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Pediatric Radiology

, Volume 47, Issue 5, pp 507–521 | Cite as

Gadolinium-based contrast agents in pediatric magnetic resonance imaging

  • Eric M. Gale
  • Peter Caravan
  • Anil G. Rao
  • Robert J. McDonald
  • Matthew Winfeld
  • Robert J. Fleck
  • Michael S. Gee
Minisymposium: MR techniques in pediatric radiology

Abstract

Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available.

Keywords

Children Contrast agent Gadolinium-based contrast agent Magnetic resonance imaging Safety 

Notes

Compliance with ethical standards

Conflicts of interest

Dr. Gale has provided consulting services to Collagen Medical LLC, and has equity in Reveal Pharmaceuticals Inc. Dr. Caravan has research funding from Pfizer, Biogen and Agilent, has provided consulting services to Guerbet, and has equity in Collagen Medical LLC, Factor 1A LLC and Reveal Pharmaceuticals Inc. Drs. Rao, McDonald, Winfeld, Fleck and Gee have no potential conflicts of interest to disclose.

References

  1. 1.
    Bhargava R, Hahn G, Hirsch W et al (2013) Contrast-enhanced magnetric resonance imaging in pediatric patients: review and recommendations for current practice. Magn Reson Insights 6:95–111PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Young IR (2000) Methods in biomedical magnetic resonance imaging and spectroscopy. Wiley, ChichesterGoogle Scholar
  3. 3.
    Edelman GM, Hesselink JR, Zlatkin MB et al (2006) Clinical magnetic resonance imaging — volume 3. Elsevier Health, St. LouisGoogle Scholar
  4. 4.
    Boros E, Gale EM, Caravan P (2015) MR imaging probes: design and applications. Dalton Trans 44:4804–4818PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Carr DH, Bydder GM, Weinmann H-J et al (1984) Intravenous chelated gadolinium as a contrast agent in NMR imaging of cerebral tumors. Lancet 323:484–486CrossRefGoogle Scholar
  6. 6.
    Caravan P, Ellison JJ, McMurry TJ et al (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics and applications. Chem Rev 99:2293–2352PubMedCrossRefGoogle Scholar
  7. 7.
    Caravan P, Farrar CT, Frullano L et al (2009) Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1-contrast agents. Contrast Media Mol Imaging 4:89–100PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Gale EM, Atanasova I, Blasi F et al (2015) A manganese alternative to gadolinium for MRI contrast. J Am Chem Soc 137:15548–15557PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Caravan P (2006) Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. Chem Soc Rev 35:512–523PubMedCrossRefGoogle Scholar
  10. 10.
    Caravan P (2009) Protein-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agents: design and mechanism of action. Acc Chem Res 42:851–862PubMedCrossRefGoogle Scholar
  11. 11.
    Caravan P, Cloutier NJ, Greenfield MT et al (2002) The interaction of MS-325 with human serum albumin and its effect on proton relaxation rates. J Am Chem Soc 124:3152–3162PubMedCrossRefGoogle Scholar
  12. 12.
    Vander Elst L, Chapelle F, Laurent S et al (2001) Stereospecific binding of MRI contrast agents to human serum albumin: the case of Gd-(S)-EOB-DTPA (Eovist) and its ® isomer. J Biol Inorg Chem 6:196–200PubMedCrossRefGoogle Scholar
  13. 13.
    Shen Y, Goerner FL, Snyder C et al (2015) T1 Relaxivities of Gadolinium-Based Magnetic Resonance Contrast Agents in Human Whole Blood at 1.5, 3, and 7 T. Investig Radiol 50:330–338CrossRefGoogle Scholar
  14. 14.
    Morcos SK (2008) Extracellular gadolinium contrast agents: Differences in stability. Eur J Radiol 66:175–179PubMedCrossRefGoogle Scholar
  15. 15.
    Laurent S, Vander Elst L, Henoumon C et al (2010) How to measure the transmetallation of a gadolinium complex. Contrast Media Mol Imaging 5:305–308PubMedCrossRefGoogle Scholar
  16. 16.
    Laurent S, Vander Elst L, Copoix F et al (2001) Stability of MRI paramagnetic contrast media: a proton relaxometric protocol for transmetallation assessment. Investig Radiol 36:115–122CrossRefGoogle Scholar
  17. 17.
    Aime S, Caravan P (2009) Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Res Imaging 30:1259–1267CrossRefGoogle Scholar
  18. 18.
    Jung G, Heindel W, Krahe T et al (1998) Influence of the hepatobiliary contrast agent mangafodipir trisodium (MN-DPDP) on the imaging properties of abdominal organs. Magn Reson Imaging 16:925–931PubMedCrossRefGoogle Scholar
  19. 19.
    Nelson SJ, Kurhanewicz J, Vigneron DB et al (2013) Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C]pyruvate. Sci Transl Med 5:198ra108PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Sieber MA, Steger-Hartmann T, Lengsfeld P et al (2009) Gadolinium-based contrast agents and NSF: evidence from animal experience. J Magn Res Imaging 30:1268–1276CrossRefGoogle Scholar
  21. 21.
    Jost G, Lenhard DC, Sieber MA et al (2016) Signal increase on unenhanced T1-weighted images in the rat brain after repeated, extended doses of gadolinium-based contrast agents comparison of linear and macrocyclic agents. Investig Radiol 51:83–89CrossRefGoogle Scholar
  22. 22.
    Anderson P (2015) FDA okays MRI contrast agent (Gadavist) in infants. Medscape. http://www.medscape.com/viewarticle/837629. Accessed 15 December 2016
  23. 23.
    Ellis JH, Davenport MS, Dillman JR et al (2015) ACR manual on contrast media v10.1. American College of Radiology, RestonGoogle Scholar
  24. 24.
    Grobner T (2006) Gadolinium — a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108PubMedCrossRefGoogle Scholar
  25. 25.
    Marckmann P, Skov L, Rossen K et al (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362PubMedCrossRefGoogle Scholar
  26. 26.
    U.S. Food & Drug Administration (2009) Joint meeting of the Cardiovascular and Renal Drugs and Drug Safety and Risk Management Advisory Committee. Gadolinium-based contrast agents and nephrogenic systemic fibrosis: FDA briefing document. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM190850.pdf. Accessed 15 December 2016
  27. 27.
    Yang L, Krefting I, Gorovets A et al (2012) Nephrogenic systemic fibrosis and class labeling of gadolinium-based contrast agents by the Food and Drug Administration. Radiology 265:248–253PubMedCrossRefGoogle Scholar
  28. 28.
    Swan SK, Lambrecht LJ, Townsend R et al (1999) Safety and pharmacokinetic profile of gadobenate dimeglumine in subjects with renal impairment. Investig Radiol 34:443–448CrossRefGoogle Scholar
  29. 29.
    Marcos SK, Thomsen HS, Dawson P (2006) Is there a causal relation between the administration of gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF)? Clin Radiol 61:905–906CrossRefGoogle Scholar
  30. 30.
    Swan SK, Baker JF, Free R et al (1999) Pharmacokinetics, safety, and tolerability of gadoversetamide injection (OptiMARK) in subjects with central nervous system or liver pathology and varying degrees of renal function. J Magn Res Imaging 9:317–321CrossRefGoogle Scholar
  31. 31.
    Schuhmann-Giampieri G, Krestin G (1991) Pharmacokinetics of Gd-DTPA in patients with chronic renal failure. Investig Radiol 26:975–979CrossRefGoogle Scholar
  32. 32.
    European Medicines Agency (2010) Assessment report for gadolinium-containing contrast agents. Procedure no. EMEA/H/A-31/1097. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/gadolinium_31/WC500099538.pdf. Accessed 15 December 2016
  33. 33.
    Davenport MS, Dillman JR, Cohan RH et al (2013) Effect of abrupt substitution of gadobenate dimeglumine for gadopentetate dimeglumine on rate of allergic-like reactions. Radiology 266:773–782PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Hahn G, Sorge I, Gruhn B et al (2009) Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in pediatric patients. Investig Radiol 44:776–783CrossRefGoogle Scholar
  35. 35.
    Kunze CW, Mentel H-J, Krishnamurthy R et al (2016) Pharmacokinetics and safety of macrocyclic gadobutrol in children aged younger than 2 years including term newborns in comparison to older populations. Investig Radiol 51:50–57CrossRefGoogle Scholar
  36. 36.
    Kanda T, Kawaguchi H (2013) Hyperintense dentate nucleas and globus pallidus on unenhanced T1-weighted MR images are associated with gadolinium-based contrast media. Neuroradiology 55:1268–1269Google Scholar
  37. 37.
    Kanda T, Ishii K, Kawaguchi H et al (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 270:834–841PubMedCrossRefGoogle Scholar
  38. 38.
    Kanda T, Fukusato T, Matsuda M et al (2015) Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 276:228–232PubMedCrossRefGoogle Scholar
  39. 39.
    Kanda T, Osawa M, Oba H et al (2015) High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology 275:803–809PubMedCrossRefGoogle Scholar
  40. 40.
    Radbruch A, Weberling LD, Kieslich PJ et al (2015) Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 275:783–791PubMedCrossRefGoogle Scholar
  41. 41.
    Miller JH, Houchun HH, Pokorney A et al (2015) MRI brain signal intensity changes of a child during the course of 35 gadolinium contrast examinations. Pediatrics 136:e1637–e1640PubMedCrossRefGoogle Scholar
  42. 42.
    Murata N, Gonzalez-Cuyar LF, Murata K et al (2016) Macrocyclic and other non–group 1 gadolinium contrast agents deposit low levels of gadolinium in brain and bone tissue: preliminary results from 9 patients with normal renal function. Investig Radiol 51:447–453CrossRefGoogle Scholar
  43. 43.
    Maximova N, Gregori M, Zennaro F et al (2016) Hepatic gadolinium deposition and reversibility after contrast agent-enhanced MR imaging of pediatric hematopoietic stem cell transplant recipients. Radiology 281:418–426PubMedCrossRefGoogle Scholar
  44. 44.
    Chavhan GB, Babyn PS, John P et al (2015) Pediatric body MR angiography: principles, techniques, and current status in body imaging. AJR Am J Roentgenol 205:173–184PubMedCrossRefGoogle Scholar
  45. 45.
    Grist TM, Thornton FJ (2005) Magnetic resonance angiography in children: technique, indications, and imaging findings. Pediatr Radiol 35:26–39PubMedCrossRefGoogle Scholar
  46. 46.
    Miyazaki M, Akahane M (2012) Non-contrast enhanced MR angiography: established techniques. J Magn Reson Imaging 35:1–19PubMedCrossRefGoogle Scholar
  47. 47.
    Chung T (2005) Magnetic resonance angiography of the body in pediatric patients: experience with a contrast-enhanced time-resolved technique. Pediatr Radiol 35:3–10PubMedCrossRefGoogle Scholar
  48. 48.
    Rofsky NM, Lee VS, Laub G et al (1999) Abdominal MR imaging with a volumetric interpolated breath-hold examination. Radiology 212:876–884PubMedCrossRefGoogle Scholar
  49. 49.
    Cornfield D, Mojibian H (2009) Clinical uses of time-resolved imaging in the body and peripheral vascular system. AJR Am J Roentgenol 193:W546–W557CrossRefGoogle Scholar
  50. 50.
    Lewis M, Yanny S, Malcolm PN (2012) Advantages of blood pool contrast agents in MR angiography: a pictorial review. J Med Imaging Radiat Oncol 56:187–191PubMedCrossRefGoogle Scholar
  51. 51.
    Krishnamurthy R, Bahouth SM, Muthapillai R (2016) 4D contrast-enhanced MR angiography with the keyhole technique in children: technique and clinical applications. Radiographics 36:14CrossRefGoogle Scholar
  52. 52.
    Sundareswaran K, Frakes D, d Zelicourt D et al (2008) Comparison of power losses, hepatic flow splits, and vortex sizes in different fontan types using non invasive phase contrast magnetic resonance imaging. Circulation 118:S1057CrossRefGoogle Scholar
  53. 53.
    Makowski M, Wiethoff A, Uribe S et al (2011) Congenital heart disease: cardiovascular MR imaging by using an intravascular blood pool contrast agent. Radiology 260:680–688PubMedCrossRefGoogle Scholar
  54. 54.
    Hsiao A, Lustig M, Alley M et al (2012) Rapid pediatric cardiac assessment of flow and ventricular volume with compressed sensing parallel imaging volumetric cine phase-contrast MRI. AJR Am J Roentgenol 198:W250–W259PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Gabbour M, Schnell S, Jarvis K et al (2015) 4-D flow magnetic resonance imaging: blood flow quantification compared to 2-D phase-contrast magnetic resonance imaging and Doppler echocardiography. Pediatr Radiol 45:804–813PubMedCrossRefGoogle Scholar
  56. 56.
    Ordovas K, Higgins C (2011) Delayed contrast enhancement on MR images of myocardium: past, present, future. Radiology 261:358–374PubMedCrossRefGoogle Scholar
  57. 57.
    Simonetti O, Kim R, Fieno D et al (2001) An improved MR imaging technique for the visualization of myocardial infarction. Radiology 218:215–223PubMedCrossRefGoogle Scholar
  58. 58.
    Kellman P, Wilson J, Xue H et al (2012) Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method. J Cardiovasc Magn Reson 14:63PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Tandon A, Villa CR, Hor KN et al (2015) Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in Duchenne muscular dystrophy. J Am Heart Assoc 4:e001338PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    O'Hanlon R, Grasso A, Roughton M et al (2010) Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 56:867–874PubMedCrossRefGoogle Scholar
  61. 61.
    Moon J, Messroghli D, Kellman P et al (2013) Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 15:92PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Gerber B, Raman S, Nayak K et al (2008) Myocardial first-pass perfusion cardiovascular magnetic resonance: history, theory, and current state of the art. J Cardiovasc Magn Reson 10:18PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Manso B, Castellote A, Dos L et al (2010) Myocardial perfusion magnetic resonance imaging for detecting coronary function anomalies in asymptomatic paediatric patients with a previous arterial switch operation for the transposition of great arteries. Cardiol Young 20:410–417PubMedCrossRefGoogle Scholar
  64. 64.
    Prakash A, Powell A, Krishnamurthy R et al (2004) Magnetic resonance imaging evaluation of myocardial perfusion and viability in congenital and acquired pediatric heart disease. Am J Cardiol 93:657–661PubMedCrossRefGoogle Scholar
  65. 65.
    Friedrich M, Sechtem U, Schulz-Menger J et al (2009) Cardiovascular magnetic resonance in myocarditis: a JACC white paper. J Am Coll Cardiol 53:1475–1487PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Banka P, Robinson J, Uppu S et al (2015) Cardiovascular magnetic resonance techniques and findings in children with myocarditis: a multicenter retrospective study. J Cardiovasc Magn Reson 17:96PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Ferreira V, Piechnik S, Dall'Armellina E et al (2012) T1-mapping has a high diagnostic performance in patients presenting with acute myocarditis: a cardiovascular magnetic resonance study. Heart 98:A52–A53CrossRefGoogle Scholar
  68. 68.
    Ferreira V, Piechnik S, Dall'Armellina E et al (2013) T(1) mapping for the diagnosis of acute myocarditis using CMR: comparison to T2-weighted and late gadolinium enhanced imaging. JACC Cardiovasc Imaging 6:1048–1058PubMedCrossRefGoogle Scholar
  69. 69.
    Seale MK, Catalano OA, Saini S et al (2009) Hepatobiliary-specific MR contrast agents: role in imaging the liver and biliary tree. Radiographics 29:1725–1748PubMedCrossRefGoogle Scholar
  70. 70.
    Tran VT, Vasanawala S (2013) Pediatric hepatobiliary magnetic resonance imaging. Radiol Clin N Am 51:599–614PubMedCrossRefGoogle Scholar
  71. 71.
    Guglielmo FF, Mitchell DG, Gupta S (2014) Gadolinium contrast agent selection and optimal use for body MR imaging. Radiol Clin N Am 52:637–656PubMedCrossRefGoogle Scholar
  72. 72.
    Nandwana SB, Moreno CC, Osipow MT et al (2015) Gadobenate dimeglumine administration and nephrogenic systemic fibrosis: is there a real risk in patients with impaired renal function? Radiology 276:741–747PubMedCrossRefGoogle Scholar
  73. 73.
    Lauenstein T, Ramirez-Garrido F, Kim YH et al (2015) Nephrogenic systemic fibrosis risk after liver magnetic resonance imaging with gadoxetate disodium in patients with moderate to severe renal impairment: results of a prospective, open-label, multicenter study. Investig Radiol 50:416–422CrossRefGoogle Scholar
  74. 74.
    Vaneckova M, Herman M, Smith MP et al (2015) The benefits of high relaxivity for brain tumor imaging: results of a multicenter intraindividual crossover comparison of gadobenate dimeglumine with gadoterate meglumine (The BENEFIT study). AJNR Am J Neuroradiol 36:1589–1598PubMedCrossRefGoogle Scholar
  75. 75.
    Rigsby CK, Popescu AR, Nelson P et al (2015) Safety of blood pool contrast agent administration in children and young adults. AJR Am J Roentgenol 205:1114–1120PubMedCrossRefGoogle Scholar
  76. 76.
    Rigsby CK, Hilpipre N, McNeal GR et al (2014) Analysis of an automated background correction method for cardiovascular MR phase contrast imaging in children and young adults. Pediatr Radiol 44:265–273PubMedCrossRefGoogle Scholar
  77. 77.
    Farmakis SG, Khanna G (2014) Extracardiac applications of MR blood pool contrast agent in children. Pediatr Radiol 44:1598–1609PubMedCrossRefGoogle Scholar
  78. 78.
    Cha S (2006) Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in pediatric patients. Neuroimaging Clin N Am 16:137–147PubMedCrossRefGoogle Scholar
  79. 79.
    Wang Y-XJ, Hussain SM, KRestin GP (2001) Superparamaganetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11:2319–2331PubMedCrossRefGoogle Scholar
  80. 80.
    Wang Y-XJ (2011) Superparamagnetic iron oxide based MRI contrast agents: current status of clinical application. Quant Imaging Med Surg 11:35–40Google Scholar
  81. 81.
    Hope MD, Hope TA, Zhu C et al (2015) Vascular imaging with ferumoxytol as a contrast agent. AJR Am J Roentgenol 205:W366–W374PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Bellin M-F, Roy C, Kinkel K et al (1998) Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles —initial clinical experience. Radiology 207:799–808PubMedCrossRefGoogle Scholar
  83. 83.
    Li S-D, Huang L (2008) Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm 5:496–504PubMedCrossRefGoogle Scholar
  84. 84.
    Arami H, Khandhar A, Liggitt D et al (2015) In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles. Chem Sci Rev 44:8576–8607CrossRefGoogle Scholar
  85. 85.
    Li W, Tutton S, Vu AT et al (2004) First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent. J Magn Res Imaging 21:46–52CrossRefGoogle Scholar
  86. 86.
    Harisinghani MG, Berentsz J, Hahn PF et al (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499PubMedCrossRefGoogle Scholar
  87. 87.
    Heesakkers RAM, Jager GJ, Hövels AM et al (2009) Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10 - enhanced MR imaging. Radiology 251:408–414PubMedCrossRefGoogle Scholar
  88. 88.
    Prince MR, Zhang HL, Chabra SG et al (2003) A pilot investigation of new superparamagnetic iron oxide (ferumoxytol) as a contrast agent for cardiovascular MRI. J Xray Sci Technol 11:231–240PubMedGoogle Scholar
  89. 89.
    Ruangwattanapaisarn N, Hsiao A, Vasanawala SS (2015) Ferumoxytol as an off-label contrast agent in body 3T MR angiography: a pilot study in children. Pediatr Radiol 45:831–839PubMedCrossRefGoogle Scholar
  90. 90.
    Luhar A, Khan S, Finn JP et al (2016) Contrast-enhanced magnetic resonance venography in pediatric patients with chronic kidney disease: initial experience with ferumoxytol. Pediatr Radiol 46:1332–1340PubMedCrossRefGoogle Scholar
  91. 91.
    Thompson EM, Guillaume DJ, Dósa E et al (2012) Dual contrast perfusion MRI in a single imaging session for assessment of pediatric brain tumors. J Neurooncol 109:105–114PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Schiller B, Bhat P, Sharma A (2014) Safety and effectiveness of ferumoxytol in hemodialysis patients at 3 dialysis chains in the United States over a 12-month period. Clin Ther 36:70–83PubMedCrossRefGoogle Scholar
  93. 93.
    Muehe AM, Fang D, von Eyben R et al (2016) Safety report of ferumoxytol for magnetic resonance imaging in children and young adults. Investig Radiol 51:221–227CrossRefGoogle Scholar
  94. 94.
    Lauffer RB (1987) Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chem Rev 87:901–927CrossRefGoogle Scholar
  95. 95.
    Elizondo G, Fretz CJ, Stark DD et al (1991) Preclinical evaluation of MnDPDP: new paramagnetic hepatobiliary contrast agent for MR imaging. Radiology 178:73–78PubMedCrossRefGoogle Scholar
  96. 96.
    Hamm B, Vogl TJ, Branding G et al (1992) Focal liver lesions: MR imaging with MnDPDP initial clinical results in 40 patients. Radiology 182:167–174PubMedCrossRefGoogle Scholar
  97. 97.
    Vogl TJ, Hamm B, Schnell B et al (1993) Mn-DPDP enhancement patterns of hepatocellular lesions on MR images. J Magn Res Imaging 3:51–58CrossRefGoogle Scholar
  98. 98.
    Gallez B, Bacic G, Swartz HM (1996) Evidence for the dissociation of the hepatobiliary MRI contrast agent Mn-DPDP. Magn Reson Med 35:14–19PubMedCrossRefGoogle Scholar
  99. 99.
    Toft KG, Hustvedt SO, Grat D et al (1997) Metabolism and Pharmacokinetics of MnDPDP in man. Acta Radiol 38:677–689PubMedCrossRefGoogle Scholar
  100. 100.
    Crossgrove J, Zheng W (2004) Manganese toxicity upon overexposure. NMR Biomed 17:544–553PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    O'Neal SL, Zheng W (2015) Manganese toxicity upon overexposure: a decade in review. Curr Environ Health Rep 2:315–328PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Aschner JL, Aschner M (2005) Nutritional aspects of manganese homeostasis. Mol Asp Med 26:353–362CrossRefGoogle Scholar
  103. 103.
    Yang Y, Schühle DT, Dai G et al (2012) 1H chemical shift magnetic resonance imaging probes with high sensitivity for multiplex imaging. Contrast Media Mol Imaging 7:276–279PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Harvey P, Blamire AM, Wilson JI et al (2013) Moving the goal posts: enhancing the sensitivity of PARASHIFT proton magnetic resonance imaging and spectroscopy. Chem Sci 4:4251–4258CrossRefGoogle Scholar
  105. 105.
    Mizukami S, Takikawa R, Sugihara F et al (2008) Paramagnetic relaxation-based 19F MRI probe to detect protease activity. J Am Chem Soc 130:794–795PubMedCrossRefGoogle Scholar
  106. 106.
    Tirotta I, Mastropietro A, Cordiglieri C et al (2014) A superfluorinated molecular probe for highly sensitive in vivo19F‐MRI. J Am Chem Soc 136:8524–8527PubMedCrossRefGoogle Scholar
  107. 107.
    Sherry AD, Woods M (2008) Chemical exchange saturation transfer contrast agents for magnetic resonance imaging. Annu Rev Biomed Eng 10:391–411PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Liu G, Gilad AA, Bulte JWM et al (2010) High-Throuput Screening of Chemical Exchange Saturation Transfer MR Contrast Agents. Contrast Media Mol Imaging 5:162–170PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Brindle KM, Bohndiek SE, Gallagher FA, Kettunen MI (2011) Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy. Magn Reson Med 66(2):505–19Google Scholar
  110. 110.
    Svenningsen S, Kirby M, Starr D et al (2013) Hyperpolarized 3He and 129Xe MRI: differences in asthma before bronchodilation. J Magn Res Imaging 38:1521–1530CrossRefGoogle Scholar
  111. 111.
    Qing K, Ruppert K, Jiang Y et al (2014) Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI. J Magn Reson Imaging 39:346–359PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Eric M. Gale
    • 1
  • Peter Caravan
    • 1
  • Anil G. Rao
    • 2
  • Robert J. McDonald
    • 3
  • Matthew Winfeld
    • 4
  • Robert J. Fleck
    • 5
  • Michael S. Gee
    • 6
  1. 1.Department of Radiology, The Martinos Center for Biomedical ImagingMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Department of Radiology and Radiological ScienceMedical University of South CarolinaCharlestonUSA
  3. 3.Department of RadiologyCollege of Medicine, Mayo ClinicRochesterUSA
  4. 4.University of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  5. 5.Department of Pediatric RadiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  6. 6.Division of Pediatric Imaging, Department of RadiologyMassGeneral Hospital for Children, Harvard Medical SchoolBostonUSA

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