Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Assessing gene expression in vivo: magnetic resonance imaging and spectroscopy

Gene Therapy volume 7, pages 1259–1264 (2000)Cite this article

Abstract

Recent developments in magnetic resonance imaging and spectroscopy afford the possibility of detecting and assessing transfer, expression and subsequent therapeutic changes of effector or marker transgenes noninvasively. In the field of MR imaging, ‘smart’ MR contrast agents are being developed, so called because they change their conformational structure and in so doing induce MR detectable changes in a given tissue. These agents become ‘switched on’ in response to physiological changes brought about by the enzymatic action of a given gene product (enzymes), and are being developed for use in intact cells, isolated organs and animal models. Ultimately, these agents hold the promise of bridging the gap between the laboratory and the patient with noninvasive detection of transgene expression in vivo in man. Similarly, magnetic resonance spectroscopy is being developed as a noninvasive method to assess transgene expression indirectly by means of MR visible intracellular markers. These markers take the form of intracellular endo/exogenous metabolites associated with exogenous enzyme expression and function. Again, this technique will be applicable to a variety of different situations, from cell suspensions through to clinical imaging of the whole body. In this article the unique opportunities for laboratory-based and clinical studies afforded by MR techniques are discussed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Theodore WH, Delgado-Escueta AV, Porter RJ . Frontiers in brain imaging and therapeutics. Introduction Adv Neurol 1999 79: 865–871

    CAS  PubMed  Google Scholar 

  2. Grimm C et al. A comparison between electric source localisation and fMRI during somatosensory stimulation Electroencephalogr Clin Neurophysiol 1998 106: 22–29

    Article  CAS  Google Scholar 

  3. Huppertz HJ et al. Estimation of the accuracy of a surface matching technique for registration of EEG and MRI data Electroencephalogr Clin Neurophysiol 1998 106: 409–415

    Article  CAS  Google Scholar 

  4. Morucci JP, Rigaud B . Bioelectrical impedance techniques in medicine. Part III: Impedance imaging. Third section: medical applications Crit Rev Biomed Eng 1996 24: 655–677

    Article  CAS  Google Scholar 

  5. Roberts TP, Poeppel D, Rowley HA . Magnetoencephalography and magnetic source imaging Neuropsychiatry Neuropsychol Behav Neurol 1998 11: 49–64

    CAS  PubMed  Google Scholar 

  6. Nakaya Y, Mori H . Magnetocardiography Clin Phys Physiol Meas 1992 13: 191–229

    Article  CAS  Google Scholar 

  7. Caorsi S, Gragnani GL, Pastorino M . An electromagnetic imaging approach using a multi-illumination technique IEEE Trans Biomed Eng 1994 41: 406–409

    Article  CAS  Google Scholar 

  8. Pasini P et al. Chemiluminescence imaging in bioanalysis J Pharm Biomed Anal 1998 18: 555–564

    Article  CAS  Google Scholar 

  9. Bloch F, Hansen WW, Packard ME . Nuclear Induction Physics Rev 1946 69: 127

    Article  Google Scholar 

  10. Purcell EM, Torrey HC, Pound RV . Resonance absorption by nuclear magnetic movements in a solid Physics Rev 1946 69: 37–38

    Article  CAS  Google Scholar 

  11. Gadian DG . Nuclear Magnetic Resonance and its Application to Living Systems Oxford University Press: London 1982

    Google Scholar 

  12. Bowtell RW et al. NMR microscopy of single neurons using spin echo and line narrowed 2DFT imaging Magn Reson Med 1995 33: 790–794

    Article  CAS  Google Scholar 

  13. Mathur de Vre R, Lemort M . Biophysical properties and clinical applications of magnetic resonance imaging contrast agents Br J Radiol 1995 68: 225–247

    Article  CAS  Google Scholar 

  14. Kirsch JE . Basic principles of magnetic resonance contrast agents Top Magn Reson Imaging 1991 2: 1–18

    Google Scholar 

  15. Tweedle MF et al. Reaction of gadolinium chelates with endogenously available ions Magn Reson Imaging 1991 9: 409–415

    Article  CAS  Google Scholar 

  16. Watson AD, Rocklage SM, Carvlin MJ . Contrast agents. In: Stark D, Bradley WG (eds) Magnetic Resonance Imaging Mosby-Year Book: Missouri 1992 372–437

    Google Scholar 

  17. Desser TS et al. Dynamics of tumour imaging with Gd-DTPA-polyethylene glycol: dependence on molecular weight J Magn Reson Imaging 1994 4: 467–472

    Article  CAS  Google Scholar 

  18. Earls JP, Bluemke DA . New MR imaging contrast agents Magn Reson Imaging Clin N Am 1999 7: 255–273

    CAS  PubMed  Google Scholar 

  19. Clement O et al. Contrast agents in magnetic resonance imaging of the liver: present and future Biomed Pharmacother 1998 52: 51–58

    Article  CAS  Google Scholar 

  20. Low RN . Contrast agents for MR imaging of the liver J Magn Reson Imaging 1997 7: 56–67

    Article  CAS  Google Scholar 

  21. Cady EB . Clinical Magnetic Resonance Spectroscopy Plenum Press: New York 1990

    Book  Google Scholar 

  22. Rothman DL et al. 1H-[13C] NMR measurements of [4-13C] glutamate turnover in human brain Proc Natl Acad Sci USA 1992 89: 9603–9606

    Article  CAS  Google Scholar 

  23. Roden M, Shulman GI . Applications of NMR spectroscopy to study muscle glycogen metabolism in man Annu Rev Med 1999 50: 277–290

    Article  CAS  Google Scholar 

  24. Thomas EL et al. An in vivo13C magnetic resonance spectroscopic study of the relationship between diet and adipose tissue composition Lipids 1996 31: 145–151

    Article  CAS  Google Scholar 

  25. Cheng LL, Chang IW, Louis DN, Gonzalez RG . Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy of histopathology of intact human brain tumor specimens Cancer Res 1998 58: 1825–1832

    CAS  PubMed  Google Scholar 

  26. Barton SJ et al. Comparison of in vivo1H MRS of human brain tumours with 1H HR-MAS spectroscopy of intact biopsy samples in vitro MAGMA 1999 8: 121–128

    CAS  PubMed  Google Scholar 

  27. Tsien RY . Rosy dawn for fluorescent proteins Nat Biotechnol 1999 17: 956–957

    Article  CAS  Google Scholar 

  28. Szczepaniak LS et al. Nuclear magnetic spin-lattice relaxation of water protons caused by metal cage compounds Bioconjug Chem 1992 3: 27–31

    Article  CAS  Google Scholar 

  29. Moats RA, Fraser SE, Meade TJ . A ‘smart’ magnetic resonance imaging agent that reports on specific enzymatic activity Angew Chem Int Ed Engl 1997 36: 726–728

    Article  CAS  Google Scholar 

  30. Jacobs RE, Ahrens ET, Meade TJ, Fraser SE . Looking deeper into vertebrate development Cell Biology 1999 9: 73–76

    CAS  Google Scholar 

  31. Hüber MM et al. Fluorescently detectable magnetic resonance imaging agents Bioconjug Chem 1998 9: 242–249

    Article  Google Scholar 

  32. Li W-H, Fraser SE, Meade TJ . A calcium sensitive magnetic resonance contrast agent Proc 7th Ann Mtg Internat Soc Magn Reson Med 1999 1: 343

    Google Scholar 

  33. Li W-H, Fraser SE, Meade TJ . A calcium-sensitive magnetic resonance imaging contrast agent J Am Chem Soc 1999 121: 1413–1414

    Article  CAS  Google Scholar 

  34. Kayyem JF, Kumar RM, Fraser SE, Meade TJ . Receptor-targeted co-transport of DNA and magnetic resonance contrast agents Chem Biol 1995 2: 615–620

    Article  CAS  Google Scholar 

  35. Jalan R, Taylor-Robinson SD, Hodgson HJF . In vivo hepatic magnetic resonance spectroscopy: clinical or research tool? J Hepatol 1996 25: 414–424

    Article  CAS  Google Scholar 

  36. Menon DK et al. Effect of functional grade and aetiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances Hepatology 1995 21: 417–427

    CAS  PubMed  Google Scholar 

  37. Taylor-Robinson SD et al. In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver Liver 1997 17: 198–209

    Article  CAS  Google Scholar 

  38. Stegman LD et al. Noninvasive quantitation of cytosine deaminase transgene expression in human tumour xenografts with in vivo magnetic resonance spectroscopy Proc Natl Acad Sci USA 1999 96: 9821–9826

    Article  CAS  Google Scholar 

  39. Ikehira H et al. A preliminary study for clinical pharmacokinetics of oral fluorine anticancer medicines using the commercial MRI system 19F-MRS Br J Radiol 1999 72: 584–589

    Article  CAS  Google Scholar 

  40. Kievit E et al. Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts Cancer Res 1999 59: 1417–1421

    CAS  PubMed  Google Scholar 

  41. Walter G, Barton-Davis E, Shoturma DI, Sweeney HL . Noninvasive measurement of gene expression in skeletal muscle Proc 7th Ann Mtg Internat Soc Magn Reson Med 1999 1: 343

    Google Scholar 

  42. Bell JD et al. A 31P and 1H-NMR investigation in vitro of normal and abnormal human liver Biochem Biophys Acta 1993 1225: 71–77

    CAS  PubMed  Google Scholar 

  43. Hofmann C, Strauss M . Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system Gene Therapy 1998 5: 531–536

    Article  CAS  Google Scholar 

  44. Bell JD, Preece NE, Parkes HG . NMR of body fluids and tissue extracts. In: Gillies RJ (ed) NMR in Physiology and Biomedicine Academic Press: London 1994 221–236

    Chapter  Google Scholar 

  45. Nicholson JK, Lindon JC, Holmes E . ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data Xenobiotica 1999 29: 1181–1189

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr Michael J McGarvey, Department of Medicine, Imperial College School of Medicine, London, UK for his advice and Dr Tom Meade and Angelique Louie, Beckman Institute, California Institute of Technology, Pasadena, CA, USA for useful discussions and the reproduction of their diagrams in this review.

Author information

Authors and Affiliations

  1. Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    JD Bell

  2. Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    SD Taylor-Robinson

Authors
  1. JD Bell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. SD Taylor-Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bell, J., Taylor-Robinson, S. Assessing gene expression in vivo: magnetic resonance imaging and spectroscopy. Gene Ther 7, 1259–1264 (2000). https://doi.org/10.1038/sj.gt.3301218

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3301218

Keywords

This article is cited by

Search

Advanced search

Quick links