate of washout from the aorta was slower in the SV40 mice than in the FVB/N mice, but this difference was not statistically significant. Nevertheless, the ratio of washout rate between mammary gland and aorta for the SV40 mice was significantly higher (p <0.05) than the FVB/N mice (Figure 4).These preliminary results suggest that the walls of mammary ductal lumens in SV40 mice with in situ cancer are more permeable to low molecular weight contrast agents than the ductal lumens of control FVB/N mice. The volume of enhancement measured in FVB/N mice is much greater than the volume of enhancement in SV40 mice at 10 – 20 minutes post-intraductal injection; this is consistent with more rapid washout from ductal lumens in SV40 mice. In addition, the measured contrast media washout rate is significantly more rapid in the SV40 mice than the FVB/N mice, and the enhancement in the aorta at 10 – 20 minutes is greater in SV40 mice than in FVB/N mice. This is also consistent with more rapid leakage from ductal lumens in SV40 mice. These results are consistent with previous XFM (X-Ray Fluorescence Microscopy) work that suggests increased permeability in mouse mammary ducts with in situ cancer (5).Increased ductal permeability may be a new MRI-detectable biomarker for early in situ cancer. In this study, we measured leakage from lumens into the surrounding epithelia, stroma, and eventually blood vessels following intra-ductal injection. The results imply that in conventional clinical DCE-MRI leakage occurs in the reverse direction, from blood vessels to stroma, and epithelia, and into ductal lumens. This is consistent with previous XFM studies from this laboratory, and has implications for the design and analysis of clinical DCE-MRI scans.