Identification of variable stages in murine pancreatic tumors by a multiparametric approach employing hyperpolarized C MRSI, H diffusivity and H T MRI.

This study explored the usefulness of multiple quantitative MRI approaches to detect pancreatic ductal adenocarcinomas in two murine models, PAN-02 and KPC. Methods assayed included H T and T measurements, quantitative diffusivity mapping, magnetization transfer (MT) H MRI throughout the abdomen and hyperpolarized C spectroscopic imaging. The progress of the disease was followed as a function of its development; studies were also conducted for wildtype control mice and for mice with induced mild acute pancreatitis. Customized methods developed for scanning the motion- and artifact-prone mice abdomens allowed us to obtain quality H images for these targeted regions. Contrasts between tumors and surrounding tissues, however, were significantly different. Anatomical images, T maps and MT did not yield significant contrast unless tumors were large. By contrast, tumors showed statistically lower diffusivities than their surroundings (≈8.3 ± 0.4 x 10 for PAN-02 and ≈10.2 ± 0.6 x 10 for KPC vs 13 ± 1 x 10 mm s for surroundings), longer T relaxation times (≈1.44 ± 0.05 for PAN-02 and ≈1.45 ± 0.05 for KPC vs 0.95 ± 0.10 seconds for surroundings) and significantly higher lactate/pyruvate ratios by hyperpolarized C MR (0.53 ± 0.2 for PAN-02 and 0.78 ± 0.2 for KPC vs 0.11 ± 0.04 for control and 0.31 ± 0.04 for pancreatitis-bearing mice). Although the latter could also distinguish early-stage tumors from healthy animal controls, their response was similar to that in our pancreatitis model. Still, this ambiguity could be lifted using the H-based reporters. If confirmed for other kinds of pancreatic tumors this means that these approaches, combined, can provide a route to an early detection of pancreatic cancer.