Use of ¹³C Isotopes in MR Research

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 13}C 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/He¹⁵ 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.