MR Microscopy of premalignant pancreatic lesion in a transgenic mouse model of pancreatic cancer Free

LB-276

The EL-Kras FVB6 F1 transgenic (Tg) mouse is an ideal model for evaluating the progression of intraepithelial cellular changes that precede pancreatic cancer [Cancer Res. 63:2016, 2003; Clin. Cancer Res. 6:2969, 2000]. All mice develop premalignant pancreatic intraepithelial neoplastic lesions (PanINs) before 6 months of age. We have used high field MR imaging to investigate morphological and cellular changes in the EL-Kras mouse. We are able to differentiate transgenic from normal mouse pancreata using MR microscopic imaging, based only on classical endogenous contrast. Pancreas was surgically removed from 11-month old EL-Kras FVB6 F1 mice and normal B6 mice and immersion-fixed in paraformaldehyde (n=4). MR imaging experiments were performed on a Bruker 600MHz (field strength 14.1T) microimager. High resolution RARE8-3D (T2-weighted) images of fixed pancreas were acquired with fat suppression using the following parameters: TR/TE 2000ms/10ms (effective TE 40ms), and pixel size 50μm. T1 and T2 relaxation times were measured on 0.25mm thick slices using progressive saturation and CPMG methods, respectively. Images of normal mouse pancreas reveal that high field MR imaging is capable of spatial resolution that is high enough to visualize acinar cells, pancreatic islets and ducts. Different components of exocrine and endocrine pancreas have distinct contrast in T2-weighted images, ductal fluid appearing the brightest and acinar cells appearing the darkest. Islets appear with intermediate signal intensity and vary in size and number between samples. Images of EL-Kras mouse pancreas show multiple lesions with hypointense core and bright irregular rim. The size of the lesions ranged from 50-250μm. Lesions detected by MR imaging were verifed by comparison with histology. T1 of acini (~1.6s) and ductal fluid (~3.0s) were similar between the two groups of mice. On the other hand, T2 of these pancreatic substructures were different between the groups. T2 of Tg mouse acini (28.2±1.21msec) was longer than that of the normal mouse (22.6±1.37msec), whereas T2 of ductal fluid in the Tg mouse (73.8±1.34msec) was shorter than that of the normal mouse (79.6±1.01msec). The observed differences in spin-spin relaxation times most likely reflect cellular level changes in the acini and duct of EL-Kras mouse pancreas. Ability to detect premalignant lesions using MR imaging may translate to earlier detection of pancreatic cancer by bridging the gap between structural tissue correlates and the molecular correlates associated with them. (Supported by NIH/NCRR instrumentation grant 1S10RR13880-01)