Dual-tracer background subtraction approach for fluorescent molecular tomography

Abstract. Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction approaches.

[1]  E. Sevick-Muraca,et al.  Truncated Newton's optimization scheme for absorption and fluorescence optical tomography: Part II Reconstruction from synthetic measurements. , 1999, Optics express.

[2]  Ranadhir Roy,et al.  Evaluation of anatomical structure and non-uniform distribution of imaging agent in near-infrared fluorescence-enhanced optical tomography. , 2005, Optics express.

[3]  T. Hasan,et al.  Advantages of a dual-tracer model over reference tissue models for binding potential measurement in tumors , 2012, Physics in medicine and biology.

[4]  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.

[5]  Vasilis Ntziachristos,et al.  Three-Dimensional in Vivo Imaging of Green Fluorescent Protein-Expressing T Cells in Mice with Noncontact Fluorescence Molecular Tomography , 2007, Molecular imaging.

[6]  Hjalmar Brismar,et al.  Cellular studies of binding, internalization and retention of a radiolabeled EGFR-binding affibody molecule. , 2007, Nuclear medicine and biology.

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

[8]  Antony K. Chen,et al.  Ratiometric bimolecular beacons for the sensitive detection of RNA in single living cells , 2010, Nucleic acids research.

[9]  M. Iester,et al.  Pre-injection fluorescence in indocyanine green angiography. , 1996, Ophthalmology.

[10]  Anand T. N. Kumar,et al.  Two postprocessing techniques for the elimination of background autofluorescence for fluorescence lifetime imaging microscopy. , 2008, Journal of biomedical optics.

[11]  Brian W. Pogue,et al.  High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas , 2011, Molecular Imaging and Biology.

[12]  Hamid Dehghani,et al.  Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction. , 2009, Communications in numerical methods in engineering.

[13]  Stephen B. Tuttle,et al.  Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue. , 2008, The Review of scientific instruments.

[14]  Xin Liu,et al.  Extraction of target fluorescence signal from in vivo background signal using image subtraction algorithm , 2012, International Journal of Automation and Computing.

[15]  Daniel J. Hawrysz,et al.  Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: Near-infrared fluorescence tomography , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Brian W. Pogue,et al.  Imaging workflow and calibration for CT-guided time-domain fluorescence tomography , 2011, Biomedical optics express.

[17]  E M Sevick-Muraca,et al.  Origin of phosphorescence signals reemitted from tissues. , 1994, Optics letters.

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

[19]  Vasilis Ntziachristos,et al.  Effects of background fluorescence in fluorescence molecular tomography. , 2005, Applied optics.

[20]  Jason R. Gunn,et al.  Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers , 2012, Journal of visualized experiments : JoVE.

[21]  H L Graber,et al.  Improved Reconstruction Algorithm for Luminescence Optical Tomography when Background Lumiphore is Present. , 1998, Applied optics.

[22]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[23]  Scott C Davis,et al.  Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications. , 2010, Journal of photochemistry and photobiology. B, Biology.

[24]  B. Wilson,et al.  In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications , 1998, Photochemistry and photobiology.

[25]  D. M. Olive,et al.  A systematic approach to the development of fluorescent contrast agents for optical imaging of mouse cancer models. , 2007, Analytical biochemistry.

[26]  Britton Chance,et al.  Multichannel photon counting instrument for spatially resolved near infrared spectroscopy , 1999 .

[27]  Hamid Dehghani,et al.  A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging. , 2009, The Review of scientific instruments.

[28]  Jason R. Gunn,et al.  In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging , 2012, Molecular Imaging and Biology.

[29]  M. Schweiger,et al.  Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans. , 2007, Optics express.

[30]  Tayyaba Hasan,et al.  Improved tumor contrast achieved by single time point dual-reporter fluorescence imaging. , 2012, Journal of biomedical optics.

[31]  C. Bouman,et al.  Fluorescence optical diffusion tomography. , 2003, Applied optics.

[32]  S. Arridge.  Optical tomography in medical imaging , 1999 .

[33]  Richard M Levenson,et al.  Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging. , 2005, Journal of biomedical optics.

[34]  Sharon Bloch,et al.  Monomolecular multimodal fluorescence-radioisotope imaging agents. , 2005, Bioconjugate chemistry.

[35]  Tayyaba Hasan,et al.  Imaging tumor variation in response to photodynamic therapy in pancreatic cancer xenograft models. , 2010, International journal of radiation oncology, biology, physics.

[36]  E. Sevick-Muraca,et al.  Truncated Newton's optimization scheme for absorption and fluorescence optical tomography: Part I theory and formulation. , 1999, Optics express.

[37]  Tayyaba Hasan,et al.  Imaging targeted-agent binding in vivo with two probes. , 2010, Journal of biomedical optics.

[38]  Vasilis Ntziachristos,et al.  Fluorescence molecular tomography in the presence of background fluorescence , 2006, Physics in medicine and biology.

[39]  Tayyaba Hasan,et al.  Detecting epidermal growth factor receptor tumor activity in vivo during cetuximab therapy of murine gliomas. , 2010, Academic radiology.