Image-guided treatment planning for pleural Photodynamic Therapy Abstract The overall objective of this grant is to develop an integrated system for real-time PDT dosimetry and light source monitoring during intracavitary photodynamic therapy. We propose to develop an infra- red camera-based system for real-time tracking of the motion of the light source used for treatment. The same tracking system will be used to digitize the surface contour of the cavity being treated for light fluence rate calculation. An optical fiber-based spectroscopic probe, coupled with the IR camera tracking device, will be used to determine absorption spectra at multiple points on the pleural cavity surface before and after PDT. Analysis of the absorption spectrum will determine the tissue oxygenation and the sensitizer concentration at these points. The same probe will be capable of performing fluorescence spectroscopy to verify drug concentration in-vivo before and after PDT. The absorption spectrum will also be used to determine the tissue optical properties in-vivo and use these points as input for light fluence rate calculation. To improve the spatial resolution of the heterogeneous tissue optical properties, we plan to develop a spectral reflectance imaging system to determine the surface distribution of optical properties in tissue before and after PDT. The temporal variations of light fluence rate, absorption spectrum, and fluorescence emission will be measured in- vivo at 7 selected points and compared with calculations using a light fluence calculation algorithm which takes into account the geometry and optical properties of the cavity. PDT dose will be calculated as a product of drug concentration and light fluence rate. We hypothesize that using PDT dose as a PDT dosimetry quantity to optimize light source movement will result in improvement of the spatial uniformity of PDT treatment and thus its efficacy. Further improvement of the PDT dose by a new dosimetric quantity, reacted singlet oxygen concentration that takes into account of light fluence rate effect, will be examined in a preclinical model.

Public Health Relevance

Statement: Pleural cancer is a serious public health problem for which there is no curative treatment available. Photodynamic therapy in combination with surgery offers a potential locally curative treatment, which has been demonstrated to substantially prolong patient's lives. The result of this project will substantially improve the light delivery homogeneity and quantification of PDT dose for pleural PDT, potentially resulting improved effectiveness of PDT as a curative therapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Radiation Therapeutics and Biology Study Section (RTB)
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Wong, Rosemary S
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University of Pennsylvania
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Kim, Michele M; Ghogare, Ashwini A; Greer, Alexander et al. (2017) On the in vivo photochemical rate parameters for PDT reactive oxygen species modeling. Phys Med Biol 62:R1-R48
Penjweini, Rozhin; Kim, Michele M; Zhu, Timothy C (2017) Three-dimensional finite-element based deformable image registration for evaluation of pleural cavity irradiation during photodynamic therapy. Med Phys 44:3767-3775
Penjweini, Rozhin; Kim, Michele M; Liu, Baochang et al. (2017) Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling [J. Biophotonics 9, No. 11-12, 1344-1354 (2016)]. J Biophotonics 10:473-474
Zhu, Timothy C; Kim, Michele M; Ong, Yi-Hong et al. (2017) A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT. Proc SPIE Int Soc Opt Eng 10047:
Gemmell, Nathan R; McCarthy, Aongus; Kim, Michele M et al. (2017) A compact fiber-optic probe-based singlet oxygen luminescence detection system. J Biophotonics 10:320-326
Kim, Michele M; Penjweini, Rozhin; Zhu, Timothy C (2017) Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy. J Biomed Opt 22:28002
Qiu, Haixia; Kim, Michele M; Penjweini, Rozhin et al. (2016) Macroscopic singlet oxygen modeling for dosimetry of Photofrin-mediated photodynamic therapy: an in-vivo study. J Biomed Opt 21:88002
Penjweini, Rozhin; Kim, Michele M; Dimofte, Andrea et al. (2016) Deformable medical image registration of pleural cavity for photodynamic therapy by using finite-element based method. Proc SPIE Int Soc Opt Eng 9701:970106
Penjweini, Rozhin; Kim, Michele M; Finlay, Jarod C et al. (2016) Investigating the impact of oxygen concentration and blood flow variation on photodynamic therapy. Proc SPIE Int Soc Opt Eng 9694:
Zhu, Timothy C; Lu, Amy; Ong, Yi-Hong (2016) An improved analytic function for predicting light fluence rate in circular fields on a semi-infinite geometry. Proc SPIE Int Soc Opt Eng 9706:97061D

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