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Rooney CHE, Gamliel A, Shaul D, Tyler DJ, Grist JT, and Katz-Brull R. (2023) Directly bound deuterons increase X-nuclei hyperpolarization using dynamic nuclear polarization. ChemPhysChem 24(18): e202300144.

Read the Paper: DOI: 10.1002/cphc.202300144

Primary Data

Abstract Deuterated 13C sites in sugars (D-glucose and 2-deoxy-Dglucose) showed 6.3-to-17.5-fold higher solid-state dynamic nuclear polarization (DNP) levels than their respective protonated sites at 3.35T. This effect was found to be unrelated to the protonation of the bath. Deuterated 15N in sites bound to exchangeable protons ([15N2]urea) showed a 1.3-fold higher polarization than their respective protonated sites at the same magnetic field. This relatively smaller effect was attributed to incomplete deuteration of the 15N sites due to the solvent mixture. For a 15N site that is not bound to protons or deuterons ([15N]nitrate), deuteration of the bath did not affect the polarization level. These findings suggest a phenomenon related to DNP of X-nuclei directly bound to deuteron(s) as opposed to proton(s). It appears that direct binding to deuterons increases the solid-state DNP polarization level of X-nuclei which are otherwise bound to protons.

Shaul D, Lev-Cohain N, Sapir G, Sosna J, Gomori JM, Joskowicz L, Katz-Brull R. (2023) Real-time influence of intracellular acidification and NHE1 inhibition on in-cell pyruvate metabolism in the perfused mouse heart – A 31P- and hyperpolarized 13C-NMR study. NMR Biomed. e4993.

Read the Paper: DOI:10.1002/nbm.4993

Primary Data

Abstract Disruption of acid–base balance is linked to various diseases and conditions. In the heart, intracellular acidification is associated with heart failure, maladaptive cardiac hypertrophy, and myocardial ischemia. Previously, we have reported that the ratio of the in-cell lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) activities is correlated with cardiac pH. To further characterize the basis for this correlation, these in-cell activities were investigated under induced intracellular acidification without and with Na+/H+ exchanger (NHE1) inhibition by zoniporide. Male mouse hearts (n = 30) were isolated and perfused retrogradely. Intracellular acidification was performed in two ways: (1) with the NH4Cl prepulse methodology; and (2) by combining the NH4Cl prepulse with zoniporide. 31P NMR spectroscopy was used to determine the intracellular cardiac pH and to quantify the adenosine triphosphate and phosphocreatine content. Hyperpolarized [1-13C]pyruvate was obtained using dissolution dynamic nuclear polarization. 13C NMR spectroscopy was used to monitor hyperpolarized [1-13C]pyruvate metabolism and determine enzyme activities in real time at a temporal resolution of a few seconds using the product-selective saturating excitation approach. The intracellular acidification induced by the NH4Cl prepulse led to reduced LDH and PDH activities (16% and 39%, respectively). This finding is in line with previous evidence of reduced myocardial contraction and therefore reduced metabolic activity upon intracellular acidification. Concomitantly, the LDH/PDH activity ratio increased with the reduction in pH, as previously reported. Combining the NH4Cl prepulse with zoniporide led to a greater reduction in LDH activity (29%) and to increased PDH activity (+40%). These changes resulted in a surprising decrease in the LDH/PDH ratio, as opposed to previous predictions. Zoniporide alone (without intracellular acidification) did not change these enzyme activities. A possible explanation for the enzymatic changes observed during the combination of the NH4Cl prepulse and NHE1 inhibition may be related to mitochondrial NHE1 inhibition, which likely negates the mitochondrial matrix acidification. This effect, combined with the increased acidity in the cytosol, would result in an enhanced H+ gradient across the mitochondrial membrane and a temporarily higher pyruvate transport into the mitochondria, thereby increasing the PDH activity at the expense of the cytosolic LDH activity. These findings demonstrate the complexity of in-cell cardiac metabolism and its dependence on intracellular acidification. This study demonstrates the capabilities and limitations of hyperpolarized [1-13C] pyruvate in the characterization of intracellular acidification as regards cardiac pathologies.


Katz-Brull R. (2022) Tolerance of rodents to an intravenous bolus injection of sodium nitrate in a high-concentration. Biology 11(5): 794.

DOI: 10.3390/biology11050794 [PDF]


Gamliel A, Shaul D, Gomori JM, and Katz-Brull R. (2022) Signal enhancement of hyperpolarized 15N sites in solution - Increase in solid-state polarization at 3.35T and prolongation of relaxation in deuterated water mixtures. NMR Biomed. e4787

DOI: 10.1002/nbm.4787 [PDF]

Shaul D, Grieb B, Lev-Cohain N, Sosna J, Gomori JM, and Katz-Brull R. (2022) Accumulation of 3-APP in the ex vivo brain - observed by 31P NMR. NMR Biomed. e4721. DOI: 10.1002/nbm.4721 [PDF]



Sapir G#, Steinberg DJ#, Aqeilan RI, and Katz-Brull R. (2021) Real-time non-invasive and direct determination of lactate dehydrogenase activity in cerebral organoids – a new method to characterize the metabolism of brain organoids? # - equal contribution. Pharmaceuticals 14: 878. DOI: 10.3390/ph14090878 [PDF]

Grieb B, Uppala S, Sapir G, Shaul D, Gomori JM, and Katz-Brull R. (2021) Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices.

Sci. Rep. 11:10211. DOI: 10.1038/s41598-021-89534-4 [PDF]


Sapir G, Shaul D, Lev-Cohain N, Sosna J, Gomori JM, and Katz-Brull R. (2021) LDH and PDH activities in the ischemic brain and the effect of reperfusion – An ex vivo MR study in rat brain slices using hyperpolarized [1-13C]pyruvate.

Metabolites 11, 210. DOI: 10.3390/metabo11040210 [PDF]


Shaul D, Grieb B, Sapir G, Uppala S, Sosna J, Gomori JM, and Katz-Brull R. (2021) The metabolic representation of ischemia in rat brain slices – a hyperpolarized 13C magnetic resonance study.

NMR Biomed. e4509. DOI: 10.1002/nbm.4509 [Publisher]


Lev-Cohain N#, Sapir G#, Uppala S, Nardi-Schreiber A, Goldberg SN, Adler-Levy Y, Sosna J, Gomori JM, and Katz-Brull R.# Equal contribution. (2021) Differentiation of heterogeneous mouse liver from HCC by hyperpolarized 13C magnetic resonance.

Sci. 3(1):8. DOI: 10.3390/sci3010008 [PDF]


Shaul D, Azar A, Sapir G, Uppala S, Nardi-Schreiber A, Gamliel A, Sosna J, Gomori JM, and Katz-Brull R. (2021) Correlation between LDH/PDH activities ratio and tissue pH in the perfused mouse heart – a potential non-invasive indicator of cardiac pH provided by hyperpolarized magnetic resonance.

NMR Biomed. 34:e4444. DOI: 10.1002/nbm.4444 [Publisher]




Uppala S, Gamliel A, Sapir G, Sosna J, Gomori JM, and Katz-Brull R. (2020) Observation of glucose-6-phosphate anomeric exchange in real-time using dDNP hyperpolarised NMR.

RSC Adv. 10:41197-41120. DOI: 10.1039/d0ra08022e [PDF]


Kreis F, Wright AJ, Somai V, Katz-Brull R, Brindle KM. (2020) Increasing the sensitivity of hyperpolarized [15N2]urea detection by serial transfer of polarization to spin-coupled protons.

Magn. Reson. Med. 84:1844–1856. DOI: 10.1002/mrm.28241 [PDF]


Harris T, Uppala S, Lev-Cohain N, Adler-Levy Y, Shaul D, Nardi-Schreiber A, Sapir G, Azar A, Gamliel A, Sosna J, Gomori JM, and Katz-Brull R. (2020) Hyperpolarized product selective saturating-excitations for determination of changes in metabolic reaction rates in real-time.

NMR Biomed. e4189. DOI: 10.1002/nbm.4189 [Publisher]


Harris T, Gamliel A, Nardi-Schreiber A, Sosna J, Gomori JM, and Katz-Brull R. (2020) The effect of Gadolinium doping in [13C6,2H7]glucose formulations on 13C dynamic nuclear polarization at 3.35T.

ChemPhysChem 21:1–7. DOI: 10.1002/cphc.201900946 [Publisher]



Sapir G, Harris T, Uppala S, Nardi-Schreiber A, Sosna J, Gomori JM, and Katz-Brull R. (2019) [13C6,D8]2-deoxyglucose phosphorylation by hexokinase shows selectivity for the b-anomer.

Sci. Rep. 9:19683. DOI: 10.1038/s41598-019-56063-0 [PDF]


Adler-Levy Y#, Nardi-Schreiber A#, Harris T, Shaul D, Uppala S, Sapir G, Lev-Cohain N, Sosna J, Goldberg SN, Gomori JM, and Katz-Brull R. (2019) In-cell determination of lactate dehydrogenase activity in a luminal breast cancer model – ex vivo investigation of excised xenograft tumor slices using dDNP hyperpolarized [1-13C]pyruvate.

Sensors 19(9): 2089. # - Equal contribution. DOI: 10.3390/s19092089 [PDF]


Uppala S, Gamliel A, Harris T, Sosna J, Gomori JM, Jerschow A, and Katz-Brull R. (2019) 1H-decoupling and isotopic labeling for the measurement of the longitudinal relaxation time of hyperpolarized 13C-methylenes in choline analogs.

Isr. J. Chem. 59: 1–7. DOI: 10.1002/ijch.201900016 [Publisher]


Lev-Cohain N, Sapir G, Harris T, Azar A, Gamliel A, Nardi-Schreiber A, Uppala S, Sosna J, Gomori JM, and Katz-Brull R (2019) Real-time ALT and LDH activities determined in viable precision-cut mouse liver slices using hyperpolarized [1-13C]pyruvate – implications for studies on biopsied liver tissues.

NMR Biomed. 32:e4043. DOI: 10.1002/nbm.4043 [Publisher]


Gamliel A, Uppala S, Sapir G, Harris T, Nardi-Schreiber A, Shaul D, Sosna J, Gomori JM, and Katz-Brull R. (2019) Hyperpolarized [15N]nitrate as a potential long lived hyperpolarized contrast agent for MRI.

J. Magn. Reson. 299: 188–195. DOI: 10.1016/j.jmr.2019.01.001 [Publisher]




Harris T, Gamliel A, Sosna J, Gomori JM, and Katz-Brull R. (2018) Impurities of [1-13C]pyruvic acid and a method to minimize their signals for hyperpolarized pyruvate metabolism studies.

Appl. Magn. Reson. 49(10):1085–1098. DOI: 10.1007/s00723-018-1030-1 [PDF]


Harris T, Azar A, Sapir G, Gamliel A, Nardi-Schreiber A, Sosna J, Gomori JM, and Katz-Brull R. (2018) Real-time ex-vivo measurement of brain metabolism using hyperpolarized [1-13C]pyruvate.

Sci. Rep. 8:9564. DOI: 10.1038/s41598-018-27747-w [PDF]


Harris T, Gamliel A, Uppala S, Nardi-Schreiber A, Sosna J, Gomori JM, and Katz-Brull R. (2018) Long-lived 15N hyperpolarization and rapid relaxation as a potential basis for repeated first pass perfusion imaging – marked effects of deuteration and temperature.

ChemPhysChem 19: 2148– 2152. DOI: 10.1002/cphc.201800261 [Publisher]




Hövener J-B, Pravdivtsev AN, Kidd B, Bowers CR, Glöggler S, Kovtunov KV, Plaumann M, Katz-Brull R, Buckenmaier K, Jerschow A, Reineri F, Theis T, Shchepin RV, Wagner S, Bhattacharya P, Zacharias NM, and Chekmenev EY (2017) Parahydrogen-based Hyperpolarization for Biomedicine.

Angew. Chem. Int. Ed. 57: 11140–11162. DOI: 10.1002/anie.201711842 [Publisher]


Nardi-Schreiber A, Sapir G, Gamliel A, Kakhlon O, Sosna J, Gomori JM, Meiner V, Lossos A, and Katz-Brull R. (2017) Defective ATP breakdown activity related to an ENTPD1 gene mutation demonstrated using 31P NMR.

Chem. Commun. 53: 9121 – 9124. DOI: 10.1039/c7cc00426e [Publisher]


Nardi-Schreiber A, Gamliel A, Harris T, Sapir G, Sosna J, Gomori JM, and Katz-Brull R. (2017) Biochemical phosphates observed using hyperpolarized 31P in physiological aqueous solutions.

Nat. Commun. 8(1): 341. DOI: 10.1038/s41467-017-00364-3 [PDF]


Grigoletto J, Puka K, Gamliel A, Komisarov D, Katz-Brull R, Richter-Landsberg C, Sharon R (2017) Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss.

Acta Neuropathol. Commun. 5(1):37. DOI: 10.1186/s40478-017-0439-3 [PDF]




Banne E, Meiner V, Shaag A, Katz-Brull R, Gamliel A, Korman S, Horowitz S, Plesser M, Frumkin A, Zilkha A, Kapuller V, Arbell D, Cohen E, Eventov-Friedman S. (2016) Transaldolase deficiency: A new case expands the phenotypic spectrum.

J. Inherit. Metab. Dis. Rep. 26: 31–36. DOI: 10.1007/8904_2015_474 [PDF]




Martin M, Albensi B, Cross A, Katz-Brull R, Thiessen J, King S, Lin A. (2015) New concepts in magnetic resonance as applied to cellular and in vivo applications.

Magn. Reson. Insights 8(Suppl 1):49-52 (Editorial). DOI: 10.4137/MRI.S37997 [PDF]


Gamliel A, Chendler N, Gomori JM, Sosna J, and Katz-Brull R. (2015) The sensitivity of phosphocholine 13C chemical shifts to pH.

Appl. Magn. Reson. 47(1): 111-120. DOI:10.1007/s00723-015-0734-8 [PDF]


Jupin M, Gamliel A, Hovav Y, Sosna J, Gomori JM, and Katz-Brull R. (2015) Application of the steady-state variable nutation angle method for faster determinations of long T1s – an approach useful for the design of hyperpolarized MR molecular probes.

Magn. Reson. Insights 8(Suppl 1):41-47.  DOI: 10.4137/MRI.S29358 [PDF]


Friesen-Waldner L, Wade T, Thind K, Chen AP, Gomori JM, Sosna J, McKenzie CA, and Katz-Brull R. (2015) Hyperpolarized choline as an MR imaging molecular probe: feasibility of imaging in a rat model.

J. Magn. Reson. Imaging 41(4):917-23. DOI: 10.1002/jmri.24659 [PDF]



Friesen–Waldner LJ, Wiens CN, Wade TP, Thind K, Sinclair KP, Hovav Y, Gomori JM, Sosna J, McKenzie CA, and Katz-Brull R. (2014) Direct enzyme-substrate affinity determination by real-time hyperpolarized 13C-MRS.

Chem. Commun. 50 (89) 13801-13804. DOI: 10.1039/c4cc05418k [Publisher]


Allouche-Arnon H, Hovav Y, Friesen-Waldner L, Sosna J, Gomori JM, Vega S, and Katz-Brull R. (2014) Quantification of rate constants for successive enzymatic reactions with DNP hyperpolarized MR.

NMR Biomed. 27 (6), 656-662. DOI: 10.1002/nbm.3102 [Publisher]




Allouche-Arnon H, Gamliel A, Sosna J, Gomori JM, Katz-Brull R. (2013) In vitro visualization of betaine aldehyde synthesis and oxidation using hyperpolarized magnetic resonance spectroscopy.

Chem. Commun. 49 (63), 7076-7078. DOI: 10.1039/c3cc42542h [Publisher]


Allouche-Arnon H, Wade T, Friesen-Waldner L, Miller VN, Gomori JM, Katz-Brull R#, McKenzie CA#. (2013) In vivo magnetic resonance imaging of glucose – initial experience.

Contrast Media Mol. Imaging 8(1):72-82. # - Equal contribution. DOI: 10.1002/cmmi.1497 [PDF]




Allouche-Arnon H, Lerche MH, Karlsson M, Lenkinski RE, and Katz-Brull R. (2011) Deuteration of a molecular probe for DNP hyperpolarization – a new approach and validation for choline chloride.

Contrast Media Mol. Imaging 6(6): 499–506. DOI: 10.1002/cmmi.452 [PDF]


Allouche-Arnon H, Gamliel A, Barzilay CM, Nalbandian R, Gomori JM, Karlsson M, Lerche MH, and Katz-Brull R. (2011) A hyperpolarized choline molecular probe for monitoring acetylcholine synthesis.

Contrast Media Mol. Imaging 6(3):139–147. DOI: 10.1002/cmmi.418 [PDF]




Gamliel A, Allouche-Arnon H, Nalbandian R, Barzilay CM, Gomori JM, Katz-Brull R. (2010) An apparatus for production of isotopically and spin enriched hydrogen for induced polarization studies.

Appl. Magn. Reson. 39:329–345. DOI: 10.1007/s00723-010-0161-9 [PDF]


Edvardson S, Korman SH, Livne A, Shaag A, Saada A, Nalbandian R, Allouche-Arnon H, Gomori JM, and Katz-Brull R. (2010) L-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.

Molec. Genetics Metabol. 101(2-3):228-32. DOI: 10.1016/j.ymgme.2010.06.021 [Publisher]




Lima MA, Katz-Brull R, Lenkinski RE, Nunez R, Feinrider D, and Koralnik IJ. (2007) Remission of progressive multifocal leukoencephalopathy and primary central nervous system lymphoma in an HIV-infected patient.

Eur. J. Neurol. 14(6):598-602. DOI: 10.1111/j.1468-1331.2007.01820.x [Publisher]




Katz-Brull R, Alsop DC, Marquis RP, and Lenkinski RE. (2006) Limits on activation induced temperature and metabolic changes in the human primary visual cortex.

Magn. Reson. Med. 56(2):348-355. DOI: 10.1002/mrm.20972 [PDF]




Katz-Brull R, Koudinov AR, and Degani H. (2005) Direct detection of brain acetylcholine synthesis by magnetic resonance spectroscopy.

Brain Res. 1048(1-2):202-210. DOI: 10.1016/j.brainres.2005.04.080 [Publisher]


Katz-Brull R, Rofsky NM, Morrin M, Pedrosa I, George DJ, Michaelson MD, Marquis RP, Maril M, Noguera C, and Lenkinski RE. (2005) Decrease in free cholesterol and fatty acids unsaturation in renal cell carcinoma, demonstrated by breath hold magnetic resonance spectroscopy.

Am. J. Physiol.-Renal 288(4):F637-641. DOI: 10.1152/ajprenal.00140.2004 [PDF]




Katz-Brull R, Lenkinski RE, Du Pasquier RA, and Koralnik IJ. (2004) Elevation of myo-Inositol is associated with disease containment in progressive multifocal leukoencephalopathy.

Neurology 63(5):897-900. DOI: 10.1212/01.wnl.0000137420.58346.9f [Publisher]


Katz-Brull R and Lenkinski RE. (2004) Frame-by-frame PRESS 1H-MRS of the brain at 3T: The effects of physiological motion.

Magn. Reson. Med. 51:184-187. DOI: 10.1002/mrm.10670 [PDF]




Katz-Brull R, Rofsky NM, and Lenkinski RE. (2003) Breathhold abdominal and thoracic proton magnetic resonance spectroscopy at 3T.

Magn. Reson. Med. 50:461-467. DOI: 10.1002/mrm.10560 [PDF]




Katz-Brull R, Lavin PT, and Lenkinski RE. (2002) The clinical utility of proton MRS in characterizing breast lesions.

JNCI-J. Natl. Cancer. I. (16):1197-1203. (Review and Meta-Analysis) DOI: 10.1093/jnci/94.16.1197 [PDF]


Katz-Brull R, Seger D, Rivenson-Segal D, Rushkin E, and Degani H. (2002) Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline-ether-phospholipid synthesis. Cancer Res. 62(7):1966-1970. PMID: 11929812 [PDF]


Katz-Brull R, Koudinov A, and Degani H. (2002) Choline in the aging brain.

Brain Res. 951(2):158-165. DOI: 10.1016/s0006-8993(02)03155-4 [Publisher]




Katz-Brull R, Margalit R, Degani H. (2001) Differential routing of choline in implanted breast cancer and normal organs.

Magn. Reson. Med. 46: 31-38. DOI: 10.1002/mrm.1157 [PDF]



Katz-Brull R, Margalit R, Bendel P, Degani H. (1998) Choline metabolism in breast cancer; 2H, 13C & 31P NMR studies of cells and tumors.

MAGMA Magn. Reson. Materials Physics Biol. Med. 6: 44-52. DOI: 10.1007/BF02662511 [PDF]




Katz-Brull R and Degani H. (1996) Kinetics of choline transport and phosphorylation in human breast cancer cells; NMR application of the zero trans method.

Anticancer Res. 16: 1375-1380. PMID: 8694504 [PDF]

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