Identification Of Variable Stages In Murine Pancreatic Tumors By A Multiparametric Approach Employing Hyperpolarized C-13 Mrsi, H-1 Diffusivity And H-1 T-1 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-1 T-1 and T-2 measurements, quantitative diffusivity mapping, magnetization transfer (MT) H-1 MRI throughout the abdomen and hyperpolarized C-13 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-1 images for these targeted regions. Contrasts between tumors and surrounding tissues, however, were significantly different. Anatomical images, T-2 maps and MT did not yield significant contrast unless tumors were large. By contrast, tumors showed statistically lower diffusivities than their surroundings (approximate to 8.3 +/- 0.4 x 10(-4) for PAN-02 and approximate to 10.2 +/- 0.6 x 10(-4) for KPC vs 13 +/- 1 x 10(-3) mm(2) s(-1) for surroundings), longer T-1 relaxation times (approximate to 1.44 +/- 0.05 for PAN-02 and approximate to 1.45 +/- 0.05 for KPC vs 0.95 +/- 0.10 seconds for surroundings) and significantly higher lactate/pyruvate ratios by hyperpolarized C-13 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-1-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.