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  • Print publication year: 2010
  • Online publication date: September 2010

4 - Noninvasive Imaging of Gene Expression with Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy

Summary

INTRODUCTION

Magnetic resonance imaging (MRI) has developed from an intriguing research project initially conceived in 1973 to an essential diagnostic method in the armamentarium of clinical radiologists. An estimated 26.6 million MRI procedures were performed in 2006 in the United States that generated approximately $20 billion in service revenue. The demand for clinical MRI diagnoses is expected to increase by 30% by 2020. This projected growth is due in part to the rising prevalence of age-related pathologies of soft tissues that can be conveniently monitored with MRI, such as the anatomy of pathologies in the cardiopulmonary system (e.g., regions of myocardial infarcts), neurological system (e.g., regions of cerebral infarcts, morphological changes during multiple sclerosis), and musculoskeletal system (e.g., tears in ligaments, tendons, and cartilage). MRI offers advantages relative to optical imaging methods limited to making diagnoses only near tissue surfaces, and relative to PET, SPECT, CT, and X-ray imaging methods that use potentially harmful ionizing radiation. Unlike these other imaging modalities, MRI also provides excellent spatial resolution at or smaller than 1 mm3 for clinical diagnostics and approaching 0.1 mm3 for small-animal research studies. MRI can also assess physiological function, such as the function of the cardiopulmonary system (e.g., MR angiography of vasculature), neurological system (e.g., fMRI of brain activity), renal system (e.g., perfusion imaging of kidney function), musculoskeletal system (e.g., MR elastography of connective tissues), and cancer lesions (e.g., dynamic contrast enhancement MRI of angiogenic tumors).

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REFERENCES
Lauterbur, P. C. (1973). Image formation by induced local interactions: Examples employing nuclear magnetic resonance. Nature 242: 190–191.
2006 MRI Market Summary Report. (2007). IMV International: Des Plaines, Ill.
Ahrens, E. T., Rothbacher, U., Jacobs, R. E., Fraser, S. E. (1998). A model for MRI contrast enhancement using T1 agents. Proc Nat Acad Sci USA 95(15): 8443–8448.
Mills, P. H., Ahrens, E. T. (2007). Theoretical MRI contrast model for exogenous T2 agents. Magn Res Med 57(2): 442–447.
Massoud, T. F., Gambhir, S. S. (2003). Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes & Dev 17: 545–580.
Weissleder, R., Mahmood, U. (2001). Molecular imaging. Radiology 219: 316–333.
Bloch, F., Hansen, W. W., Packard, M. (1946). The nuclear induction experiment. Phys Rev 70: 474–485.
Purcell, E.M., Torrey, H. C., Pound, R. V. (1946). Resonance absorption by nuclear magnetic moments in a solid. Phys Rev 69: 37–38.
Abragam, A. (1961). Principles of Nuclear Magnetism. Oxford University Press: New York.
Schlicter, C. P. (1978). Principles of Magnetic Resonance. Springer-Verlag: New York.
Conradi, M. S., Saam, B. T., Yablonsky, D. A., Woods, J. C. (2006). Hyperpolarized 3He and perfluorocarbon gas diffusion MRI of lungs. Prog NMR Spect 48: 63–83.
Mansson, S., Johansson, E., Magnusson, P., Chai, C.-M., Hansson, G., Petersson, J. S., Stahlberg, F., Golman, K. (2006). 13C imaging – a new diagnostic platform. Eur Radiol 16: 57–67.
Wu, X. (2003). Optical pumping and hyperpolarized spin relaxation. Proceedings of SPIE-The International Society for Optical Engineering (Photonics and Imaging in Biology and Medicine) 5254: 97–107.
Golman, K., Olsson, L. E., Axelsson, O., Mansson, S., Karlsson, M., Petersson, J. S. (2003). Molecular imaging using hyperpolarized 13C. Brit J Radiol 76(Spec. Iss. 2): S118–S127.
Hersman, F. W., Ruset, I. C., Ketel, S., Muradian, I., Covrig Silviu, D., Distelbrink, J., Porter, W., Watt, D., Ketel, J., Brackett, J., Hope, A., Patz, S. (2008). Large production system for hyperpolarized 129Xe for human lung imaging studies. Acad Radiol 15(6): 683–692.
Mansson, S., Johansson, E., Magnusson, P., Chai, C.-M., Hansson, G., Petersson, J. S., Stahlberg, F., Golman, K. (2006). 13C imaging – a new diagnostic platform. European Radiol 16(1): 57–67.
Dugas, J. P., Garbow, J. R., Kobayashi, D. K., Conradi, M. S. (2004). Hyperpolarized 3He MRI of mouse lung. Magn Reson Med 52(6): 1310–1317.
Beek, E. J. R., Wild, J. M., Kauczor, H.-U., Schreiber, W., Mugler, J. P., Lange, E. E. (2004). Functional MRI of the lung using hyperpolarized 3-helium gas. J Magn Reson Imaging 20(4): 540–554.
Driehuyst, B., Cofer, G. P., Pollaro, J., Mackel, J. B., Hedlund, L. W., Johnson, G. A. (2006). Imaging alveolar-capillary gas transfer using hyperpolarized 129Xe MRI. Proc Nat Acad Sci USA 103(48): 18278–18283.
Johansson, E., Mansson, S., Wirestam, R., Svensson, J., Petersson, J. S., Golman, K., Stahlberg, F. (2004). Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C. Magn Reson Med 51(3): 464–472.
Olsson, L. E., Chai, C.-M., Axelsson, O., Karlsson, M., Golman, K., Petersson, J. S. (2006). MR coronary angiography in pigs with intraarterial injections of a hyperpolarized 13C substance. Magn Reson Med 55(4): 731–737.
Ishii, M., Emami, K., Kadlecek, S., Petersson, J. S., Golman, K., Vahdat, V., Yu, J., Cadman, R. V., MacDuffie-Woodburn, J., Stephen, M., Lipson, D. A., Rizi, R. R. (2007). Hyperpolarized 13C MRI of the pulmonary vasculature and parenchyma. Magn Reson Med 57(3): 459–463.
Golman, K., Petersson, J. S., Magnusson, P., Johansson, E., Aakeson, P., Chai, C.-M., Hansson, G., Maansson, S. (2008). Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med 59(5): 1005–1013.
Schroeder, M. A., Cochlin, L. E., Heather, L. C., Clarke, K., Radda, G. K., Tyler, D. J. (2008). In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Nat Acad Sci USA 105(33): 12051–12056.
Golman, K., in't Zandt, R., Lerche, M., Pehrson, R., Ardenkjaer-Larsen, J. H. (2006). Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. Cancer Res 66(22): 10855–10860.
Chen, A. P., Albers, M. J., Cunningham, C. H., Kohler, S. J., Yen, Y-F., Hurd, R. E., Tropp, J., Bok, R., Pauly, J. M., Nelson, S. J., Kurhanewicz, J., Vigneron, D. B. (2007). Hyperpolarized C-13 spectroscopic imaging of the TRAMP mouse at 3T-initial experience. Magn Reson Med 58(6): 1099–1106.
Day, S. E., Kettunen, M. I., Gallagher, F. A., Hu, D.-E., Lerche, M., Wolber, J., Golman, K., Ardenkjaer-Larsen, J. H., Brindle, K. M. (2007). Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nature Med 13(11): 1382–1387.
Gallagher, F. A., Kettunen, M. I., Day, S. E., Lerche, M., Brindle, K. M. (2008). 13C MR spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine. Magn Reson Med 60(2): 253–257.
Wei, Q., Seward, G. K., Hill, P. A., Patton, B., Dimitrov, I. E., Kuzma, N. N., Dmochowski, I. J. (2006). Designing 129Xe NMR biosensors for matrix metalloproteinase detection. J Am Chem Soc 128(40): 13274–13283.
Schroder, L., Lowery, T. J., Hilty, C., Wemmer, D. E., Pines, A. (2006). Molecular imaging using a targeted magnetic resonance hyperpolarized biosensor. Science 314: 446–449.
Haacke, E. M., Brown, R. W., Thompson, M. R., Venkatesan, R. (1999). Magnetic Resonance Imaging: Physical Principles and Sequence Design. John Wiley & Sons: New York.
Ward, K. M., Aletras, A. H., Balaban, R. S. (2000). A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson 143: 79–87.
Woessner, D. E., Zhang, S., Merritt, M. E., Sherry, A. D. (2005). Numerical solutions of the bloch equations provides insights into the optimum design of PARACEST agents for MRI. Magn Reson Med 53: 790–799.
Zijl, P. C. M., Jones, C. K., Ren, J., Malloy, C. R., Sherry, A. D. (2007). MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST). Proc Nat Acad Sci USA 104(11): 4359–4364.
Ward, K. M., Balaban, R. S. (2000). Determination of pH using water protons and chemical exchange dependent saturation transfer. Magn Reson Med 44: 799–802.
Zijl, P. C. M., Duyn, J. H., Bryant, L. H., Bulte, J. W. M. (2003). The use of starburst dendrimers as pH contrast agents. Proc Int Soc Magn Reson Med 9: 878.
Zhang, S., Winter, P., Wu, K., Sherry, A. D. (2001). A novel europium(III)-based MRI contrast agent. J Am Chem Soc 123: 1517–1518.
Zhang, S., Merritt, M., Woessner, D. E., Lenkinski, R. E., Sherry, A. D. (2003). PARACEST agents: modulating MRI contrast via water proton exchange. Acc Chem Res 36: 783–790.
Yoo, B., Pagel, M. D. (2006). A PARACEST MRI contrast agent to detect enzyme activity. J Am Chem Soc 128: 14302–14303.
Zhang, S., Trokowski, R., Sherry, A. D. (2003). A paramagnetic CEST agent for imaging glucose by MRI. J Am Chem Soc 125(50): 15288–15289.
Trokowski, R., Zhang, S., Sherry, A. D. (2004). Cyclen-based phenylborate ligands and their Eu3+ complexes for sensing glucose by MRI. Bioconj Chem 15: 1431–1440.
Aime, S., Castelli, D. D., Fedeli, F., Terreno, E. (2002). A paramagnetic MRI-CEST agent responsive to lactate concentration. J Am Chem Soc 124: 9364–9365.
Trokowski, R., Ren, J., Kalman, F. K., Sherry, A. D. (2005). Selective sensing of zinc ions with a PARACEST contrast agent. Angew Chem Int Ed 44: 6920–6923.
Zhang, S., Malloy, C. R., Sherry, A. D. (2005). MRI thermometry based on PARACEST agents. J Am Chem Soc 127: 17572–17573.
Artemov, D. (2003). Molecular magnetic resonance imaging with targeted contrast agents. J Cell Biochem 90: 518–524.
Heckl, S., Piplorn, R., Waldeck, W., Spring, H., Jenne, J., der Lieth, C-W., Corban-Wilhelm, H., Debus, J., Braun, K. (2003). Intracellular visualization of prostate cancer using magnetic resonance imaging. Cancer Res 63: 4766–4772.
Artemov, D., Bhujwalla, Z. M., Bulte, J. W. M. (2004). Magnetic resonance imaging of cell surface receptors using targeted contrast agents. Curr Pharm Biotech 5: 485–494.
Flacke, S., Fischer, S., Scott, M. J., Fuhrhop, R. J., Allen, J. S., McLean, M., Winter, P., Sicard, G. A., Gaffney, P. J., Wickline, S. A., Lanza, G. M. (2001). Novel MRI contrast agent for molecular imaging of fibrin. Implications for detecting vulnerable plaques. Circulation 104: 1280–1285.
Caruthers, S. D., Winter, P. M., Wickline, S. A., Lanza, G. M. (2006). Targeted magnetic resonance imaging contrast agents. Methods Molec Med 124: 387–400.
Torchilin, V. P. (2000). Polymeric contrast agents for medical imaging. Curr Pharm Biotech 1(2): 183–215.
Raghunand, N., Howison, C., Sherry, A. D., Zhang, S., Gillies, R. J. (2003). Renal and systemic pH imaging by contrast-enhanced MRI. Magn Reson Med 49: 249–257.
Garcia-Martin, M. L., Martinez, G. V., Raghunand, N., Sherry, A. D., Zhang, S., Gillies, R. J. (2006). High resolution pHe imaging of rat glioma using pH-dependent relaxivity. Magn Reson Med 55(2): 309–315.
Aime, S., Barge, A., Castelli, D. D., Fedeli, F., Mortillaro, A., Nielsen, F. U., Terreno, E. (2002). Paramagnetic lanthanide(III) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications. Magn Reson Med 47: 639–648.
Terreno, E., Castelli, D. D., Cravotto, G., Milone, L., Aime, S. (2004). Ln(III)-DOTAMGly complexes: a versatile series to assess the determinants of the efficacy of paramagnetic chemical exchange saturation transfer agents for magnetic resonance imaging applications. Invest Radiol 39(4): 235–243.
Yoo, B., Raam, M., Rosenblum, R., Pagel, M. D. (2007). Enzyme-responsive PARACEST MRI contrast agents: A new biomedical imaging approach for studies of the proteasome. Contrast Media Molec Imag 2(4): 189–198.
Nori, A., Kopecek, J. (2004). Intracellular targeting of polymer-bound drugs for cancer chemotherapy. Adv Drug Delivery Rev 57: 609–636.
Lee, C. C., MacKay, J. A., Frechet, J. M. J., Szoka, F. C. (2005). Designing dendrimers for biological applications. Nature Biotech 23(12): 1517–1526.
Gaucher, G., Dufresne, M.-H., Sant, V. P., Kang, N., Maysinger, D., Leroux, J.-C. (2005). Block copolymer micelles : preparation, characterization and application in drug delivery. J Control Rel 109(1–3): 169–188.
Drummond, D. C., Meyer, O., Hong, K., Kirpotin, D. B., Papahadjopoulos, D. (1999). Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharm Rev 51(4): 691–743.
Coiffier, B. (2004). Chemotherapy combined with monoclonal antibodies in the treatment of patients with diffuse large B-cell lymphoma. In Progress in Oncology. Jones and Bartlett Publishers: Sudbury, MA, pp. 220–235.
Taylor, J. S., Tofts, P. S., Port, R., Evelhoch, J. L., Knopp, M., Reddick, W. E., Runge, V. M., Mayr, N. (1999). MR imaging of tumor microcirculation: Promise for the new millennium. J Magn Reson Imag 10(6): 903–907.
Maeda, H., Wua, J., Sawa, T., Matsumura, Y., Hori, K. (2000). Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Rel 65: 271–284.
Allen, M. J., MacRenaris, K. W., Venkatasubramanian, P. N., Meade, T. J. (2004). Cellular delivery of MRI contrast agents. Chem & Biol 11: 301–307.
Fischer, R., Kohler, K., Fotin-Mlezek, M., Brock, R. (2004). A stepwise dissection of the intracellular fate of cationic cell-penetrating peptides. J Biol Chem 279(13): 12625–12635.
Melikov, K., Chernomordik, L. V. (2005). Arginine-rich cell penetrating peptides: from endosomal uptake to nuclear delivery. Cell Mol Life Sci 62: 2739–2749.
Perez, J. M., Josephson, L., O'Loughlin, T., Hogemann, D., Weissleder, R. (2002). Magnetic relaxation switches capable of sensing molecular interactions. Nature Biotech 20: 816–820.
Perez, J., O'Loughlin, T., Simeone, F. J., Weissleder, R., Josephson, L. (2002). DNA-based magnetic naoparticle assembly acts as a magnetic relaxation nanoswitch allowing screening of DNA-cleaving agents. J Am Chem Soc 124: 2856–2857.
Su, W., Mishra, R., Pfeuffer, J., Wiesmueller, K.-H., Ugurbil, K., Engelmann, J. (2007). Synthesis and cellular uptake of a MR contrast agent coupled to an antisense peptide nucleic acid – cell-penetrating peptide conjugate. Contrast Media Molec Imag 2(1): 42–49.
Tian, X., Chakrabarti, A., Amirkhanov, N., Aruva, M. R., Zhang, K., Cardi, C. A., Lai, S., Thakur, M. L.Receptor-mediated internalization of chelator-PNA-peptide hybridization probes for radioimaging or magnetic resonance imaging of oncogene mRNAs in tumours. Biochem Soc Trans 35(1): 72–76.
Bremer, C., Weissleder, R. (2001). In vivo imaging of gene expression: MR and optical technologies. Acad Radiol 8: 15–23.
Hogemann, D., Basilion, J. P. (2002). “Seeing inside the body:”: MR imaging of gene expression. Eur J Nucl Med 29: 400–408.
Bulte, J. W. M., Verkuyl, J. M., Herynek, V., Katsanis, E., Brocke, S., Holla, M., Frank, J. A. (1998). Magnetoimmunodetection of (transfected) ICAM-1gene expression. Proc Int Soc Magn Reson Med 6: 307.
So, P.W., Hotee, S., Herlihy, A. H., Bell, J. D. (2005). Generic method for imaging transgene expression. Magn Reson Med 54: 218–221.
Mantyla, T., Hakumaki, J. M., Huhtala, T., Narvanen, A., Yla-Herttuala, S. (2006). Targeted magnetic resonance imaging of Scavidin-receptor in human umbilical vein endothelial cells in vitro. Magn Reson Med 55: 800–804.
Gilad, A. A., McMahon, M. T., Walczak, P., Winnard, P. T., Raman, V., Laarhoven, H. W. M., Skoglund, C. M., Bulte, J. W. M., Zijl, P. C. M. (2007). Artificial reporter gene providing MRI contrast based on proton exchange. Nature Biotech 25(2): 217–219.
Koretsky, A., Lin, Y.-J., Schorle, H., Jaenisch, R. (1996). Genetic control of MRI contrast by expression of the transferrin receptor. Proc Int Soc Magn Reson Med 4: 69.
Ichikawa, T., Hoegemann, D., Saeki, Y., Tyminski, E., Terada, K., Weissleder, R., Chiocca, E. A., Basilion, J. P. (2002). MRI of transgene expression: correlation to therapeutic gene expression. Neoplasia 4(6): 523–530.
Hoegemann, D., Josephson, L., Weissleder, R., Basilion, J. P. (2000). Improvement of MRI probes to allow efficient detection of gene expression. Bioconj Chem 11(6): 941–946.
Weissleder, R., Moore, A., Mahmood, U., Bhorade, R., Benveniste, H., Chiocca, E. A., Basilion, J. P. (2000). In vivo magnetic resonance imaging of transgene expression. Nature Med 6(3): 351–354.
Hogemann-Savellano, D., Bos, E., Blondet, C., Sato, F., Abe, T., Josephson, L., Weissleder, R., Gaudet, J., Sgroi, D., Peters, P. J., Basilion, J. P. (2003). The transferrin receptor: a potential molecular imaging marker for human cancer. Neoplasia 5(6): 495–506.
Gilad, A. A., Winnard, P. T., Zijl, P. C. M., Bulte, J. W. M. (2007). Developing MR reporter genes: promises and pitfalls. NMR Biomed 20: 275–290.
Bulte, J. M., Vymazal, J., Brooks, R. A., Pierpaoli, C., Frank, J. A. (1993). Frequency dependence of MR relaxation times. II. Iron oxides. J Magn Reson Imag 3: 641–648.
Gottesfeld, Z., Neeman, M. (1996). Ferritin effect on the transverse relaxation of water: NMR microscopy at 9.4 T. Magn Reson Med 35: 514–520.
Cohen, B., Dafni, H., Meir, G., Harmelin, A., Neeman, M. (2005). Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors. Neoplasia 7: 109–117.
Cohen, B., Ziv, K., Plaks, V., Israely, T., Kalchenko, V., Harmelin, A., Benjamin, L. E., Neeman, M. (2007). MRI detection of transcriptional regulation of gene expression in transgenic mice. Nature Med 13(4): 498–503.
Genove, G., Demarco, U., Xu, H., Goins, W. F., Ahrens, E. T. (2005). A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 11: 450–454.
Zurkiya, O., Chan, W. S., Hu, X. (2008). MagA is sufficient for producing magnetic nanoparticles in mammalian cells, making it an MRI reporter. Magn Reson Med 59: 1225–1231.
Weissleder, R., Simonova, M., Bogdanova, A., Bredow, S., Enochs, W. S., Bogdanov, A.MR imaging and scintigraphy of gene expression through melanin induction. Radiology 204: 425–429.
Moats, R. A., Fraser, S. E., Meade, T. (1997). A “smart” magnetic resonance imaging agent that reports on specific enzyme activity. Angew Chem Intl Edn Engl 36: 726–728.
Louie, A. Y., Huber, M. M., Ahrens, E. T., Rothbacher, U., Moats, R., Jacobs, R. E., Fraser, S. E., Meade, T. J. (2000). In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotech 18: 321–325.
Cui, W., Otten, P., Li, Y., Koeneman, K. S., Yu, J., Mason, R. P. (2004). Novel NMR approach to assessing gene transfection: 4-fluoro-2-nitrophenolbeta-d-galactopyranoside as a prototype reporter molecule for β-galactosidase. Magn Reson Med 51: 616–620.
Kodibagkar, V. D., Yu, J., Liu, L., Hetherington, H. P., Mason, R. P. (2006). Imaging beta-galactosidase activity using (19)F chemical shift imaging of LacZ gene-reporter molecule 2-fluoro-4-nitrophenolbeta-d-galactopyranoside. Magn Reson Imaging 24: 959–962.
Cui, W., Liu, L., Adam, A., Yu, J., Li, X., Mason, R. P. (2005). Detection of beta-galactosidase activity in a human tumor xenograft by 1H MRI in vivo using S-Gal. Proc Int Soc Magn Reson Med 13: 2593.
Lauffer, R., McMurry, T. J., Dunham, S. O., Scott, D. M., Parmelee, D. J., Dumas, S. (1997). Bioactivated diagnostic imaging contrast agents. WIPO Patent Application97/36619.
Nivorozhkin, A., Kolodziej, A. F., Caraban, P., Greenfield, M. T., Lauffer, R. B., McMurry, T. J. (2001). Enzyme activated Gd3+ magnetic resonance imaging contrast agents with a prominent receptor induced magnetization enhancement. Angew Chem Int Ed 40: 2903–2906.
Bogdanov, A., Matuszewski, L., Bremer, C., Petrovski, A., Weissleder, R. (2002). Oligomerization of paramagnetic substrates result in signal amplification and can be used for MR imaging of molecular targets. Molec Imag 1: 16–23.
Chen, J., Pham, W., Weissleder, R., Bogdanov, A.Human myeloperoxidase: a potential target for molecular MR imaging in atherosclerosis. Magn Reson Med 52: 1021–1028.
Chen, J., Querol, M., Bogdanov, A., Weissleder, R. (2006). Imaging myeloperoxidase in mice by using novel amplifiable paramagnetic substrates. Radiology 240: 473–481.
Querol, M., Chen, J. W., Weissleder, R., Bogdanov, A. (2005). DTPA-bisamide-based MR sensor agents for peroxidase imaging. Org Lett 7: 1719–1722.
Querol, M., Chen, J. W., Bogdanov, A. (2006). A paramagnetic contrast agent with myeloperoxidase-sensing properties. Org Biomol Chem 4: 1887–1895.
Perez, J., Simeone, F. J., Tsourkas, A., Josephson, L., Weissleder, R.Peroxidase substrate nanosensors for MR imaging. Nanolett 4: 119–122.
Aime, S., Cabella, C., Colombatto, S., Crich, S. G., Gianolio, E., Maggioni, F. (2002). Insight into the use of paramagnetic Gd(III) complexes in MR molecular imaging investigations. J Magn Reson Imag 16: 394–406.
Duimstra, J., Meade, T. J. (2005). Self-immolative magnetic resonance imaging contrast agents sensitive to beta-glucuronidase. WIPO Patent Application 05/115105.
Shiftan, L., Israely, T., Cohen, M., Frydman, V., Dafni, H., Stern, R., Neeman, M. (2005). Magnetic resonance imaging visualization of hyaluronidase in ovarian carcinoma. Cancer Res 65: 10316–10323.
Shiftan, L., Neeman, M. (2006). Kinetic analysis of hyaluronidase activity using a bioactive MRI contrast agent. Contrast Media Molec Imag 1: 106–112.
Zhao, M., Josephson, L., Tang, Y., Weissleder, R. (2003). Magnetic sensors for protease assays. Angew Chem Int Ed 43: 1375–1378.
Liu, G., Lu, Y., Pagel, M. D. (2007). Design and characterization of new irreversible responsive PARACEST MRI contrast agent that detects nitric oxide. Magn Reson Med 58: 1249–1256.
Rohovec, J., Maschmeyer, T., Aime, S., Peters, J. A. (2003). The structure of the sugar residue in glycated human serum albumin and its molecular recognition by phenylboronate. Chem Eur J 9: 2193–2199.
Glogard, C., Stensrud, G., Aime, S. (2003). Novel radical-responsive MRI contrast agent based on paramagnetic liposomes. Magn Reson Chem 41(8): 585–588.
Koretsky, A. P., Brosnan, M. J., Chen, L. H., Chen, J. D., Dyke, T. (1990). NMR detection of creatine kinase expressed in liver of transgenic mice: determination of free ADP levels. Proc Natl Acad Sci USA 87: 3112–3116.
Auricchio, A., Zhou, R., Wilson, J. M., Glickson, J. D. (2001). In vivo detection of gene expression in liver by 31P nuclear magnetic resonance spectroscopy employing creatine kinase as a marker gene. Proc Natl Acad Sci USA 98: 5205–5210.
Li, Z., Qiao, H., Lebherz, C., Choi, S. R., Zhou, X., Gao, G., Kung, H. F., Rader, D. J., Wilson, J. M., Glickson, J. D., Zhou, R. (2005). Creatine kinase, a magnetic resonance-detectable marker gene for quantification of liver-directed gene transfer. Hum Gene Ther 16: 1429–1438.
Askenasy, N., Koretsky, A. P. (2002). Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels. Am J Physiol Cell Physiol 282: C338–C346.
Walter, G., Barton, E. R., Sweeney, H. L. (2000). Noninvasive measurement of gene expression in skeletal muscle. Proc Natl Acad Sci USA 97: 5151–5155.
Landis, C. S., Yamanouchi, K., Zhou, H., Mohan, S., Roy-Chowdhury, N., Shafritz, D. A., Koretsky, A., Roy-Chowdhury, J., Hetherington, H. P., Guha, C.Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice. Hepatology 44(5): 1250–1258.
Ki, S., Sugihara, F., Kasahara, K., Tochio, H., Okada-Marubayashi, A., Tomita, S., Morita, M., Ikeguchi, M., Shirakawa, M., Kokubo, T. (2006). A novel magnetic resonance-based method to measure gene expression in living cells. Nucleic Acids Res 34: e51.
Weiss, R. G., Gerstenblith, G., Bottomley, P. A. (2005). ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci USA 102: 808–813.
Stegman, L. D., Rehemtulla, A., Beattie, B., Kievit, E., Lawrence, T. S., Blasberg, R. G., Tjuvajev, J. G., Ross, B. D. (1999). Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. Proc Natl Acad Sci USA 96: 9821–9826.
Kraitchman, D. L., Bulte, J. W. (2008). Imaging of stem cells using MRI. Basic Res Cardiol 103(2): 105–113.
Walczak, P., Kedziorek, D. A., Gilad, A. A., Barnett, B. P., Bulte, J. W. M. (2007). Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover: the case of the shiverer dysmyelinated mouse brain. Magn Reson Med 58: 261–269.
Serganova, I., Blasberg, R. (2005). Reporter gene imaging: potential impact on therapy. Nucl Med Bio 32: 763–780.
Ahrens, E. T., Flores, R., Xu, H., Morel, P. A. (2005). In vivo imaging platform for tracking immunotherapeutic cells. Nature Biotech 23: 983–987.
Harisinghani, M. G., Barentsz, J., Hahn, P. F., Deserno, W. M., Tabatabaei, S., Kaa, C. H., Rosette, J., Weissleder, R. (2003). Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348(25): 2491–2499.