In vivo quantitative three-dimensional localization of tumor labeled with exogenous specific fluorescence markers.

We introduce a diffused optical detection system based on the administration of a fluorophore-antibody conjugate to diseased tissue. The conjugate interacts with the antigens expressed by the diseased tissue, resulting in fluorescent labeling of the antigen. By combining an optical detection system with a reconstruction algorithm developed on the basis of the random-walk model, we were able to determine the position of the fluorophore (and, thus, of the diseased cells) in the tissue. We present three-dimensional reconstructions of the location of a fluorophore (FITC-fluorescein isothiocyanate) in the tongues of mice. Measurements were performed with the fluorophore embedded at various simulated depths. The simulations were performed with agarose-based gel slabs applied to the tongue as tissuelike phantoms. Reconstructed fluorophore locations agree well with the actual values.

[1]  J Lee,et al.  Error consideration in contrast-enhanced three-dimensional optical tomography. , 2001, Optics letters.

[2]  Israel Gannot,et al.  Inverse method 3-D reconstruction of localized in vivo fluorescence-application to Sjogren syndrome , 1999 .

[3]  A H Gandjbakhche,et al.  Optical simulations of a noninvasive technique for the diagnosis of diseased salivary glands in situ. , 1998, Medical physics.

[4]  E M Sevick-Muraca,et al.  Three-dimensional unconstrained and constrained image-reconstruction techniques applied to fluorescence, frequency-domain photon migration. , 2001, Applied optics.

[5]  R Nossal,et al.  Effects of multiple-passage probabilities on fluorescent signals from biological media. , 1997, Applied optics.

[6]  Daniel J. Hawrysz,et al.  Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents. , 2000, Neoplasia.

[7]  M. Zellweger,et al.  An optical phantom with tissue-like properties in the visible for use in PDT and fluorescence spectroscopy. , 1997, Physics in medicine and biology.

[8]  J A Rowlands,et al.  X-ray detectors for digital radiography. , 1997, Physics in medicine and biology.

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

[10]  I. Gannot,et al.  Quantitative fluorescent imaging of specific markers of diseased tissue , 1996 .

[11]  K Svanberg,et al.  In vivo fluorescence imaging for tissue diagnostics. , 1997, Physics in medicine and biology.

[12]  Raphael Aronson,et al.  Recovery of optical cross-section perturbations in dense-scattering media by transport-theory-based imaging operators and steady-state simulated data. , 1996, Applied optics.

[13]  George H. Weiss,et al.  V: Random Walk and Diffusion-Like Models of Photon Migration in Turbid Media , 1995 .

[14]  S. Arridge,et al.  Optical imaging in medicine: II. Modelling and reconstruction , 1997, Physics in medicine and biology.

[15]  Brian W. Pogue,et al.  Mathematical model for time-resolved and frequency-domain fluorescence spectroscopy in biological tissues. , 1994, Applied optics.

[16]  A. Welch,et al.  Determining the optical properties of turbid mediaby using the adding-doubling method. , 1993, Applied optics.

[17]  I. Gannot,et al.  Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma , 2002, British Journal of Cancer.

[18]  S R Arridge,et al.  Optical imaging in medicine: I. Experimental techniques , 1997, Physics in medicine and biology.

[19]  R. Rava,et al.  Analytical model for extracting intrinsic fluorescence in turbid media. , 1993, Applied optics.

[20]  A. Gandjbakhche Diffuse optical imaging and spectroscopy, in vivo , 2001 .

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

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

[23]  D. Delpy,et al.  Optical Imaging in Medicine , 1998, CLEO/Europe Conference on Lasers and Electro-Optics.