Ex Vivo Fluorescence Molecular Tomography of the Spine

We investigated the potential of fluorescence molecular tomography to image ex vivo samples collected from a large animal model, in this case, a dog spine. Wide-field time-gated fluorescence tomography was employed to assess the impact of multiview acquisition, data type, and intrinsic optical properties on the localization and quantification accuracy in imaging a fluorescent inclusion in the intervertebral disk. As expected, the TG data sets, when combining early and late gates, provide significantly better performances than the CW data sets in terms of localization and quantification. Moreover, the use of multiview imaging protocols led to more accurate localization. Additionally, the incorporation of the heterogeneous nature of the tissue in the model to compute the Jacobians led to improved imaging performances. This preliminary imaging study provides a proof of concept of the feasibility of quantitatively imaging complex ex vivo samples nondestructively and with short acquisition times. This work is the first step towards employing optical molecular imaging of the spine to detect and characterize disc degeneration based on targeted fluorescent probes.

[1]  Mark Dewhirst,et al.  Optical clearing of unsectioned specimens for three-dimensional imaging via optical transmission and emission tomography. , 2008, Journal of biomedical optics.

[2]  Xavier Intes,et al.  Development of an optical imaging platform for functional imaging of small animals using wide-field excitation , 2010, Biomedical optics express.

[3]  Cosimo D'Andrea,et al.  In vivo label-free three-dimensional imaging of zebrafish vasculature with optical projection tomography. , 2011, Journal of biomedical optics.

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

[5]  J. Mansfield,et al.  Multispectral imaging in biology and medicine: Slices of life , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[6]  T. Wurdinger,et al.  In-vivo imaging of murine tumors using complete-angle projection fluorescence molecular tomography. , 2009, Journal of biomedical optics.

[7]  F Lesage,et al.  Time Domain Fluorescent Diffuse Optical Tomography: analytical expressions. , 2005, Optics express.

[8]  R R Alfano,et al.  Photon migration in turbid media using a cumulant approximation to radiative transfer. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[9]  R. Alfano,et al.  Erratum: When does the diffusion approximation fail to describe photon transport in random media\? [Phys. Rev. Lett. 64, 2647 (1990)] , 1990 .

[10]  Xavier Intes,et al.  Monte Carlo based method for fluorescence tomographic imaging with lifetime multiplexing using time gates , 2011, Biomedical optics express.

[11]  Andreas H Hielscher,et al.  Optical tomographic imaging of small animals. , 2005, Current opinion in biotechnology.

[12]  Jeffrey C Lotz,et al.  Animal Models of Intervertebral Disc Degeneration: Lessons Learned , 2004, Spine.

[13]  Alfano,et al.  When does the diffusion approximation fail to describe photon transport in random media? , 1990, Physical review letters.

[14]  S. Gambhir,et al.  Noninvasive Molecular Neuroimaging Using Reporter Genes: Part I, Principles Revisited , 2008, American Journal of Neuroradiology.

[15]  Experimental measurement of time-dependent photon scatter for diffuse optical tomography. , 2010, Journal of biomedical optics.

[16]  Xavier Intes,et al.  Comparison of Monte Carlo methods for fluorescence molecular tomography-computational efficiency. , 2011, Medical physics.

[17]  Junjie Yao,et al.  Full-angle optical imaging of near-infrared fluorescent probes implanted in small animals , 2008 .

[18]  Vasilis Ntziachristos,et al.  Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo , 2008, Proceedings of the National Academy of Sciences.

[19]  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.

[20]  Xavier Intes,et al.  Full-field time-resolved fluorescence tomography of small animals. , 2010, Optics letters.

[21]  Britton Chance,et al.  Diffuse optical tomography with a priori anatomical information , 2003, SPIE BiOS.

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

[23]  D T Delpy,et al.  Measurement of the optical properties of the skull in the wavelength range 650-950 nm , 1993, Physics in medicine and biology.

[24]  J. Mansfield,et al.  Distinguished photons: a review of in vivo spectral fluorescence imaging in small animals. , 2010, Current pharmaceutical biotechnology.

[25]  A. Welch,et al.  A review of the optical properties of biological tissues , 1990 .

[26]  Frank Bradke,et al.  Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury , 2011, Nature Medicine.

[27]  V. Ntziachristos,et al.  Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons. , 2010, Optics letters.

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

[29]  Xavier Intes,et al.  Mesh-based Monte Carlo method in time-domain widefield fluorescence molecular tomography , 2012, Journal of biomedical optics.

[30]  Xavier Intes,et al.  Time-resolved diffuse optical tomography with patterned-light illumination and detection. , 2010, Optics letters.

[31]  Gregory Boverman,et al.  Time resolved fluorescence tomography of turbid media based on lifetime contrast. , 2006, Optics express.

[32]  J. Ripoll,et al.  In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green. , 2003, Medical physics.

[33]  Jan Huisken,et al.  Selective plane illumination microscopy techniques in developmental biology , 2009, Development.

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

[35]  V. Ntziachristos Going deeper than microscopy: the optical imaging frontier in biology , 2010, Nature Methods.

[36]  Hisataka Kobayashi,et al.  In vivo real-time, multicolor, quantum dot lymphatic imaging. , 2009, The Journal of investigative dermatology.

[37]  M. Haskins,et al.  Large animal models and gene therapy , 2006, European Journal of Human Genetics.

[38]  M S Feld,et al.  Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms. , 1997, Proceedings of the National Academy of Sciences of the United States of America.