Multispectral Optoacoustic Tomography (MSOT) of Human Breast Cancer

Purpose: In a pilot study, we introduce fast handheld multispectral optoacoustic tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and noncancerous breast tissue. Experimental Design: We imaged 10 female patients ages 48–81 years with malignant nonspecific breast cancer or invasive lobular carcinoma. Three healthy volunteers ages 31–36 years were also imaged. Fast-MSOT was based on unique single-frame-per-pulse (SFPP) image acquisition employed to improve the accuracy of spectral differentiation over using a small number of wavelengths. Breast tissue was illuminated at the 700–970 nm spectral range over 0.56 seconds total scan time. MSOT data were guided by ultrasonography and X-ray mammography or MRI. Results: The extended spectral range allowed the computation of oxygenated hemoglobin (HBO2), deoxygenated hemoglobin (HB), total blood volume (TBV), lipid, and water contributions, allowing first insights into in vivo high-resolution breast tissue MSOT cancer patterns. TBV and Hb/HBO2 images resolved marked differences between cancer and control tissue, manifested as a vessel-rich tumor periphery with highly heterogeneous spatial appearance compared with healthy tissue. We observe significant TBV variations between different tumors and between tumors over healthy tissues. Water and fat lipid layers appear disrupted in cancer versus healthy tissue; however, offer weaker contrast compared with TBV images. Conclusions: In contrast to optical methods, MSOT resolves physiologic cancer features with high resolution and revealed patterns not offered by other radiologic modalities. The new features relate to personalized and precision medicine potential. Clin Cancer Res; 23(22); 6912–22. ©2017 AACR.

[1]  B. Pogue,et al.  Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging. , 2016, Cancer research.

[2]  Vasilis Ntziachristos,et al.  Mesoscopic and macroscopic optoacoustic imaging of cancer. , 2015, Cancer research.

[3]  Lihong V. Wang,et al.  A practical guide to photoacoustic tomography in the life sciences , 2016, Nature Methods.

[4]  F. M. van den Engh,et al.  Photoacoustic image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology , 2015, Scientific Reports.

[5]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[6]  Vasilis Ntziachristos,et al.  Fast Semi-Analytical Model-Based Acoustic Inversion for Quantitative Optoacoustic Tomography , 2010, IEEE Transactions on Medical Imaging.

[7]  Nirmala Ramanujam,et al.  Quantitative optical spectroscopy: a robust tool for direct measurement of breast cancer vascular oxygenation and total hemoglobin content in vivo. , 2009, Cancer research.

[8]  B. Pogue,et al.  Evaluation of breast tumor response to neoadjuvant chemotherapy with tomographic diffuse optical spectroscopy: case studies of tumor region-of-interest changes. , 2009, Radiology.

[9]  Andrew Hanby,et al.  Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial , 2010, The Lancet.

[10]  Brian W Pogue,et al.  Tumor angiogenesis change estimated by using diffuse optical spectroscopic tomography: demonstrated correlation in women undergoing neoadjuvant chemotherapy for invasive breast cancer? , 2011, Radiology.

[11]  David Hsiang,et al.  Baseline tumor oxygen saturation correlates with a pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy. , 2012, Cancer research.

[12]  André Conjusteau,et al.  Detection and noninvasive diagnostics of breast cancer with 2-color laser optoacoustic imaging system , 2007, SPIE BiOS.

[13]  L. Liberman,et al.  Breast imaging reporting and data system (BI-RADS). , 2002, Radiologic clinics of North America.

[14]  David A Boas,et al.  Assessing the future of diffuse optical imaging technologies for breast cancer management. , 2008, Medical physics.

[15]  Vasilis Ntziachristos,et al.  Hybrid multispectral optoacoustic and ultrasound tomography for morphological and physiological brain imaging , 2016, Journal of biomedical optics.

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

[17]  Stanley J. Wiegand,et al.  Vascular-specific growth factors and blood vessel formation , 2000, Nature.

[18]  Wiendelt Steenbergen,et al.  The state of the art in breast imaging using the Twente Photoacoustic Mammoscope: results from 31 measurements on malignancies , 2016, European Radiology.

[19]  B. Pogue,et al.  A Comparison of Near-Infrared Diffuse Optical Imaging and 18F-FDG PET/CT for the Early Prediction of Breast Cancer Response to Neoadjuvant Chemotherapy , 2016, The Journal of Nuclear Medicine.

[20]  B. Pogue,et al.  In vivo quantitative imaging of normal and cancerous breast tissue using broadband diffuse optical tomography. , 2010, Medical physics.

[21]  Vasilis Ntziachristos,et al.  Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues , 2015, Nature Communications.

[22]  R. Gillies,et al.  Why do cancers have high aerobic glycolysis? , 2004, Nature Reviews Cancer.

[23]  G. Yancopoulos,et al.  Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. , 1999, Science.

[24]  Ketan Mehta,et al.  Real-time optoacoustic imaging of breast cancer using an interleaved two laser imaging system coregistered with ultrasound , 2010, BiOS.

[25]  Phil-Sang Chung,et al.  Differential diagnosis of breast masses in South Korean premenopausal women using diffuse optical spectroscopic imaging , 2016, Journal of biomedical optics.

[26]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[27]  Vasilis Ntziachristos,et al.  Advances in real-time multispectral optoacoustic imaging and its applications , 2015, Nature Photonics.

[28]  Doreen Steed,et al.  Dedicated 3D photoacoustic breast imaging. , 2013, Medical physics.

[29]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[30]  Hirohisa Yano,et al.  Angiogenesis in Cancer , 2006, Vascular health and risk management.

[31]  Vasilis Ntziachristos,et al.  Performance of a Multispectral Optoacoustic Tomography (MSOT) System equipped with 2D vs. 3D Handheld Probes for Potential Clinical Translation , 2015, Photoacoustics.

[32]  M. Yaffe,et al.  American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography , 2007, CA: a cancer journal for clinicians.

[33]  Rebecca S Lewis,et al.  Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. , 2004, Radiology.

[34]  Soren D. Konecky,et al.  Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI. , 2005, Medical physics.

[35]  Robert A Kruger,et al.  Photoacoustic angiography of the breast. , 2010, Medical physics.

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

[37]  B. Tromberg,et al.  Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment , 2011, Proceedings of the National Academy of Sciences.

[38]  S. Negrotto,et al.  [Angiogenesis in cancer]. , 2002, Medicina.

[39]  Ketan Mehta,et al.  Development of laser optoacoustic and ultrasonic imaging system for breast cancer utilizing handheld array probes , 2009, BiOS.

[40]  Paola Taroni,et al.  Review of optical breast imaging and spectroscopy , 2016, Journal of biomedical optics.

[41]  Vasilis Ntziachristos,et al.  Real-time handheld multispectral optoacoustic imaging. , 2013, Optics letters.

[42]  E. Sickles Breast imaging: from 1965 to the present. , 2000, Radiology.

[43]  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.

[44]  Brian W. Pogue,et al.  Predicting Breast Tumor Response to Neoadjuvant Chemotherapy with Diffuse Optical Spectroscopic Tomography prior to Treatment , 2014, Clinical Cancer Research.

[45]  Makoto Yamakawa,et al.  Characterization of photoacoustic tomography system with dual illumination , 2011, BiOS.

[46]  Jan Menke Photoacoustic breast tomography prototypes with reported human applications , 2015, European Radiology.

[47]  A. Wilson,et al.  The role of ultrasound in breast cancer screening. A consensus statement by the European Group for Breast Cancer Screening. , 1998, European journal of cancer.

[48]  E. Miller,et al.  Combined optical and X-ray tomosynthesis breast imaging. , 2011, Radiology.

[49]  Diagnostic imaging of breast cancer microvasculature with optoacoustic tomography , 2002, Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology.

[50]  H. D. de Koning,et al.  Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. , 2004, The New England journal of medicine.

[51]  L. Fallowfield,et al.  Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.