MRS/MRI

Use of 13C Isotopes

Use of 13C Isotopes in MR Research
Dr. Pratip Bhattacharya
California Institute of Technology and Huntington Medical Research Institutes, Pasadena, California

Stable isotopes have played a very useful role in MR research which involves both MRI and MRS. Of the various NMR active nuclei, 13C, 15N 31P, 23Na and 19F are the most biologically relevant. 13C MR research is the most comprehensive of all of them because of the versatile availability of organic molecules in the biological systems.

13C MRS : The power of 13C MRS lies in its unique chemical specificity, enabling detection and quantification of metabolic intermediates which would not be so readily monitored using conventional radiochemical techniques. Improvements in NMR technologies, now permits us to obtain in vivo localized (1) and non-localized (2) 13C NMR spectra from rodent and human brain with similar quantity to those obtained earlier only under in vitro conditions, providing in this way a wealth of information on neurotransmitter recycling, cerebral bioenergetics in situ. In vivo and in vitro13C MRS was also accomplished in liver, skeletal muscle, heart, adipose tissue, kidney and pancreatic islets yielding a variety of invaluable information. Furthermore, 13C NMR has applied in clinical scene and has received FDA approval. Novel 13C neurochemical data has contributed to the understanding of Alzheimer’ Disease, Canavan’s Disease, mitochondrial and hepatic encephalopathy, epilepsy, childhood leuco dystrophy, schizophrenia normal brain development and lipid uptake (3,4,5). Both in vivo ,in vitro and clinical 13C NMR methods employing labeled glucose and acetate, methionine, propionate, fatty acids have provided invaluable information on various aspects of modern biochemistry and neurochemistry, including the activity of the neuronal and glial TCA cycles and the operation of the intracellular glutamate-glutamine-GABA cycle in vivo (6), on carbohydrate metabolism and cerebral glycogen turnover (7), on cerebral metabolic pathways like pyruvate recycling system (8), on the exchange of metabolities between neuronal and glial cells (9), on the subcellular compartmentation of neurotransmitter amino acids (10), dynamic isotopomer analysis (11) etc. However 13C MRS is severely limited by its inherent low sensitivity and the clinical applications remain at low level because of the considerable cost of the 13C enriched isotopes.

Hyperpolarization: The sensitivity issue associated with the in vivo 13C NMR can be largely overcome by hyperpolarization techniques. Hyperpolarization involves several techniques like PHIP-PASADENA (12,13), DNP (14), Xe/He(15) and are currently coming of age where 13C labeled molecules can be polarized exceeding the thermal equilibrium polarization by several orders of magnitude (SNR>10,000), which can then be employed to yield high resolution ultra fast MR images and spectra. Even though these techniques are under intense research, 13C isotopes will be used for various in vivo applications like high speed and high resolution angiography /morphology, quantitative and regional perfusion, metabolic mapping, molecular imaging, tissue pathology etc.

Pratip Bhattacharya, PhD is the James G. Boswell Fellow at California Institute of Technology and Huntington Medical Research Institute, Pasadena. His research includes 13C MRS, development of hyperpolarization techniques and its applications in chemistry, biology and in vivo systems.

References

  1. Blu¨ml S, Hwang JH, Moreno A, Ross BD., (2000) J. Magn. Reson. 143, 292-298.
  2. Gruetter R, Adriany G, Choi IY, Henry PG, Lei H, Oz G., (2003) NMR Biomed. 16, 313-338.
  3. Ross BD, Lin AP, Harris KC, Bhattacharya P, Schweinsburg BC., (2003) NMR Biomed. 16, 358-369.
  4. Hwang JH, Blu¨ml S, Leaf A, Ross BD. (2003) NMR Biomed.16, 160-167.
  5. Harris K, Lin AP, Bhattacharya P, Tran T, Wong W, Ross BD., (2004) Proceedings of First International Symposium of N-Acetyl Aspartate NIH, Bethesda, Maryland.
  6. Rothman DL, Behar KL, Hyder F, Shulman RG. A., (2003) Rev. Physiol. 65, 401–427.
  7. Gruetter R. (2002) Neurochem. Int. 41, 143–154.
  8. Cruz F, Cerdan S., (1999) NMR Biomed.12, 451–462.
  9. Sonnewald U, Qu H, Aschner, M., (2002) J. Pharmac. Exp. Ther. 301, 1–6.
  10. Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A. Glia, (2001) 35, 246–252.
  11. Henry PG, Oz G, Provencher S, Gruetter R. (2003) NMR Biomed.16, 400-412.
  12. Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K., (2003) Proc Natl. Acad Sci U S A 100, 10158-63.
  13. Bhattacharya P, Weitekamp D, Harris K, Lin AP, Ross BD., (2004) Abstract of the 21st ESMRMB Meeting.
  14. Golman K, Ardenaer-Larsen JH, Petersson JS, Mansson S, Leunbach I. (2003) Proc Natl. Acad Sci U S A 100, 10435-439.
  15. Cherubini A, Payne GS, Leach MO, Bifone A., (2003) Chem. Phys. Lett. 371, 640-644