Abstract

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.

© 2007 Optical Society of America

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References

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  1. D. M. Parkin, F. Bray, J. Ferlay and P. Pisani, "Global Cancer Statistics, 2002," C. A. Cancer J. Clin. 55, 74-108 (2005).
    [CrossRef]
  2. S. J. Nass, I. C. Henderson and J. C. Lashof, Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer (National Academy Press, 2001).
  3. M. A. Franceschini, K. T. Moesta, S. Fantini, G. Gaida, E. Gratton, H. Jess, W. W. Mantulin, M. Seeber, P. M. Schlag and M. Kaschke, "Frequency-domain techniques enhance optical mammography: Initial clinical results," PNAS 94, 6468-6473 (1997).
    [CrossRef] [PubMed]
  4. D. Grosenick, H. Wabnitz, H. H. Rinneberg, K. T. Moesta and P. M. Schlag, "Development of a time domain optical mammograph and first in vivo applications," Appl. Opt. 38, 2927-2943 (1999).
    [CrossRef]
  5. P. Carmeliet and R. K. Jain, "Angiogenesis in cancer and other diseases," Nature 407, 249-257 (2000).
    [CrossRef] [PubMed]
  6. P. Vaupel, F. Kallinowski and P. Okunieff, "Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review," Cancer Res. 49, 6449-6465 (1989).
    [PubMed]
  7. B. J. Tromberg, N. Shah, R. Lanning, A. Cerussi, J. Espinoza, T. Pham, L. Svaasand and J. Butler, "Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy," Neoplasia 2, 26-40 (2000).
    [CrossRef] [PubMed]
  8. B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg and K. D. Paulsen, "Quantitative Hemoglobin Tomography with Diffuse Near-Infrared Spectroscopy: Pilot Results in the Breast," Radiology 218, 261-266 (2001).
    [PubMed]
  9. M. Xu and L. V. Wang, "Photoacoustic imaging in biomedicine," Rev. Sci. Instrum. 77, 041101 (2006).
    [CrossRef]
  10. A. A. Oraevsky, E. V. Savateeva, S. V. Solomatin, A. A. Karabutov, V. G. Andreev, Z. Gatalica, T. Khamapirad and P. M. Henrichs, "Optoacoustic imaging of blood for visualization and diagnostics of breast cancer," Proc. SPIE 4618, 81-94 (2002).
    [CrossRef]
  11. T. Khamapirad, P. M. Henrichs, K. Mehta, T. G. Miller, A. T. Yee and A. A. Oraevsky, "Diagnostic imaging of breast cancer with LOIS: clinical feasibility," Proc. SPIE 5697, 35-44 (2005).
    [CrossRef]
  12. R. A. Kruger, K. D. Miller, H. E. Reynolds, W. L. KiserJr., D. R. Reinecke, G. A. Kruger, "Breast Cancer in vivo: Contrast Enhancement with Thermoacoustic CT at 434 MHz-Feasibility Study," Radiology 216, 279-283 (2000).
    [PubMed]
  13. S. Manohar, A. Kharine, J. C. G. van Hespen, W. Steenbergen and T. G. van Leeuwen, "The Twente Photoacoustic Mammoscope: system overview and performance," Phys. Med. Biol. 502543-2557 (2005).
    [CrossRef] [PubMed]
  14. S. Manohar, A. Kharine, J. C. G. van Hespen, W. Steenbergen and T. G. van Leeuwen, "Photoacoustic mammography laboratory prototype: imaging of breast tissue phantoms," J. Biomed. Opt. 9, 1172-1181 (2004).
    [CrossRef] [PubMed]
  15. F. A. Duck, Physical Properties of Tissue (Academic Press, 1990).
  16. L. Spinelli, A. Torricelli, A. Pifferi, P. Taroni, G. M. Danesini and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
    [CrossRef] [PubMed]
  17. T. P. Padera, B. R. Stoll, J. B. Tooredman, D. Capen, E. Di Tomaso and R. K. Jain, "Cancer cells compress intratumour vessels," Nature 427, 695 (2004).
    [CrossRef] [PubMed]
  18. M. Sarntinoranont, F. Rooney and M. Ferrari, "Interstitial stress and fluid pressure within a growing tumor," Ann. Biomed. Eng. 31, 327-335 (2003).
    [CrossRef] [PubMed]
  19. J. Holash, P. C. Maisonpierre, D. Compton, P. Boland, C. R. Alexander, D. Zagzag. G. D. Yancopoulos and S. J. Wiegand, "Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF," Science 284, 1994-1998 (1999).
    [CrossRef] [PubMed]
  20. G. D. Yancopoulos, S. Davis, N. W. Gale, J. S. Rudge, S. J. Wiegand and J. Holash, "Vascular-specific growth factors and blood vessel formation," Nature 407, 242-248 (2000).
    [CrossRef] [PubMed]
  21. R. Matsubayashi, Y. Matsuo, G. Edakuni, T. Satoh, O. Tokunaga and S. Kudo, "Breast Masses with Peripheral Rim Enhancement on Dynamic Contrast-enhanced MR Images: Correlation of MR Findings with Histologic Features and Expression of Growth Factors," Radiology 217, 841-848 (2000).
    [PubMed]
  22. J. Laufer, D. Delpy, C. Elwell and P. Beard, "Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy:application to the measurement of blood oxygenation and haemoglobin concentration," Phys. Med. Biol. 52, 141-168 (2007).
    [CrossRef]

2007

J. Laufer, D. Delpy, C. Elwell and P. Beard, "Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy:application to the measurement of blood oxygenation and haemoglobin concentration," Phys. Med. Biol. 52, 141-168 (2007).
[CrossRef]

2006

M. Xu and L. V. Wang, "Photoacoustic imaging in biomedicine," Rev. Sci. Instrum. 77, 041101 (2006).
[CrossRef]

2005

D. M. Parkin, F. Bray, J. Ferlay and P. Pisani, "Global Cancer Statistics, 2002," C. A. Cancer J. Clin. 55, 74-108 (2005).
[CrossRef]

S. Manohar, A. Kharine, J. C. G. van Hespen, W. Steenbergen and T. G. van Leeuwen, "The Twente Photoacoustic Mammoscope: system overview and performance," Phys. Med. Biol. 502543-2557 (2005).
[CrossRef] [PubMed]

T. Khamapirad, P. M. Henrichs, K. Mehta, T. G. Miller, A. T. Yee and A. A. Oraevsky, "Diagnostic imaging of breast cancer with LOIS: clinical feasibility," Proc. SPIE 5697, 35-44 (2005).
[CrossRef]

2004

S. Manohar, A. Kharine, J. C. G. van Hespen, W. Steenbergen and T. G. van Leeuwen, "Photoacoustic mammography laboratory prototype: imaging of breast tissue phantoms," J. Biomed. Opt. 9, 1172-1181 (2004).
[CrossRef] [PubMed]

L. Spinelli, A. Torricelli, A. Pifferi, P. Taroni, G. M. Danesini and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

T. P. Padera, B. R. Stoll, J. B. Tooredman, D. Capen, E. Di Tomaso and R. K. Jain, "Cancer cells compress intratumour vessels," Nature 427, 695 (2004).
[CrossRef] [PubMed]

2003

M. Sarntinoranont, F. Rooney and M. Ferrari, "Interstitial stress and fluid pressure within a growing tumor," Ann. Biomed. Eng. 31, 327-335 (2003).
[CrossRef] [PubMed]

2002

A. A. Oraevsky, E. V. Savateeva, S. V. Solomatin, A. A. Karabutov, V. G. Andreev, Z. Gatalica, T. Khamapirad and P. M. Henrichs, "Optoacoustic imaging of blood for visualization and diagnostics of breast cancer," Proc. SPIE 4618, 81-94 (2002).
[CrossRef]

2001

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg and K. D. Paulsen, "Quantitative Hemoglobin Tomography with Diffuse Near-Infrared Spectroscopy: Pilot Results in the Breast," Radiology 218, 261-266 (2001).
[PubMed]

2000

B. J. Tromberg, N. Shah, R. Lanning, A. Cerussi, J. Espinoza, T. Pham, L. Svaasand and J. Butler, "Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy," Neoplasia 2, 26-40 (2000).
[CrossRef] [PubMed]

P. Carmeliet and R. K. Jain, "Angiogenesis in cancer and other diseases," Nature 407, 249-257 (2000).
[CrossRef] [PubMed]

R. A. Kruger, K. D. Miller, H. E. Reynolds, W. L. KiserJr., D. R. Reinecke, G. A. Kruger, "Breast Cancer in vivo: Contrast Enhancement with Thermoacoustic CT at 434 MHz-Feasibility Study," Radiology 216, 279-283 (2000).
[PubMed]

G. D. Yancopoulos, S. Davis, N. W. Gale, J. S. Rudge, S. J. Wiegand and J. Holash, "Vascular-specific growth factors and blood vessel formation," Nature 407, 242-248 (2000).
[CrossRef] [PubMed]

R. Matsubayashi, Y. Matsuo, G. Edakuni, T. Satoh, O. Tokunaga and S. Kudo, "Breast Masses with Peripheral Rim Enhancement on Dynamic Contrast-enhanced MR Images: Correlation of MR Findings with Histologic Features and Expression of Growth Factors," Radiology 217, 841-848 (2000).
[PubMed]

1999

J. Holash, P. C. Maisonpierre, D. Compton, P. Boland, C. R. Alexander, D. Zagzag. G. D. Yancopoulos and S. J. Wiegand, "Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF," Science 284, 1994-1998 (1999).
[CrossRef] [PubMed]

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

1997

M. A. Franceschini, K. T. Moesta, S. Fantini, G. Gaida, E. Gratton, H. Jess, W. W. Mantulin, M. Seeber, P. M. Schlag and M. Kaschke, "Frequency-domain techniques enhance optical mammography: Initial clinical results," PNAS 94, 6468-6473 (1997).
[CrossRef] [PubMed]

1989

P. Vaupel, F. Kallinowski and P. Okunieff, "Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review," Cancer Res. 49, 6449-6465 (1989).
[PubMed]

Ann. Biomed. Eng.

M. Sarntinoranont, F. Rooney and M. Ferrari, "Interstitial stress and fluid pressure within a growing tumor," Ann. Biomed. Eng. 31, 327-335 (2003).
[CrossRef] [PubMed]

Appl. Opt.

C. A. Cancer J. Clin.

D. M. Parkin, F. Bray, J. Ferlay and P. Pisani, "Global Cancer Statistics, 2002," C. A. Cancer J. Clin. 55, 74-108 (2005).
[CrossRef]

Cancer Res.

P. Vaupel, F. Kallinowski and P. Okunieff, "Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review," Cancer Res. 49, 6449-6465 (1989).
[PubMed]

J. Biomed. Opt.

S. Manohar, A. Kharine, J. C. G. van Hespen, W. Steenbergen and T. G. van Leeuwen, "Photoacoustic mammography laboratory prototype: imaging of breast tissue phantoms," J. Biomed. Opt. 9, 1172-1181 (2004).
[CrossRef] [PubMed]

L. Spinelli, A. Torricelli, A. Pifferi, P. Taroni, G. M. Danesini and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

Nature

T. P. Padera, B. R. Stoll, J. B. Tooredman, D. Capen, E. Di Tomaso and R. K. Jain, "Cancer cells compress intratumour vessels," Nature 427, 695 (2004).
[CrossRef] [PubMed]

P. Carmeliet and R. K. Jain, "Angiogenesis in cancer and other diseases," Nature 407, 249-257 (2000).
[CrossRef] [PubMed]

G. D. Yancopoulos, S. Davis, N. W. Gale, J. S. Rudge, S. J. Wiegand and J. Holash, "Vascular-specific growth factors and blood vessel formation," Nature 407, 242-248 (2000).
[CrossRef] [PubMed]

Neoplasia

B. J. Tromberg, N. Shah, R. Lanning, A. Cerussi, J. Espinoza, T. Pham, L. Svaasand and J. Butler, "Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy," Neoplasia 2, 26-40 (2000).
[CrossRef] [PubMed]

Phys. Med. Biol.

S. Manohar, A. Kharine, J. C. G. van Hespen, W. Steenbergen and T. G. van Leeuwen, "The Twente Photoacoustic Mammoscope: system overview and performance," Phys. Med. Biol. 502543-2557 (2005).
[CrossRef] [PubMed]

J. Laufer, D. Delpy, C. Elwell and P. Beard, "Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy:application to the measurement of blood oxygenation and haemoglobin concentration," Phys. Med. Biol. 52, 141-168 (2007).
[CrossRef]

PNAS

M. A. Franceschini, K. T. Moesta, S. Fantini, G. Gaida, E. Gratton, H. Jess, W. W. Mantulin, M. Seeber, P. M. Schlag and M. Kaschke, "Frequency-domain techniques enhance optical mammography: Initial clinical results," PNAS 94, 6468-6473 (1997).
[CrossRef] [PubMed]

Proc. SPIE

A. A. Oraevsky, E. V. Savateeva, S. V. Solomatin, A. A. Karabutov, V. G. Andreev, Z. Gatalica, T. Khamapirad and P. M. Henrichs, "Optoacoustic imaging of blood for visualization and diagnostics of breast cancer," Proc. SPIE 4618, 81-94 (2002).
[CrossRef]

T. Khamapirad, P. M. Henrichs, K. Mehta, T. G. Miller, A. T. Yee and A. A. Oraevsky, "Diagnostic imaging of breast cancer with LOIS: clinical feasibility," Proc. SPIE 5697, 35-44 (2005).
[CrossRef]

Radiology

R. A. Kruger, K. D. Miller, H. E. Reynolds, W. L. KiserJr., D. R. Reinecke, G. A. Kruger, "Breast Cancer in vivo: Contrast Enhancement with Thermoacoustic CT at 434 MHz-Feasibility Study," Radiology 216, 279-283 (2000).
[PubMed]

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg and K. D. Paulsen, "Quantitative Hemoglobin Tomography with Diffuse Near-Infrared Spectroscopy: Pilot Results in the Breast," Radiology 218, 261-266 (2001).
[PubMed]

R. Matsubayashi, Y. Matsuo, G. Edakuni, T. Satoh, O. Tokunaga and S. Kudo, "Breast Masses with Peripheral Rim Enhancement on Dynamic Contrast-enhanced MR Images: Correlation of MR Findings with Histologic Features and Expression of Growth Factors," Radiology 217, 841-848 (2000).
[PubMed]

Rev. Sci. Instrum.

M. Xu and L. V. Wang, "Photoacoustic imaging in biomedicine," Rev. Sci. Instrum. 77, 041101 (2006).
[CrossRef]

Science

J. Holash, P. C. Maisonpierre, D. Compton, P. Boland, C. R. Alexander, D. Zagzag. G. D. Yancopoulos and S. J. Wiegand, "Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF," Science 284, 1994-1998 (1999).
[CrossRef] [PubMed]

Other

S. J. Nass, I. C. Henderson and J. C. Lashof, Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer (National Academy Press, 2001).

F. A. Duck, Physical Properties of Tissue (Academic Press, 1990).

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Figures (6)

Fig. 1.
Fig. 1.

The Twente Photoacoustic Mammoscope. a – aperture to insert breast, b – ultrasound detector matrix, c – glass window of d – scanning system compartment, e – Q-switched Nd:YAG laser operated at 1064 nm with 5 ns pulses, f – laser safety curtain which is drawn around the instrument during the measurement, g – interface electronics between detector and computer, h – linear stage carrying detector matrix driven by handwheel to apply mild compression to breast, I – laser remote control unit, j – laser power supply.

Fig. 2.
Fig. 2.

Case 1 of 50 year old woman with invasive ductal carcinoma in right breast. (a) Craniocaudal x-ray mammogram reveals architectural distortion with spiculations. Window shows expected location of the ROI for the photoacoustic scan. (b) Transverse sonographic scan image shows 17 mm irregular hypoechoic solid mass. (c) Craniocaudal photoacoustic MIP image in top-view reveals higher intensity regions attributed to tumor vascularization. Contour lines (black dotted) are drawn using the level indicated in the image histogram above. The possible extent of the tumor mass (major axis 35 mm) is indicated by the white dotted line encompassing the cluster of vascular regions. The photoacoustic image cannot be compared point by point with the x-ray image in ROI due to differences in compression and in ROI positioning.

Fig. 3.
Fig. 3.

Case 1 of 50 year old woman with invasive ductal carcinoma in right breast. Montage of selected slice images of photoacoustic reconstructed data set in craniocaudal view. The inter-slice spacing is 1.5 mm with the first slice 6.5 mm below the illuminated breast surface and the last 17 mm. High intensity regions correspond to vascular ‘hot spots’.

Fig. 4.
Fig. 4.

Case 2 of 57 year old woman with invasive ductal carcinoma exhibiting neuroendocrine differentiation in right breast. Gross features in craniocaudal x-ray mammogram (a) and transverse sonographic scan image (b) indicate benignity, but presence of microcalcifications in (a) and age of patient prompted core biopsy. Craniocaudal photoacoustic MIP image (c) in ROI (red window in x-ray mammogram) shows high intensity distributions in a ring shape attributable to higher vascular densities at tumor periphery. Contour lines (black dotted) are superposed using level indicated in the image histogram above. The photoacoustic image cannot be compared point by point with the x-ray image in ROI due to differences in compression and in ROI positioning.

Fig. 5.
Fig. 5.

Magnified region-of-interest of craniocaudal x-ray mammogram (inset) of Case 2. Image shows oval mass with predominantly circumscribed borders with a small number of irregular microcalcifications within dotted red oval.

Fig. 6.
Fig. 6.

Case 2 of 57 year old woman with invasive ductal carcinoma exhibiting neuroendocrine differentiation in right breast. Selected slice images of photoacoustic reconstructed data set in craniocaudal view. The inter-slice spacing is 1 mm with the first slice 9.5 mm below the illuminated breast surface. The ring pattern of higher intensity which depicts strong vascularization at the tumor periphery is evident in the slices at depths 11.5 to 14.5 mm

Tables (1)

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Table 1. Specifications of the Photoacoustic Mammoscope

Equations (2)

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S V ( t ) = i w i V [ S i ( t ) h ( t + τ + δ i V ) ] max min i w i V ,
h ( t + τ ) = { 1 for t τ 2 0 otherwise

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