Volumetric tomography of fluorescent proteins through small animals in vivo.

Volumetric detection and accurate quantification of fluorescent proteins in entire animals would greatly enhance our ability to monitor biological processes in vivo. Here we present a quantitative tomographic technique for visualization of superficial and deep-seated (>2-3 mm) fluorescent protein activity in vivo. We demonstrate noninvasive imaging of lung tumor progression in a murine model, as well as imaging of gene delivery using a herpes virus vector. This technology can significantly improve imaging capacity over the current state of the art and should find wide in vivo imaging applications in drug discovery, immunology, and cancer research.

[1]  R. Weissleder,et al.  Fluorescence molecular tomography resolves protease activity in vivo , 2002, Nature Medicine.

[2]  H. Shimada,et al.  Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Hoffman,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group. Review Gfp Imaging in Vivo Green Fluorescent Protein Imaging of Tumour Growth, Metastasis, and Angiogenesis in Mouse Models , 2022 .

[4]  Avinash C. Kak,et al.  Principles of computerized tomographic imaging , 2001, Classics in applied mathematics.

[5]  V. Verkhusha,et al.  The molecular properties and applications of Anthozoa fluorescent proteins and chromoproteins , 2004, Nature Biotechnology.

[6]  F. Wouters,et al.  Imaging biochemistry inside cells. , 2001, Trends in cell biology.

[7]  Vasilis Ntziachristos,et al.  Looking and listening to light: the evolution of whole-body photonic imaging , 2005, Nature Biotechnology.

[8]  I. Verma,et al.  Transduction of liver cells by lentiviral vectors: analysis in living animals by fluorescence imaging. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[9]  R. Pepperkok,et al.  Spectral imaging and its applications in live cell microscopy , 2003, FEBS letters.

[10]  Vasilis Ntziachristos,et al.  Experimental fluorescence tomography of tissues with noncontact measurements , 2004, IEEE Transactions on Medical Imaging.

[11]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[12]  Vasilis Ntziachristos,et al.  A submillimeter resolution fluorescence molecular imaging system for small animal imaging. , 2003, Medical physics.

[13]  George Nikiforidis,et al.  A novel spectral microscope system: application in quantitative pathology , 2003, IEEE Transactions on Biomedical Engineering.

[14]  S. Lukyanov,et al.  Fluorescent proteins from nonbioluminescent Anthozoa species , 1999, Nature Biotechnology.

[15]  Meng Yang,et al.  Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Weissleder,et al.  MRI of transgene expression: correlation to therapeutic gene expression. , 2002, Neoplasia.

[17]  R Weissleder,et al.  Novel gliosarcoma cell line expressing green fluorescent protein: A model for quantitative assessment of angiogenesis. , 1998, Microvascular research.

[18]  Vasilis Ntziachristos,et al.  Fluorescent protein tomography scanner for small animal imaging , 2005, IEEE Transactions on Medical Imaging.

[19]  Y Chen,et al.  Novel fluorescent protein from Discosoma coral and its mutants possesses a unique far‐red fluorescence , 2000, FEBS letters.

[20]  Vasilis Ntziachristos,et al.  Complete-angle projection diffuse optical tomography by use of early photons. , 2005, Optics letters.

[21]  X. Breakefield,et al.  Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[22]  R. Aronson,et al.  Photon diffusion coefficient in an absorbing medium. , 1999, Journal of the Optical Society of America. A, Optics, image science, and vision.

[23]  R. Weissleder,et al.  Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media. , 2002, Medical physics.

[24]  R. Tsien.  Building and breeding molecules to spy on cells and tumors , 2005, FEBS letters.

[25]  R. Tsien,et al.  Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein , 2004, Nature Biotechnology.

[26]  Vasilis Ntziachristos,et al.  Shedding light onto live molecular targets , 2003, Nature Medicine.

[27]  J. Ripoll,et al.  Experimental determination of photon propagation in highly absorbing and scattering media. , 2005, Journal of the Optical Society of America. A, Optics, image science, and vision.

[28]  Vasilis Ntziachristos,et al.  Singular-value analysis and optimization of experimental parameters in fluorescence molecular tomography. , 2004, Journal of the Optical Society of America. A, Optics, image science, and vision.

[29]  R. Weissleder,et al.  Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation. , 2001, Optics letters.

[30]  R. Tsien,et al.  Evolution of new nonantibody proteins via iterative somatic hypermutation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[31]  B. Pogue,et al.  Comparison of imaging geometries for diffuse optical tomography of tissue. , 1999, Optics express.

[32]  Vasilis Ntziachristos,et al.  Accuracy of fluorescent tomography in the presence of heterogeneities:study of the normalized born ratio , 2005, IEEE Transactions on Medical Imaging.