High Resolution $^{13}$C MRI With Hyperpolarized Urea: In Vivo $T_{2}$ Mapping and $^{15}$N Labeling Effects

(13)C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [(13)C] urea and [(13) C,(15)N2] urea injected intravenously in rats. (15)N labeling gave large T2 increases both in solution and in vivo due to the elimination of a strong scalar relaxation pathway. The T2 increase was pronounced in the kidney, with [(13) C,(15) N2] urea giving T2 values of 6.3±1.3 s in the cortex and medulla, and 11±2 s in the renal pelvis. The measured T2 in the aorta was 1.3±0.3 s. [(13)C] urea showed shortened T2 values in the kidney of 0.23±0.03 s compared to 0.28±0.03 s measured in the aorta. The enhanced T2 of [(13)C,(15)N2] urea was utilized to generate large signal enhancement by SSFP acquisitions with flip angles approaching the fully refocused regime. Projection images at 0.94 mm in-plane resolution were acquired with both urea isotopes, with [(13)C,(15) N2] urea giving a greater than four-fold increase in signal-to-noise ratio over [(13)C] urea.

[1]  N. Cheng.  Formula for the Viscosity of a Glycerol−Water Mixture , 2008 .

[2]  J. Svensson,et al.  Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C , 2004, Magnetic resonance in medicine.

[3]  T Asakura,et al.  NMR Relaxation Times of Blood: Dependence on Field Strength, Oxidation State, and Cell Integrity , 1987, Journal of computer assisted tomography.

[4]  John Kurhanewicz,et al.  Hyperpolarized 13C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging , 2011, Proceedings of the National Academy of Sciences.

[5]  O. Yu,et al.  NMR relaxation rates and blood oxygenation level , 1995, Magnetic resonance in medicine.

[6]  M. Thaning,et al.  Real-time metabolic imaging. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Lenkinski,et al.  Perfusion imaging with a freely diffusible hyperpolarized contrast agent , 2011, Magnetic resonance in medicine.

[8]  Sarah E Bohndiek,et al.  Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors , 2009, Proceedings of the National Academy of Sciences.

[9]  John Kurhanewicz,et al.  Imaging of blood flow using hyperpolarized [13C]Urea in preclinical cancer models , 2011, Journal of magnetic resonance imaging : JMRI.

[10]  Jan H. Ardenkjær-Larsen,et al.  Molecular imaging with endogenous substances , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Wild,et al.  Variable flip angle schedules in bSSFP imaging of hyperpolarized noble gases , 2012, Magnetic resonance in medicine.

[12]  John Kurhanewicz,et al.  Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. , 2011, Neoplasia.

[13]  D. McCafferty,et al.  Hepatic venous dysregulation contributes to blood volume pooling in cirrhotic rats , 2006, Gut.

[14]  J. Ardenkjær-Larsen,et al.  Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Jürgen Hennig,et al.  Fast multiecho balanced SSFP metabolite mapping of 1H and hyperpolarized 13C compounds , 2009, Magnetic Resonance Materials in Physics, Biology and Medicine.

[16]  Lars E Olsson,et al.  Hyperpolarized 13C MR angiography using trueFISP , 2003, Magnetic resonance in medicine.

[17]  M D Blaufox,et al.  Blood volume in the rat. , 1985, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[18]  Valerie A. Norton,et al.  Ultra-fast three dimensional imaging of hyperpolarized 13C in vivo , 2005, Magnetic Resonance Materials in Physics, Biology and Medicine.

[19]  Jan Henrik Ardenkjaer-Larsen,et al.  Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. , 2006, Cancer research.

[20]  P. Kuchel,et al.  Urea exchange across the human erythrocyte membrane measured using 13C NMR lineshape analysis , 2004, European Biophysics Journal.

[21]  E. G. Finer,et al.  Nuclear magnetic resonance studies of aqueous urea solutions , 1972 .

[22]  C. Collins,et al.  Calculation of radiofrequency electromagnetic fields and their effects in MRI of human subjects , 2011, Magnetic resonance in medicine.

[23]  F. Gallagher,et al.  Hyperpolarized [1-13C]-Ascorbic and Dehydroascorbic Acid: Vitamin C as a Probe for Imaging Redox Status in Vivo , 2011, Journal of the American Chemical Society.

[24]  A. Gryff-Keller,et al.  Scalar relaxation of the second kind: a potential source of information on the dynamics of molecular movements. 1. Investigation of solution reorientation of N-methylpyridone and 1,3-dimethyluracil using measurements of longitudinal relaxation rates in the rotating frame. , 2012, The journal of physical chemistry. A.

[25]  G. Radda,et al.  Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field. , 1982, Biochimica et biophysica acta.

[26]  R. Scott,et al.  Age- and sex-related reference ranges for eight plasma constituents derived from randomly selected adults in a Scottish new town. , 1980, Journal of Clinical Pathology.

[27]  F. Gallagher,et al.  Imaging pH with hyperpolarized 13C , 2011, NMR in biomedicine.

[28]  F. Gallagher,et al.  Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy , 2011, Magnetic resonance in medicine.

[29]  M. Paley,et al.  Steady-state free precession with hyperpolarized 3He: experiments and theory. , 2006, Journal of magnetic resonance.

[30]  John P. Mugler,et al.  Hyperpolarized 129Xe MRI of the human lung , 2013, Journal of magnetic resonance imaging : JMRI.

[31]  Marion I Menzel,et al.  Earth's magnetic field enabled scalar coupling relaxation of 13C nuclei bound to fast-relaxing quadrupolar 14N in amide groups. , 2013, Journal of magnetic resonance.

[32]  W. J. Johnson,et al.  Effects of urea loading in patients with far-advanced renal failure. , 1972, Mayo Clinic proceedings.

[33]  P. Joseph,et al.  Water content and NMR relaxation time gradients in the rabbit kidney. , 1985, Investigative radiology.

[34]  Oskar Axelsson,et al.  MR coronary angiography in pigs with intraarterial injections of a hyperpolarized 13C substance , 2006, Magnetic resonance in medicine.

[35]  F. Ståhlberg,et al.  Perfusion assessment with bolus differentiation: A technique applicable to hyperpolarized tracers , 2004, Magnetic resonance in medicine.

[36]  P. Larson,et al.  Diffusion MR of hyperpolarized 13C molecules in solution. , 2013, The Analyst.

[37]  J. Brahm.  Urea permeability of human red cells , 1983, The Journal of general physiology.

[38]  Klaus Scheffler,et al.  On the transient phase of balanced SSFP sequences , 2003, Magnetic resonance in medicine.

[39]  J. Kurhanewicz,et al.  Hyperpolarized 13C-pyruvate magnetic resonance reveals rapid lactate export in metastatic renal cell carcinomas. , 2013, Cancer research.

[40]  Adolf Pfefferbaum,et al.  T2 relaxation times of 13C metabolites in a rat hepatocellular carcinoma model measured in vivo using 13C‐MRS of hyperpolarized [1‐13C]pyruvate , 2010, NMR in biomedicine.

[41]  E. Purcell,et al.  Effects of Diffusion on Free Precession in Nuclear Magnetic Resonance Experiments , 1954 .

[42]  John M Pauly,et al.  Double spin-echo sequence for rapid spectroscopic imaging of hyperpolarized 13C. , 2007, Journal of magnetic resonance.

[43]  Jan Henrik Ardenkjaer-Larsen,et al.  Dynamic Nuclear Polarization of [1-13C]pyruvic acid at 4.6 tesla. , 2009, Journal of magnetic resonance.

[44]  E. Purcell,et al.  Relaxation Effects in Nuclear Magnetic Resonance Absorption , 1948 .