Identification of variable stages in murine pancreatic tumors by a multiparametric approach employing hyperpolarized 13 C MRSI, 1 H diffusivity and 1 H T1 MRI

NMR Biomed. 2021 Feb;34(2):e4446. doi: 10.1002/nbm.4446. Epub 2020 Nov 21.

Abstract

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 1 H T1 and T2 measurements, quantitative diffusivity mapping, magnetization transfer (MT) 1 H MRI throughout the abdomen and hyperpolarized 13 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 1 H 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 13 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 1 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.

Keywords: animal model study; body; cancer; diffusion-weighted imaging; hyperpolarized C13; pancreatic cancer; pancreatitis; relaxation methods.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Artifacts
  • Carbon Isotopes
  • Carcinoma, Pancreatic Ductal / diagnostic imaging*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor / transplantation
  • Diffusion
  • Genes, Reporter
  • Luminescent Proteins
  • Magnetic Resonance Imaging / methods*
  • Magnetic Resonance Spectroscopy / methods*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motion
  • Neoplasm Staging
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / pathology
  • Pancreatitis / diagnostic imaging
  • Proton Magnetic Resonance Spectroscopy / methods
  • Red Fluorescent Protein

Substances

  • Carbon Isotopes
  • Luminescent Proteins
  • Carbon-13