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Optical Medical Imaging

Working Group 8.31

In vivo optical properties of breast tissue


Breast cancer is the most common cancer among females. Approximately one out of ten women in industrial countries will experience this disease during her life span. In addition to conventional diagnostic modalities like x-ray mammography, MR mammography and ultrasound, there are many research activities to develop optical imaging as a tool for the characterization of lesions in the female breast.

Near-infrared spectroscopy offers the possibility to measure local concentrations of oxyhaemoglobin and deoxyhaemoglobin in the breast, which are altered in carcinomas due to neoangiogenesis. Further aproaches comprise the determination of the water and collagen content in lesions and in the surrounding healthy tissue. At PTB methods have been developed that enable the measurement of optical properties of malignant and benign lesions in the breast in vivo.


PTB uses a time-resolved method. As an example, the Fig. below shows the block diagram of an optical mammograph that was recently developed at the PTB in close cooperation with the companies Philips Research Europe (Hamburg), Bayer Schering Pharma AG (Berlin) and PicoQuant GmbH (Berlin) within a common research project funded by the German Federal Ministry of Education and Research (2005 to 2008). The breast tissue is transilluminated by short near infrared laser pulses. Hereby, the breast is slightly compressed between two parallel glass plates, and optical fibers are used to scan the tissue. 

Block diagram and photo of a time-domain fluorescence mammograph developed at the PTB. The device employs 4 lasers for spectroscopic investigations and one additional laser for fluorescence measurements with the exogeneous contrast agent indocyanine green.

Models of light propagation in tissue are used to generate optical mammograms and to determine the absorption and scattering properties of the tissue. When an exogeneous contrast agent has been applied then laser photons can excite the molecules of this agent which subsequently emit fluorescence. Hereby the detectors additionally measure the fluorescence light in order to determine the local distribution of the contrast agent in the tissue.

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Optical properties and physiological parameters of breast tumors

A clinical study on more than 150 patients has shown that breast carcinomas essentially differ from the surrounding healthy tissue by an increased total haemoglobin concentration. For some carcinomas, additionally a decreased blood oxygen saturation was observed which indicates an increased metabolism in the tumor tissue.

Blood oxygen saturation versus total hemoglobin concentration for 87 carcinomas and for the corresponding healthy breast tissue

The results of the clinical study showed that, besides the carcinomas, a large number of benign lesions were characterized by an increased hemoglobin concentration, too. Accordingly, the optical measurements did not allow to obtain a sufficient differentiation between malignant and benign lesions. Therefore, optical measurements without contrast agent are less suited for detection and differentiation of breast tumors, but they can be applied, e.g., to periodically investigate lesions with increased hemoglobin concentration, e.g. to check the response of a carcinoma to a chemotherapy.

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D. Grosenick, H. Wabnitz, B. Ebert,
Review: Recent advances in contrast-enhanced near infrared diffuse optical imaging of diseases using indocyanine green,
J. Near Infrared Spectrosc. 20 (2012) 203-221.

A. Poellinger, S. Burock, D. Grosenick, A. Hagen, L. Lüdemann, F. Diekmann, F. Engelken, R. Macdonald, H. Rinneberg, P. M. Schlag,
Breast cancer: early- and late-fluorescence near-infrared imaging with indocyanine green - a preliminary study,
Radiology 258 (2011) 409-416.

D. Grosenick, A. Hagen, O. Steinkellner, A. Poellinger, S. Burock, P.M. Schlag, H. Rinneberg, R. Macdonald,
A multichannel time-domain scanning fluorescence mammograph: performance assessment and first in vivo results,
Rev. Sci. Instrum. 82 (2011) 024302.

A. Hagen, D. Grosenick, R. Macdonald, H. Rinneberg, S. Burock, P. Warnick, A. Poellinger, P. M. Schlag,
Late-fluorescence mammography assesses tumor capillary permeability and differentiates malignant from benign lesions ,
Opt. Expr. 17 (2009) 17016 - 17033.

H. Rinneberg, D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, G. Wübbeler, R. Macdonald, P. M. Schlag,
Detection and characterization of breast tumours by time-domain scanning optical mammography,
Opto-Electr. Rev. 16 (2008) 147 - 162.

D. Grosenick, A. Kummrow, R. Macdonald, P. M. Schlag, H. Rinneberg,
Evaluation of higher-order time-domain perturbation theory of photon diffusion on breast-equivalent phantoms and optical mammograms,
Phys. Rev. E 76 (2007) 061908.

D. Grosenick, K. T. Moesta, M. Möller, J. Mucke, H. Wabnitz, B. Gebauer, C. Stroszczynski, B. Wassermann, P. M. Schlag, H. Rinneberg,
Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients,
Phys. Med. Biol. 50 (2005) 2429-2449.

D. Grosenick, H. Wabnitz, K. T. Moesta, J. Mucke, P. M. Schlag, H. Rinneberg,
Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas,
Phys. Med. Biol. 50 (2005) 2451-2468.

H. Rinneberg, D. Grosenick, K. T. Moesta, J. Mucke, B. Gebauer, C. Stroszczynski, H. Wabnitz, M. Moeller, B. Wassermann, P. M. Schlag,
Scanning Time-domain Optical Mammography: Detection and Characterization of Breast Tumors In Vivo,
Opens external link in new windowTechnol. Cancer Res. Treat. 4 (2005) 483 - 496.

T. Dierkes, D. Grosenick, K. T. Moesta, M. Möller, P. M. Schlag, H. Rinneberg, S. Arridge,
Reconstruction of optical properties of phantom and breast lesion in vivo from paraxial scanning data,
Phys. Med. Biol. 50 (2005) 2519-2542.

B. Wassermann, A. Kummrow, K. T. Moesta, D. Grosenick, J. Mucke, H. Wabnitz, M. Möller, R. Macdonald, P. M. Schlag, H. Rinneberg,
In-vivo tissue optical properties derived by linear perturbation theory for edge-corrected time domain mammograms,
Opt. Expr. 13 (2005) 8571-8583.

A. Pifferi, A. Torricelli, A. Bassi, P. Taroni, R. Cubeddu, H. Wabnitz, D. Grosenick, M. Möller, R. Macdonald, J. Swartling, T. Svensson, S. Andersson-Engels, R. L. P. van Veen, H. J. C. M. Sterenborg, J. M. Tualle, H. L. Nghiem, S. Avrillier, M. Whelan, and H. Stamm,
Performance assessment of photon migration instruments: the MEDPHOT protocol,
Appl. Opt. 44 (2005) 2104-2114.

D. Grosenick, H. Wabnitz, K. T. Moesta, J. Mucke, M. Möller, C. Stroszczynski, J. Stößel, B. Wassermann, P. M. Schlag, H. Rinneberg,
Concentration and oxygen saturation of haemoglobin of 50 breast tumours determined by time-domain optical mammography,
Phys. Med. Biol. 49 (2004) 1165-1181.

D. Grosenick, K. T. Moesta, H. Wabnitz, J. Mucke, C. Stroszczynski, R. Macdonald, P. M. Schlag, H. Rinneberg,
Time-domain optical mammography: Initial clinical results on detection and characterization of breast tumors,
Appl. Opt. 42 (2003) 3170-3186.

V. Chernomordik, D. W. Hattery, D. Grosenick, H. Wabnitz, H. Rinneberg, K. T. Moesta, P. M. Schlag, A. Gandjbakhche,
Quantification of optical properties of a breast tumor using random walk theory,
J. Biomed. Opt. 7 (2002) 80-87.

B. Ebert, U. Sukowski, D. Grosenick, H. Wabnitz, K. T. Moesta, K. Licha, A. Becker, W. Semmler, P. M. Schlag, H. Rinneberg,
Near-infrared fluorescent dyes for enhanced contrast in optical mammography: phantom experiments,
J. Biomed. Opt. 6 (2001) 134-140.

D. Grosenick, H. Wabnitz, H. Rinneberg, K. T. Moesta, P. Schlag,
Development of a time-domain optical mammograph and first in vivo applications,
Appl. Opt. 38 (1999) 2927-2943.

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