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Purpose Proton radiography (PR) and proton computed tomography (PCT) can be used to measure proton stopping power directly. However, practical and cost effective proton imaging detectors are not widely available. In this study, the authors investigated the feasibility of proton imaging using a silicon diode array. Methods A one-dimensional silicon diode detector array (1DSDA) was aligned with the central axis (CAX) of the proton beam. Polymethyl methacrylate (PMMA) slabs were used to find the correspondence between the water equivalent thickness (WET) and 1DSDA channel number. Two-dimensional proton radiographs were obtained by translation and rotation of a phantom relative to CAX while the proton nozzle and 1DSDA were kept stationary. A PCT image of one slice of the phantom was reconstructed using filtered backprojection. Results PR and PCT images of the PMMA cube were successfully acquired using the 1DSDA. The WET of the phantom was measured using PR data. The resolution and maximum error in WET measurement are 2.0 and 1.5 mm, respectively. Structures down to 2.0 mm in size could be resolved completely. Reconstruction of a PCT image showed very good agreement with simulation. Limitations in spatial resolution are attributed to limited spatial sampling, beam collimation, and proton scatter. Conclusions The results demonstrate the feasibility of using silicon diode arrays for proton imaging. Such a device can potentially offer fast image acquisition and high spatial and energy resolution for PR and PCT.

Purpose: Quality assurance (QA) of dose homogeneity in total skin electron therapy (TSET) is challenging since each patient is positioned in six standing poses with two beam angles. Our study tested the feasibility of a unique approach for TSET QA through computational display of the cumulative dose, constructed and synthesized by computer animation methods. Approach: Dose distributions from Cherenkov emission images were projected onto a scanned 3D body model. Topographically mapped surfaces of the patient were recorded in each of six different delivery positions, while a Cherenkov camera acquired images. Computer animation methods allowed a fitted 3D human body model of the patient to be created with deformation of the limbs and torso to each position. A two-dimensional skin map was extracted from the 3D model of the full surface of the patient. This allowed the dose mapping to be additively accumulated independent of body position, with the total dose summed in a 2D map and reinterpreted on the 3D body display. Results: For the body model, the mean Hausdorff error distance was below 2 cm, setting the spatial accuracy limit. The dose distribution over the patient’s 3D model generally matched the Cherenkov/dose images. The dose distribution mapping was estimated to be near 1.5 cm accuracy based upon a phantom study. The body model must most closely match at the edges of the mesh to ensure that high dose gradients are not projected onto the wrong location. Otherwise 2 to 3 cm level errors in positioning in the mesh do not appear to cause larger than 5% dose errors. The cumulative dose images showed regions of overlap laterally and regions of low intensity in the posterior arms. Conclusions: The proposed modeling and animation can be used to visualize and analyze the accumulated dose in TSET via display of the summed dose/Cherenkov images on a single body surface.

Guest Editors introduce the Special Section on Photodynamic Therapy for the Journal of Biomedical Optics, Volume 25, Issue 6.

Photodynamic therapy (PDT) that employs the photochemical interaction of light, photosensitizer and oxygen is an established modality for the treatment of cancer. However, dosimetry for PDT is becoming increasingly complex due to the heterogeneous photosensitizer uptake by the tumor, and complicated relationship between the tissue oxygenation ([(3)O(2)]), interstitial light distribution, photosensitizer photobleaching and PDT effect. As a result, experts argue that the failure to realize PDT’s true potential is, at least partly due to the complexity of the dosimetry problem. In this study, we examine the efficacy of singlet oxygen explicit dosimetry (SOED) based on the measurements of the interstitial light fluence rate distribution, changes of [(3)O(2)] and photosensitizer concentration during Photofrin-mediated PDT to predict long-term control rates of radiation-induced fibrosarcoma tumors. We further show how variation in tissue [(3)O(2)] between animals induces variation in the treatment response for the same PDT protocol. PDT was performed with 5 mg kg(−1) Photofrin (a drug-light interval of 24 h), in-air fluence rates (ϕ(air)) of 50 and 75 mW cm(−2) and in-air fluences from 225 to 540 J cm(−2). The tumor regrowth was tracked for 90 d after the treatment and Kaplan–Meier analyses for local control rate were performed based on a tumor volume ⩽100 mm(3) for the two dosimetry quantities of PDT dose and SOED. Based on the results, SOED allowed for reduced subject variation and improved treatment evaluation as compared to the PDT dose.

Successful outcome of Photodynamic therapy (PDT) depends on accurate delivery of prescribed light dose. A quality assurance program is necessary to ensure that light dosimetry is correctly measured. We have instituted a QA program that include examination of long term calibration uncertainty of isotropic detectors for light fluence rate, power meter head intercomparison for laser power, stability of the light-emitting diode (LED) light source integrating sphere as a light fluence standard, laser output and calibration of in-vivo reflective fluorescence and absorption spectrometers. We examined the long term calibration uncertainty of isotropic detector sensitivity, defined as fluence rate per voltage. We calibrate the detector using the known calibrated light fluence rate of the LED light source built into an internally baffled 4″ integrating sphere. LED light sources were examined using a 1mm diameter isotropic detector calibrated in a collimated beam. Wavelengths varying from 632nm to 690nm were used. The internal LED method gives an overall calibration accuracy of ±4%. Intercomparison among power meters was performed to determine the consistency of laser power and light fluence rate measured among different power meters. Power and fluence readings were measured and compared among detectors. A comparison of power and fluence reading among several power heads shows long term consistency for power and light fluence rate calibration to within 3% regardless of wavelength. The standard LED light source is used to calibrate the transmission difference between different channels for the diffuse reflective absorption and fluorescence contact probe as well as isotropic detectors used in PDT dose dosimeter.

Accurate light dosimery is critical to ensure consistent outcome for pleural photodynamic therapy (pPDT). Ellipsoid shaped cavities with different sizes surrounded by turbid medium are used to simulate the intracavity lung geometry. An isotropic light source is introduced and surrounded by turbid media. Direct measurements of light fluence rate were compared to Monte Carlo simulated values on the surface of the cavities for various optical properties. The primary component of the light was determined by measurements performed in air in the same geometry. The scattered component was found by submerging the air-filled cavity in scattering media (Intralipid) and absorbent media (ink). The light source was located centrally with the azimuthal angle, but placed in two locations (vertically centered and 2 cm below the center) for measurements. Light fluence rate was measured using isotropic detectors placed at various angles on the ellipsoid surface. The measurements and simulations show that the scattered dose is uniform along the surface of the intracavity ellipsoid geometries in turbid media. One can express the light fluence rate empirically as ϕ =4S/As *Rd/(1 - Rd), where Rd is the diffuse reflectance, As is the surface area, and S is the source power. The measurements agree with this empirical formula to within an uncertainty of 10% for the range of optical properties studied. GPU voxel-based Monte-Carlo simulation is performed to compare with measured results. This empirical formula can be applied to arbitrary geometries, such as the pleural or intraperitoneal cavity.

PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption μ a (λ) and scattering μs ’ (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%S t O 2 ), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

The incident field size and the interplay of absorption and scattering can influence the in-vivo light fluence rate distribution and complicate the absolute quantification of fluorophore concentration in-vivo. In this study, we use Monte Carlo simulations to evaluate the effect of incident beam radius and optical properties to the fluorescence signal collected by isotropic detector placed on the tissue surface. The optical properties at the excitation and emission wavelengths are assumed to be identical. We compute correction factors to correct the fluorescence intensity for variations due to incident field size and optical properties. The correction factors are fitted to a 4-parameters empirical correction function and the changes in each parameter are compared for various beam radius over a range of physiologically relevant tissue optical properties (μa = 0.1 – 1 cm-1 , μs’= 5 – 40 cm-1 ).

Type I photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive oxygen species (ROS). The goal of this study is to develop a model to calculate reactive oxygen species concentration ([ROS]rx) after Tookad®-mediated vascular PDT. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration were made via diffuse reflective absorption spectrum using a contact probe before and after PDT. Blood flow and tissue oxygen concentration over time were measured during PDT as a mean to validate the photochemical parameters for the ROSED calculation. Cure index was computed from the rate of tumor regrowth after treatment and was compared against three calculated dose metrics: total light fluence, PDT dose, reacted [ROS]rx. The tumor growth study demonstrates that [ROS]rx serves as a better dosimetric quantity for predicting treatment outcome, as a clinically relevant tumor growth endpoint.

We demonstrate a noninvasive system for real-time monitoring of tumor blood flow and automatic adjustment of treatment light fluence-rate to conserve tumor perfusion during PDT. Improved efficacy was observed using blood-flow informed light delivery.

Fluorescence-guided surgery (FGS) and other interventions are rapidly evolving as a class of technologically driven interventional approaches in which many surgical specialties visualize fluorescent molecular tracers or biomarkers through associated cameras or oculars to guide clinical decisions on pathological lesion detection and excision/ablation. The technology has been commercialized for some specific applications, but also presents technical challenges unique to optical imaging that could confound the utility of some interventional procedures where real-time decisions must be made. Accordingly, the AAPM has initiated the publication of this Blue Paper of The Emerging Technology Working Group (TETAWG) and the creation of a Task Group from the Therapy Physics Committee within the Treatment Delivery Subcommittee. In describing the relevant issues, this document outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS technology and its applications. The presentation is not intended to be conclusive, but rather to inform the field of medical physics and stimulate the discussions needed in the field with respect to a seemingly low-risk imaging technology that has high potential for significant therapeutic impact. This AAPM Task Group is working toward consensus around guidelines and standards for advancing the field safely and effectively.

Photosensitizer fluorescence excited by photodynamic therapy (PDT) treatment light can be used to monitor the in vivo concentration of the photosensitizer and its photobleaching. The temporal integral of the product of in vivo photosensitizer concentration and light fluence is called PDT dose, which is an important dosimetry quantity for PDT. However, the detected photosensitizer fluorescence may be distorted by variations in the absorption and scattering of both excitation and fluorescence light in tissue. Therefore, correction of the measured fluorescence for distortion due to variable optical properties is required for absolute quantification of photosensitizer concentration. In this study, we have developed a four-channel PDT dose dosimetry system to simultaneously acquire light dosimetry and photosensitizer fluorescence data. We measured PDT dose at four sites in the pleural cavity during pleural PDT. We have determined an empirical optical property correction function using Monte Carlo simulations of fluorescence for a range of physiologically relevant tissue optical properties. Parameters of the optical property correction function for Photofrin fluorescence were determined experimentally using tissue-simulating phantoms. In vivo measurements of photosensitizer fluorescence showed negligible photobleaching of Photofrin during the PDT treatment, but large intra- and inter-patient heterogeneities of in vivo Photofrin concentration are observed. PDT doses delivered to 22 sites in the pleural cavity of 8 patients were different by 2.9 times intra-patient and 8.3 times inter-patient.

Background With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. Aims This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. Materials & methods We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. Results We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. Discussion Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. Conclusion Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.

Uniform delivery of light fluence is an important goal for photodynamic therapy. We present summary results for an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, 8 detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. A MATLAB-based GUI program is developed to display the light dose in real-time during PDT to guide the PDT treatment delivery to improve the uniformity of the light dose. A dualcorrection algorithm is used to improve the agreement between calculations and in-situ measurements. A comprehensive analysis of the distribution of light fluence during PDT is presented in both phantom conditions and in clinical cases.

Purpose: For flattening‐filter free (FFF) photon beams, conventional algorithm based on equivalent‐square to calculate dose per MU is invalid because of the non‐uniform profile. In this study, an empirical algorithm is developed to calculate the dose accurately, which can be used for secondary MU check for IMRT using FFF beams. Methods: A kernel‐based algorithm based on three parameters (a0, w0, d0) is used to quantify the phantom scatter characteristics of the photon beam. The model is modified to quantify the shape of the FFF at off‐axis locations by fitting the primary off‐axis ratio (POAR) by a linear function 1 ‐ br, where b is a constant and r is the radial distance. The resulting parameters are used in a kernel‐based dose calculation algorithm for dose calculation. Results: It is found that the proposed model can fit the product of the fractional depth doses (FDD) and phantom scatter factors (Sp) for field sizes between 2 and 40 cm and depth between 0 and 40 cm to a max and standard deviations of 1.7% and 0.01% and 1.8% and 0.01%, respectively, for 6 and 10 MV FFF beams. The value of b is 0.025 and 0.0323 for 6 MV and 10 MV photons, respectively, from fitting the POAR. The resulting phantom scatter parameters are consistent with those obtained from MC simulation. If the slope is not taken into account (b = 0), then the model cannot fit the central‐axis Sp*FDD accurately and resulted in a maximum error of 3% and 4% for 6 and 10 MV, respectively. Conclusions: We have demonstrated that the shape of POAR from FFF beam will impact on the dose calculation on the central‐axis. Conventional equivalent square law concept will not be applicable for dose calculation for FFF beams.

Purpose: To examine the relationship between the primary SCERMA, Sp, and the primary collision KERMA, Kcp, as a function of depth for clinically relevant energy spectra, and to accurately model the SCERMA to KERMA ratio (SKR) for clinical photon beams. Method and Materials: Sp, Kcp, Sp / Kcp (=SKR) for the energy spectra of Cobalt‐60 (Co‐60), and Mohan 4 MV, 6 MV, 10 MV, 15 MV, and 24 MV photons are analytically calculated over depths from 0 to 40 centimeters in water. The Sp and Kcp are fitted to exponential functions, Sp0exp(−μ′d(l−η′d)) and Kp0exp(−μd(l‐ηd)), respectively, with depth d, linear attenuation coefficient μ and beam hardening coefficient η; μ′ and η′ are the corresponding quantities for Sp. The relationships between μ′, η′, and SKR vs. μ are examined. Trends between the fitting parameters and μ were also determined, and the results applied to model the SKR of 6× and 15× clinical beams as functions of only μ, η, and depth. Results: SKR decreases with depth for all spectra. We found μ′ = (0.80496 + 4.8748μ)μ + 0.005736 and η′ = (−0.13076 + 2.6571μ)μ + 0.0036151 for 0.0273/cm

Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates (ϕ). A macroscopic model was adopted to evaluate using calculated reacted singlet oxygen concentration ([O21]rx) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma tumors, as singlet oxygen is the primary cytotoxic species responsible for cell death in type II PDT. Using a combination of fluences (50, 135, 200, and 250 J/cm2) and ϕ (50, 75, and 150 mW/cm2), tumor regrowth rate, k, was determined for each condition. A tumor cure index, CI=1−k/kcontrol, was calculated based on the k between PDT-treated groups and that of the control, kcontrol. The measured Photofrin concentration and light dose for each mouse were used to calculate PDT dose and [O21]rx, while mean optical properties (μa=0.9 cm−1, μs′=8.4 cm−1) were used to calculate ϕ for all mice. CI was correlated to the fluence, PDT dose, and [O21]rx with R2=0.35, 0.79, and 0.93, respectively. These results suggest that [O21]rx serves as a better dosimetric quantity for predicting PDT outcome.

This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [1 O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm-2 ) and in-air fluence rates (50-150 mW cm-2 ) at Photofrin dosages of 5 and 15 mg kg-1 and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [1 O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [1 O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [1 O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm-2 but cannot be predicted with fluence alone. LCR increases with increasing [1 O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [1 O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.

Intrapleural photodynamic therapy (PDT) has been used in combination with lung sparing surgery to treat patients with malignant pleural mesothelioma. The light, photosensitizers and tissue oxygen are the three most important factors required by type II PDT to produce singlet oxygen, 1O2, which is the main photocytotoxic agent that damages the tumor vasculature and stimulates the body’s anti-tumor immune response. Although light fluence rate and photosensitizer concentrations are routinely monitored during clinical PDT, there is so far a lack of a Food and Drug Administration (FDA)-approved non-invasive technique that can be employed clinically to monitor tissue oxygen in vivo. In this paper, we demonstrated that blood flow correlates well with tissue oxygen concentration during PDT and can be used in place of [3O2] to calculate reacted singlet oxygen concentration [1O2]rx using the macroscopic singlet oxygen model. Diffuse correlation spectroscopy (DCS) was used to monitor the change in tissue blood flow non-invasively during pleural PDT. A contact probe with three source and detectors separations, 0.4, 0.7 and 1.0-cm, was sutured to the pleural cavity wall of the patients after surgical resection of the pleural mesothelioma tumor to monitor the tissue blood flow during intraoperative PDT treatment. The changes of blood flow during PDT of 2 patients are found to be in good correlation with the treatment light fluence rate recorded by the isotropic detector placed adjacent to the DCS probe. [1O2]rx calculated based on light fluence, mean photosensitizer concentration, and relative blood flow was found to be 32% higher in patient #4 (0.50mM) than that for patient #3 (0.38mM).

Photodynamic therapy (PDT) involves interactions between the three main components of light fluence, photosensitizer concentration, and oxygenation. Currently, singlet oxygen explicit dosimetry (SOED) has focused on the first two of these components. The macroscopic model to calculate reacted singlet oxygen has previously involved a fixed initial ground state oxygen concentration. A phosphorescence-based oxygen probe was used to measure ground state oxygen concentration throughout treatments for mice bearing radioactively induced fibroscarcoma tumors. Photofrin-, BPD-, and HPPH-mediated PDT was performed on mice. Model-calculated oxygen and measured oxygen was compared to evaluate the macroscopic model as well as the photochemical parameters involved. Oxygen measurements at various depths were compared to calculated values. Furthermore, we explored the use of noninvasive diffuse correlation spectroscopy (DCS) to measure tumor blood flow changes in response to PDT to improve the model calculation of reacted singlet oxygen. Mice were monitored after treatment to see the effect of oxygenation on long-term recurrence-free survival as well as the efficacy of using reacted singlet oxygen as a predictive measure of outcome. Measurement of oxygenation during treatment helps to improve SOED as well as confirm the photochemical parameters involved in the macroscopic model. Use of DCS in predicting oxygenation changes was also investigated.

Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ (75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier analyses for LCR were done for an endpoint of tumor volume ≤ 100 mm3 using four dose metrics: light fluence, photosensitizer photobleaching rate, PDT dose, and [1O2]rx. PDT dose was defined as the product of the timeintegral of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume ≤100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

We have developed a four-channel PDT dose dosimetry system to simultaneously acquire light dosimetry and sensitizer fluorescence data from four sites in the thoracic cavity during pleural photodynamic therapy (PDT). Photosensitizer fluorescence emitted during PDT is of interest for the monitoring of local concentration of the photosensitizer and its photobleaching. However, the variation in tissue optical properties will cause the photosensitizer fluorescence to alter. Optical properties correction to the measured fluorescence is required for absolute quantification of photosensitizer concentration. In this study, we determine an empirical optical properties correction function using Monte Carlo (MC) simulations of fluorescence for a range of physiologically relevant tissue optical properties. Optical properties correction factors for Photofrin fluorescence were determined experimentally using the same empirical function to recover the Photofrin concentration from measured fluorescence during PDT. The results showed no photobleaching of Photofrin during the course of PDT. PDT doses delivered to multiple sites in the thoracic cavity of 4 patients were presented and showed that PDT dose can be different by 4.4 times intra-patients and 9.1 times inter-patients.

Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([1O2]rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm2 and in-air fluence rate (φair) of 50 and 75 mW/cm2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [1O2]rx is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume ≤100 mm3, for the four dose metrics light fluence, photosensitizer photobleaching rate, PDT dose and [1O2]rx. PDT dose is defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [1O2]rx is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [1O2]rx calculated using the blood flow changes was in agreement with [1O2]rx calculated based on the actual tissue oxygenation.

Photosensitizer photochemical parameters are crucial data in accurate dosimetry for photodynamic therapy (PDT) based on photochemical modeling. Progress has been made in the last few decades in determining the photochemical properties of commonly used photosensitizers (PS), but mostly in solution or in vitro. Recent developments allow for the estimation of some of these photochemical parameters in vivo. This review will cover the currently available in vivo photochemical properties of photosensitizers as well as the techniques for measuring those parameters. Furthermore, photochemical parameters that are independent of environmental factors or are universal for different photosensitizers will be examined. Most photosensitizers discussed in this review are of the type II (singlet oxygen) photooxidation category, although type I photosensitizers that involve other reactive oxygen species (ROS) will be discussed as well. The compilation of these parameters will be essential for ROS modeling of PDT.

Photodynamic therapy (PDT) is known as a non-invasive treatment modality that is based on photochemical reactions between oxygen, photosensitizer, and a special wavelength of light. However, a dosimetric predictor for PDT outcome is still elusive because current dosimetric quantities do not account for the differences in the PDT oxygen consumption rate for different fluence rates. In this study, we evaluate several dose metrics, total fluence, photobleaching ratio, PDT dose, and mean reacted singlet oxygen (mean [1 O2 ]rx ) for predicting the PDT outcome and a clinically relevant tumor re-growth endpoint. For this reason, radiation-induced fibrosarcoma (RIF) mice tumors are treated with 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) and different in-air fluences (30 J/cm2 , 50 J/cm2 , 135 J/cm2 , 250 J/cm2 , and 350 J/cm2 ) and in-air fluence rates (20, 50, 75, 150 mW/cm2 ). Explicit measurements of HPPH and oxygen concentration as well as tissue optical properties are performed pre- and post-treatment. Then, this information is incorporated into a macroscopic model to calculate the photobleaching, PDT dose, and mean [1 O2 ]rx . Changes in tumor volume are tracked following the treatment and compared with the dose metrics. The correlation demonstrates that mean [1 O2 ]rx serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor re-growth endpoint.

As a nonionizing radiation treatment, photodynamic therapy (PDT) has been used effectively for the treatment of various easily accessible lesions, such as head and neck cancers, esophageal cancers, microinvasive lung cancer, and skin lesions such as premalignant actinic keratosis.1–4 PDT requires the administration of a photosensitizer that localizes in tumor tissue and is excited by the appropriate treatment wavelength of light. With the absorption of light, the photosensizer transitions from its ground state to a short-lived excited singlet state. The singlet state photosensitizer transitions to a longer-lived electronically excited triplet state via intersystem crossing. In typical type II PDT, which is the focus of this study, the triplet state transfers energy to molecular ground state oxygen (O23) that is present in the treatment environment to produce singlet-state oxygen (O21). The production of O21 and reactions with the surrounding biological molecules are thought to be the major cause of cytotoxicity.5 Due to the high reactivity and short lifetime of O21, only cells that are proximal to the area of O21 production are directly affected by PDT.6 For that reason, PDT causes significantly less harm to healthy tissue than chemotherapy or radiation.6,7 A well-defined dosimetric metric for PDT that is able to predict clinical outcomes that can also be implemented in a clinical setting would benefit the advance of the PDT field. Benzoporphyrin derivative monoacid ring A (BPD, trademark Visudyne®) is a commonly used photosensitizer that was approved by the US Food and Drug Administration in 2000 for the treatment of wet age-related macular degeneration.8 Utilizing a macroscopic model, reacted singlet oxygen ([O21]rx) can be calculated to evaluate its effectiveness as a dosimetric predictor for BPD-mediated PDT outcome. In addition, several other dose metrics were evaluated in this study, including total light fluence, photobleaching ratio, and PDT dose, to predict the PDT outcome. Radiation-induced fibrosarcoma (RIF) tumors on mice were treated with BPD-PDT and a range of in-air fluences (30 to 350 J/cm2) and in-air fluence rates (50 to 150 mW/cm2). For each PDT treatment group, explicit measurements of BPD concentration in tumor and tissue optical properties were performed pre- and posttreatment. For a subset of mice, real-time in-vivo measurement of BPD concentration and tissue oxygenation level ([O23]) throughout PDT were taken to optimize the photosensitizer-specific PDT photochemical parameters (ξ, σ, and g), reduce their uncertainty from a previous study, and calculate [O21]rx. These photochemical parameters were used to calculate [O21]rx for each PDT treatment group. Other dose metrics, such as photobleaching ratio and PDT dose, were determined either directly using explicit measurements pre- and post-PDT or calculated using the time dependence of BPD concentration based on the macroscopic model and the definition of PDT dose. This study, to our knowledge, is the first to investigate the threshold value of [O21]rx and the relationship between various dose metrics (fluence, PDT dose, and [O21]rx) and the cure index (CI) at 14 days in an in-vivo mouse model for BPD-mediated PDT. The results of our study with additional real-time measurements of BPD concentration and [O23] provide reduced uncertainties for the photochemical parameters determined for BPD-mediated PDT, as well as a validation that our macroscopic model can accurately predict the oxygen consumption for BPD-mediated PDT, making it feasible to determine [O21]rx without oxygen measurements.

Accurate photodynamic therapy (PDT) dosimetry is critical for the use of PDT in the treatment of malignant and nonmalignant localized diseases. A singlet oxygen explicit dosimetry (SOED) model has been developed for in vivo purposes. It involves the measurement of the key components in PDT—light fluence (rate), photosensitizer concentration, and ground-state oxygen concentration ([3O2])—to calculate the amount of reacted singlet oxygen ([1O2]rx), the main cytotoxic component in type II PDT. Experiments were performed in phantoms with the photosensitizer Photofrin and in solution using phosphorescence-based singlet oxygen luminescence dosimetry (SOLD) to validate the SOED model. Oxygen concentration and photosensitizer photobleaching versus time were measured during PDT, along with direct SOLD measurements of singlet oxygen and triplet state lifetime (τΔ and τt), for various photosensitizer concentrations to determine necessary photophysical parameters. SOLD-determined cumulative [1O2]rx was compared to SOED-calculated [1O2]rx for various photosensitizer concentrations to show a clear correlation between the two methods. This illustrates that explicit dosimetry can be used when phosphorescence-based dosimetry is not feasible. Using SOED modeling, we have also shown evidence that SOLD-measured [1O2]rx using a 523 nm pulsed laser can be used to correlate to singlet oxygen generated by a 630 nm laser during a clinical malignant pleural mesothelioma (MPM) PDT protocol by using a conversion formula.

Accurate determination of in-vivo light fluence rate is critical for preclinical and clinical studies involving photodynamic therapy (PDT). The light fluence distribution in tissue depends on both the tissue optical properties and the incident field size. This study compares the longitudinal light fluence distribution inside biological tissue in the central axis of circular uniform light field with different radii for a range of in-vivo tissue optical properties (absorption coefficients (µa) between 0.01 and 1 cm−1 and reduced scattering coefficients (µs’) between 2 and 40 cm−1). This was done using Monte-Carlo simulations for a semi-infinite turbid medium in an air-tissue interface. The end goal is to develop simple analytical expressions that would fit the results from the Monte Carlo simulation for circular beams with different radii. A 6-parameter model (ϕ/ϕair=(1−b⋅e−λ1d)(C2e−λ2d+C3e−λ3d)) can be used to fit MC simulation. Each of these parameters (b, C2, C3, λ1, λ2, and λ3) is expressed as a function of tissue optical properties and beam radius. These results can then be compared against the existing expressions in the literature for broad beam for analysis in both accuracy and applicable range. The analytical function can be used as rapid guide in PDT to calculate in vivo light fluence distribution for known tissue optical properties.

Interstitial diffuse optical tomography (DOT) has been used to characterize spatial distribution of optical properties for prostate photodynamic therapy (PDT) dosimetry. We have developed an interstitial DOT method using cylindrical diffuse fibers (CDFs) as light sources, so that the same light sources can be used for both DOT measurement and PDT treatment. In this novel interstitial CDF-DOT method, absolute light fluence per source strength (in unit of 1 cm(-2)) is used to separate absorption and scattering coefficients. A mathematical phantom and a solid prostate phantom including anomalies with known optical properties were used, respectively, to test the feasibility of reconstructing optical properties using interstitial CDF-DOT. Three dimension spatial distributions of the optical properties were reconstructed for both scenarios. Our studies show that absorption coefficient can be reliably extrapolated while there are some cross talks between absorption and scattering properties. Even with the suboptimal reduced scattering coefficients, the reconstructed light fluence rate agreed with the measured values to within ±10%, thus the proposed CDF-DOT allows greatly improved light dosimetry calculation for interstitial PDT.

Proton radiography (PR) and proton computed tomography (PCT) can be used to measure proton stopping power directly. However, practical and cost effective proton imaging detectors are not widely available. In this study, the authors investigated the feasibility of proton imaging using a silicon diode array.A one-dimensional silicon diode detector array (1DSDA) was aligned with the central axis (CAX) of the proton beam. Polymethyl methacrylate (PMMA) slabs were used to find the correspondence between the water equivalent thickness (WET) and 1DSDA channel number. Two-dimensional proton radiographs were obtained by translation and rotation of a phantom relative to CAX while the proton nozzle and 1DSDA were kept stationary. A PCT image of one slice of the phantom was reconstructed using filtered backprojection.PR and PCT images of the PMMA cube were successfully acquired using the 1DSDA. The WET of the phantom was measured using PR data. The resolution and maximum error in WET measurement are 2.0 and 1.5 mm, respectively. Structures down to 2.0 mm in size could be resolved completely. Reconstruction of a PCT image showed very good agreement with simulation. Limitations in spatial resolution are attributed to limited spatial sampling, beam collimation, and proton scatter.The results demonstrate the feasibility of using silicon diode arrays for proton imaging. Such a device can potentially offer fast image acquisition and high spatial and energy resolution for PR and PCT.

This paper presents a novel compact fiberoptic based singlet oxygen near-infrared luminescence probe coupled to an InGaAs/InP single photon avalanche diode (SPAD) detector. Patterned time gating of the single-photon detector is used to limit unwanted dark counts and eliminate the strong photosensitizer luminescence background. Singlet oxygen luminescence detection at 1270 nm is confirmed through spectral filtering and lifetime fitting for Rose Bengal in water, and Photofrin in methanol as model photosensitizers. The overall performance, measured by the signal-to-noise ratio, improves by a factor of 50 over a previous system that used a fiberoptic-coupled superconducting nanowire single-photon detector. The effect of adding light scattering to the photosensitizer is also examined as a first step towards applications in tissue in vivo.

When the pleural cavity is opened during the surgery portion of pleural photodynamic therapy (PDT) of malignant mesothelioma, the pleural volume will deform. This impacts the delivered dose when using highly conformal treatment techniques. To track the anatomical changes and contour the lung and chest cavity, an infrared camera–based navigation system (NDI) is used during PDT. In the same patient, a series of computed tomography (CT) scans of the lungs are also acquired before the surgery. The reconstructed three-dimensional contours from both NDI and CTs are imported into COMSOL Multiphysics software, where a finite element-based (FEM) deformable image registration is obtained. The CT contour is registered to the corresponding NDI contour by overlapping the center of masses and aligning their orientations. The NDI contour is considered as the reference contour, and the CT contour is used as the target one, which will be deformed. Deformed Geometry model is applied in COMSOL to obtain a deformed target contour. The distortion of the volume at X, Y and Z is mapped to illustrate the transformation of the target contour. The initial assessment shows that FEM-based image deformable registration can fuse images acquired by different modalities. It provides insights into the deformation of anatomical structures along X, Y and Z-axes. The deformed contour has good matches to the reference contour after the dynamic matching process. The resulting three-dimensional deformation map can be used to obtain the locations of other critical anatomic structures, e.g., heart, during surgery.

The macroscopic singlet oxygen model has been used for singlet oxygen explicit dosimetry in photodynamic therapy (PDT). The photophysical parameters for commonly used sensitizers, HPPH and BPD, have been investigated in pre-clinical studies using mouse models. So far, studies have involved optimizing fitting algorithms to obtain the some of the photophysical parameters (ξ, σ, g) and the threshold singlet oxygen dose ([1O2]rx,sh), while other parameters such as the low concentration correction, δ, has been kept as a constant. In this study, using photobleaching measurements of mice in vivo, the value of δ was also optimized and fit to better describe experimental data. Furthermore, the value of the specific photobleaching ratio (σ) was also fine-tuned using the photobleaching results. Based on literature values of δ, σ for photosensitizers can be uniquely determined using the additional photobleaching measurements. This routine will further improve the macroscopic model of singlet oxygen production for use in explicit dosimetry.

Accurate determination of in-vivo light fluence rate is critical for preclinical and clinical studies involving photodynamic therapy (PDT). This study compares the longitudinal light fluence distribution inside biological tissue in the central axis of a 1 cm diameter circular uniform light field for a range of in-vivo tissue optical properties (absorption coefficients ( P a ) between 0.01 and 1 cm -1 and reduced scattering coefficients ( P s ’) between 2 and 40 cm -1 ). This was done using Monte-Carlo simulations for a semi -infinite turbid medium in an air-tissue interface. The end goal is to develop an analytical expression that would fit the results from the Monte Carlo simulation for both the 1 cm diameter circular beam and the broad beam. Each of these parameters is expressed as a function of tissue optical properties. These results can then be compared against the existing expressions in the literature for broad beam for analysis in both accuracy and applicable range. Using the 6-parameter model, the range and accuracy for light transport through biological tissue is improved and may be used in the future as a guide in PDT for light fluence distribution for known tissue optical properties. Keywords: MC, PDT, semi-infinite medium, analytical expression

Cerenkov contamination is a significant issue in radiation detection by fiber-coupled scintillators. To enhance the scintillation signal transmission while minimizing Cerenkov contamination, we designed a fiber probe using a silver-only coated hollow waveguide (HWG). The HWG tip with inserted scintillator, embedded in tissue mimicking phantoms, was irradiated with clinical electron and photon beams. Optical spectra of irradiated tips were taken using a fiber spectrometer, and the signal was deconvolved with a linear fitting algorithm. The resultant decomposed spectra of the scintillator with and without Cerenkov correction were in good agreement with measurements performed by an electron diode and ion chamber for electron and photon beam dosimetry, respectively, indicating the minimal effect of Cerenkov contamination. Compared with a silver/dielectric coated HWG fiber dosimeter design we observed higher signal transmission in our design based on the use of silver-only HWG.

Type II photodynamic therapy (PDT) is used for cancer treatment based on the combined action of a photosensitizer, a special wavelength of light, oxygen (3O2) and generation of singlet oxygen (1O2). Intra-patient and inter-patient variability of oxygen concentration ([3O2]) before and after the treatment as well as photosensitizer concentration and hemodynamic parameters such as blood flow during PDT has been reported. Simulation of these variations is valuable, as it would be a means for the rapid assessment of treatment effect. A mathematical model has been previously developed to incorporate the diffusion equation for light transport in tissue and the macroscopic kinetic equations for simulation of [3O2], photosensitizers in ground and triplet states and concentration of the reacted singlet oxygen ([1O₂]rx) during PDT. In this study, the finite-element based calculation of the macroscopic kinetic equations is done for 2-(1- Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated PDT by incorporating the information of the photosensitizer photochemical parameters as well as the tissue optical properties, photosensitizer concentration, initial oxygen concentration ([3O2]0), blood flow changes and Φ that have been measured in mice bearing radiation-induced fibrosarcoma (RIF) tumors. Then, [1O2]rx calculated by using the measured [3O2] during the PDT is compared with [1O2]rx calculated based on the simulated [3O₂]; both calculations showed a reasonably good agreement. Moreover, the impacts of the blood flow changes and [3O2]0 on [1O2]rx have been investigated, which showed no pronounced effect of the blood flow changes on the long-term 1O2 generation. When [3O2]0 becomes limiting, small changes in [3O₂] have large effects on [1O2]rx.

An explicit dosimetry model has been developed to calculate the apparent reacted 1O2 concentration ([1O2]rx) in an in-vivo model. In the model, a macroscopic quantity, g, is introduced to account for oxygen perfusion to the medium during PDT. In this study, the SOED model is extended for PDT treatment in phantom conditions where vasculature is not present; the oxygen perfusion is achieved through the air-phantom interface instead. The solution of the SOED model is obtained by solving the coupled photochemical rate equations incorporating oxygen perfusion through the air-liquid interface. Experiments were performed for two photosensitizers (PS), Rose Bengal (RB) and Photofrin, in solution, using SOED and SOLD measurements to determine both the instantaneous [1O2] as well as cumulative [1O2]rx concentrations, where [1O2=(1/τ▵)•∫[1O2]dt. The PS concentrations varied between 10 and 100 mM for RB and ~200 mM for Photofrin. The resulting magnitudes of [1O2] were compared between SOED and SOLD. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

It is well known in photodynamic therapy (PDT) that there is a large variability between PDT light dose and therapeutic outcomes. An explicit dosimetry model using apparent reacted 1 O 2 concentration [ 1 O 2 ] rx has been developed as a PDT dosimetric quantity to improve the accuracy of the predicted ability of therapeutic efficacy. In this study, this explicit macroscopic singlet oxygen model was adopted to establish the correlation between calculated reacted [ 1 O 2 ] rx and the tumor growth using Photofrin-mediated PDT in a mouse tumor model. Mice with radiation-induced fibrosarcoma (RIF) tumors were injected with Photofrin at a dose of 5 mg/kg. PDT was performed 24h later with different fluence rates (50, 75 and 150 mW/cm 2 ) and different fluences (50 and 135 J/cm2) using a collimated light applicator coupled to a 630nm laser. The tumor volume was monitored daily after PDT and correlated with the total light fluence and [ 1 O 2 ] rx . Photophysical parameters as well as the singlet oxygen threshold dose for this sensitizer and the RIF tumor model were determined previously. The result showed that tumor growth rate varied greatly with light fluence for different fluence rates while [ 1 O 2 ] rx had a good correlation with the PDT-induced tumor growth rate. This preliminary study indicated that [ 1 O 2 ] rx could serve as a better dosimetric predictor for predicting PDT outcome than PDT light dose.

Summary Objectives Management of early superficial lesions in the head and neck remains complex. We performed a phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA). Materials and methods Thirty-five subjects with high grade dysplasia, carcinoma in situ, or microinvasive (⩽1.5 mm depth) squamous cell carcinoma were enrolled. Cohorts of 3–6 patients were given escalating intraoperative light doses of 50–200 J/cm2 4–6 h after oral administration of 60 mg/kg ALA. Light at 629–635 nm was delivered in a continuous (unfractionated) or fractionated (two-part) schema. Results PDT was delivered to 30/35 subjects, with 29 evaluable. There was one death possibly due to the treatment. The regimen was otherwise tolerable, with a 52% rate of grade 3 mucositis which healed within several weeks. Other toxicities were generally grade 1 or 2, including odynophagia (one grade 4), voice alteration (one grade 3), and photosensitivity reactions. One patient developed grade 5 sepsis. With a median follow-up of 42 months, 10 patients (34%) developed local recurrence; 4 of these received 50 J/cm2 and two each received 100, 150, and 200 J/cm2. Ten (34%) patients developed recurrence adjacent to the treated field. There was a 69% complete response rate at 3 months. Conclusions ALA-PDT is well tolerated. Maximum Tolerated Dose appears to be higher than the highest dose used in this study. Longer followup is required to analyze effect of light dose on local recurrence. High marginal recurrence rates suggest use of larger treatment fields.

We present a novel fiber optic based singlet oxygen luminescence probe coupled to an InGaAs/InP single photon avalanche diode (SPAD) detector. Patterned time gating limited unwanted dark counts and eliminated the strong photosensitizer luminescence background.

A thorough understanding of optical properties of biological tissues is critical to effective treatment planning for therapies such as photodynamic therapy (PDT). In the last two decades, new technologies, such as broadband diffuse spectroscopy, have been developed to obtain in vivo data in humans that was not possible before. We found that the in vivo optical properties generally vary in the ranges μ(a) = 0.03-1.6 cm⁻¹ and μ'(s) = 1.2-40 cm⁻¹, although the actual range is tissue-type dependent. We have also examined the overall trend of the absorption spectra (for μ(a) and μ'(s)) as a function of wavelength within a 95% confidence interval for various tissues in vivo. The impact of optical properties on light fluence rate is also discussed for various light application geometries including superficial, interstitial, and within a cavity.

Purpose: For routine clinical dosimetry of photon beams, it is often necessary to know the minimum thickness of backscatter phantom material to ensure that full backscatter condition exists. Methods: In case of insufficient backscatter thickness, one can determine the backscatter correction factor,BCF(s,d,t), defined as the ratio of absorbed dose measured on the central-axis of a phantom with backscatter thickness of t to that with full backscatter for square field sizes and forward depth d. Measurements were performed in SAD geometry for 6 and 15 MV photon beams using a 0.125 cc thimble chamber for field sizes between 10 × 10 and 30 × 30 cm at depths between d max (1.5 cm for 6 MV and 3 cm for 15 MV) and 20 cm. Results: A convolution method was used to calculateBCF using Monte-Carlo simulated point-spread kernels generated for clinical photon beams for energies between Co-60 and 24 MV. The convolution calculation agrees with the experimental measurements to within 0.8% with the same physical trend. The value of BCF deviates more from 1 for lower energies and larger field sizes. According to our convolution calculation, the minimum BCF occurs at forward depth d max and 40 × 40 cm field size, 0.970 for 6 MV and 0.983 for 15 MV. Conclusions: The authors concluded that backscatter thickness is 6.0 cm for 6 MV and 4.0 cm for 15 MV for field size up to 10 × 10 cm whenBCF = 0.998. If 4 cm backscatter thickness is used, BCF is 0.997 and 0.983 for field size of 10 × 10 and 40 × 40 cm for 6 MV, and is 0.998 and 0.990 for 10 × 10 and 40 × 40 cm for 15 MV, respectively.

Photodynamic therapy (PDT) has been used for head and neck carcinomas with little experience in the oropharynx due to technical challenges in achieving adequate exposure. We present the case of a patient with a second right tonsil carcinoma following previous treatment with transoral robotic surgery (TORS) and postoperative chemoradiation for a left tonsil carcinoma. Repeat TORS for the right tonsil carcinoma reviewed multiple positive surgical margins. The power output from the robotic camera was modified to facilitate safe intraoperative three dimensional visualization of the tumor bed. The robotic arms facilitated clear exposure of the tonsil and tongue base with stable administration of the fluence. Real-time measurements confirmed stable photobleaching with augmentation of the prescribed light fluence secondary to light scatter in the oropharynx. We report a potential new role using TORS for exposure and accurate PDT in the oropharynx.

The requirement of an independent verification of the monitor units (MU) or time calculated to deliver the prescribed dose to a patient has been a mainstay of radiation oncology quality assurance. The need for and value of such a verification was obvious when calculations were performed by hand using look-up tables, and the verification was achieved by a second person independently repeating the calculation. However, in a modern clinic using CT/MR/PET simulation, computerized 3D treatment planning, heterogeneity corrections, and complex calculation algorithms such as convolution/superposition and Monte Carlo, the purpose of and methodology for the MU verification have come into question. In addition, since the verification is often performed using a simpler geometrical model and calculation algorithm than the primary calculation, exact or almost exact agreement between the two can no longer be expected. Guidelines are needed to help the physicist set clinically reasonable action levels for agreement. This report addresses the following charges of the task group: (1) To re-evaluate the purpose and methods of the “independent second check” for monitor unit calculations for non-IMRT radiation treatment in light of the complexities of modern-day treatment planning. (2) To present recommendations on how to perform verification of monitor unit calculations in a modern clinic. (3) To provide recommendations on establishing action levels for agreement between primary calculations and verification, and to provide guidance in addressing discrepancies outside the action levels. These recommendations are to be used as guidelines only and shall not be interpreted as requirements.