Metabolic MR Imaging //
Science

Goal

Pathological processes influence the metabolic balance of brain and other organs. Often these metabolic changes precede structural alterations in tissue and could therefore give an early warning sign of the developing disease. Our group is interested in developing novel hyperpolarised metabolic MR imaging methods and combining them with advanced 1H MRI to gain a better understanding of potential biomarkers for metabolic diseases in brain and in other organs.

Research interests

  • Applying hyperpolarisation techniques for studying tissue metabolism. Of particular interest are normal and pathological brain and cardiac metabolism
  • Developing novel hyperpolarization techniques

Methodological approach

Magnetic Resonance Spectroscopic Imaging allows non-invasive detection of a range of metabolites offering a window into tissue metabolism. MRSI is inherently insensitive method, however, because only a small fraction of total nuclei provide the observed magnetization (at 9.4 T and room temperature proton polarization is only 31ppm, i.e. only 31 protons out of million contribute to signal. For other nuclei the number is even lower). The high water concentration in tissue (~40 M in human brain) offsets this inherent insensitivity allowing MRI provide detailed anatomical and dynamic images but the situation changes for metabolic imaging where concentrations are much lower (mM-range). Dynamic metabolic imaging using e.g. 13C-labelled molecules suffers particularly from the sensitivity issues limiting its use.

Dynamic nuclear polarisation (DNP) enhances 13C-polarisation levels up to 700,000 ppm leading to a massive increase in 13C sensitivity. The method makes it possible to inject highly polarised marker molecule into a patient and image its metabolic conversion in real-time. The high signal levels remain for up to 2 minutes depending of the used 13C-labelled marker molecule. Hyperpolarised MRSI has shown great promise in cancer imaging where alterations in tumor glycolysis e.g. after therapy, can be observed as changes in lactate signal observed after injection of hyperpolarised pyruvate. Similarly, altered cardiac metabolism can be imaged. A clinical translation of the methodology is on-going.

Kuopio-BIU has pre-clinical Hyperpolariser with adjustable polarisation field 3.35-10.1 T and automated dissolution system capable of providing samples up to tens of ml (HYPERMAG, The Technical University of Denmark). The polariser is situated next to our 9.4 T horizontal imaging magnet with capabilities to image X nuclei. We apply spectroscopy and spectroscopic imaging to study metabolical diseases in rats and mice using 13C-labelled metabolites such as pyruvate. Hyperpolarised experiments are combined with modern 1H imaging techniques to yield a comprehensive picture of the tissue status.

Funding

Academy of Finland

Selected publications

  1. Kettunen MI. Hyperpolarized MRI for Studying Tumor Metabolism. Methods Mol Biol. 2019,1928:409-426.
  2. Serrao EM/Kettunen MI et al. Analysis of 13C and 14C labeling in pyruvate and lactate in tumor and blood of lymphoma-bearing mice injected with 13C- and 14C-labeled pyruvate. NMR Biomed 2018, 31(5):e3901.
  3. Dzien P/Tee SS et al. 13C magnetic resonance spectroscopy measurements with hyperpolarized [1-13C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo. Magn Reson Med 2016, 76(2):391-401.
  4. Serrao EM et al. MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model. Gut 2016, 65(3):465-75.
  5. Rodrigues TB et al. Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose. Nat Med 2014, 20(1):93-7.
  6. Clatworthy MR/Kettunen MI et al. Magnetic resonance imaging with hyperpolarized [1,4-(13)C2]fumarate allows detection of early renal acute tubular necrosis. Proc Natl Acad Sci U S A 2012, 109(33):13374-9.
  7. Gallagher FA/Kettunen MI et al. Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature 2008, 453(7197):940-3.
  8. Day SE/Kettunen MI et al. Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 2007, 13(11):1382-7.