Late-fluorescence mammography assesses tumor capillary permeability and differentiates malignant from benign lesions.

Using scanning time-domain instrumentation we recorded fluorescence projection mammograms on few breast cancer patients prior, during and after infusion of indocyanine green (ICG), while monitoring arterial ICG concentration by transcutaneous pulse densitometry. Late-fluorescence mammograms recorded after ICG had been largely cleared from the blood by the liver, showed invasive carcinomas at high contrast over a rather homogeneous background, whereas benign lesions did not produce (focused) fluorescence contrast. During infusion, tissue concentration contrast and hence fluorescence contrast is determined by intravascular contributions, whereas late-fluorescence mammograms are dominated by contributions from protein-bound ICG extravasated into the interstitium, reflecting relative microvascular permeabilities of carcinomas and normal breast tissue. We simulated intravascular and extravascular contributions to ICG tissue concentration contrast within a two-compartment unidirectional pharmacokinetic model.

[1]  H. Rinneberg,et al.  Detection and characterization of breast tumours by time-domain scanning optical mammography , 2008 .

[2]  D. Boas,et al.  Dynamic functional and mechanical response of breast tissue to compression. , 2008, Optics express.

[3]  B. Chance,et al.  Pharmacokinetic-rate images of indocyanine green for breast tumors using near-infrared optical methods , 2008, Physics in medicine and biology.

[4]  E. Uzgiris Tumor Microvasculature: Endothelial Leakiness and Endothelial Pore Size Distribution in a Breast Cancer Model , 2008, Breast cancer : basic and clinical research.

[5]  B. Tromberg,et al.  Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy. , 2007, Journal of biomedical optics.

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

[7]  Jennifer J. Gibson,et al.  Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms. , 2007, Radiology.

[8]  B. Tromberg,et al.  Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy , 2007, Proceedings of the National Academy of Sciences.

[9]  O. Steinkellner,et al.  Development of a multi-channel time-domain fluorescence mammograph , 2007, SPIE BiOS.

[10]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[11]  B. Tromberg,et al.  In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy. , 2006, Journal of biomedical optics.

[12]  Hamid Dehghani,et al.  Image analysis methods for diffuse optical tomography. , 2006, Journal of biomedical optics.

[13]  M. Dewhirst,et al.  Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. , 2006, Journal of the National Cancer Institute.

[14]  K. T. Moesta,et al.  Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas , 2005, Physics in medicine and biology.

[15]  K. T. Moesta,et al.  Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients , 2005, Physics in medicine and biology.

[16]  Alessandro Torricelli,et al.  Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions , 2005, Physics in medicine and biology.

[17]  Peter Hauff,et al.  Comparison of Two Tricarbocyanine-Based Dyes for Fluorescence Optical Imaging , 2005, Journal of Fluorescence.

[18]  R. Lucht,et al.  Microcirculation and microvasculature in breast tumors: Pharmacokinetic analysis of dynamic MR image series , 2004, Magnetic resonance in medicine.

[19]  Heidrun Wabnitz,et al.  Four-wavelength multichannel time-resolved optical mammograph , 2003, European Conference on Biomedical Optics.

[20]  Heidrun Wabnitz,et al.  A four-wavelength multi-channel scanning time-resolved optical mammograph , 2003 .

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

[22]  Anthony J. Durkin,et al.  In vivo quantification of optical contrast agent dynamics in rat tumors by use of diffuse optical spectroscopy with magnetic resonance imaging coregistration. , 2003, Applied optics.

[23]  Robert C. Brasch,et al.  Macromolecular contrast agents for MR mammography: current status , 2003, European Radiology.

[24]  H. Dvorak,et al.  Ultrastructural studies define soluble macromolecular, particulate, and cellular transendothelial cell pathways in venules, lymphatic vessels, and tumor‐associated microvessels in man and animals , 2002, Microscopy research and technique.

[25]  P. Vaupel,et al.  Blood supply, oxygenation status and metabolic micromilieu of breast cancers: characterization and therapeutic relevance. , 2000, International journal of oncology.

[26]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[27]  Eva M. Sevick-Muraca,et al.  Pharmacokinetics of ICG and HPPH-car for the Detection of Normal and Tumor Tissue Using Fluorescence, Near-infrared Reflectance Imaging: A Case Study¶ , 2000, Photochemistry and photobiology.

[28]  R K Jain,et al.  Openings between defective endothelial cells explain tumor vessel leakiness. , 2000, The American journal of pathology.

[29]  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.

[30]  S. Colak,et al.  Clinical optical tomography and NIR spectroscopy for breast cancer detection , 1999 .

[31]  P M Schlag,et al.  Development of a time-domain optical mammograph and first in vivo applications. , 1999, Applied optics.

[32]  D M Shames,et al.  Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media. , 1998, AJR. American journal of roentgenology.

[33]  Josephine,et al.  Binding properties of indocyanine green in human blood. , 1998, Investigative ophthalmology & visual science.

[34]  P. Ott,et al.  Nontraditional effects of protein binding and hematocrit on uptake of indocyanine green by perfused rat liver. , 1997, The American journal of physiology.

[35]  P M Schlag,et al.  Frequency-domain techniques enhance optical mammography: initial clinical results. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P. Ott,et al.  The kinetics of continuously infused indocyanine green in the pig , 1996, Journal of Pharmacokinetics and Biopharmaceutics.

[37]  A A Lammertsma,et al.  Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method. , 1992, Cancer research.

[38]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[39]  N. Ishibashi,et al.  Determination of protein in human serum by high-performance liquid chromatography with semiconductor laser fluorometric detection. , 1986, Analytical chemistry.

[40]  D. Meijer,et al.  Pharmacokinetics of biliary excretion in man V , 1983, European Journal of Clinical Pharmacology.

[41]  J. Hodges,et al.  Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit. , 1962, The Journal of clinical investigation.

[42]  D. Meijer,et al.  Pharmacokinetics of biliary excretion in man. VI. Indocyanine green , 2004, European Journal of Clinical Pharmacology.

[43]  B. Pogue,et al.  Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results. , 2003, Applied optics.

[44]  D Artemov,et al.  Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts. , 2001, Neoplasia.

[45]  P S Tofts,et al.  Measurement of capillary permeability from the Gd enhancement curve: a comparison of bolus and constant infusion injection methods. , 1994, Magnetic resonance imaging.

[46]  P. Ott,et al.  Enhancement of unbound clearance of ICG by plasma proteins, demonstrated in human subjects and interpreted without assumption of facilitating structures. , 1993, Journal of hepatology.