Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2025-01-03T16:02:07.965Z Has data issue: false hasContentIssue false

7 - Physics, Instrumentation, and Methods for Imaging Reporter Gene Expression in Living Subjects

Published online by Cambridge University Press:  07 September 2010

Sanjiv Sam Gambhir  and
Shahriar S. Yaghoubi
By
Craig S. Levin
Sanjiv Sam Gambhir
Affiliation:
Stanford University School of Medicine, California
Shahriar S. Yaghoubi
Affiliation:
Stanford University School of Medicine, California
Get access

Summary

INTRODUCTION

Achieving in vivo imaging of gene transfer provides molecular imaging with exciting opportunities in applications such as tracking stem or progenitor cells after transplantation or guiding efficacy studies of gene therapy. Monitoring of transgene expression is routinely accomplished by coexpressing marker genes with potential therapeutic transgenes in small laboratory animals. In this standard approach, the animals are sacrificed and methods such as histology or fluorescence microscopy (e.g., see) are performed on appropriate tissue samples to analyze the presence of marker gene expression. As with other biological studies, it is desirable to perform these studies routinely using noninvasive imaging to increase efficiency and information content associated with monitoring transgene expression over time in the same research subject.

In this chapter we describe currently available imaging technologies utilized in the reporter gene imaging research described in this book. These technologies exploit energy emissions that span nearly the entire range of the electromagnetic spectrum. The imaging system's function is to collect these signals and form images that can be analyzed to monitor the spatiotemporal characteristics of certain cellular and molecular processes occurring in cells located within tissues of living subjects. Certain imaging systems actually excite the processes that produce the detected signal, as in the case of optical fluorescence or magnetic resonance imaging. The molecular imaging technologies described in this book for noninvasive reporter gene imaging include optical techniques that utilize fluorescence or bioluminescence light photon emissions, the radionuclide methods of positron emission tomography and single photon emission tomography that collect positron annihilation or gamma ray photons, respectively, and magnetic resonance methods that rely on emissions from the radiofrequency portion of the electromagnetic spectrum.

Type
Chapter
Information
Molecular Imaging with Reporter Genes , pp. 151 - 192
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Gambhir, S. S., Herschman, H. R., Cherry, S. R. et al. (2000). Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2: 118–138.CrossRefGoogle ScholarPubMed
Weissleder, R., Mahmood, U. (2001). Molecular imaging. Radiology 219: 316–333.CrossRefGoogle ScholarPubMed
Luers, G. H., Jess, N., Franz, T. (2000). Reporter-linked monitoring of transgene expression in living cells using the ecdysone-inducible promoter system. Eur. J. Cell Bio 79(9): 653–657.CrossRefGoogle ScholarPubMed
Kain, S. R., Adams, M., Kondepudi, A., Yang, T. T. et al. (1995). Green fluorescent protein as a reporter of gene expression and protein localization. BioTechniques 19: 650–655.Google ScholarPubMed
Prasher, D. C., Eckenrode, V. K., Ward, W. W. et al. (1992). Primary structure of the Aequorea Victoria green fluorescent protein. Gene 111: 229–233.CrossRefGoogle ScholarPubMed
Tsien, R. Y. (1998). The green fluorescent protein. Annu Rev Biochem 67: 509–544.CrossRefGoogle ScholarPubMed
Baird, G. S., Zacharias, D. A., Tsien, R. Y. (2000). Biochemistry, mutagenesis, and oligomerization of DsRed, a red fluorescent-protein from coral. Proc Natl Acad Sci 22: 11984–11989.CrossRefGoogle Scholar
Matz, M. V., Fradkov, A. F., Labas, Y. A. et al. (1999). Fluorescent proteins from nonbioluminescent Anthozoa species. Nat Biotechnol 10: 969–973.CrossRefGoogle Scholar
Zhang, J., Cambell, R. E., Ting, A. Y., Tsien, R. Y. (2002). Creating new fluorescent probes for cell biology. Nat Rev Mol Cell Biol 12: 906–918.CrossRefGoogle Scholar
Contag, C. H., Contag, P. R., Mullins, J. I., et al. (1995). Photonic detection of bacterial pathogens in living hosts. Mol Microbiol 18: 593–603.CrossRefGoogle ScholarPubMed
Contag, C. H., Spilman, S., Contag, P. (1997). Visualizing gene expression in living animals using a bioluminescent reporter. Photochem Photobiol 66: 523–531.CrossRefGoogle ScholarPubMed
Mahmood, U., Weissleder, R. (2003). Near-infrared optical imaging of proteases in cancer. Mol Cancer Ther 2: 489–496.Google Scholar
Tung, C. H. et al. (2004). In vivo imaging of beta-galactosidase activity using far red fluorescent switch. Cancer Res 64: 1579–1583.CrossRefGoogle ScholarPubMed
West, J. L., Hlas, N. J. (2003). Engineered nanomaterials for biophotonics applications: improving sensing, imaging, and therapeutics. Annu Rev Biomed Eng 5: 285–292.CrossRefGoogle ScholarPubMed
Chance, B. (1998). Near-infrared images using continuous, phase-modulated, and pulsed light with quantitation of blood and blood oxygenation. Ann New York Acad Sci 838: 29–45.CrossRefGoogle ScholarPubMed
Levin, C. S. (2005). Primer on molecular imaging technology. Eur J Nucl Med Mol Imaging 32: S325–S345.CrossRefGoogle ScholarPubMed
Natasha, S. et al. (2001). Noninvasive functional optical spectroscopy of human breast tissue. Proc Natl Acad Sci USA 98: 4420–4425.Google Scholar
Ishimaru, A. (1978). Wave Propagation and Scattering in Random Media. Academic Press: New York.Google Scholar
Cheong, W. F., Prahl, S. A., Welch, A. J. (1990). A review of the optical properties of biological tissues. IEEE J. Quantum Electronics 26: 2166–2185.CrossRefGoogle Scholar
Rice, B. W., Cable, M. D., Nelson, M. B. (2001). In vivo imaging of light-emitting probes. J Biomed Opt 6(4), 432–440.CrossRefGoogle ScholarPubMed
Bogdanov, A., Wiessledder, R. (2002). In vivo imaging of gene delivery and expression. Trends in Biotech 20(8): S11–S18.CrossRefGoogle Scholar
Ruthel, G., Ribot, W. J., Bavari, S., Hoover, T. A. (2004). Time-lapse confocal imaging of development of Bacillus anthracis in macrophages. J Infect Dis 189: 1313–1316.CrossRefGoogle ScholarPubMed
Ray, P., De, A., Min, J. J., Tsien, R. Y., Gambhir, S. S. (2004). Imaging tri-fusion multimodality reporter gene expression in living subjects. Cancer Research 64: 1323–1330.CrossRefGoogle ScholarPubMed
Campbell, R. E., Tour, O., Palmer, A. E. et al. (2002). A monomeric red fluorescent protein. Proc Natl Acad Sci USA 99: 7877–7882.CrossRefGoogle ScholarPubMed
Hoffman, R. M. (2002). In vivo imaging of metastatic cancer with fluorescent proteins. Cell Death & Diff 9(8): 786–789.CrossRefGoogle ScholarPubMed
Holst, G. C. (1998). CCD Arrays, Cameras, and Displays. SPIE: Bellingham, WA.Google Scholar
Wessleder, R., Ntziachristos, V. (2003). Shedding light onto live molecular targets. Technol Trends Nat Med 2:123–128.CrossRefGoogle Scholar
Nickell, S. et al. (2000). Anisotropy of light propagation in human skin. Phys Med Biol 45: 2873–2886.CrossRefGoogle ScholarPubMed
Roblyer, D., Richards-Kortum, R., Sokolov, K. et al. (2008). Multispectral optical imaging device for in vivo detection of oral neoplasia. J Biomed Opt 13(2): 024019.CrossRefGoogle ScholarPubMed
Miller, P. J., Hoyt, C. C. (1995). Multispectral imaging with a liquid crystal tunable filter. Proc SPIE 2345: 354.CrossRefGoogle Scholar
Duda, R. O., Hart, P. E., Stork, D. G. (2001). Pattern Classification. 2nd ed. John Wiley and Sons: New York.Google Scholar
Kak, A. C., Slaney, M. (1998). Principles of Computerized Tomographic Imaging. IEEE Press: New York.Google Scholar
Graves, E. E., Ripoll, J., Weissleder, R., Ntziachristos, V. (2003). A submillimeter resoution fluorescence molecular imaging system for small animal imaging. Med Phys 5: 901–911.CrossRefGoogle Scholar
Ntziachristos, V., Bremer, C., Weissleder, R. (2003). Fluorescence imaging with near-infrared light: New technological advances that enable in vivo molecular imaging. Eur Radiol 13: 195–208.Google ScholarPubMed
Ntziachristos, V., Bremer, C., Graves, E. E. et al. (2002). In vivo tomographic imaging of near-infrared fluorescent probes. Mol Imaging 2: 82–88.CrossRefGoogle Scholar
Ntziachristos, V., Tung, C. H., Bremer, C., Weissleder, R. (2002). Fluorescence molecular tomography resolves protease activity in vivo. Nat Med 7: 757–760.CrossRefGoogle Scholar
Patwardhan, S. V., Bloch, S., Achilefu, S., Culver, J. P. (2006). Quantitative small animal fluorescence tomography using an ultrafast gated image intensifier. Proc 28th IEEE EMBS Ann Intl Conf, New York City, Aug. 30–Sept 3, 2006, 2675–2678.Google Scholar
Domañski, A. W. (2002). Optical sensors and microsystems. In: Martellucci, S., Chester, A. N., Mignani, A. G. (Eds.), Optical Tomography: Techniques and Applications. Springer: New York.Google Scholar
Hutchinson, C. L., Troy, T. L., Sevick-Muraca, E. M. (1996). Fluorescence lifetime determination in tissues and other random media from measurement of excitation and emission kinetics. Applied Optics 35: 2325–2332.CrossRefGoogle Scholar
Milstein, A. B., Oh, S., Webb, K. J. et al. (2003). Flurorescence optical diffusion tomography. Appl Opt 42(16): 3081–3094.CrossRefGoogle Scholar
Cai, W., Lax, W., Alfano, R. R. (2000). Cumulant solution of the elastic Boltzmann transport equation in an infinite uniform medium. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 61(4A): 3871–3876.Google Scholar
Cai, W., Das, B. B., Liu, F. et al. (1996). Time-resolved optical diffusion tomographic image reconstruction in highly scattering turbid media. Proc Nat Acad Sci USA 93(24): 13561–13564.CrossRefGoogle ScholarPubMed
Ye, J. C., Bouman, C. A., Webb, K. J., Millane, R. P. (2001). Nonlinear multigrid algorithms for Bayesian optical diffusion tomography. IEEE Trans Imag Proc 10(5): 909–922.Google Scholar
Oh, S., Milstein, A. B., Bouman, C. A.Webb, K. J. (2005). A general framework for nonlinear multigrid inversion. IEEE Trans Imag Proc 1: 125–140.Google Scholar
Ntziachristos, V., Weissleder, R. (2001). Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized born approximation. Optics Letters 26: 893–895.CrossRefGoogle ScholarPubMed
Arridge, S. R. (1993). Diffuse optical tomography. In: Muller, G. (Ed.), Medical Optical Tomography: Functional Imaging and Monitoring. for Advanced /Optical/ Technologies Series, Vol. IS11, SPIE /Optical/ Engineering Press: 31–64.Google Scholar
Pogue, B. W., McBride, T. O. et al. (1999). Comparison of imaging geometries for diffuse optical tomography of tissue. Opt Express 4: 270–286.CrossRefGoogle Scholar
Schmidt, F. E. W., Fry, M. E., Hillman, E. M. C. et al. (2000). A 32-channel time-resolved instrument for medical optical tomography. Rev Sci Instr 71(1): 256–265.CrossRefGoogle Scholar
ART Advanced Research Technologies Inc. (2003). Pre-clinical optical molecular imager. (white paper). September 2003. (http://www.art.ca).
Culver, J. P., Choe, R., Holboke, M. J. et al. (2003). 3d diffuse optical tomography in the plane parallel transmission geometry; Evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging. Medical Physics 30(2): 235–247.CrossRefGoogle ScholarPubMed
Yu, G., Durduran, T., Furuya, D. et al. (2003). Frequency-domain multiplexing system for in vivo diffuse light measurements of rapid cerebral hemodynamics. Appl Opt 42(16): 2931–2939.CrossRefGoogle ScholarPubMed
Hawrysz, D. J., Sevick-Muraca, E. M. (2000). Developments towards breast cancer imaging using near-infrared optical measurements and fluorescence contrast agents. Neoplasia 2: 388–417.CrossRefGoogle Scholar
Sevick-Muraca, E. M., Houston, J. P., Gurfinkel, M. (2002). Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents. Curr Opin Chem Biol 6: 642–650.CrossRefGoogle ScholarPubMed
Corlu, A., Durduran, T., Choe, R. et al. (2003). Uniqueness and wavelength optimization in continous-wave multispectral diffuse optical tomography. Opt Lett 28: 2339–2341.CrossRefGoogle Scholar
Wang, G., Hoffman, E. A. et al. (2003). Development of the first bioluminescent CT scanner. Radiology 229: 566–572.Google Scholar
Corlu, A. (2007). Multi-spectral and fluorescence diffuse optical tomography of breast cancer. Ph.D. Dissertation, University of Pennsylvania, 2007.Google Scholar
Chaudhari, A. J. (2006). Hyperspectral and multispectral optical bioluminescence and fluorescence tomography in small animal imaging. Ph.D. Dissertation, University of Southern California, 2006.Google Scholar
Psycharakis, S., Zacharakis, G., Garofalakis, A. et al. (2007). Autofluorescence removal from fluorescence tomography data using multispectral imaging. Proc SPIE 6626: 662601–662607.Google Scholar
Chaudhari, A. J., Darvas, F., Bading, J. R. et al. (2005). Hyperspectral and multispectral bioluminescence optical tomography for small animal imaging. Phys Med Biol 50: 5421–5441.CrossRefGoogle ScholarPubMed
Jain, R. K., Munn, L. I., Fukumura, D. (2002). Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer 4: 266–276.CrossRefGoogle Scholar
Dobschuetz, E., Pahernik, S., Hoffmann, T. et al. (2004). Dynamic intravital fluorescence microscopy – A novel method for the assessment of microvascular permeability in acute pancreatitis. Microvasc Res 67(1): 55–63.CrossRefGoogle Scholar
Kimura, T., Muguruma, N., Ito, S. et al. (2007). Infrared fluorescence endoscopy for the diagnosis of superficial gastric tumors. Gastrointest Endosc 66(1): 37–43.CrossRefGoogle Scholar
Pawley, J. B. (1995). Handbook of Biological Confocal Microscopy. (2nd ed.) Plenum Press: New York.CrossRefGoogle Scholar
Nakano, A. (2002). Spinning-disk confocal microscopy – a cutting-edge tool for imaging of membrane traffic. Cell Struct Funct 27(5): 349–355.CrossRefGoogle ScholarPubMed
Williams, R. M., Zipfel, W. R., Webb, W. W. (2001). Multiphoton microscopy in biological research. Curr Opin Chem Biol 5: 603–608.CrossRefGoogle ScholarPubMed
Oheim, M. et al. (2001). Two-photon microscopy in brain tissue: parameters influencing the imaging depth. J Neurosci Meth 111: 29–37.CrossRefGoogle ScholarPubMed
Mason, W. T. (ed.) (1999). Fluorescent and Luminescent Probes for Biological Activity. Academic Press: London.
Contag, C. H., Jenkins, D., Contag, P. R., Negrin, R. S. (2000). Use of reporter genes for optical measurements of neoplastic disease in vivo. Neoplasia 2, 41–52.CrossRefGoogle ScholarPubMed
Zhao, H., Doyle, T. C., Coquoz, O. et al. (2005). Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo. Journal of Biomedical Optics 10(4).CrossRefGoogle ScholarPubMed
Wang, G., Li, Y., Jiang, M. (2004). Uniqueness theorems in bioluminescence tomography. Med Phys 31(8): 2289–2299.CrossRefGoogle ScholarPubMed
Gu, X., Zhang, Q., Larcom, L., Jiang, H. (2004). Three-dimensional bioluminescence tomography with model-based reconstruction. Opt Express 12(17): 3996–4000.CrossRefGoogle ScholarPubMed
Weissleder, R., Tung, C. H., Mahmood, U., Bogdanov, A. (1999). In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 17: 375–378.CrossRefGoogle ScholarPubMed
Qi, J., Leahy, R. M., Cherry, S. R. et al. (1998). High resolution 3D Bayesian image reconstruction using the microPET small animal scanner. Phys Med Biol 43: 1001–1013.CrossRefGoogle ScholarPubMed
Alession, A. M., Kinahan, P. E. (2006). Improved quantitation for PET/CT image reconstruction with system modeling and anatomical priors. Med Phys 33(11): 4095–4103.CrossRefGoogle Scholar
Tjuvajev, J. G., Stockhammer, G., Desai, R. et al. (1995). Imaging the expression of transfected genes in vivo. Cancer Res 55: 6126–6132.Google ScholarPubMed
Gambhir, S. S., Barrio, J. R., Herschman, H. R., Phelps, M. E. (1999). Assays for noninvasive imaging of reporter gene expression. Nucl Med Biol 26: 481–490.CrossRefGoogle ScholarPubMed
Soghomonyan, S. A., Doubrovin, M., Pike, J. et al. (2005). Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK. Cancer Gene Ther 12: 101–108.CrossRefGoogle ScholarPubMed
Bettegowda, C., Foss, C. A., Chong, I. et al. (2005). Imaging bacterial infections with radiolabeled 1-(2′deoxy-2′-fluoro-beta-D-arabinofuranosyl)-5-iodouracil. Proc Natl Acad Sci USA 102: 1145–1150.CrossRefGoogle Scholar
Ivanova, A., Ponomarev, V., Ageyeva, L. et al. (2002). Imaging adoptive stem cell therapy with HSV-tk/GFP reporter gene. Mol Imaging 1: 208–209.Google Scholar
Koehne, G., Doubrovin, M., Doubrovina, E. et al. (2003). Seriel in vivo imaging of the target migration of human HSV-TK-transduced antigen-specific lymphocytes. Nat Biotechnol 21: 405–413.CrossRefGoogle Scholar
Dubey, P., Su, H., Adonai, N. et al. (2003). Quantitative imaging of the T cell anti-tumor response by positron emission tomography. Proc Natl Acad Sci USA 100: 1232–1237.CrossRefGoogle Scholar
Minn, A. J., Kang, Y., Serganova, I. et al. (2005). Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115: 44–55.CrossRefGoogle ScholarPubMed
Ponomarev, V., Doubrovin, M., Lyddane, C. et al. (2001). Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. Neoplasia 3: 480–488.CrossRefGoogle ScholarPubMed
Wernick, M., Aarsvold, J. (eds.). (2004). Emission Tomography: The Fundamentals of PET and SPECT. Elsevier Academic Press: San Diego.
Levin, C. S., Zaidi, H. (2007). Current trends in preclinical PET system design. In Zaidi, , Alavi, A. (Eds.), PET Instrumentation and Quantification 2(2): 125–160.
Tai, Y. C., Chatziioannou, A. et al. (2001). Performance evaluation of the microPET P4: a PET system dedicated to animal imaging. Phys Med Biology 46(7): 1845–1862.CrossRefGoogle ScholarPubMed
Tai, Y. C., Ruangma, A., Laforest, R., Siegel, S., Newport, D. F. (2003). Performance evaluation of the microPET (R) Focus: A second generation small animal PET system. J Nucl Med 44(5): 159–160.Google Scholar
Karp, J. S., Surti, S., Daube-Witherspoon, M. E. et al. (2003). Performance of a brain PET camera based on anger-logic gadolinium oxyorthosilicate detectors. J Nucl Med 44(8): 1340–1349.Google ScholarPubMed
Bettinardi, V., Danna, M., Savi, A. (2004). Performance evaluation of the new whole-body PET/CT scanner: Discovery ST. European Journal of Nucl Med and Mol Im 31(6): 867–881.CrossRefGoogle ScholarPubMed
Schmand, M., Eriksson, L., Casey, M. E., Wienhard, K., Flugge, G., Nutt, R. (1999). Advantages using pulse shape discrimination to assign the depth of interaction information (DOI) from a multi layer phoswich detector. IEEE Trans Nucl Sci 46(4): 985–990.CrossRefGoogle Scholar
Seidel, J., Vaquero, J. J., Green, M. V. (2003). Resolution uniformity and sensitivity of the NIH ATLAS small animal PET scanner: Comparison to simulated LSO scanners without depth-of-interaction capability. IEEE Trans Nucl Sci 50(5): 1347–1350.CrossRefGoogle Scholar
Levin, C. S., Dahlbom, M., Hoffman, E. J. (1995). A Monte Carlo correction for the effect of Compton scattering in 3-D PET brain imaging. IEEE Trans Nucl Sci 42: 1181–1188.CrossRefGoogle Scholar
Levin, C. S., Tai, Y.-C., Hoffman, E. J., Dahlbom, M. et al. (1995). Removal of the effect of Compton scattering in 3-D whole body positron emission tomography by Monte Carlo. 1995 IEEE MIC Conf Rec II: 1050–1054.Google Scholar
Kinahan, P. E., Rogers, J. G. (1989). Analytic 3D image reconstruction using all detected events. IEEE Trans Nucl Sci 36: 964–968.CrossRefGoogle Scholar
Defrise, M., Kinahan, P. E., Townsend, D. W., Michel, C., Sibomana, M., Newport, D. F. (1997). Exact and approximate rebinning algorithms for 3-D PET data. IEEE Trans Med Imaging 16(2): 145–158.CrossRefGoogle ScholarPubMed
Lange, K., Carson, R. (1984). EM reconstruction algorithms for emission and transmission tomography. J Comput Assist Tomography 8: 306–316.Google ScholarPubMed
Vardi, Y., Shepp, L. A., Kaufman, L. (1985). A statistical model for positron emission tomography. J Amer Stat Assoc 80: 8–37.CrossRefGoogle Scholar
Hebert, T., Leahy, R. (1989). A generalized EM algorithm for 3-D Bayesian reconstruction from Poisson data using Gibbs priors. IEEE Trans Med Imaging 8: 194–202.CrossRefGoogle ScholarPubMed
Green, P. J. (1982). Bayesian reconstructions from emission tomography data using a modified EM algorithm. IEEE Trans Med Imaging 1: 113–122.Google Scholar
Hudson, H. M., Larkin, R. S. (1994). Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imaging 13: 601–609.CrossRefGoogle ScholarPubMed
Liu, X., Comtat, C., Michel, C. et al. (2001). Comparison of 3-D reconstruction with 3D-OSEM and FORE+OSEM for PET. IEEE Trans Med Imag 20: 804–814.Google ScholarPubMed
Qi, J., Leahy, R. M. (2006). Iterative reconstruction techniques in emission computed tomography. Phys Med Biol 51: R541–578.CrossRefGoogle ScholarPubMed
Levin, C. S., Hoffman, E. J. (1999). Calculation of positron range and its effect on the fundamental limit of positron emission tomography system spatial resolution. Phys Med Biol 44: 781–799.CrossRefGoogle ScholarPubMed
Levin, C. S. (2002). Design of a high resolution and high sensitivity scintillation crystal array for PET with nearly complete light collection. IEEE Trans Nucl Sci 45(5): 2236–2243.CrossRefGoogle Scholar
Tai, Y. C., Chatziioannou, A. F., Yang, Y. F., Silverman, R. W., Meadors, K., Siegel, S., Newport, D. F., Stickel, J. R., Cherry, S. R. (2003). The MicroPET II: design, development and initial performance of an improved microPET scanner for small-animal imaging. Phys Medicine Biol 48(11): 1519–1537.CrossRefGoogle ScholarPubMed
Miyaoka, R. S., Kohlmyer, S. G., Lewellen, T. K. (2001). Performance characteristics of micro crystal element (MiCE) detectors. IEEE Trans Nucl Sci 48(4;2): 1403–1407.CrossRefGoogle Scholar
Levin, C. S. (2008). New imaging technologies to enhance the molecular sensitivity of positron emission tomography. Proc IEEE 2008(96): 439–467.CrossRefGoogle Scholar
Wu, H., Pal, D., O'Sullivan, J. A., Tai, Y. C. (2008). A feasibility study of a prototype PET insert device to convert a general-purpose animal PET scanner to higher resolution. J Nucl Med 49: 79–87.CrossRefGoogle Scholar
Tai, Y. C., Wu, H., Pal, D., O'Sullivan, J. A. (2008). Virtual-pinhole PET. J Nucl Med 49: 471–479.CrossRefGoogle ScholarPubMed
Pratx, P. D., Olcott, G., Chinn, G., and Levin, C. S. (2009). Accelerated Fully 3-D List-Mode OSEM for High-Resolution PET using Graphics Processing Units. IEEE Transactions in Medical Imaging 28(3): 435–445.CrossRefGoogle Scholar
Anderson, J., Oz, O., Brandon, D. et al. (2008). Initial evaluation of a new spatial resolution-recovery method for PET reconstruction. J Nucl Med 49(Suppl 1): 391.Google Scholar
Moses, W. W. (2003). Time of flight PET revisited. IEEE Trans Nucl Sci 50: 1325–1330.CrossRefGoogle Scholar
Karp, J. S., Surti, S., Daube-Witherspoon, M. E., Muehllehner, G. (2008). Benefit of time-of-flight in PET: Experimental and clinical results. J Nucl Med 49(3): 462–470.CrossRefGoogle ScholarPubMed
Surti, S., Karp, J. S., Popescu, L. M. et al. (2006). Investigation of time-of-flight benefit for fully 3-D PET. IEEE Trans Med Imag 25: 529–538.CrossRefGoogle ScholarPubMed
Conti, M. (2006). Effect of randoms on signal-to-noise ratio in TOF PET. IEEE Trans Nucl Sci 53: 1183–1193.CrossRefGoogle Scholar
Budinger, T. F. (1983). Time-of-flight positron emission tomography; status relative to conventional PET. J Nucl Med 24: 73–78.Google ScholarPubMed
Schramm, N. U., Ebel, G., Engeland, U. et al. (2003). High resolution SPECT using multi-pinhole collimation. IEEE Trans Nucl Sci 51: 757–763.Google Scholar
Beekman, F. J., Vastenbouw, B. (2004). Design and simulation of a high-resolution stationary SPECT system for small animals. Phys Med Biol 49: 4579–4592.CrossRefGoogle ScholarPubMed
Weisenberger, A. G., Wojcik, R., Bradley, E. L., Brewer, P., Majewski, S., Qian, J., Ranck, A., Saha, M. S., Smith, M. F., Welsh, R. E. (2003). SPECT-CT system for small animal imaging. IEEE Trans Nucl Sci 50(1): 74–79.CrossRefGoogle Scholar
MacDonald, L. R., Patt, B. E., Iwanczyk, J. S. et al. (2001). Pinhole SPECT of mice using the LumaGEM Gamma Camera. IEEE Trans Nucl Sci 48(3).CrossRefGoogle Scholar
Cherry, S. R., Sorenson, J. A., Phelps, M. E. (Eds.). (2003). Physics in Nuclear Medicine. (3rd. ed.). Elsevier Science: Philadelphia.Google Scholar
Levin, C. S. (2003). Detector design issues for compact nuclear emission cameras dedicated to breast imaging. Nucl Inst Meth A 497(1): 60–74.CrossRefGoogle Scholar
Graham, L. S., Levin, C. S., Muehllehner, G. (2003). Anger scintillation camera. In: Sandler, M. P., Coleman, R. E., Patton, J. A., Wackers, F. J., Gottschalk, A. (Eds.), Diagnostic Nuclear Medicine. 4th ed. Lippincott Williams & Wilkins: Philadelphia.Google Scholar
Lewellen, T. K., Miyaoka, R. S., Jansen, F., Kaplan, M. S. (1997). A data acquisition system for coincidence imaging using a conventional dual-headed gamma camera. IEEE Trans Nucl Sci 44(3): 1214–1218.CrossRefGoogle Scholar
Vastenhouw, B., Beekman, F. (2007). Submillimeter total-body murine imaging with U-SPECT-I. J Nucl Med 48: 487–493.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Hogemann, D., Basilion, J. P. (2002). Seeing inside the body: MR imaging of gene expression. Eur J Nucl Med 29(3): 400–408.CrossRefGoogle ScholarPubMed
Massoud, T. F., Gambhir, S. S. (2003). Molecular imaging in living subjects: Seeing fundamental biological processes in a new light. Genes & Develop 17: 545–580.CrossRefGoogle Scholar
Smith, R. C., Lange, R. C. (1997). Understanding Magnetic Resonance Imaging. CRC Press, Taylor & Francis Group, New York, NY.Google Scholar
Mitchell, D. G. (1999). MRI Principles. W.B. Saunders CompanyPhiladelphia, PA.Google Scholar
Liang, Z.-P., Lauterbur, P. C. (2000). Principles of Magnetic Resonance Imaging: A Signal Processing //Perspective/. IEEE Press, New York, NY.
Vlaardingerbroek, M. T., Boer, J. A. (2004). Magnetic Resonance Imaging. Springer Verlag Berlin, Germany.Google Scholar
Jin, J. (1998). Electromagnetic Analysis and Design in Magnetic Resonance Imaging. Taylor & Francis New York, NY.Google Scholar
Weissleder, R., Moore, A., Mahmood, U. et al. (2000). In vivo magnetic resonance imaging of transgene expression. Nat Med 6(3): 351–354.CrossRefGoogle ScholarPubMed
Hogemann, D., Josephson, L., Weissleder, R., Basilion, J. P. (2000). Improvement of MRI probes to allow efficient detection of gene expression. Bioconj Chem 11: 941–946.CrossRefGoogle ScholarPubMed
Louie, A. Y., Huber, M. M., Ahrens, E. T. et al. (2000). In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotech 18: 321–325.CrossRefGoogle ScholarPubMed
Gilad, A. A., McMahon, M. T., Walczak, P. et al. (2007). Artificial reporter gene providing MRI contrast based on proton exchange. Nat Biotech 25(2): 217–219.CrossRefGoogle ScholarPubMed
Hoge, W. S., Brooks, D. H., Madore, B., Kyriakos, W. E. (2005). A tour of accelerated parallel MR imaging from a linear systems perspective. Conc Magn Reson 27A: 17–37.CrossRefGoogle Scholar
Brown, M. A., Semelka, R. C. (2003). MRI: Basic Principles and Applications. 3rd ed. Wiley-Liss. New York, NY.CrossRefGoogle Scholar
Haacke, E. M., Brown, R. W., Thomson, M. R., Venkatesan, R. (1999). Magnetic Resonance Imaging. Physical Principles and Sequence Design. Wiley-Liss (John Wiley & Sons): New York.Google Scholar
Bernstein, M. A., King, K. F., Zhou, X. J. (2004). Handbook of MRI Pulse Sequences. Academic Press Amsterdam, NetherlandsGoogle Scholar
Shen, T., Weissleder, R., Papisov, M. et al. (1993). Monocrystalline iron oxide nanocompounds (MION): physicochemical properties. Magn Reson Med 29: 599–604.CrossRefGoogle ScholarPubMed
Genove, G., DeMarco, U., Xu, H. et al. (2005). A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 11(4): 450–454.CrossRefGoogle ScholarPubMed
Gilad, A. A., McMahon, M. T., Walczak, P. et al. (2007). Artificial reporter gene providing MRI contrast based on proton exchange. Nat Biotech 25(2): 217–219.CrossRefGoogle ScholarPubMed
Roberts, R. A., Barton, B. F. (1965). Theory of Signal Detectability: Composite Deferred Decision Theory. R. A. Roberts and B. F. Barton, Theory of Signal Detectability: Composite Deferred Decision Theory. Ann Arbor, MI: Univ. of Michigan, 1965.Google Scholar
Hill, D. L. G., Batchelor, P. G., Holden, M., Hawkes, D. (2001). Medical image registration. Phys Med Biol 46: R1–45.CrossRefGoogle ScholarPubMed
Schoder, H., Erdi, Y. E., Larson, S. M., Yeung, H. W. (2003). PET/CT: a new imaging technology in nuclear medicine. European J Nucl Med and Mol Imaging 30 (10): 1419–1437.CrossRefGoogle ScholarPubMed
Kinahan, P. E., Townsend, D. W., Beyer, T., Sashin, D. (1998). Attenuation correction for a combined 3D PET/CT scanner. Medical Physics 25(10): 2046–2053.CrossRefGoogle ScholarPubMed
Townsend, D. W., Beyer, T. (2002). A combined PET/CT scanner: the path to true image fusion. British Journal of Radiology 75: S24–30.CrossRefGoogle ScholarPubMed
Forster, G. J., Laumann, C., Nickel, O. et al. (2003). SPECT/CT image co-registration in the abdomen with a simple and cost-effective tool. Eur J Nucl Med and Mol Im 30(1): 32–39.Google Scholar
Keidar, Z., Israel, O., Krausz, Y. (2003). SPECT/CT in tumor imaging: Technical aspects and clinical applications. Seminars in Nuclear Medicine 33(3): 205–218.CrossRefGoogle ScholarPubMed
Goertzen, A. L., Meadors, A. K., Silverman, R. W., Cherry, S. R. (2002). Simultaneous molecular and anatomical imaging of the mouse in vivo. Phys Med Biol 47: 4315–4328.CrossRefGoogle ScholarPubMed
Liang, H., Yang, Y., Yang, K., Wu, Y., Boone, J. M., Cherry, S. R. (2007). A microPET/CT system for in vivo small animal imaging. Phys Med Biol 52: 3881–3894.CrossRefGoogle ScholarPubMed
Bérard, P., Riendeau, J., Pepin, C. et al. (2007). Investigation of the LabPETTM detector and electronics for photon-counting CT imaging. Nucl Instr Meth A 571: 114–117.CrossRefGoogle Scholar
Goertzen, A. L., Jones, D. W., Seidel, J. et al. (2005). First results from the high-resolution mouseSPECT annular scintillation camera. IEEE Trans Med Imaging 24: 863–867.CrossRefGoogle ScholarPubMed
Kim, H., Furenlid, L. R., Crawford, M. J. et al. (2006). Semi-SPECT: a small-animal single-photon emission computed tomography (SPECT) imager based on eight cadmium zinc telluride (CZT) detector arrays. Med Phys 33: 465–474.CrossRefGoogle Scholar
Madsen, M. T. (2007). Recent advances in SPECT imaging. J Nucl Med 48(4): 661–673.CrossRefGoogle ScholarPubMed
Parnham, K. B., Chowdhury, S., Li, J., Wagenaar, D. J., Patt, B. E. (2006). Second-generation, tri-modality pre-clinical imaging system. IEEE Nuclear Science Symposium Conference Record, Oct. 29–Nov. 4, 2006, San Diego: 1802–1805.Google Scholar
Patt, B., Parnham, K., Li, J., Iwata, K., Vandehei, T. (2005). FLEX: Tri-modality small animal tomography combining PET, SPECT and CT in a single modular gantry [abstract]. J Nucl Med 46: 207.Google Scholar
Saoudi, A., Lecomte, R. (1999). A novel APD-based detector module for multi-modality PET/SPECT/CT scanners. IEEE Trans Nucl Sci 46: 479–484.CrossRefGoogle Scholar
Farahani, K., Slates, R., Shao, Y., Silverman, R., Cherry, S. (1999). Contemporaneous positron emission tomography and MR imaging at 1.5 T. J Magn Reson Imaging 9: 497–500.3.0.CO;2-6>CrossRefGoogle Scholar
Shao, Y., Cherry, S. R., Farahani, K., Meadors, K. (1997). Simultaneous PET and MR imaging. Phys Med Biol 42: 1965–1970.CrossRefGoogle ScholarPubMed
Marsden, P. K., Strul, D., Keevil, S. F., Williams, S. C., Cash, D.Simultaneous PET and NMR. Br J Radiol 75: S53–59.CrossRef
Mackewn, J. E., Strul, D., Hallett, W. A. et al. (2005). Design and development of an MR-compatible PET scanner for imaging small animals. IEEE Trans Nucl Sci 52: 1376–1380.CrossRefGoogle Scholar
Pichler, B. J., Judenhofer, M. S., Catana, C. et al. (2006). Performance test of an LSO-APD detector in a 7-T MRI scanner for simultaneous PET/MRI. J Nucl Med 47: 639–647.Google Scholar
Judenhofer, M. S., Catana, C., Swann, B. K. et al. (2007). Simultaneous PET/MR images, acquired with a compact MRI compatible PET detector in a 7 Tesla magnet. Radiology 244: 807–814.CrossRefGoogle Scholar
Catana, C., Wu, Y., Judenhofer, M. S., Qi, J., Pichler, B. J., Cherry, S. R. (2006). Simultaneous acquisition of multislice PET and MR images: Initial results with a MR-compatible PET scanner. J Nucl Med 47: 1968–1976.Google Scholar
Raylman, R. R., Majewski, S., Velan, S. S. et al. (2007). Simultaneous acquisition of magnetic resonance spectroscopy (MRS) data and positron emission tomography (PET) images with a prototype MR-compatible, small animal PET imager. J Magn Reson 186: 305–310.CrossRefGoogle ScholarPubMed
Woody, C., Schlyer, D., Vaska, P. et al. (2007). Preliminary studies of a simultaneous PET/MRI scanner based on the RatCAP small animal tomograph. Nucl Instr Meth A 571: 102–105.CrossRefGoogle Scholar
Handler, W. B., Gilbert, K. M., Peng, H., Chronik, B. A. (2006). Simulation of scattering and attenuation of 511 keV photons in a combined PET/field-cycled MRI system. Phys Med Biol 51: 2479–2491.CrossRefGoogle Scholar
Lucas, A. J., Hawkes, R. C., Ansorge, R. E. et al. (2006). Development of a combined microPET-MR system. Technol Cancer Res Treat 5: 337–341.CrossRefGoogle ScholarPubMed
Yamamoto, S., Takamatsu, S., Murayama, H., Minato, K. (2005). A block detector for a multislice, depth-of-interaction MR-compatible PET. IEEE Trans Nucl Sci 52: 33–37.CrossRefGoogle Scholar
Rannou, F. R., Kohli, V., Prout, D. L., Chatziioannou, A. F. (2004). Investigation of OPET performance using GATE, a Geant4-based simulation software. IEEE Trans Nucl Sci 51: 2713–2717.CrossRefGoogle ScholarPubMed
Alexandrakis, G., Rannou, F. R., Chatziioannou, A. F. (2005). Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study. Phys Med Biol 50: 4225–4241.CrossRefGoogle ScholarPubMed
Vu, N. T., Silverman, R. W., Chatziioannou, A. F. (2006). Preliminary performance of optical PET (OPET) detectors for the detection of visible light photons. Nucl Instr Meth Phys Res A 569: 563–566.CrossRefGoogle Scholar
Peter, J., Ruehle, H., Stamm, V. et al. (2005). Development and initial results of a dual-modality SPECT/Optical small animal imager. IEEE Nucl Sci Symp Conf Rec 4.Google Scholar
Peter, J., Semmler, W. (2007). A modular design triple-modality SPECT-CT-ODT small animal imager [abstract]. Eur J Nuc Med Mol Imaging 34: S158.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×