Hyperpolarized C-13 MRI
Hyperpolarized carbon-13 (13C or C-13) MRI is an investigational magnetic resonance imaging technique that uses tracers/probes containing carbon-13 to interrogate metabolic pathways.
Carbon-13 is a naturally occurring, stable isotope of carbon that is magnetically active, with a spin quantum number of 1/2 (like the proton, 1H), allowing its detection through magnetic resonance. Its natural abundance is low (~1%) compared to the dominant isotope carbon-12, so tracer compounds are synthesized and then isotopically enriched for the form containing carbon-13 at a particular position (usually to 99%).
The sensitivity of detection of carbon-13 in vivo is nevertheless low compared to conventional proton MRI because of a lower gyromagnetic ratio and, more importantly, the much lower concentration of the administered tracer compound compared to naturally occurring water protons. To overcome the low receptivity, carbon-13 labeled compounds are prepared by a dynamic nuclear polarization technique, which transiently increases the proportion of spins aligned with rather than against the magnetic field and therefore increases the MR signal.
Dynamic nuclear polarization is achieved in a polarizer, wherein the tracer is mixed with a source of unpaired electrons (the free radical trityl) that are polarized in a magnetic field (e.g. 3-5 T) at low temperature (e.g. 1 Kelvin). The polarization of the electrons is transferred to the carbon-13 upon exposure to microwave radiation. The sample is then rapidly thawed and reconstituted in a biologically acceptable solution before administration into the subject.
Following this process, the degree of polarization of the tracer is much higher than would be achievable in normal operating conditions (30-40% polarization, compared to 2.5 parts per million at 3 T at room temperature), thus the term "hyperpolarized" 1. The polarization decays toward its thermal equilibrium at a rate governed by T1 (spin-lattice) relaxation time of the carbon-13 nucleus, so the enhanced MR signal is only available for a few minutes. Thus, the target biological processes of uptake and metabolism as well as the imaging acquisition must occur rapidly.
The most widely studied tracer is [1-13C]pyruvate (i.e., pyruvate labeled with carbon-13 at the first carbon position). This molecule can be metabolized in one of several relevant pathways to lactate, alanine, bicarbonate, or acetyl-coenzyme A. The carbon-13 spectra can then be imaged to determine the relative concentrations of these metabolites, which can serve as biomarkers. For example, cancer cells have elevated lactate production (Warburg effect) 2.
- 1. Wang ZJ, Ohliger MA, Larson PEZ, Gordon JW, Bok RA, Slater J, Villanueva-Meyer JE, Hess CP, Kurhanewicz J, Vigneron DB. Hyperpolarized C MRI: State of the Art and Future Directions. (2019) Radiology. 291 (2): 273-284. doi:10.1148/radiol.2019182391 - Pubmed
- 2. Kurhanewicz J, Vigneron DB, Ardenkjaer-Larsen JH, Bankson JA, Brindle K, Cunningham CH, Gallagher FA, Keshari KR, Kjaer A, Laustsen C, Mankoff DA, Merritt ME, Nelson SJ, Pauly JM, Lee P, Ronen S, Tyler DJ, Rajan SS, Spielman DM, Wald L, Zhang X, Malloy CR, Rizi R. Hyperpolarized C MRI: Path to Clinical Translation in Oncology. (2019) Neoplasia (New York, N.Y.). 21 (1): 1-16. doi:10.1016/j.neo.2018.09.006 - Pubmed