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Photodynamic therapy (PDT) has been used to treat malignant pleural mesothelioma. Current practice involves delivering light to a prescribed light fluence with a point source, monitored by eight isotropic detectors inside the pleural cavity. An infrared (IR) navigation system was used to track the location of the point source throughout the treatment. The recorded data were used to reconstruct the pleural cavity and calculate the light fluence to the whole cavity. An automatic algorithm was developed recently to calculate the detector positions based on recorded data within an hour. This algorithm was applied to patient case studies and the calculated results were compared to the measured positions, with an average difference of 2.5 cm. Calculated light fluence at calculated positions were compared to measured values. The differences between the calculated and measured light fluence were within 14% for all cases, with a fixed scattering constant and a dual correction method. Fluence-surface histogram (FSH) was calculated for photofrin-mediated PDT to be able to cover 80% of pleural surface area to 50 J cm

Total skin electron therapy (TSET) has proven to be one of the most effective treatments for advanced-stage cutaneous T-cell lymphoma. Two most used techniques are the Stanford six-field and rotational techniques. This study compares patient skin dose distributions as a function of depth between these two techniques.The EGSnrc system was used to simulate electron beams and calculate patient dose distributions. The calculations assumed the same patient standing on a platform, and the patient's different postures were ignored for the Stanford technique in the comparison of dose distributions. The skin doses were analyzed as a function of skin depth-dose coverage and evaluated using dose-volume-histograms (DVH). The comparisons were performed in three realistic clinical settings in which dual-field were used for patients treated at extended distances of 316 and 500 cm, and a single field was used at 700 cm. In all cases the realistic patient treatment beam delivery geometry was simulated.Although small dose differences were observed in some local areas, no clinically significant differences were found in the patient 3D dose distributions between the Stanford and rotational techniques. Virtually the same DVH curves between two the techniques were observed for mean dose to skin depth of 0-5, 5-10, and 10-15 mm from the skin surface, respectively. It is found that the skin depth dose coverage is 2 mm shallower for patient treatment at 500 cm compared to at 316 cm due to the additional air attenuation. However, very similar dose coverage and uniformity can be achieved at these two different extended treatment distances by adjusting the thickness of acrylic scatter plate. Adequate thickness of a scattering plate improves the skin dose uniformity.Both the Stanford and rotational techniques deliver very similar skin dose coverage in DVH plots, and only small differences are seen in local areas. It is worth to emphasize that the DVH is a graphical representation of the distribution of dose within a structure, and it does not contain spatial information. Therefore, comparison of entire skin dose using DVH may mask some variations at different locations of the surface area. In addition, the comparison did not consider different patient postures of the Stanford technique. Including the different patient postures in the calculation may affect the result of doses to the limbs.

The emergence of the Halcyon linear accelerator has allowed for increased patient throughput and improved treatment times for common treatment sites in radiation oncology. However, it has been shown that this can lead to increased surface dose in sites like breast cancer compared with treatments on conventional machines with flattened radiation beams. Cherenkov imaging can be used to estimate surface dose by detection of Cherenkov photons emitted in proportion to energy deposition from high energy electrons in tissue. Phantom studies were performed with both square beams in reference conditions and with clinical treatments, and dosimeter readings and Cherenkov images report higher surface dose (25% for flat phantom entrance dose, 5.9% for breast phantom treatment) from Halcyon beam deliveries than for equivalent deliveries from a TrueBeam linac. Additionally, the first Cherenkov images of a patient treated with Halcyon were acquired, and superficial dose was estimated.

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.

We developed a simulation method for modeling the light fluence delivery in intracavity Photodynamic Therapy (icav-PDT) for pleural lung cancer using a moving light source. Due to the large surface area of the pleural lung cavity, the light source needs to be moved to deliver a uniform dose around the entire cavity. While multiple fixed detectors are used for dosimetry at a few locations, an accurate simulation of light fluence and fluence rate is still needed for the rest of the cavity. We extended an existing Monte Carlo (MC) based light propagation solver to support moving light sources by densely sampling the continuous light source trajectory and assigning the proper number of photon packages launched along the way. The performance of Simphotek GPU CUDA-based implementation of the method – PEDSy-MC – has been demonstrated on a life-size lung-shaped phantom, custom printed for testing icav-PDT navigation system at the Perlman School of Medicine (PSM) – calculations completed under a minute (for some cases) and within minutes have been achieved. We demonstrate results within a 5% error of the analytic solution for multiple detectors in the phantom. PEDSy-MC is accompanied by a dose-cavity visualization tool that allows real-time inspection of dose values of the treated cavity in 2D and 3D, which will be expanded to ongoing clinical trials at PSM. PSM has developed a technology to measure 8-detectors in a pleural cavity phantom using Photofrin-mediated PDT that has been used during validation.

Silicon phantom models have been utilized to calculate light fluence in patients being treated with Photodynamic Therapy (PDT). This application can be utilized for other non-ionizing wavelength therapies such as Photobiomodulation (PBM). We have developed a novel protocol to validate homogeneity for 3-dimensional silicon phantom models of the human maxilla. Accurately quantifying the light profiles of human tissue can accommodate for varying optical properties that occur between subjects. More importantly, this can help optimize light fluence dosimetry calculations to achieve intended results. Silicon models of identical composition were fabricated into two different shapes: 1 flat-planar cylindrical shaped model, 2) non-flat planar (3-dimensional) mold of the human maxilla. Fabricating homogenous silicon phantom models continues to be a challenge as micro-bubbles can contaminate the compound during the curing process. Integrating both proprietary CBCT and handheld surface acquisition imaging devices confirmed our results to be within 0.5mm of accuracy. This protocol was specifically used to cross-reference and validate homogeneity at various depths of penetration. These results present the first known successful validation of identical silicon tissue phantoms with a flat-planar surface vs. a non-flat 3D planar surface. This proof-of-concept phantom validation protocol is sensitive to the specific variations of 3-dimensional surfaces and can be applied to a workflow used to capture accurate light fluence calculations in the clinical setting.

Dosimetry for photodynamic therapy is dependent on multiple parameters. Critically, in vivo tissue optical properties and hemodynamics must be determined carefully to calculate the total delivered light dose.Spectroscopic analysis of diffuse reflectance measurements of tissues taken during a clinical trial of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy for pleural malignancies.Diffuse reflectance measurements were taken immediately before and after photodynamic therapy. Measurements were analyzed with a nonlinearly constrained multiwavelength, multi-distance algorithm to extract tissue optical properties, tissue oxygen saturation, StO2, and total hemoglobin concentration (THC).A total of 25 patients were measured, 23 of which produced reliable fits for optical property extraction. For all tissue types, StO2 ranged through [24, 100]% and [22, 97]% for pre-photodynamic therapy (PDT) and post-PDT conditions, respectively. Mean THC ranged through [ 69,152 ] μM and [ 48,111 ] μM, for pre-PDT and post-PDT, respectively. Absorption coefficients, μa, ranged through [ 0.024 , 3.5 ] cm - 1 and [ 0.039 , 3 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. Reduced scattering coefficients, μs', ranged through [ 1.4 , 73.4 ] cm - 1 and [ 1.2 , 64 ] cm - 1 for pre-PDT and post-PDT conditions, respectively.There were similar pre- and post-PDT tissue optical properties and hemodynamics. The high variability in each parameter for all tissue types emphasizes the importance of these measurements for accurate PDT dosimetry.

PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), an eight-channel PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously from eight different sites in the pleural cavity during PDT. An isotropic detector with bifurcated fibers was used for each channel to ensure detected light was split equally to the photodiode and spectrometer. The light fluence rate distribution is monitored using an IR navigation system. The navigation system allows 2D light fluence mapping throughout the whole pleural cavity rather than just the selected points. The fluorescence signal is normalized by the light fluence measured at treatment wavelength. We have shown that the absolute photosensitizer concentration can be obtained by applying optical properties correction and linear spectral fitting to the measured fluorescence data. The detection limit and the optical property correction factor of each channel were determined and validated using tissue-simulating phantoms with known varying concentration of Photofrin. Tissue optical properties are determined using an absorption spectroscopy probe immediately before PDT at the same sites. The combination of 8-channel PDT dosimeter system and IR navigation system, which can calculate light fluence rate in the pleural cavity in real-time, providing a mean to determine the distribution of PDT dose on the entire pleural cavity to investigate the heterogeneity of PDT dose on the pleural cavity.

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 be an effective dosimetric quantity which can be used to predict PDT outcome. In this study, ROSED was performed for photofrin-mediated PDT for mice bearing radiation-induced fibrosacorma (RIF) tumor. PDT treatments were performed using single or fractionated illumination to a same total fluence of 135 Jcm(−2). The effects of light fractionation on the total reacted [ROS](rx) and treatment outcomes were evaluated.

Accurate dosimetry is crucial for the ongoing development and clinical study of photodynamic therapy (PDT). Current dosimetry standards range from less accurate methods involving measurement of only light fluence and photosensitizer concentration during treatment, to significantly improved methods such as singlet oxygen explicit dosimetry (SOED), a macroscopic model that includes an additional important parameter in its dosimetric calculations: ground-state oxygen concentration ([(3)O(2)]). However, neither of these models is a method of direct dosimetry. Multispectral singlet oxygen luminescence dosimetry (MSOLD) shows promise in this regard but requires significant improvement in signal quality and remains to be validated in a clinical setting. In this study, we validate a linearly increasing MSOLD signal with an InGaAs photodiode detector for increasing concentration (0 mg/kg to 200 mg/kg) in tissue-simulating phantoms containing photofrin, calculating a calibration curve based on 1270 nm peak-intensity signal and area under the curve for background-subtracted singlet oxygen emission. Additionally, we validate MSOLD against the current clinical dosimetry standard, SOED, through simultaneous measurement of SOED parameters and MSOLD signal for varying concentrations (50 μM – 300 μM). Finally, we investigate the effects of using very high gain amplification on InGaAs photodiode detectors to amplify the MSOLD signal for use in clinical models. We show that a calibration curve relating photosensitizer concentration (PS) and MSOLD signal can be established. Additionally, we demonstrate good correlation between MSOLD signal and SOED-calculated [(1)O(2)](rx). However, we show that when using high amplification on InGaAs photodiodes for long illumination times, the inherent instability in these detectors becomes apparent.