Clinical Radiology
Volume 65, Issue 7 , Pages 557-566 , July 2010

An introduction to functional and molecular imaging with MRI

  • F.A. Gallagher

      Affiliations

    • Corresponding Author InformationGuarantor and correspondent: F. A. Gallagher, Department of Radiology, University of Cambridge, Box 218 Level 5, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK. Tel.: +44 (0)1223 336890; fax: +44 (0)1223 330915.

Received 20 November 2009 ,Revised 22 April 2010 ,Accepted 30 April 2010.

References 

  1. Bloch F. Nuclear induction. Phys Rev. 1946;70:460–474
  2. Purcell EM, Torrey HC, Pound RV. Resonance absorption by nuclear magnetic moments in a solid. Phys Rev. 1945;69:37–38
  3. Rabi I. A new method of measuring nuclear magnetic moment. Phys Rev. 1938;53:318
  4. Damadian R. Tumor detection by nuclear magnetic resonance. Science. 1971;171:1151–1153
  5. Lauterbur P. Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature. 1973;242:190–191
  6. Johnson GA, Cofer GP, Fubara B, et al. Magnetic resonance histology for morphologic phenotyping. J Magn Reson Imaging. 2002;16:423–429
  7. McRobbie DW, Moore EA, Graves MJ, et al. MRI from picture to proton. 2nd ed.. Cambridge: Cambridge University Press; 2007;
  8. Gadian DG. NMR and its applications to living systems. 2nd ed.. Oxford: Oxford University Press; 1995;
  9. Ma J. Dixon techniques for water and fat imaging. J Magn Reson Imaging. 2008;28:543–558
  10. Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 2003;17:545–580
  11. Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature. 2008;452:580–589
  12. Smith JJ, Sorensen AG, Thrall JH. Biomarkers in imaging: realizing radiology’s future. Radiology. 2003;227:633–638
  13. Padhani AR. Dynamic contrast-enhanced MRI in clinical oncology: current status and future directions. J Magn Reson Imaging. 2002;16:407–422
  14. Zaharchuk G. Theoretical basis of hemodynamic MR imaging techniques to measure cerebral blood volume, cerebral blood flow, and permeability. AJNR Am J Neuroradiol. 2007;28:1850–1858
  15. Tofts PS, Brix G, Buckley DL, et al. Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging. 1999;10:223–232
  16. Tofts PS. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging. 1997;7:91–101
  17. Maxwell RJ, Wilson J, Prise VE, et al. Evaluation of the anti-vascular effects of combretastatin in rodent tumours by dynamic contrast enhanced MRI. NMR Biomed. 2002;15:89–98
  18. O’Connor JP, Jackson A, Parker GJ, et al. DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Br J Cancer. 2007;96:189–195
  19. Turkbey B, Kobayashi H, Ogawa M, et al. Imaging of tumor angiogenesis: functional or targeted?. AJR Am J Roentgenol. 2009;193:304–313
  20. Degani H, Gusis V, Weinstein D, et al. Mapping pathophysiological features of breast tumors by MRI at high spatial resolution. Nat Med. 1997;3:780–782
  21. Gilles R, Guinebretiere JM, Shapeero LG, et al. Assessment of breast cancer recurrence with contrast-enhanced subtraction MR imaging: preliminary results in 26 patients. Radiology. 1993;188:473–478
  22. Gillies RJ, Raghunand N, Karczmar GS, et al. MRI of the tumor microenvironment. J Magn Reson Imaging. 2002;16:430–450
  23. Hahn OM, Yang C, Medved M, et al. Dynamic contrast-enhanced magnetic resonance imaging pharmacodynamic biomarker study of sorafenib in metastatic renal carcinoma. J Clin Oncol. 2008;26:4572–4578
  24. Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007;11:83–95
  25. Dafni H, Landsman L, Schechter B, et al. MRI and fluorescence microscopy of the acute vascular response to VEGF165: vasodilation, hyper-permeability and lymphatic uptake, followed by rapid inactivation of the growth factor. NMR Biomed. 2002;15:120–131
  26. O’Connor JP, Carano RA, Clamp AR, et al. Quantifying antivascular effects of monoclonal antibodies to vascular endothelial growth factor: insights from imaging. Clin Cancer Res. 2009;15:6674–6682
  27. Dennie J, Mandeville JB, Boxerman JL, et al. NMR imaging of changes in vascular morphology due to tumor angiogenesis. Magn Reson Med. 1998;40:793–799
  28. Knopp EA, Cha S, Johnson G, et al. Glial neoplasms: dynamic contrast-enhanced T2*-weighted MR imaging. Radiology. 1999;211:791–798
  29. Fuss M, Wenz F, Essig M, et al. Tumor angiogenesis of low-grade astrocytomas measured by dynamic susceptibility contrast-enhanced MRI (DSC-MRI) is predictive of local tumor control after radiation therapy. Int J Radiat Oncol Biol Phys. 2001;51:478–482
  30. Fuss M, Wenz F, Scholdei R, et al. Radiation-induced regional cerebral blood volume (rCBV) changes in normal brain and low-grade astrocytomas: quantification and time and dose-dependent occurrence. Int J Radiat Oncol Biol Phys. 2000;48:53–58
  31. Norris DG. The effects of microscopic tissue parameters on the diffusion weighted magnetic resonance imaging experiment. NMR Biomed. 2001;14:77–93
  32. Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol. 2007;188:1622–1635
  33. Moseley ME, Cohen Y, Mintorovitch J, et al. Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med. 1990;14:330–346
  34. Padhani AR, Liu G, Koh DM, et al. Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia. 2009;11:102–125
  35. Thoeny HC, De Keyzer F, Vandecaveye V, et al. Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging. Radiology. 2005;237:492–499
  36. Urenjak J, Williams SR, Gadian DG, et al. Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytes in vitro. J Neurochem. 1992;59:55–61
  37. Bruhn H, Frahm J, Gyngell ML, et al. Cerebral metabolism in man after acute stroke: new observations using localized proton NMR spectroscopy. Magn Reson Med. 1989;9:126–131
  38. Luyten PR, Marien AJ, Heindel W, et al. Metabolic imaging of patients with intracranial tumors: H-1 MR spectroscopic imaging and PET. Radiology. 1990;176:791–799
  39. Glunde K, Ackerstaff E, Mori N, et al. Choline phospholipid metabolism in cancer: consequences for molecular pharmaceutical interventions. Mol Pharm. 2006;3:496–506
  40. Daly PF, Cohen JS. Magnetic resonance spectroscopy of tumors and potential in vivo clinical applications: a review. Cancer Res. 1989;49:770–779
  41. Negendank W. Studies of human tumors by MRS: a review. NMR Biomed. 1992;5:303–324
  42. Moon RB, Richards JH. Determination of intracellular pH by 31P magnetic resonance. J Biol Chem. 1973;248:7276–7278
  43. Radda GK, Bore PJ, Gadian DG, et al. 31P NMR examination of two patients with NADH-CoQ reductase deficiency. Nature. 1982;295:608–609
  44. Ross BD, Radda GK, Gadian DG, et al. Examination of a case of suspected McArdle’s syndrome by 31P nuclear magnetic resonance. N Engl J Med. 1981;304:1338–1342
  45. Aime S, Castelli DD, Crich SG, et al. Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications. Acc Chem Res. 2009;42:822–831
  46. Aime S, Cabella C, Colombatto S, et al. Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J Magn Reson Imaging. 2002;16:394–406
  47. Aime S, Frullano L, Geninatti Crich S. Compartmentalization of a gadolinium complex in the apoferritin cavity: a route to obtain high relaxivity contrast agents for magnetic resonance imaging. Angew Chem Int Ed Engl. 2002;41:1017–1019
  48. Sherry AD, Woods M. Chemical exchange saturation transfer contrast agents for magnetic resonance imaging. Annu Rev Biomed Eng. 2008;10:391–411
  49. Zhao M, Beauregard DA, Loizou L, et al. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat Med. 2001;7:1241–1244
  50. Krishnan AS, Neves AA, de Backer MM, et al. Detection of cell death in tumors by using MR imaging and a gadolinium-based targeted contrast agent. Radiology. 2008;246:854–862
  51. Flacke S, Fischer S, Scott MJ, et al. Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation. 2001;104:1280–1285
  52. Curtet C, Maton F, Havet T, et al. Polylysine-Gd-DTPAn and polylysine-Gd-DOTAn coupled to anti-CEA F(ab’)2 fragments as potential immunocontrast agents. Relaxometry, biodistribution, and magnetic resonance imaging in nude mice grafted with human colorectal carcinoma. Invest Radiol. 1998;33:752–761
  53. Sipkins DA, Cheresh DA, Kazemi MR, et al. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med. 1998;4:623–626
  54. Weissleder R, Moore A, Mahmood U, et al. In vivo magnetic resonance imaging of transgene expression. Nat Med. 2000;6:351–355
  55. Cunningham CH, Arai T, Yang PC, et al. Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn Reson Med. 2005;53:999–1005
  56. Bulte JW, Zhang S, van Gelderen P, et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A. 1999;96:15256–15261
  57. Schmitz SA, Taupitz M, Wagner S, et al. Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles. J Magn Reson Imaging. 2001;14:355–361
  58. Ye Y, Bogaert J. Cell therapy in myocardial infarction: emphasis on the role of MRI. Eur Radiol. 2008;18:548–569
  59. Biancone L, Crich SG, Cantaluppi V, et al. Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation. NMR Biomed. 2007;20:40–48
  60. Bos C, Delmas Y, Desmouliere A, et al. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology. 2004;233:781–789
  61. de Vries IJ, Lesterhuis WJ, Barentsz JO, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol. 2005;23:1407–1413
  62. Toso C, Vallee JP, Morel P, et al. Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am J Transplant. 2008;8:701–706
  63. Gilad AA, Winnard PT, van Zijl PC, et al. Developing MR reporter genes: promises and pitfalls. NMR Biomed. 2007;20:275–290
  64. Bulte JWM, Verkuyl JM, Herynek V, et al. Magnetoimmunodetection of (transfected) ICAM-1 gene expression. Proc Intl Soc Mag Reson Med. 1998;6:307
  65. Louie AY, Huber MM, Ahrens ET, et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol. 2000;18:321–325
  66. Schlemmer HP, Pichler BJ, Krieg R, et al. An integrated MR/PET system: prospective applications. Abdom Imaging. 2009;34:668–674
  67. Judenhofer MS, Wehrl HF, Newport DF, et al. Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat Med. 2008;14:459–465
  68. Marsden PK, Strul D, Keevil SF, et al. Simultaneous PET and NMR. Br J Radiol. 2002;75:S53–S59Spec No
  69. Gilbert KM, Handler WB, Scholl TJ, et al. Design of field-cycled magnetic resonance systems for small animal imaging. Phys Med Biol. 2006;51:2825–2841
  70. Lucas AJ, Hawkes RC, Ansorge RE, et al. Development of a combined microPET-MR system. Technol Cancer Res Treat. 2006;5:337–341
  71. Schlemmer HP, Pichler BJ, Schmand M, et al. Simultaneous MR/PET imaging of the human brain: feasibility study. Radiology. 2008;248:1028–1035
  72. Fain SB, Korosec FR, Holmes JH, et al. Functional lung imaging using hyperpolarized gas MRI. J Magn Reson Imaging. 2007;25:910–923
  73. Ardenkjaer-Larsen JH, Fridlund B, Gram A, et al. Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003;100:10158–10163
  74. Day SE, Kettunen MI, Gallagher FA, et al. Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med. 2007;13:1382–1387
  75. Gallagher FA, Kettunen MI, Day SE, et al. Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature. 2008;453:940–943
  76. Gallagher FA, Kettunen MI, Day SE, et al. 13C magnetic resonance spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine. Magn Reson Med. 2008;60:253–257
  77. Gallagher FA, Kettunen MI, Hu DE, 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. Proc Natl Acad Sci U S A. 2009;106:19801–19806
  78. Gallagher FA, Kettunen MI, Brindle KM. Biomedical applications of hyperpolarized 13C magnetic resonance imaging. Prog in NMR Spect. 2009;55:285–295
  79. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–247
  80. McLean MA, Cross JJ. Magnetic resonance spectroscopy: principles and applications in neurosurgery. Br J Neurosurg. 2009;23:5–13

PII: S0009-9260(10)00183-2

doi: 10.1016/j.crad.2010.04.006

Clinical Radiology
Volume 65, Issue 7 , Pages 557-566 , July 2010