A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging.

A prototype small animal imaging system was created for coupling fluorescence tomography (FT) with x-ray microcomputed tomography (microCT). The FT system has the potential to provide synergistic information content resultant from using microCT images as prior spatial information and then allows overlay of the FT image onto the original microCT image. The FT system was designed to use single photon counting to provide maximal sensitivity measurements in a noncontact geometry. Five parallel detector locations are used, each allowing simultaneous sampling of the fluorescence and transmitted excitation signals through the tissue. The calibration and linearity range performance of the system are outlined in a series of basic performance tests and phantom studies. The ability to image protoporphyrin IX in mouse phantoms was assessed and the system is ready for in vivo use to study biological production of this endogenous marker of tumors. This multimodality imaging system will have a wide range of applications in preclinical cancer research ranging from studies of the tumor microenvironment and treatment efficacy for emerging cancer therapeutics.

[1]  Jamey P Weichert,et al.  Imaging of murine liver tumor using microCT with a hepatocyte-selective contrast agent: accuracy is dependent on adequate contrast enhancement. , 2004, The Journal of surgical research.

[2]  R. Weissleder,et al.  In vivo imaging of tumors with protease-activated near-infrared fluorescent probes , 1999, Nature Biotechnology.

[3]  R. Weissleder.  Scaling down imaging: molecular mapping of cancer in mice , 2002, Nature Reviews Cancer.

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

[5]  A. Tischler,et al.  MicroCT for high‐resolution imaging of ectopic pheochromocytoma tumors in the liver of nude mice , 2006, International journal of cancer.

[6]  Hamid Dehghani,et al.  Subsurface diffuse optical tomography can localize absorber and fluorescent objects but recovered image sensitivity is nonlinear with depth. , 2007, Applied optics.

[7]  Harry L. Graber,et al.  MRI-guided optical tomography: prospects and computation for a new imaging method , 1995 .

[8]  B. Pogue,et al.  Image-guided optical spectroscopy provides molecular-specific information in vivo: MRI-guided spectroscopy of breast cancer hemoglobin, water, and scatterer size. , 2007, Optics letters.

[9]  Hamid Dehghani,et al.  Magnetic-resonance-imaging-coupled broadband near-infrared tomography system for small animal brain studies. , 2005, Applied optics.

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

[11]  Bin Chen,et al.  Fluorescence Imaging in Vivo: Raster Scanned Point-Source Imaging Provides More Accurate Quantification than Broad Beam Geometries , 2004, Technology in cancer research & treatment.

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

[13]  V. Ntziachristos,et al.  MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions. , 2002, Neoplasia.

[14]  M. Schweiger,et al.  Diffuse optical tomography with spectral constraints and wavelength optimization. , 2005, Applied optics.

[15]  Quing Zhu,et al.  Imaging tumor angiogenesis by use of combined near-infrared diffusive light and ultrasound. , 2003, Optics letters.

[16]  Sabrina S Wilson.  Radiology , 1938, Glasgow Medical Journal.

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

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

[19]  V. Ntziachristos,et al.  Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[21]  Vasilis Ntziachristos,et al.  Volumetric tomography of fluorescent proteins through small animals in vivo. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[22]  B. Pogue,et al.  Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization. , 2007, Optics express.

[23]  R. Weissleder,et al.  Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging , 2002, European Radiology.

[24]  B. Pogue,et al.  Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Rinaldo Cubeddu,et al.  Localization and quantification of fluorescent inclusions embedded in a turbid medium , 2005, Physics in medicine and biology.

[26]  J. Culver,et al.  Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice. , 2005, Optics express.

[27]  M. Huang,et al.  Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers. , 2005, Neoplasia.

[28]  Vasilis Ntziachristos,et al.  Free-space fluorescence molecular tomography utilizing 360° geometry projections , 2007 .

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

[30]  Eva M Sevick-Muraca,et al.  Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents. , 2002, Current opinion in chemical biology.

[31]  B. Pogue,et al.  Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast. , 2001, Radiology.

[32]  M J Paulus,et al.  High resolution X-ray computed tomography: an emerging tool for small animal cancer research. , 2000, Neoplasia.

[33]  Dr. Andreas von Deimling.  Neoplasia , 1997, Laboratory investigation; a journal of technical methods and pathology.

[34]  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.

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