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Research in Biomedical Optics

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Efficient light delivery for photodynamic therapy
The presence of metastasis is one of the most important prognosis factors of cancer [1].  While understanding factors governing metastasis is important, it is also critical to eliminate cancer cells sufficiently early preventing metastasis while sparing surrounding normal tissues.  Photodynamic therapy (PDT) has been shown to be a powerful method in which a light-activatable molecule that can selectively accumulate in tumors is used to generate local cytotoxicity [2].

Tissue is a heterogeneous, turbid medium, which causes multiple scattering of a light propagating within it; thus the light becomes diffused over transmission distances of a few mean-free paths.  For typical PDT-relevant wavelengths, one mean-free path is on the order of 100 µm, thus, the depth at which a photosensitizer can be activated efficiently is of the order of a few millimeters. Moreover, the ability to focus the illumination beam to a target location within a lesion is lost.  However, elastic-scattering effects are deterministic and reversible [3]. The goal of this study is to develop efficient methods for appropriate illumination wavefield so that the light both penetrates deep within the sample, and is concentrated at a region of interest. In the context of PDT, this would permit lower light doses to be delivered while achieving the same drug activation effect, reducing the risk of tissue photodamage, and increasing the depth at which treatment may be effective, potentially up to several centimeters.

The application of turbidity-suppression for enhanced PDT is highly clinically relevant. PDT is presently in clinical trials for both ovarian [4-8]  and pancreatic [9, 10]  cancers. Pancreatic cancer patients are often moribund and poor candidates for therapies with high systemic toxicity, making PDT an attractive option, particularly with the greater control in light delivery that the new turbidity surpression approach will offer.

  1. Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 6, 449-58 (2006)
  2. Celli JP, Spring BQ, Rizvi I, Evans CL, Samkoe KS, Verma S, Pogue BW, Hasan T. Imaging and photodynamic therapy: mechanisms, monitoring, and optimization. CHEM REV. 110, 2795-838.
  3. Yaqoob Z, Psaltis D, Feld MS, Yang CH. Optical phase conjugation for turbidity suppression in biological samples. Nature Photonics. 2, 110-5 (2008).
  4. DeLaney TF, Sindelar WF, Tochner Z, Smith PD, Friauf WS, Thomas G, Dachowski L, Cole JW, Steinberg SM, Glatstein E. Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. International journal of radiation oncology, biology, physics. 25, 445-57 (1993).
  5. Sindelar WF, DeLaney TF, Tochner Z, Thomas GF, Dachoswki LJ, Smith PD, Friauf WS, Cole JW, Glatstein E. Technique of photodynamic therapy for disseminated intraperitoneal malignant neoplasms. Phase I study. Arch Surg. 126, 318-24 (1991).
  6. Hendren SK, Hahn SM, Spitz FR, Bauer TW, Rubin SC, Zhu T, Glatstein E, Fraker DL. Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Annals of Surgical Oncology. 8, 65-71 (2001).
  7. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q. Photodynamic therapy. Journal of the National Cancer Institute. 90, 889-905 (1998).
  8. Wierrani F, Fiedler D, Grin W, Henry M, Dienes E, Gharehbaghi K, Krammer B, Grunberger W. Clinical effect of meso-tetrahydroxyphenylchlorine based photodynamic therapy in recurrent carcinoma of the ovary: preliminary results. Br J Obstet Gynaecol. 104, 376-8 (1997).
  9. Sandanayake NS, Huggett MT, Bown SG, Pogue BW, Hasan T, Pereira SP, editors. PDT for locally advanced pancreatic cancer: early clinical results. Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX; 2010; San Francisco, California, USA: SPIE.
  10. Ayaru L, Bown S, Pereira S. Photodynamic therapy for pancreatic and biliary tract carcinoma. International Journal of Gastrointestinal Cancer. 35, 1-13 (2005).