Advertisement

Molecular Imaging and Biology

, Volume 20, Issue 6, pp 902–918 | Cite as

Metabolic and Molecular Imaging with Hyperpolarised Tracers

  • Jason Graham Skinner
  • Luca Menichetti
  • Alessandra Flori
  • Anna Dost
  • Andreas Benjamin Schmidt
  • Markus Plaumann
  • Ferdia Aiden Gallagher
  • Jan-Bernd Hövener
Review Article
  • 569 Downloads

Abstract

Since reaching the clinic, magnetic resonance imaging (MRI) has become an irreplaceable radiological tool because of the macroscopic information it provides across almost all organs and soft tissues within the human body, all without the need for ionising radiation. The sensitivity of MR, however, is too low to take full advantage of the rich chemical information contained in the MR signal. Hyperpolarisation techniques have recently emerged as methods to overcome the sensitivity limitations by enhancing the MR signal by many orders of magnitude compared to the thermal equilibrium, enabling a new class of metabolic and molecular X-nuclei based MR tracers capable of reporting on metabolic processes at the cellular level. These hyperpolarised (HP) tracers have the potential to elucidate the complex metabolic processes of many organs and pathologies, with studies so far focusing on the fields of oncology and cardiology. This review presents an overview of hyperpolarisation techniques that appear most promising for clinical use today, such as dissolution dynamic nuclear polarisation (d-DNP), parahydrogen-induced hyperpolarisation (PHIP), Brute force hyperpolarisation and spin-exchange optical pumping (SEOP), before discussing methods for tracer detection, emerging metabolic tracers and applications and progress in preclinical and clinical application.

Key Words

Imaging Magnetic resonance imaging MRI Magnetic resonance spectroscopy MRS Hyperpolarisation Metabolic imaging Molecular imaging DNP Parahydrogen Xenon 

Notes

Acknowledgements

We gratefully thank the European Society for Molecular Imaging for their support and the possibility of establishing a study group for Hyperpolarisation as a platform for scientific exchange within the society and beyond.

Funding Information

This study was supported by Marie Sklodowska-Curie grant no. 642773 (JGS, AD, JBH); CNR-Fondazione Toscana Gabriele Monasterio, and the Italian Multi-sited Multi-Modal Molecular Imaging site of Eurobioimaging in Pisa (LM, AF); Heinrich-Böll-Stiftung grant no. P131623 (ABS); DFG BE 1824/12-1 (MP); Cancer Research UK and the National Institute of Health Research Biomedical Research Centre (FG); DFG Emmy Noether Programme, award no. HO-4604/2-1, HO-4604/2-2 the Faculty of Medicine of Kiel University, EXC 306 and DFG GRK 2154 Materials for Brain (JBH).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Xu V, Chan H, Lin AP et al (2008) MR spectroscopy in diagnosis and neurological decision-making. Semin Neurol 28:407–422PubMedGoogle Scholar
  2. 2.
    Ardenkjær-Larsen JH, Fridlund B, Gram A et al (2003) Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci 100:10158–10163PubMedGoogle Scholar
  3. 3.
    Walker TG, Happer W (1997) Spin-exchange optical pumping of noble-gas nuclei. Rev Mod Phys 69:629–642Google Scholar
  4. 4.
    Bowers CR, Weitekamp DP (1987) Parahydrogen and synthesis allow dramatically enhanced nuclear alignment. J Am Chem Soc 109:5541–5542Google Scholar
  5. 5.
    Kurhanewicz J, Vigneron DB, Brindle K et al (2011) Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia 13:81–97PubMedPubMedCentralGoogle Scholar
  6. 6.
    Comment A, Merritt ME (2014) Hyperpolarized magnetic resonance as a sensitive detector of metabolic function. Biochemistry (Mosc) 53:7333–7357Google Scholar
  7. 7.
    Keshari KR, Wilson DM (2014) Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization. Chem Soc Rev 43:1627–1659PubMedGoogle Scholar
  8. 8.
    Schroeter A, Rudin M, Gianolio E et al (2017) MRI. In: Small animal imaging. Springer, Heidelberg, Dordrecht, London, New York, Berlin, pp 227–324Google Scholar
  9. 9.
    Hövener J-B, Lange T, Leibfritz D (2016) Metabolic magnetic resonance. In: Samii A, Nabavi A, Fahlbusch R (eds) Visualization of the brain and its pathologies—technical and neurosurgical aspects. Uelvesbüll, Der Andere Verlag, pp 3–32Google Scholar
  10. 10.
    Bastiaansen JAM, Cheng T, Mishkovsky M et al (2013) In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by 13C turnover from hyperpolarized [1-13C]acetate to [1-13C]acetylcarnitine. Biochim Biophys Acta BBA - Gen Subj 1830:4171–4178Google Scholar
  11. 11.
    Chattergoon N, Martínez-Santiesteban F, Handler WB et al (2013) Field dependence of T 1 for hyperpolarized [1-13C]pyruvate. Contrast Media Mol Imaging 8:57–62PubMedGoogle Scholar
  12. 12.
    Cheng T, Mishkovsky M, Bastiaansen JAM et al (2013) Automated transfer and injection of hyperpolarized molecules with polarization measurement prior to in vivo NMR. NMR Biomed 26:1582–1588PubMedGoogle Scholar
  13. 13.
    Bowen S, Hilty C (2010) Rapid sample injection for hyperpolarized NMR spectroscopy. Phys Chem Chem Phys 12:5766–5770PubMedGoogle Scholar
  14. 14.
    Shang H, Skloss T, von Morze C et al (2016) Handheld electromagnet carrier for transfer of hyperpolarized carbon-13 samples: electromagnet carrier for hyperpolarized 13 C samples. Magn Reson Med 75:917–922PubMedGoogle Scholar
  15. 15.
    Adams RW, Aguilar JA, Atkinson KD et al (2009) Reversible interactions with Para-hydrogen enhance NMR sensitivity by polarization transfer. Science 323:1708–1711PubMedGoogle Scholar
  16. 16.
    Hirsch ML, Smith BA, Mattingly M et al (2015) Transport and imaging of brute-force 13C  hyperpolarization. J Magn Reson 261:87–94PubMedGoogle Scholar
  17. 17.
    Driehuys B, Cates GD, Miron E et al (1996) High-volume production of laser-polarized 129 Xe. Appl Phys Lett 69:1668–1670Google Scholar
  18. 18.
    Nikolaou P, Coffey AM, Walkup LL et al (2013) Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI. Proc Natl Acad Sci 110:14150–14155PubMedGoogle Scholar
  19. 19.
    Atsarkin VA, Kessenikh AV (2012) Dynamic nuclear polarization in solids: the birth and development of the many-particle concept. Appl Magn Reson 43:7–19Google Scholar
  20. 20.
    Pinto LF, Marín-Montesinos I, Lloveras V et al (2017) NMR signal enhancement of >50000 times in fast dissolution dynamic nuclear polarization. Chem Commun 53:3757–3760Google Scholar
  21. 21.
    Hall DA, Maus DC, Gerfen GJ et al (1997) Polarization-enhanced NMR spectroscopy of biomolecules in frozen solution. Science 276:930–932PubMedGoogle Scholar
  22. 22.
    Jähnig F, Kwiatkowski G, Ernst M (2016) Conceptual and instrumental progress in dissolution DNP. J Magn Reson 264:22–29PubMedGoogle Scholar
  23. 23.
    Macholl S, Jóhannesson H, Henrik Ardenkjaer-Larsen J (2010) Trityl biradicals and 13C dynamic nuclear polarization. Phys Chem Chem Phys 12:5804–5817PubMedGoogle Scholar
  24. 24.
    Guarin D, Marhabaie S, Rosso A et al (2017) Characterizing thermal mixing dynamic nuclear polarization via cross-talk between spin reservoirs. J Phys Chem Lett 8:5531–5536PubMedGoogle Scholar
  25. 25.
    Wenckebach WT (2017) Dynamic nuclear polarization via thermal mixing: beyond the high temperature approximation. J Magn Reson 277:68–78PubMedGoogle Scholar
  26. 26.
    Hovav Y, Feintuch A, Vega S (2013) Theoretical aspects of dynamic nuclear polarization in the solid state—spin temperature and thermal mixing. Phys Chem Chem Phys 15:188–203PubMedGoogle Scholar
  27. 27.
    Colombo Serra S, Rosso A, Tedoldi F (2012) Electron and nuclear spin dynamics in the thermal mixing model of dynamic nuclear polarization. Phys Chem Chem Phys 14:13299–13308Google Scholar
  28. 28.
    Ardenkjaer-Larsen JH, Macholl S, Jóhannesson H (2008) Dynamic nuclear polarization with Trityls at 1.2 K. Appl Magn Reson 34:509–522Google Scholar
  29. 29.
    Vuichoud B, Bornet A, de Nanteuil F et al (2016) Filterable agents for hyperpolarization of water, metabolites, and proteins. Chem – Eur J 22:14696–14700PubMedGoogle Scholar
  30. 30.
    Ardenkjaer-Larsen JH, Leach AM, Clarke N et al (2011) Dynamic nuclear polarization polarizer for sterile use intent. NMR Biomed 24:927–932PubMedGoogle Scholar
  31. 31.
    Lipsø KW, Bowen S, Rybalko O, Ardenkjær-Larsen JH (2017) Large dose hyperpolarized water with dissolution-DNP at high magnetic field. J Magn Reson 274:65–72PubMedGoogle Scholar
  32. 32.
    Cudalbu C, Comment A, Kurdzesau F et al (2010) Feasibility of in vivo 15N MRS detection of hyperpolarized 15N labeled choline in rats. Phys Chem Chem Phys 12:5818–5823PubMedGoogle Scholar
  33. 33.
    Cassidy MC, Chan HR, Ross BD et al (2013) In vivo magnetic resonance imaging of hyperpolarized silicon particles. Nat Nanotechnol 8:363–368PubMedGoogle Scholar
  34. 34.
    Lumata L, Merritt M, Malloy C et al (2012) Fast dissolution dynamic nuclear polarization NMR of 13C-enriched 89Y-DOTA complex: experimental and theoretical considerations. Appl Magn Reson 43:69–79Google Scholar
  35. 35.
    Ardenkjaer-Larsen JH, Laustsen C, Bowen S, Rizi R (2014) Hyperpolarized H2O MR angiography: hyperpolarized 1H2O MR angiography. Magn Reson Med 71:50–56PubMedGoogle Scholar
  36. 36.
    Comment A, Jannin S, Hyacinthe J-N et al (2010) Hyperpolarizing gases via dynamic nuclear polarization and sublimation. Phys Rev Lett 105:018104PubMedGoogle Scholar
  37. 37.
    Lee Y, Zeng H, Ruedisser S et al (2012) Nuclear magnetic resonance of hyperpolarized fluorine for characterization of protein–ligand interactions. J Am Chem Soc 134:17448–17451PubMedGoogle Scholar
  38. 38.
    van Heeswijk RB, Uffmann K, Comment A et al (2009) Hyperpolarized lithium-6 as a sensor of nanomolar contrast agents. Magn Reson Med 61:1489–1493PubMedPubMedCentralGoogle Scholar
  39. 39.
    Balzan R, Mishkovsky M, Simonenko Y et al (2016) Hyperpolarized 6Li as a probe for hemoglobin oxygenation level. Contrast Media Mol Imaging 11:41–46PubMedGoogle Scholar
  40. 40.
    Nardi-Schreiber A, Gamliel A, Harris T et al (2017) Biochemical phosphates observed using hyperpolarized 31P in physiological aqueous solutions. Nat Commun 8:341PubMedPubMedCentralGoogle Scholar
  41. 41.
    Eichhorn TR, Takado Y, Salameh N et al (2013) Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging. Proc Natl Acad Sci 110:18064–18069PubMedGoogle Scholar
  42. 42.
    Capozzi A, Hyacinthe J-N, Cheng T et al (2015) Photoinduced nonpersistent radicals as polarizing agents for X-nuclei dissolution dynamic nuclear polarization. J Phys Chem C 119:22632–22639Google Scholar
  43. 43.
    Capozzi A, Cheng T, Boero G et al (2017) Thermal annihilation of photo-induced radicals following dynamic nuclear polarization to produce transportable frozen hyperpolarized 13C-substrates. Nat Commun 8:15757PubMedPubMedCentralGoogle Scholar
  44. 44.
    Batel M, Krajewski M, Weiss K et al (2012) A multi-sample 94GHz dissolution dynamic-nuclear-polarization system. J Magn Reson 214:166–174PubMedGoogle Scholar
  45. 45.
    Aggarwal R, Vigneron DB, Kurhanewicz J (2017) Hyperpolarized 1-[13C]-pyruvate magnetic resonance imaging detects an early metabolic response to androgen ablation therapy in prostate cancer. Eur Urol 72:1028–1029PubMedGoogle Scholar
  46. 46.
    Nelson SJ, Kurhanewicz J, Vigneron DB et al (2013) Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C]pyruvate. Sci Transl Med 5:198ra108 198ra108PubMedPubMedCentralGoogle Scholar
  47. 47.
    Park I, Larson PEZ, Gordon JW et al (2018) Development of methods and feasibility of using hyperpolarized carbon-13 imaging data for evaluating brain metabolism in patient studies. Magn Reson Med 80:864–873PubMedGoogle Scholar
  48. 48.
    Cunningham CH, Lau JY, Chen AP, et al. (2016) Hyperpolarized 13C metabolic MRI of the human heart: initial experience. Circ Res 119:1177–1182PubMedPubMedCentralGoogle Scholar
  49. 49.
    Plainchont B, Berruyer P, Dumez J-N et al (2018) Dynamic nuclear polarization opens new perspectives for NMR spectroscopy in analytical chemistry. Anal Chem 90:3639–3650PubMedGoogle Scholar
  50. 50.
    Yoshihara HAI, Can E, Karlsson M et al (2016) High-field dissolution dynamic nuclear polarization of [1-13C]pyruvic acid. Phys Chem Chem Phys 18:12409–12413PubMedGoogle Scholar
  51. 51.
    Yoon D, Dimitriadis AI, Soundararajan M et al (2018) High-field liquid-state dynamic nuclear polarization in microliter samples. Anal Chem 90:5620–5626PubMedGoogle Scholar
  52. 52.
    Capozzi A, Karlsson M, Petersen JR et al (2018) Liquid-state 13C polarization of 30% through photoinduced nonpersistent radicals. J Phys Chem C 122:7432–7443Google Scholar
  53. 53.
    Wang X, McKay JE, Lama B et al (2018) Gadolinium based endohedral metallofullerene Gd2@C79N as a relaxation boosting agent for dissolution DNP at high fields. Chem Commun 54:2425–2428Google Scholar
  54. 54.
    Wagner S (2014) Conversion rate of Para-hydrogen to ortho-hydrogen by oxygen: implications for PHIP gas storage and utilization. Magn Reson Mater Phys Biol Med 27:195–199Google Scholar
  55. 55.
    Natterer J, Bargon J (1997) Parahydrogen induced polarization. Prog Nucl Magn Reson Spectrosc 31:293–315Google Scholar
  56. 56.
    Kuhn LT (2013) Hyperpolarization methods in NMR spectroscopy. Springer, Berlin, HeidelbergGoogle Scholar
  57. 57.
    Pravica MG, Weitekamp DP (1988) Net NMR alignment by adiabatic transport of parahydrogen addition products to high magnetic field. Chem Phys Lett 145:255–258Google Scholar
  58. 58.
    Hövener J-B, Schwaderlapp N, Borowiak R et al (2014) Toward biocompatible nuclear hyperpolarization using signal amplification by reversible exchange: quantitative in situ spectroscopy and high-field imaging. Anal Chem 86:1767–1774PubMedPubMedCentralGoogle Scholar
  59. 59.
    Jóhannesson H, Axelsson O, Karlsson M (2004) Transfer of para-hydrogen spin order into polarization by diabatic field cycling. Comptes Rendus Phys 5:315–324Google Scholar
  60. 60.
    Bommerich U, Trantzschel T, Mulla-Osman S et al (2010) Hyperpolarized 19F-MRI: parahydrogen-induced polarization and field variation enable 19F-MRI at low spin density. Phys Chem Chem Phys 12:10309PubMedGoogle Scholar
  61. 61.
    Goldman M, Jóhannesson H, Axelsson O, Karlsson M (2005) Hyperpolarization of 13C through order transfer from parahydrogen: a new contrast agent for MRI. Magn Reson Imaging 23:153–157PubMedGoogle Scholar
  62. 62.
    Bär S, Lange T, Leibfritz D et al (2012) On the spin order transfer from parahydrogen to another nucleus. J Magn Reson 225:25–35PubMedGoogle Scholar
  63. 63.
    Bhattacharya P, Chekmenev EY, Reynolds WF et al (2011) PHIP hyperpolarized MR receptor imaging in vivo: a pilot study of 13C imaging of atheroma in mice. NMR Biomed 24:1023–1028PubMedPubMedCentralGoogle Scholar
  64. 64.
    Waddell KW, Coffey AM, Chekmenev EY (2011) In situ detection of PHIP at 48 mT: demonstration using a centrally controlled polarizer. J Am Chem Soc 133:97–101PubMedGoogle Scholar
  65. 65.
    Coffey AM, Shchepin RV, Truong ML et al (2016) Open-source automated parahydrogen hyperpolarizer for molecular imaging using 13 C metabolic contrast agents. Anal Chem 88:8279–8288PubMedPubMedCentralGoogle Scholar
  66. 66.
    Coffey AM, Shchepin RV, Feng B et al (2017) A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer. J Magn Reson 284:115–124PubMedPubMedCentralGoogle Scholar
  67. 67.
    Hövener J-B, Bär S, Leupold J et al (2013) A continuous-flow, high-throughput, high-pressure parahydrogen converter for hyperpolarization in a clinical setting: a high-throughput parahydrogen converter for hyperpolarization. NMR Biomed 26:124–131PubMedGoogle Scholar
  68. 68.
    Schmidt AB, Berner S, Schimpf W et al (2017) Liquid-state carbon-13 hyperpolarization generated in an MRI system for fast imaging. Nat Commun 8:14535PubMedPubMedCentralGoogle Scholar
  69. 69.
    Kovtunov KV, Kidd BE, Salnikov OG et al (2017) Imaging of biomolecular NMR signals amplified by reversible exchange with parahydrogen inside an MRI scanner. J Phys Chem C 121:25994–25999Google Scholar
  70. 70.
    Buckenmaier K, Rudolph M, Back C et al (2017) SQUID-based detection of ultra-low-field multinuclear NMR of substances hyperpolarized using signal amplification by reversible exchange. Sci Rep 7:13431PubMedPubMedCentralGoogle Scholar
  71. 71.
    Barskiy DA, Kovtunov KV, Koptyug IV et al (2014) The feasibility of formation and kinetics of NMR signal amplification by reversible exchange (SABRE) at high magnetic field (9.4 T). J Am Chem Soc 136:3322–3325PubMedPubMedCentralGoogle Scholar
  72. 72.
    Knecht S, Kiryutin AS, Yurkovskaya AV, Ivanov KL (2018) Mechanism of spontaneous polarization transfer in high-field SABRE experiments. J Magn Reson 287:74–81PubMedGoogle Scholar
  73. 73.
    Mewis RE, Green RA, Cockett MCR et al (2015) Strategies for the hyperpolarization of acetonitrile and related ligands by SABRE. J Phys Chem B 119:1416–1424PubMedGoogle Scholar
  74. 74.
    Moreno KX, Nasr K, Milne M et al (2015) Nuclear spin hyperpolarization of the solvent using signal amplification by reversible exchange (SABRE). J Magn Reson San Diego Calif 1997 257:15–23Google Scholar
  75. 75.
    Olaru AM, Roy SS, Lloyd LS et al (2016) Creating a hyperpolarised pseudo singlet state through polarisation transfer from parahydrogen under SABRE. Chem Commun 52:7842–7845Google Scholar
  76. 76.
    Olaru AM, Burt A, Rayner PJ et al (2016) Using signal amplification by reversible exchange (SABRE) to hyperpolarise 119Sn and 29Si NMR nuclei. Chem Commun 52:14482–14485Google Scholar
  77. 77.
    Roy SS, Appleby KM, Fear EJ, Duckett SB (2018) SABRE-Relay: a versatile route to hyperpolarization. J Phys Chem Lett 9:1112–1117PubMedPubMedCentralGoogle Scholar
  78. 78.
    Reineri F, Boi T, Aime S (2015) ParaHydrogen induced polarization of 13C carboxylate resonance in acetate and pyruvate. Nat Commun 6:5858PubMedGoogle Scholar
  79. 79.
    Cavallari E, Carrera C, Aime S, Reineri F (2017) 13C MR hyperpolarization of lactate by using paraHydrogen and metabolic transformation in vitro. Chem Eur J 23:1200–1204PubMedGoogle Scholar
  80. 80.
    Cavallari E, Carrera C, Aime S, Reineri F (2018) Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate. J Magn Reson 289:12–17PubMedGoogle Scholar
  81. 81.
    Trantzschel T, Bernarding J, Plaumann M et al (2012) Parahydrogen induced polarization in face of keto–enol tautomerism: proof of concept with hyperpolarized ethanol. Phys Chem Chem Phys 14:5601PubMedGoogle Scholar
  82. 82.
    Körner M, Sauer G, Heil A et al (2013) PHIP-label: parahydrogen-induced polarization in propargylglycine-containing synthetic oligopeptides. Chem Commun 49:7839Google Scholar
  83. 83.
    Cavallari E, Carrera C, Sorge M et al (2018) The 13C hyperpolarized pyruvate generated by parahydrogen detects the response of the heart to altered metabolism in real time. Sci Rep 8:8366PubMedPubMedCentralGoogle Scholar
  84. 84.
    Koptyug IV, Kovtunov KV, Burt SR et al (2007) Para-hydrogen-induced polarization in heterogeneous hydrogenation reactions. J Am Chem Soc 129:5580–5586PubMedGoogle Scholar
  85. 85.
    Stefan G, Grunfeld AM, Ertas YN et al (2015) A nanoparticle catalyst for heterogeneous phase para-hydrogen-induced polarization in water. Angew Chem Int Ed 54:2452–2456Google Scholar
  86. 86.
    Francesca R, Alessandra V, Silvano E et al (2011) Use of labile precursors for the generation of hyperpolarized molecules from hydrogenation with parahydrogen and aqueous-phase extraction. Angew Chem Int Ed 50:7350–7353Google Scholar
  87. 87.
    Hövener J-B, Chekmenev EY, Harris KC et al (2009) Quality assurance of PASADENA hyperpolarization for 13C biomolecules. Magn Reson Mater Phys Biol Med 22:123–134Google Scholar
  88. 88.
    Zacharias NM, Chan HR, Sailasuta N et al (2012) Real-time molecular imaging of tricarboxylic acid cycle metabolism in vivo by hyperpolarized 1-13C diethyl succinate. J Am Chem Soc 134:934–943PubMedGoogle Scholar
  89. 89.
    Shchepin RV, Pham W, Chekmenev EY (2014) Dephosphorylation and biodistribution of 1-13C-phospholactate in vivo. J Label Compd Radiopharm 57:517–524Google Scholar
  90. 90.
    Schmidt AB, Berner S, Braig M et al (2018) In vivo 13C-MRI using SAMBADENA. PLoS One 13:e0200141PubMedPubMedCentralGoogle Scholar
  91. 91.
    Zeng H, Xu J, Gillen J et al (2013) Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid. J Magn Reson 237:73–78PubMedPubMedCentralGoogle Scholar
  92. 92.
    Hoevener J-B, Schwaderlapp N, Lickert T et al (2013) A hyperpolarized equilibrium for magnetic resonance. Nat Commun 4:2946Google Scholar
  93. 93.
    Colell JFP, Emondts M, Logan AWJ et al (2017) Direct hyperpolarization of Nitrogen-15 in aqueous media with parahydrogen in reversible exchange. J Am Chem Soc 139:7761–7767PubMedPubMedCentralGoogle Scholar
  94. 94.
    Theis T, Truong ML, Coffey AM et al (2015) Microtesla SABRE enables 10% nitrogen-15 nuclear spin polarization. J Am Chem Soc 137:1404–1407PubMedPubMedCentralGoogle Scholar
  95. 95.
    Colell JFP, Logan AWJ, Zhou Z et al (2017) Generalizing, extending, and maximizing nitrogen-15 hyperpolarization induced by parahydrogen in reversible exchange. J Phys Chem C 121:6626–6634Google Scholar
  96. 96.
    Rovedo P, Knecht S, Bäumlisberger T et al (2016) Molecular MRI in the Earth’s magnetic field using continuous hyperpolarization of a biomolecule in water. J Phys Chem B 120:5670–5677PubMedGoogle Scholar
  97. 97.
    Hövener J-B, Knecht S, Schwaderlapp N et al (2014) Continuous re-hyperpolarization of nuclear spins using parahydrogen: theory and experiment. ChemPhysChem 15:2451–2457PubMedGoogle Scholar
  98. 98.
    Frossati G (1998) Polarization of 3He, 2D and (eventually) 129Xe using low temperatures and high magnetic fields. J Low Temp Phys 111:521–532Google Scholar
  99. 99.
    Krjukov EV, O’Neill JD, Owers-Bradley JR (2005) Brute force polarization of 129Xe. J Low Temp Phys 140:397–408Google Scholar
  100. 100.
    Hirsch ML, Kalechofsky N, Belzer A et al (2015) Brute-force hyperpolarization for NMR and MRI. J Am Chem Soc 137:8428–8434PubMedGoogle Scholar
  101. 101.
    Cates GD, Benton DR, Gatzke M et al (1990) Laser production of large nuclear-spin polarization in frozen xenon. Phys Rev Lett 65:2591–2594PubMedGoogle Scholar
  102. 102.
    Gatzke M, Cates GD, Driehuys B et al (1993) Extraordinarily slow nuclear spin relaxation in frozen laser-polarized 129Xe. Phys Rev Lett 70:690–693PubMedGoogle Scholar
  103. 103.
    Chupp TE, Coulter KP (1985) Polarization of 21Ne by spin exchange with optically pumped Rb vapor. Phys Rev Lett 55:1074–1077PubMedGoogle Scholar
  104. 104.
    Pavlovskaya GE, Cleveland ZI, Stupic KF et al (2005) Hyperpolarized krypton-83 as a contrast agent for magnetic resonance imaging. Proc Natl Acad Sci U S A 102:18275–18279PubMedPubMedCentralGoogle Scholar
  105. 105.
    Stupic KF, Cleveland ZI, Pavlovskaya GE, Meersmann T (2011) Hyperpolarized 131Xe NMR spectroscopy. J Magn Reson 208:58–69PubMedPubMedCentralGoogle Scholar
  106. 106.
    Chupp TE, Wagshul ME, Coulter KP et al (1987) Polarized, high-density, gaseous 3He targets. Phys Rev C 36:2244–2251Google Scholar
  107. 107.
    Spence MM, Rubin SM, Dimitrov IE et al (2001) Functionalized xenon as a biosensor. Proc Natl Acad Sci 98:10654–10657PubMedGoogle Scholar
  108. 108.
    Schröder L, Lowery TJ, Hilty C et al (2006) Molecular imaging using a targeted magnetic resonance hyperpolarized biosensor. Science 314:446–449PubMedGoogle Scholar
  109. 109.
    Desvaux H, Gautier T, Le Goff G et al (2000) Direct evidence of a magnetization transfer between laser-polarized xenon and protons of a cage-molecule in water. Eur Phys J D 12:289–296Google Scholar
  110. 110.
    Bai Y, Wang Y, Goulian M et al (2014) Bacterial spore detection and analysis using hyperpolarized 129Xe chemical exchange saturation transfer (hyper-CEST) NMR. Chem Sci 5:3197–3203PubMedPubMedCentralGoogle Scholar
  111. 111.
    Hoffmann HC, Brunner E (2015) Studies of metal–organic frameworks: xenon for probing framework porosity, breathing and gating behavior. In: Meersmann T, Brunner E (eds) Hyperpolarized xenon-129 magnetic resonance: concepts, production, techniques, and applications. Royal Society Of Chemistry, Cambridge, pp 234–248Google Scholar
  112. 112.
    Dregely I, Mugler JP, Ruset IC et al (2011) Hyperpolarized Xenon-129 gas-exchange imaging of lung microstructure: first case studies in subjects with obstructive lung disease. J Magn Reson Imaging 33:1052–1062PubMedPubMedCentralGoogle Scholar
  113. 113.
    Rao M, Stewart NJ, Norquay G et al (2016) High resolution spectroscopy and chemical shift imaging of hyperpolarized 129Xe dissolved in the human brain in vivo at 1.5 tesla. Magn Reson Med 75:2227–2234PubMedPubMedCentralGoogle Scholar
  114. 114.
    Branca RT, He T, Zhang L et al (2014) Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI. Proc Natl Acad Sci U S A 111:18001–18006PubMedPubMedCentralGoogle Scholar
  115. 115.
    Shapiro MG, Ramirez RM, Sperling LJ et al (2014) Genetically encoded reporters for hyperpolarized xenon magnetic resonance imaging. Nat Chem 6:629–634PubMedGoogle Scholar
  116. 116.
    Nikolaou P, Coffey AM, Walkup LL et al (2014) XeNA: an automated ‘open-source’ 129Xe hyperpolarizer for clinical use. Magn Reson Imaging 32:541–550PubMedPubMedCentralGoogle Scholar
  117. 117.
    Ebner L, He M, Virgincar RS et al (2017) Hyperpolarized 129Xenon magnetic resonance imaging to quantify regional ventilation differences in mild to moderate asthma: a prospective comparison between semiautomated ventilation defect percentage calculation and pulmonary function tests. Investig Radiol 52:120Google Scholar
  118. 118.
    Freeman MS, Emami K, Driehuys B (2014) Characterizing and modeling the efficiency limits in large-scale production of hyperpolarized 129Xe. Phys Rev A 90:023406PubMedPubMedCentralGoogle Scholar
  119. 119.
    Burant A, Branca RT (2016) Diffusion-mediated 129Xe gas depolarization in magnetic field gradients during continuous-flow optical pumping. J Magn Reson 273:124–129PubMedPubMedCentralGoogle Scholar
  120. 120.
    Goodson BM, Whiting N, Newton H, et al. (2015) Chapter 6: Spin-exchange optical pumping at high xenon densities and laser fluxes: principles and practice. In: Hyperpolarized Xenon-129 magnetic resonance. 4:96–121Google Scholar
  121. 121.
    Jeong K, Netirojjanakul C, Munch HK et al (2016) Targeted molecular imaging of cancer cells using MS2-based 129Xe NMR. Bioconjug Chem 27:1796–1801PubMedGoogle Scholar
  122. 122.
    Hane FT, Li T, Smylie P et al (2017) In vivo detection of cucurbit [6] uril, a hyperpolarized xenon contrast agent for a xenon magnetic resonance imaging biosensor. Sci Rep 7:41027PubMedPubMedCentralGoogle Scholar
  123. 123.
    Leupold J, Månsson S, Petersson JS et al (2009) Fast multiecho balanced SSFP metabolite mapping of 1H and hyperpolarized 13C compounds. Magn Reson Mater Phys Biol Med 22:251–256Google Scholar
  124. 124.
    Larson PEZ, Hu S, Lustig M et al (2011) Fast dynamic 3D MR spectroscopic imaging with compressed sensing and multiband excitation pulses for hyperpolarized 13C studies. Magn Reson Med 65:610–619PubMedGoogle Scholar
  125. 125.
    Daniels CJ, McLean MA, Schulte RF et al (2016) A comparison of quantitative methods for clinical imaging with hyperpolarized 13C-pyruvate. NMR Biomed 29:387–399PubMedPubMedCentralGoogle Scholar
  126. 126.
    Day SE, Kettunen MI, Cherukuri MK et al (2011) Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1-13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Magn Reson Med 65:557–563PubMedGoogle Scholar
  127. 127.
    Gallagher FA, Kettunen MI, Day SE et al (2008) Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature 453:940–943PubMedGoogle Scholar
  128. 128.
    Bohndiek SE, Kettunen MI, Hu D et al (2011) Hyperpolarized [1-13C]-ascorbic and dehydroascorbic acid: vitamin C as a probe for imaging redox status in vivo. J Am Chem Soc 133:11795–11801PubMedPubMedCentralGoogle Scholar
  129. 129.
    Larson PEZ, Hurd RE, Kerr AB et al (2013) Perfusion and diffusion sensitive 13C stimulated-echo MRSI for metabolic imaging of cancer. Magn Reson Imaging 31:635–642PubMedGoogle Scholar
  130. 130.
    Swisher CL, Larson PEZ, Kruttwig K et al (2013) Quantitative measurement of cancer metabolism using stimulated echo hyperpolarized carbon-13 MRS. Magn Reson Med 71:1–11PubMedGoogle Scholar
  131. 131.
    Lau AZ, Chen AP, Barry J et al (2013) Reproducibility study for free-breathing measurements of pyruvate metabolism using hyperpolarized 13C in the heart. Magn Reson Med 69:1063–1071PubMedGoogle Scholar
  132. 132.
    Hu S, Lustig M, Chen AP et al (2008) Compressed sensing for resolution enhancement of hyperpolarized 13C flyback 3D-MRSI. J Magn Reson 192:258–264PubMedPubMedCentralGoogle Scholar
  133. 133.
    Flori A, Frijia F, Lionetti V et al (2012) DNP methods for cardiac metabolic imaging with hyperpolarized [1-13C]pyruvate large dose injection in pigs. Appl Magn Reson 43:299–310Google Scholar
  134. 134.
    Schulte RF, Sperl JI, Weidl E et al (2013) Saturation-recovery metabolic-exchange rate imaging with hyperpolarized [1-13C] pyruvate using spectral-spatial excitation. Magn Reson Med 69:1209–1216PubMedGoogle Scholar
  135. 135.
    von Morze C, Larson PEZ, Hu S et al (2011) Imaging of blood flow using hyperpolarized [13C]urea in preclinical cancer models. J Magn Reson Imaging 33:692–697Google Scholar
  136. 136.
    Månsson S, Petersson JS, Scheffler K (2012) Fast metabolite mapping in the pig heart after injection of hyperpolarized 13C-pyruvate with low-flip angle balanced steady-state free precession imaging. Magn Reson Med 68:1894–1899PubMedGoogle Scholar
  137. 137.
    Hu S, Lustig M, Balakrishnan A et al (2010) 3D compressed sensing for highly accelerated hyperpolarized 13C MRSI with in vivo applications to transgenic mouse models of cancer. Magn Reson Med 63:312–321PubMedPubMedCentralGoogle Scholar
  138. 138.
    Shin PJ, Larson PEZ, Ohliger MA et al (2014) Calibrationless parallel imaging reconstruction based on structured low-rank matrix completion. Magn Reson Med 72:959–970PubMedGoogle Scholar
  139. 139.
    Schmidt R, Frydman L (2014) New spatiotemporal approaches for fully refocused, multislice ultrafast 2D MRI. Magn Reson Med 71:711–722PubMedPubMedCentralGoogle Scholar
  140. 140.
    Zhou L, Cabrera ME, Okere IC et al (2006) Regulation of myocardial substrate metabolism during increased energy expenditure: insights from computational studies. Am J Physiol-Heart Circ Physiol 291:H1036–H1046PubMedGoogle Scholar
  141. 141.
    Gallagher FA, Bohndiek SE, Kettunen MI et al (2011) Hyperpolarized 13C MRI and PET: in vivo tumor biochemistry. J Nucl Med 52:1333–1336PubMedGoogle Scholar
  142. 142.
    Albers MJ, Bok R, Chen AP et al (2008) Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Cancer Res 68:8607–8615PubMedPubMedCentralGoogle Scholar
  143. 143.
    Day SE, Kettunen MI, Gallagher FA et al (2007) Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 13:1382–1387PubMedGoogle Scholar
  144. 144.
    Yoshihara HAI, Bastiaansen JAM, Berthonneche C et al (2015) An intact small animal model of myocardial ischemia-reperfusion: characterization of metabolic changes by hyperpolarized 13C MR spectroscopy. Am J Physiol Heart Circ Physiol 309:H2058–H2066PubMedGoogle Scholar
  145. 145.
    Klaes G, Stefan PJ, Peter M et al (2008) Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med 59:1005–1013Google Scholar
  146. 146.
    Luca M, Francesca F, Alessandra F et al (2012) Assessment of real-time myocardial uptake and enzymatic conversion of hyperpolarized [1-13C]pyruvate in pigs using slice selective magnetic resonance spectroscopy. Contrast Media Mol Imaging 7:85–94Google Scholar
  147. 147.
    Schroeder MA, Lau AZ, Chen AP et al (2013) Hyperpolarized 13C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart. Eur J Heart Fail 15:130–140PubMedGoogle Scholar
  148. 148.
    Kennedy BWC, Kettunen MI, Hu D-E, Brindle KM (2012) Probing lactate dehydrogenase activity in tumors by measuring hydrogen/deuterium exchange in hyperpolarized l-[1-13C,U-2H]lactate. J Am Chem Soc 134:4969–4977PubMedPubMedCentralGoogle Scholar
  149. 149.
    Shchepin RV, Coffey AM, Waddell KW, Chekmenev EY (2014) Parahydrogen induced polarization of 1-13C-phospholactate-d2 for biomedical imaging with >30,000,000-fold NMR signal enhancement in water. Anal Chem 86:5601–5605PubMedPubMedCentralGoogle Scholar
  150. 150.
    Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129PubMedGoogle Scholar
  151. 151.
    Merritt ME, Harrison C, Storey C et al (2007) Hyperpolarized 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR. Proc Natl Acad Sci 104:19773–19777PubMedGoogle Scholar
  152. 152.
    Schroeder MA, Cochlin LE, Heather LC et al (2008) In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Natl Acad Sci 105:12051–12056PubMedGoogle Scholar
  153. 153.
    Atherton HJ, Dodd MS, Heather LC et al (2011) The role of PDH inhibition in the development of hypertrophy in the hyperthyroid rat heart: a combined MRI and hyperpolarized MRS study. Circulation 123:2552–2561PubMedPubMedCentralGoogle Scholar
  154. 154.
    Chen AP, Lau JYC, Alvares RDA, Cunningham H (2014) Using [1-13C]lactic acid for hyperpolarized 13C MR cardiac studies. Magn Reson Med 73:2087–2093PubMedGoogle Scholar
  155. 155.
    Gallagher FA, Kettunen MI, Brindle KM (2011) Imaging pH with hyperpolarized 13C. NMR Biomed 24:1006–1015PubMedGoogle Scholar
  156. 156.
    Gallagher FA, Sladen H, Kettunen MI et al (2015) Carbonic anhydrase activity monitored in vivo by hyperpolarized 13C-magnetic resonance spectroscopy demonstrates its importance for pH regulation in tumors. Cancer Res 75:4109–4118PubMedPubMedCentralGoogle Scholar
  157. 157.
    Rider OJ, Tyler DJ (2013) Clinical implications of cardiac hyperpolarized magnetic resonance imaging. J Cardiovasc Magn Reson 15:93PubMedPubMedCentralGoogle Scholar
  158. 158.
    Düwel S, Hundshammer C, Gersch M et al (2017) Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid. Nat Commun 8:15126PubMedPubMedCentralGoogle Scholar
  159. 159.
    Hu S, Chen AP, Zierhut ML et al (2009) In vivo Carbon-13 dynamic MRS and MRSI of normal and fasted rat liver with hyperpolarized 13C-pyruvate. Mol Imaging Biol 11:399–407PubMedPubMedCentralGoogle Scholar
  160. 160.
    Hu S, Zhu M, Yoshihara HAI et al (2011) In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-13C]alanine. Magn Reson Imaging 29:1035–1040PubMedPubMedCentralGoogle Scholar
  161. 161.
    Atherton HJ, Dodd MS, Heather LC et al (2011) Role of pyruvate dehydrogenase inhibition in the development of hypertrophy in the hyperthyroid rat HeartClinical perspective: a combined magnetic resonance imaging and hyperpolarized magnetic resonance spectroscopy study. Circulation 123:2552–2561PubMedPubMedCentralGoogle Scholar
  162. 162.
    Josan S, Park JM, Hurd R et al. (2013) In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate. NMR Biomed 26:1680–1687.PubMedGoogle Scholar
  163. 163.
    Chen AP, Hurd RE, Schroeder MA et al (2011) Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-13C2]pyruvate in vivo. NMR Biomed 25:305–311PubMedPubMedCentralGoogle Scholar
  164. 164.
    Dodd MS, Ball DR, Schroeder MA et al (2012) In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart. Cardiovasc Res 95:69–76PubMedPubMedCentralGoogle Scholar
  165. 165.
    Schroeder MA, Ali MA, Hulikova A et al (2013) Extramitochondrial domain rich in carbonic anhydrase activity improves myocardial energetics. Proc Natl Acad Sci 110:E958–E967PubMedGoogle Scholar
  166. 166.
    Schroeder MA, Atherton HJ, Dodd MS et al (2012) The cycling of acetyl-coenzyme a through acetylcarnitine buffers cardiac substrate SupplyClinical perspective: a hyperpolarized 13C magnetic resonance study. Circ Cardiovasc Imaging 5:201–209PubMedPubMedCentralGoogle Scholar
  167. 167.
    Schroeder MA, Atherton HJ, Ball DR et al (2009) Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB J 23:2529–2538PubMedPubMedCentralGoogle Scholar
  168. 168.
    Ulrich K, Gringeri CV, Giaime R et al (2014) Metabolic imaging of hyperpolarized [1-13C]acetate and [1-13C]acetylcarnitine—investigation of the influence of dobutamine induced stress. Magn Reson Med 74:1011–1018Google Scholar
  169. 169.
    Alessandra F, Matteo L, Francesca F et al (2014) Real-time cardiac metabolism assessed with hyperpolarized [1-13C]acetate in a large-animal model. Contrast Media Mol Imaging 10:194–202Google Scholar
  170. 170.
    Mishkovsky M, Comment A, Gruetter R (2012) In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance. J Cereb Blood Flow Metab 32:2108–2113PubMedPubMedCentralGoogle Scholar
  171. 171.
    Mikkelsen EFR, Mariager CØ, Nørlinger T et al (2017) Hyperpolarized [1-13C]-acetate renal metabolic clearance rate mapping. Sci Rep 7:16002PubMedPubMedCentralGoogle Scholar
  172. 172.
    Jensen PR, Peitersen T, Karlsson M et al (2009) Tissue-specific short chain fatty acid metabolism and slow metabolic recovery after ischemia from hyperpolarized NMR in vivo. J Biol Chem 284:36077–36082PubMedPubMedCentralGoogle Scholar
  173. 173.
    Bastiaansen JAM, Cheng T, Lei H et al (2015) Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized 13C magnetic resonance. J Mol Cell Cardiol 87:129–137PubMedGoogle Scholar
  174. 174.
    Jensen RP, Meier S, Ardenkjær-Larsen JH et al (2009) Detection of low-populated reaction intermediates with hyperpolarized NMR. Chem Commun 0:5168–5170Google Scholar
  175. 175.
    Yoshihara H, Bastiaansen JA, Karlsson M et al (2015) Myocardial fatty acid metabolism probed with hyperpolarized [1-13C]octanoate. J Cardiovasc Magn Reson 17:O101PubMedCentralGoogle Scholar
  176. 176.
    Ball DR, Ben R, Dodd MS et al (2014) Hyperpolarized butyrate: a metabolic probe of short chain fatty acid metabolism in the heart. Magn Reson Med 71:1663–1669PubMedGoogle Scholar
  177. 177.
    Bastiaansen JA, Merritt ME, Comment A (2015) Real time measurement of myocardial substrate selection in vivo using hyperpolarized 13C magnetic resonance. J Cardiovasc Magn Reson 17:O15PubMedCentralGoogle Scholar
  178. 178.
    Bastiaansen JAM, Merritt ME, Comment A (2016) Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-13C]butyrate and [1-13C]pyruvate. Sci Rep 6:25573.PubMedPubMedCentralGoogle Scholar
  179. 179.
    Billingsley KL, Josan S, Park JM et al (2014) Hyperpolarized [1,4-13C]-diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging. NMR Biomed 27:356–362PubMedPubMedCentralGoogle Scholar
  180. 180.
    Jakob U, Reichmann D (2013) Oxidative stress and redox regulation. Springer, Dodrecht Heidelberg New York LondonGoogle Scholar
  181. 181.
    Maritim AC, Sanders RA, Watkins JB (2013) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17:24–38Google Scholar
  182. 182.
    Keshari KR, Sai V, Wang ZJ et al (2013) Hyperpolarized [1-13C]dehydroascorbate MR spectroscopy in a murine model of prostate cancer: comparison with 18F-FDG PET. J Nucl Med 54:922–928PubMedPubMedCentralGoogle Scholar
  183. 183.
    Timm KN, Hu D-E, Williams M et al (2017) Assessing oxidative stress in tumors by measuring the rate of hyperpolarized [1-13C]dehydroascorbic acid reduction using 13C magnetic resonance spectroscopy. J Biol Chem 292:1737–1748PubMedGoogle Scholar
  184. 184.
    Keshari KR, Wilson DM, Sai V et al (2015) Noninvasive in vivo imaging of diabetes-induced renal oxidative stress and response to therapy using hyperpolarized 13C dehydroascorbate magnetic resonance. Diabetes 64:344–352PubMedGoogle Scholar
  185. 185.
    Carroll VN, Truillet C, Shen B et al (2016) [ 11C]Ascorbic and [ 11C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography. Chem Commun 52:4888–4890Google Scholar
  186. 186.
    Schröder L (2013) Xenon for NMR biosensing–inert but alert. Phys Medica Eur J Med Phys 29:3–16Google Scholar
  187. 187.
    Lowery TJ, Garcia S, Chavez L et al (2006) Optimization of xenon biosensors for detection of protein interactions. ChemBioChem 7:65–73PubMedGoogle Scholar
  188. 188.
    Aaron JA, Chambers JM, Jude KM et al (2008) Structure of a 129Xe-cryptophane biosensor complexed with human carbonic anhydrase II. J Am Chem Soc 130:6942–6943PubMedPubMedCentralGoogle Scholar
  189. 189.
    Chambers JM, Hill PA, Aaron JA et al (2008) Cryptophane xenon-129 nuclear magnetic resonance biosensors targeting human carbonic anhydrase. J Am Chem Soc 131:563–569Google Scholar
  190. 190.
    Witte C, Martos V, Rose HM et al (2015) Live-cell MRI with xenon hyper-CEST biosensors targeted to metabolically labeled cell-surface Glycans. Angew Chem Int Ed 54:2806–2810Google Scholar
  191. 191.
    Seward GK, Bai Y, Khan NS, Dmochowski IJ (2011) Cell-compatible, integrin-targeted cryptophane-129Xe NMR biosensors. Chem Sci 2:1103–1110PubMedPubMedCentralGoogle Scholar
  192. 192.
    Palaniappan KK, Ramirez RM, Bajaj VS et al (2013) Molecular imaging of cancer cells using a bacteriophage-based 129Xe NMR biosensor. Angew Chem 125:4949–4953Google Scholar
  193. 193.
    Boutin C, Stopin A, Lenda F et al (2011) Cell uptake of a biosensor detected by hyperpolarized 129Xe NMR: the transferrin case. Bioorg Med Chem 19:4135–4143PubMedGoogle Scholar
  194. 194.
    Zeng Q, Guo Q, Yuan Y et al (2017) Mitochondria targeted and intracellular biothiol triggered hyperpolarized 129Xe Magnetofluorescent biosensor. Anal Chem 89:2288–2295PubMedGoogle Scholar
  195. 195.
    Klippel S, Freund C, Schröder L (2014) Multichannel MRI labeling of mammalian cells by switchable nanocarriers for hyperpolarized xenon. Nano Lett 14:5721–5726PubMedGoogle Scholar
  196. 196.
    Wang Y, Dmochowski IJ (2016) An expanded palette of Xenon-129 NMR biosensors. Acc Chem Res 49:2179–2187PubMedPubMedCentralGoogle Scholar
  197. 197.
    Zaccagna F, Grist JT, Deen SS et al (2018) Hyperpolarized carbon-13 magnetic resonance spectroscopic imaging: a clinical tool for studying tumour metabolism. Br J Radiol 91:1085Google Scholar
  198. 198.
    Stewart NJ, Chan H-F, Hughes PJC et al (2018) Comparison of 3He and 129Xe MRI for evaluation of lung microstructure and ventilation at 1.5T. J Magn Reson imagingGoogle Scholar
  199. 199.
    Kirby M, Ouriadov A, Svenningsen S et al (2014) Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never- and ex-smokers. Physiol Rep 2(7):e12068PubMedPubMedCentralGoogle Scholar
  200. 200.
    Kirby M, Svenningsen S, Kanhere N et al (2013) Pulmonary ventilation visualized using hyperpolarized helium-3 and xenon-129 magnetic resonance imaging: differences in COPD and relationship to emphysema. J Appl Physiol 114:707–715PubMedGoogle Scholar
  201. 201.
    Svenningsen S, Miranda K, Danielle S et al (2013) Hyperpolarized 3He and 129Xe MRI: differences in asthma before bronchodilation. J Magn Reson Imaging 38:1521–1530PubMedGoogle Scholar
  202. 202.
    Horn FC, Marshall H, Collier GJ et al (2017) Regional ventilation changes in the lung: treatment response mapping by using hyperpolarized gas MR imaging as a quantitative biomarker. Radiology 284:854–861PubMedGoogle Scholar

Copyright information

© World Molecular Imaging Society 2018

Authors and Affiliations

  • Jason Graham Skinner
    • 1
  • Luca Menichetti
    • 2
    • 3
  • Alessandra Flori
    • 3
    • 4
  • Anna Dost
    • 1
  • Andreas Benjamin Schmidt
    • 1
    • 5
  • Markus Plaumann
    • 6
  • Ferdia Aiden Gallagher
    • 7
  • Jan-Bernd Hövener
    • 5
  1. 1.Department of Radiology, Medical Physics, Medical Center, Faculty of MedicineUniversity of FreiburgFreiburgGermany
  2. 2.Institute of Clinical PhysiologyNational Research Council (CNR)PisaItaly
  3. 3.Fondazione CNR/Regione Toscana G. MonasterioPisaItaly
  4. 4.Institute of Life SciencesScuola Superiore Sant’AnnaPisaItaly
  5. 5.Section Biomedical Imaging and MOIN CCUniversity Medical Center Schleswig Holstein, Kiel UniversityKielGermany
  6. 6.Institute of Biometrics and Medical InformaticsOtto-von-Guericke University MagdeburgMagdeburgGermany
  7. 7.Department of RadiologyUniversity of CambridgeCambridgeUK

Personalised recommendations