Identification of variable stages in murine pancreatic tumors by a multiparametric approach employing hyperpolarized 13C MRSI, 1H diffusivity and 1H T1 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 1H T1 and T2 measurements, quantitative diffusivity mapping, magnetization transfer (MT) 1H MRI throughout the abdomen and hyperpolarized 13C 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 1H images for these targeted regions. Contrasts between tumors and surrounding tissues, however, were significantly different. Anatomical images, T2 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 10−4 for PAN‐02 and ≈10.2 ± 0.6 x 10−4 for KPC vs 13 ± 1 x 10−3 mm2 s−1 for surroundings), longer T1 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 13C 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 1H‐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.