OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 2, Iss. 1 — Jan. 1, 2011
  • pp: 123–130

Monitoring blood flow responses during topical ALA-PDT

Theresa L. Becker, Anne D. Paquette, Kenneth R. Keymel, Barbara W. Henderson, and Ulas Sunar  »View Author Affiliations

Biomedical Optics Express, Vol. 2, Issue 1, pp. 123-130 (2011)

View Full Text Article

Enhanced HTML    Acrobat PDF (1128 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



Photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) is currently used as a clinical treatment for nonmelanoma skin cancers. In order to optimize PDT treatment, vascular disruption early in treatment must be identified and prevented. We present blood flow responses to topical ALA-PDT in a preclinical model and basal cell carcinoma patients assessed by diffuse correlation spectroscopy (DCS). Our results show that ALA-PDT induced early blood flow changes and these changes were irradiance dependent. It is clear that there exists considerable variation in the blood flow responses in patients from lesion to lesion. Monitoring blood flow parameter may be useful for assessing ALA-PDT response and planning.

© 2010 OSA

OCIS Codes
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology
(170.3660) Medical optics and biotechnology : Light propagation in tissues
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.6480) Medical optics and biotechnology : Spectroscopy, speckle

ToC Category:
Functional Imaging

Original Manuscript: November 17, 2010
Revised Manuscript: December 14, 2010
Manuscript Accepted: December 15, 2010
Published: December 15, 2010

Theresa L. Becker, Anne D. Paquette, Kenneth R. Keymel, Barbara W. Henderson, and Ulas Sunar, "Monitoring blood flow responses during topical ALA-PDT," Biomed. Opt. Express 2, 123-130 (2011)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. B. W. Henderson and T. J. Dougherty, “How does photodynamic therapy work?” Photochem. Photobiol. 55(1), 145–157 (1992). [CrossRef] [PubMed]
  2. R. M. Szeimies, C. A. Morton, A. Sidoroff, and L. R. Braathen, “Photodynamic therapy for non-melanoma skin cancer,” Acta Derm. Venereol. 85(6), 483–490 (2005). [PubMed]
  3. M. B. Ericson, A. M. Wennberg, and O. Larkö, “Review of photodynamic therapy in actinic keratosis and basal cell carcinoma,” Ther Clin Risk Manag 4(1), 1–9 (2008). [PubMed]
  4. K. Kalka, H. Merk, and H. Mukhtar, “Photodynamic therapy in dermatology,” J. Am. Acad. Dermatol. 42(3), 389–413, quiz 414–416 (2000). [CrossRef] [PubMed]
  5. C. A. Morton, C. Whitehurst, J. H. McColl, J. V. Moore, and R. M. MacKie, “Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma,” Arch. Dermatol. 137(3), 319–324 (2001). [PubMed]
  6. J. C. Kennedy, R. H. Pottier, and D. C. Pross, “Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience,” J. Photochem. Photobiol. B 6(1-2), 143–148 (1990). [CrossRef] [PubMed]
  7. I. Georgakoudi and T. H. Foster, “Singlet oxygen- versus nonsinglet oxygen-mediated mechanisms of sensitizer photobleaching and their effects on photodynamic dosimetry,” Photochem. Photobiol. 67(6), 612–625 (1998). [PubMed]
  8. G. Yu, T. Durduran, C. Zhou, H. W. Wang, M. E. Putt, H. M. Saunders, C. M. Sehgal, E. Glatstein, A. G. Yodh, and T. M. Busch, “Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy,” Clin. Cancer Res. 11(9), 3543–3552 (2005). [CrossRef] [PubMed]
  9. A. Major, S. Kimel, S. Mee, T. E. Milner, D. J. Smithies, S. M. Srinivas, Z. Chen, and J. S. Nelson, “Microvascular photodynamic effects determined in vivo using optical doppler tomography,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1168–1175 (1999). [CrossRef]
  10. G. Yu, T. Durduran, C. Zhou, T. C. Zhu, J. C. Finlay, T. M. Busch, S. B. Malkowicz, S. M. Hahn, and A. G. Yodh, “Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light,” Photochem. Photobiol. 82(5), 1279–1284 (2006). [CrossRef] [PubMed]
  11. U. Sunar, D. Rohrbach, N. Rigual, E. Tracy, K. Keymel, M. T. Cooper, H. Baumann, and B. H. Henderson, “Monitoring photobleaching and hemodynamic responses to HPPH-mediated photodynamic therapy of head and neck cancer: a case report,” Opt. Express 18(14), 14969–14978 (2010). [CrossRef] [PubMed]
  12. T. M. Busch, X. Xing, G. Yu, A. Yodh, E. P. Wileyto, H. W. Wang, T. Durduran, T. C. Zhu, and K. K. Wang, “Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy,” Photochem. Photobiol. Sci. 8(12), 1683–1693 (2009). [CrossRef] [PubMed]
  13. U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, “Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study,” J. Biomed. Opt. 11(6), 064021 (2006). [CrossRef] [PubMed]
  14. C. Zhou, R. Choe, N. Shah, T. Durduran, G. Yu, A. Durkin, D. Hsiang, R. Mehta, J. Butler, A. Cerussi, B. J. Tromberg, and A. G. Yodh, “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt. 12(5), 051903 (2007). [CrossRef] [PubMed]
  15. M. A. Herman, D. Fromm, and D. Kessel, “Tumor blood-flow changes following protoporphyrin IX-based photodynamic therapy in mice and humans,” J. Photochem. Photobiol. B 52(1-3), 99–104 (1999). [CrossRef] [PubMed]
  16. J. Leveckis, N. J. Brown, and M. W. Reed, “The effect of aminolaevulinic acid-induced, protoporphyrin IX-mediated photodynamic therapy on the cremaster muscle microcirculation in vivo,” Br. J. Cancer 72(5), 1113–1119 (1995). [PubMed]
  17. J. Bedwell, A. J. MacRobert, D. Phillips, and S. G. Bown, “Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model,” Br. J. Cancer 65(6), 818–824 (1992). [PubMed]
  18. B. W. Henderson, L. Vaughan, D. A. Bellnier, H. van Leengoed, P. G. Johnson, and A. R. Oseroff, “Photosensitization of murine tumor, vasculature and skin by 5-aminolevulinic acid-induced porphyrin,” Photochem. Photobiol. 62(4), 780–789 (1995). [CrossRef] [PubMed]
  19. N. van der Veen, K. M. Hebeda, H. S. de Bruijn, and W. M. Star, “Photodynamic effectiveness and vasoconstriction in hairless mouse skin after topical 5-aminolevulinic acid and single- or two-fold illumination,” Photochem. Photobiol. 70(6), 921–929 (1999). [CrossRef] [PubMed]
  20. I. Wang, S. Andersson-Engels, G. E. Nilsson, K. Wårdell, and K. Svanberg, “Superficial blood flow following photodynamic therapy of malignant non-melanoma skin tumours measured by laser Doppler perfusion imaging,” Br. J. Dermatol. 136(2), 184–189 (1997). [CrossRef] [PubMed]
  21. A. M. K. Enejder, C. af Klinteberg, I. Wang, S. Andersson-Engels, N. Bendsoe, S. Svanberg, and K. Svanberg, “Blood perfusion studies on basal cell carcinomas in conjunction with photodynamic therapy and cryotherapy employing laser-Doppler perfusion imaging,” Acta Derm. Venereol. 80(1), 19–23 (2000). [CrossRef] [PubMed]
  22. V. Schacht, R. M. Szeimies, and C. Abels, “Photodynamic therapy with 5-aminolevulinic acid induces distinct microcirculatory effects following systemic or topical application,” Photochem. Photobiol. Sci. 5(5), 452–458 (2006). [CrossRef] [PubMed]
  23. K. Svanberg, T. Andersson, D. Killander, I. Wang, U. Stenram, S. Andersson-Engels, R. Berg, J. Johansson, and S. Svanberg, “Photodynamic therapy of non-melanoma malignant tumours of the skin using topical delta-amino levulinic acid sensitization and laser irradiation,” Br. J. Dermatol. 130(6), 743–751 (1994). [CrossRef] [PubMed]
  24. W. J. Cottrell, A. Oseroff, and T. H. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77, 064302 (2006). [CrossRef]
  25. T. L. Becker, “Irradiance: A parameter determining oxygenation during topical photodynamic therapy (PDT),” Department of Molecular and Cellular Biophysics and Biochemistry, SUNY at Buffalo, 2010).
  26. T. Sands, U. Sunar, T. H. Foster, and A. Oseroff, “Monitoring blood flow and photobleaching during topical ALA PDT treatment,” Proc. SPIE 7164, 71640U (2009).
  27. W. J. Cottrell, A. D. Paquette, K. R. Keymel, T. H. Foster, and A. R. Oseroff, “Irradiance-dependent photobleaching and pain in delta-aminolevulinic acid-photodynamic therapy of superficial basal cell carcinomas,” Clin. Cancer Res. 14(14), 4475–4483 (2008). [CrossRef] [PubMed]
  28. P. J. Berne and R. Pecora, Dynamic Light Scattering (Wiley, New York, 1976).
  29. C. Cheung, J. P. Culver, K. Takahashi, J. H. Greenberg, and A. G. Yodh, “In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies,” Phys. Med. Biol. 46(8), 2053–2065 (2001). [CrossRef] [PubMed]
  30. U. Sunar, S. Makonnen, C. Zhou, T. Durduran, G. Yu, H. W. Wang, W. M. F. Lee, and A. G. Yodh, “Hemodynamic responses to antivascular therapy and ionizing radiation assessed by diffuse optical spectroscopies,” Opt. Express 15(23), 15507–15516 (2007). [CrossRef] [PubMed]
  31. T. Gisler, H. Rüger, S. U. Egelhaaf, J. Tschumi, P. Schurtenberger, and J. Rička, “Mode-selective dynamic light scattering: theory versus experimental realization,” Appl. Opt. 34(18), 3546–3553 (1995). [CrossRef] [PubMed]
  32. D. A. Boas, “Diffuse photon probes of structural and dynamical properties of turbid media: theory and biomedical applications ” Ph.D. dissertation (University of Pennsylvania, 1996).
  33. R. J. Gush, T. A. King, and M. I. Jayson, “Aspects of laser light scattering from skin tissue with application to laser Doppler blood flow measurement,” Phys. Med. Biol. 29(12), 1463–1476 (1984). [CrossRef] [PubMed]
  34. J. V. Moore and E. Allan, “Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control,” Br. J. Dermatol. 149(5), 1035–1040 (2003). [CrossRef] [PubMed]
  35. J. D. Gruber, A. Paliwal, V. Krishnaswamy, H. Ghadyani, M. Jermyn, J. A. O’Hara, S. C. Davis, J. S. Kerley-Hamilton, N. W. Shworak, E. V. Maytin, T. Hasan, and B. W. Pogue, “System development for high frequency ultrasound-guided fluorescence quantification of skin layers,” J. Biomed. Opt. 15(2), 026028 (2010). [CrossRef] [PubMed]
  36. C. W. Chin, A. J. Foss, A. Stevens, and J. Lowe, “Differences in the vascular patterns of basal and squamous cell skin carcinomas explain their differences in clinical behaviour,” J. Pathol. 200(3), 308–313 (2003). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.


Fig. 1 Fig. 2 Fig. 3
Fig. 4

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited