Hot Topics in MRI

A MRI image offers the image of the intrinsic organs and tissue of any living system mainly using 1H- MR principles. 13C and 15N MRI are not often used due to the low natural abundance of these isotopes and thus, low sensitivity. Hyperpolarization in MRI offers the scientific community a technology that overcomes the issue of low sensitivity of the desired nuclei (e.g. 13C, 15N) and allows real time metabolic profiling and detection of biomarkers using stable isotope precursors and quantitative in vivo imaging. These techniques offer several advantages that can be beneficial to clinical imaging research. There are three established technologies:

 Significance of Hyperpolarized 13C, 15N

Hyperpolarization of 13C and 15N containing compounds offers the research community the advantage of direct molecular imaging within a localized region or tissue and aid in understanding the metabolic processes for various diseases. Since there is no significant loss of polarization of 13C, 15N during the dissolution process and any intrinsic metabolic conversion, the decay of the signal is thus a function of the 13C, 15N T1-relaxation and/or metabolic turnover(3,4).

Advantages include:

  • Real time 13C, 15N images using DNP or PHIP
  • Increased sensitivity with S/N ratio enhancements >10,000 times for 13C, 15N
  • Selective 13C, 15N Metabolic Imaging

Products of Interest

  • 489867 L-Alanine-1-13C, 99 atom % 13C
  • 489972 L-Aspartic acid-1-13C, 99 atom % 13C
  • 665223 Acetylene Dicarboxylic acid-1-13C Disodium Salt, 99 atom % 13C
  • 679860 tert-Butan-2-13C, d9-ol , 99 atom % 13C, 98 atom % D
  • 609269 Choline -15N Chloride, 98 atom % 15N
  • 324523 Ethanol-1-13C, 99 atom % 13C
  • 427047 Ethanol-2-13C, 99 atom % 13C
  • 297046 D-Glucose-1-13C, 99 atom % 13C
  • 660655 D-Glucose-1-13C, 99 atom % 13C, S&P tested, 99 atom % 13C
  • 604968 L-Glutamic Acid-1-13C, 99 atom % 13C
  • 696471 4-Oxo-2,2,6,6-Tetramethylpiperidine-1-15N-1-Oxyl, 98 atom % 15N
  • 487740 4-Oxo-TEMPO-d16,1-15N, free radical , 98 atom % D, 98 atom % 15N
  • 677175 Pyruvic –1-13C acid (free acid), 99 atom % 13C
  • 692670 Pyruvic –2-13C acid (free acid), 99 atom % 13C, 99% CP
  • 668656 Sodium Acetate-1-13C, S&P tested, 99 atom % 13C
  • 660310 Sodium Acetate-2-13C, S&P tested, 99 atom % 13C
  • 490709 Sodium Pyruvate-1-13C , 99 atom % 13C
  • 606022 Sodium L-lactate-1-13C Solution, 99 atom % 13C
  • 589209 Sodium L-lactate-2-13C Solution, 99 atom % 13C

Significance of Hyperpolarization using Noble Gases

Acquiring high contrast images using radioactive gases for research and diagnosis of the lungs and other pulmonary disorders has been a challenge for researchers. Hyperpolarization of noble gases such as 3Helium and 129Xenon offers the following benefits in imaging:

  • Provides high contrast images for diagnostic testing in lung imaging
  • Allows rapid dynamic imaging using 3Helium for various ventilation defects
  • Increases the sensitivity of these gases by a factor of 100,000(14).
  • 129Xenon offers potential for imaging of other organs due its diffusion properties after inhalation

Products of Interest

 What is Hyperpolarization?

In the world of imaging “hyperpolarization” refers to a molecule that can be polarized in a magnetic field by artificially creating a non-equilibrium distribution of the nuclei compared to the thermal equilibrium. This is achieved using various techniques and a polarizer instrument. Even though the instrumentation is expensive, this technique offers promising advances in identifying biomarkers and metabolic alterations for various diseases in real time.






 What is DNP (Dynamic Nuclear Polarization)

With advancements in technologies, we can now acquire images of molecules enriched with 13C or 15N label and create image profiles of various metabolic processes. DNP involves mixing the substrate with a substance containing an unpaired electron (or radical) at low temperatures (approaching absolute zero) in a magnetic field. The sample is irradiated with microwaves close to the electron resonance frequency. The process allows the transfer of the polarization (up to 10-30%) from the radical species to the labeled substrate(1,2,5). The technique requires that the 13C or 15N enriched substrate is a water-soluble, endogenous or exogenous metabolite with a long T1 relaxation time in the liquid state(3). One of the limitations that the researchers are trying to overcome is the long duration (30 minutes to few hours).

References:

  1. Golman K, Olsson LE, Axelsson O, Månsson S, Karlsson M, Petersson JS. Molecular imaging using hyperpolarized 13C. Br J Radiol. 2003;76 Spec No 2:S118-27.
  2. Sowerby A. Molecules in Minute detail. Chemistry and Industry- Sept 2005.
  3. The “hype” in hyperpolarized MR: Metabolic imaging u7sing 13C MR. Wolber J, in 't Zandt R, Lerche M. Thaning M, Gtram A, Servin R, Frilund B, Ellner F, Ardenkjaer-Larsen JH, Golman K. ISMRM 2006 Annual Meeting Program.
  4. Månsson S, Johansson E, Magnusson P, Chai CM, Hansson G, Petersson JS, Ståhlberg F, Golman K. 13C imaging-a new diagnostic platform. Eur Radiol. 2006 Jan;16(1):57-67.
  5. Golman K, in 't Zandt R, Thaning M. Real-time metabolic imaging. M Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11270-5.

 What is PHIP (Para Hydrogen Induced Polarization)?

Bowers and Weitekamp initially discovered the technique of using para hydrogen gas to hydrogenate small molecules and observed an enhanced 1H-NMR signal(6). Initially named as PASADENA (Para And Synthesis Allows Dramatically Enhanced Nuclear Alingment), it is also referred as para hydrogen induced polarization (PHIP) and is now used to transfer the polarization to hetronuclei such as 13C or 15N. The non – equilibrium spin orders of the chemically induced para hydrogen molecule are transferred to the NMR visible nuclei (13C or 15N)(7). To achieve hyperpolarization using PHIP, it is necessary to use an unsaturated precursor of the target molecule(8). Recent PHIP experiments involving the use of 13C unsaturated precursors that are metabolically relevant have offered insights into identifying biomarkers for a disease(10). The relatively short time compared to DNP (few seconds to few minutes) needed to achieve hyperpolarization also offers an added advantage to this technique(9,10).

References:

  1. Bowers CR, Weitekamp DP. Parahydrogen and synsthesis allow dramatically enhanced nuclear alignment. J. Am Chem. Soc. 1987;109(18):5541-2
  2. Barkemeyr J, Haake M, Bargon J. Hetro-NMR enhancement via parahydrogen labeling. J.AM Chem Soc. 1995;117(10):2927-8
  3. Goldman M, Jóhannesson H, Axelsson O, Karlsson. Hyperpolarization of 13C through order transfer from parahydrogen: a new contrast agent for MRI. M. Magn Reson Imaging. 2005 Feb;23(2):153-7.
  4. Bhattacharya P, Harris K, Lin AP, Mansson M, Norton VA, Perman WH, Weitekamp DP, Ross BD. Ultra-fast three dimensional imaging of hyperpolarized 13C in vivo. MAGMA. 2005 Nov;18(5):245-56.
  5. Bhattacharya P, Chekmenev EY, Perman WH, Harris KC, Lin AP, Norton VA, Tan CT, Ross BD, Weitekamp DP. Towards hyperpolarized (13)C-succinate imaging of brain cancer. J Magn Reson. 2007 May;186(1):150-5.

 Hyperpolarization using Noble Gas

The challenges of using radioactive gases and obtaining high contrast images of lung for various ventilation disorders are now answered by images taken after inhalation of hyperpolarized noble gases. 3Helium or 129Xenon can be hyperpolarized by optical pumping of the Rubidium (Rb) atom via a spin-exchange collision mechanism(11,12). The use of noble gases for MRI hyperpolarization allows higher contrast images for diagnostic lung imaging. There are also studies conducted to obtain “real-time” images by simultaneously injecting a 13C substrate with administration of 3He(1). The use of 129Xenon also offers the potential for imaging organs other than the lungs for circulatory disorders, due to its diffusion properties in blood and tissues, it gets distributed throughout the body after inhalation)(13,15,16,17).

References:

  1. Happer W. Optical pumping. Rev Mod Phys 1972;44:169–249
  2. Grover BC. Noble-gas NMR detection through noble-gas rubidium hyperfine contact interaction. Phys Rev Lett. 1978;40:391–2.
  3. Salerno M, Altes TA, Mugler JP, Nakatsu M, Hatabu H. and de Lange EE. Hyperpolarized noble gas MR imaging of the lung: Potential clinical applications. European Journal of Radiology, October 2001, Volume 40, Issue 1: 33-44
  4. Möller HE, Chen JX, Saam B, Hagspiel KD, Johnson GA, Altes TA, de Lange EE, Hans-Ulrich Kauczor. MRI of the lungs using hyperpolarized noble gases. Magnetic Resonance in Medicine. 2002 Jun;47(6):1029-51.
  5. Fain SB, Korosec FR, Holmes JH, O'Halloran R, Sorkness RL, Grist TM. Functional lung imaging using hyperpolarized gas MRI. J Magn Reson Imaging. 2007 May;25(5):910-23. Review.
  6. Holmes JH, O'Halloran RL, Brodsky EK, Jung Y, Block WF, Fain SB. 3D hyperpolarized He-3 MRI of ventilation using a multi-echo projection acquisition. Magn Reson Med. 2008 May;59(5):1062-71.