Evaluation of Fractionated Photofrin-mediated Photodynamic Therapy Using Different Light Fluences with Reactive Oxygen Species Explicit Dosimetry (ROSED).

Photodynamic therapy (PDT) is an established modality for cancer treatment, and reactive oxygen species explicit dosimetry (ROSED), based on direct measurements of in-vivo light fluence (rate), in-vivo photofrin concentration, and tissue oxygenation concentration, has been proved to provide the best dosimetric quantity which can be used to predict non-fractionated PDT outcome. This study performed ROSED for Photofrin-mediated PDT for mice bearing radiation-induced fibrosacorma (RIF) tumor. As demonstrated by our previous study, fractionated PDT with a 2-hour time interval can significantly improve the long-term cure rate (from 15% to 65% at 90 days), and it tends to increase as the light dose for the first light fraction gets larger. This study focused on further improving the long-term cure rate without introducing apparent toxicity using combinations of different first light fraction lengths and total light fluences. Photofrin was injected through the mouse tail vein at a concentration of 5 mg/kg. After 18~24 hours, treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Mice were treated using two fractions of light fluences with a 2-hour dark interval. Different dose metrics were quantified, including light fluence, PDT dose, and [ROS]rx. In addition, the total reacted [ROS]rx and treatment outcomes were evaluated and compared to identify the optimal light fraction length and total light fluence.

Multispectral singlet oxygen luminescent dosimetry (MSOLD) for Photofrin-mediated Photodynamic Therapy.

Direct detection of singlet-state oxygen ([1O2]) constitutes the holy grail dosimetric method for type II PDT, a goal that can be quantified using multispectral singlet oxygen dosimetry (MSOLD). However, the short lifetime and extremely weak nature of the singlet oxygen signal produced has given rise to a need to improve MSOLD signal-to-noise ratio. This study examines methods for optimizing MSOLD signal acquisition, specifically employing an orthogonal arrangement between detection and PDT treatment light, consisting of two fiber optics - connected to a 632-nm laser and an InGaAs detector respectively. Light collected by the InGaAs detector is then passed through a filter wheel, where spectral emission measurements are taken at 1200 nm, 1240 nm, 1250 nm, 1270 nm, and 1300 nm. The data, after fitting to the fluorescence background and a gaussian-fit for the singlet oxygen peak, is established for the background-subtracted singlet oxygen emission signal. The MSOLD signal is then compared with the singlet oxygen explicit dosimetry (SOED) results, based on direct measurements of in-vivo light fluence (rate), in-vivo Photofrin concentration, and tissue oxygenation concentration. This study focuses on validating the sensitivity and minimum detectability of MSOLD signal in various in-vitro conditions. Finally, the MSOLD device will be tested in Photofrin-mediated PDT for mice bearing Radiation-Induced Fibrosarcoma (RIF) tumors.

Design and development of volume phase holographic grating based digital holographic interferometer for label-free quantitative cell imaging.

In this paper, a volume phase holographic optical element based digital holographic interferometer is designed and used for quantitative phase imaging of biological cells [white blood cells, red blood cells, platelets, and Staphylococcus aureus (S. aureus) bacteria cells]. The experimental results reveal that sharp images of the S. aureus bacteria cells of the order of ${\sim}{1}\;{\unicode{x00B5}{\rm m}}$∼1µm can be clearly seen. The volume phase holographic grating will remove the stray light from the system reaching toward the grating and will minimize the coherent noise (speckle noise). This will improve the sharpness in the image reconstructed from the recorded digital hologram.