Intraoperative radiation therapy with 50 kV x-rays: A multi-institutional review.

This report covers clinical implementation of a low kV intraoperative radiation therapy (IORT) program with the INTRABEAM® System (Carl Zeiss Meditec AG, Jena, Germany). Based on collective user experience from eight institutions, we discuss best methods of INTRABEAM quality assurance (QA) tests, commissioning measurements, clinical workflow, treatment planning, and potential avenues for research. The guide provides pertinent background information and clinical justification for IORT. It describes the INTRABEAM system and commissioning measurements along with a TG100 risk management analysis to ensure safety and accuracy of the IORT program. Following safety checks, dosimetry measurements are performed for verification of field flatness and symmetry, x-ray output, and depth dose. Also discussed are dose linearity checks, beam isotropy, ion chamber measurements, calibration protocols, and in-vivo dosimetry with optically stimulated luminescence dosimeters OSLDs, and radiochromic film. Emphasis is placed on the importance of routine QA procedures (daily, monthly, and annual) performed at regular intervals for a successful IORT program. For safe and accurate dose delivery, tests of important components of IORT clinical workflow are emphasized, such as, dose prescription, pre-treatment QA, treatment setup, safety checks, radiation surveys, and independent checks of delivered dose. Challenges associated with in-vivo dose measurements are discussed, along with special treatment procedures and shielding requirements. The importance of treatment planning in IORT is reviewed with reference to a Monte Carlo-based commercial treatment planning system highlighting its main features and limitations. The report concludes with suggested topics for research including CT-based image-guided treatment planning and improved prescription dose accuracy. We hope that this multi-institutional report will serve as a guidance document on the clinical implementation and use of INTRABEAM IORT.

Establishing a fingerprinting method for fast catheter identification in HDR brachytherapy in vivo dosimetry.

PURPOSE: To use quantities measurable during in vivo dosimetry to build unique channel identifiers, that enable detection of brachytherapy errors. MATERIALS AND METHODS: Treatment plan of 360 patients with prostate cancer who underwent high-dose-rate brachytherapy (range, 16-25 catheters; mean, 17) were used. A single point virtual dosimeter was placed at multiple positions within the treatment geometry, and the source-dosimeter distance and dwell time were determined for each dwell position in each catheter. These values were compared across all catheters, dwell position by dwell position, simulating a treatment delivery. A catheter was considered uniquely identified if, for a given dwell position, no other catheters had the same measured values. The minimum number of dwell positions needed to identify a specific catheter and the optimal dosimeter location uniquely were determined. The radial (r) and vertical (z) dimensions of the source-dosimeter distance were also examined for their utility in discriminating catheters. RESULTS: Using a virtual dosimeter with no uncertainties, all catheters were identified in 359 of the 360 cases with 9 dwell position measurements. When only the dwell time were measured, all catheters were uniquely identified after 1 dwell position. With a 2-mm spatial accuracy (r,z), all catheters were identified in 94% of the plans. Simultaneous measurement of source-dosimeter distance and dwell time ensured full catheter identification in all plans ranging from 2 to 6 dwell positions. The number of dwell positions needed to uniquely identify all catheters was lower when the distance from the implant center was higher. CONCLUSIONS: The most efficient fingerprinting approach involved combining source-dosimeter distance (i.e., source tracking) and dwell time. The further the dosimeter is placed from the center of the implant the better it can uniquely identify catheters.

Deep learning-based tools to distinguish plan-specific from generic deviations in EPID-based in vivo dosimetry.

BACKGROUND: Dose distributions calculated with electronic portal imaging device (EPID)-based in vivo dosimetry (EIVD) differ from planned dose distributions due to generic and plan-specific deviations. Generic deviations are characteristic to a class of plans. Examples include limitations in EIVD dose reconstruction, inaccuracies in treatment planning system (TPS) calculations and systematic machine deviations. Plan-specific deviations have an unpredictable character. Examples include discrepancies between the patient model used for dose calculation and the patient position or anatomy during delivery, random machine deviations, and data transfer, human or software errors. During the inspection work performed with traditional γ-evaluation statistical methods: (i) generic deviations raise alerts that need to be inspected but that rarely lead to action as their root cause is usually understood and (ii) the detection of relevant plan-specific deviations may be hindered by the presence of generic deviations. PURPOSE: To investigate whether deep learning-based tools can help in identifying γ-alerts raised by generic deviations and in improving the detectability of plan-specific deviations. METHODS: A 3D U-Net was trained as an autoencoder to reconstruct underlying patterns of generic deviations in γ-distributions. The network was trained for four treatment disease sites differently affected by generic deviations: volumetric modulated arc therapy (VMAT) lung (no known deviations), VMAT prostate (TPS inaccuracies), VMAT head-and-neck (EIVD limitations) and intensity modulated radiation therapy (IMRT) breast (large EIVD limitations). The network was trained with virtual non-transit γ-distributions: 60 train/10 validation for the VMAT sites and 30 train/10 validation for IMRT breast. It was hypothesized that in vivo γ-distributions obtained in the presence of plan-specific deviations would differ from those seen during training. For each disease site, the sensitivity of γ-analysis and the network to detect (synthetically introduced) patient-related deviations was compared by receiver operator characteristic analysis. The investigated deviations were patient positioning errors, weight gain or loss, and tumor volume changes. The clinical relevance was illustrated qualitatively with 793 in vivo clinical cases (141 lung, 136 head-and-neck, 209 prostate and 307 breast). RESULTS: Error detectability of patient-related deviations was better with the network than with γ-analysis. The average area under the curve values over all sites were 0.86 ± 0.12(1SD) and 0.69 ± 0.25(1SD), respectively. Regarding in vivo clinical results, the percentage of cases differently classified by γ-analysis and the network was 1%, 19%, 18% and 64% for lung, head-and-neck, prostate, and breast, respectively. In head-and-neck and breast cases, 45 γ-only alerts were examined, of which 43 were attributed to EPID dose reconstruction limitations. For prostate, all 15 investigated γ-only alerts were due to known TPS inaccuracies. All 59 investigated network alerts were explained by either patient-related deviations or EPID acquisition incidents. Some patient-related deviations detected by the network were not detected by γ-analysis. CONCLUSIONS: Deep learning-based tools trained to reconstruct underlying patterns of generic deviations in γ-distributions can be used to (i) automatically identify false positives within the set of γ-alerts and (ii) improve the detection of plan-specific deviations, hence minimizing the likelihood of false negatives. The presented method provides clear additional value to the γ-alert management process for large scale EIVD systems.

Towards real-time EPID-based 3D in vivo dosimetry for IMRT with Deep Neural Networks: A feasibility study.

We investigate the potential of the Deep Dose Estimate (DDE) neural network to predict 3D dose distributions inside patients with Monte Carlo (MC) accuracy, based on transmitted EPID signals and patient CTs. The network was trained using as input patient CTs and first-order dose approximations (FOD). Accurate dose distributions (ADD) simulated with MC were given as training targets. 83 pelvic CTs were used to simulate ADDs and respective EPID signals for subfields of prostate IMRT plans (gantry at 0∘). FODs were produced as backprojections from the EPID signals. 581 ADD-FOD sets were produced and divided into training and test sets. An additional dataset simulated with gantry at 90∘ (lateral set) was used for evaluating the performance of the DDE at different beam directions. The quality of the FODs and DDE-predicted dose distributions (DDEP) with respect to ADDs, from the test and lateral sets, was evaluated with gamma analysis (3%,2 mm). The passing rates between FODs and ADDs were as low as 46%, while for DDEPs the passing rates were above 97% for the test set. Meaningful improvements were also observed for the lateral set. The high passing rates for DDEPs indicate that the DDE is able to convert FODs into ADDs. Moreover, the trained DDE predicts the dose inside a patient CT within 0.6 s/subfield (GPU), in contrast to 14 h needed for MC (CPU-cluster). 3D in vivo dose distributions due to clinical patient irradiation can be obtained within seconds, with MC-like accuracy, potentially paving the way towards real-time EPID-based in vivo dosimetry.

A scintillation dosimeter with real-time positional tracking information for in vivo dosimetry error detection in HDR brachytherapy.

PURPOSE: To evaluate the performance of an electromagnetic (EM)-tracked scintillation dosimeter in detecting source positional errors of IVD in HDR brachytherapy treatment. MATERIALS AND METHODS: Two different scintillator dosimeter prototypes were coupled to 5 degrees-of-freedom (DOF) EM sensors read by an Aurora V3 system. The scintillators used were a 0.3 × 0.4 × 0.4 mm3 ZnSe:O and a BCF-60 plastic scintillator of 0.5 mm diameter and 2.0 mm in length (Saint-Gobain Crystals). The sensors were placed at the dosimeter's tip at 20.0 mm from the scintillator. The EM sampling rate was 40/s while the scintillator signal was sampled at 100 000/s using two photomultiplier tubes from Hamamatsu (series H10722) connected to a data acquisition board. A high-pass filter and a low-pass filter were used to separate the light signal into two different channels. All measurements were performed with an afterloader unit (Flexitron-Elekta AB, Sweden) in full-scattered (TG43) conditions. EM tracking was further used to provide distance/angle-dependent energy correction for the ZnSe:O inorganic scintillator. For the error detection part, lateral shifts of 0.5 to 3 mm were induced by moving the source away from its planned position. Indexer length (longitudinal) errors between 0.5 to 10 mm were also introduced. The measured dose rate difference was converted to a shift distance, with and without using the positional information from the EM sensor. RESULTS: The inorganic scintillator had both a signal-to-noise-ratio (SNR) and signal-to-background-ratio (SBR) close to 70 times higher than those of the plastic scintillator. The mean absolute difference from the dose measurement to the dose calculated with TG-43U1 was 1.5% ±0.7%. The mean absolute error for BCF-60 detector was 1.7% ± 1.2 % $\pm 1.2\%$ when compared to TG-43 calculations formalism. With the inorganic scintillator and EM tracking, a maximum area under the curve (AUC) gain of 24.0% was obtained for a 0.5-mm lateral shift when using the EMT data with the ZnSe:O. Lower AUC gains were obtained for a 3-mm lateral shifts with both scintillators. For the plastic scintillator, the highest gain from using EM tracking information occurred for a 0.5-mm lateral shift at 20 mm from the source. The maximal gain (17.4%) for longitudinal errors was found at the smallest shifts (0.5 mm). CONCLUSIONS: This work demonstrates that integrating EM tracking to in vivo scintillation dosimeters enables the detection of smaller shifts, by decreasing the dosimeter positioning uncertainty. It also serves to perform position-dependent energy correction for the inorganic scintillator,providing better SNR and SBR, allowing detection of errors at greater distances from the source.

Characterization of a diode dosimeter for UHDR FLASH radiotherapy.

BACKGROUND: Ultra-high dose rate (UHDR) FLASH beams typically deliver dose at rates of  >40 Gy/sec. Characterization of these beams with respect to dose, mean dose rate, and dose per pulse requires dosimeters which exhibit high temporal resolution and fast readout capabilities. PURPOSE: A diode EDGE Detector with a newly designed electrometer has been characterized for use in an UHDR electron beam and demonstrated appropriateness for UHDR FLASH radiotherapy dosimetry. METHODS: Dose linearity, mean dose rate, and dose per pulse dependencies of the EDGE Detector were quantified and compared with dosimeters including a W1 scintillator detector, radiochromic film, and ionization chamber that were irradiated with a 10 MeV UHDR beam. The dose, dose rate, and dose per pulse were controlled via an in-house developed scintillation-based feedback mechanism, repetition rate of the linear accelerator, and source-to-surface distance, respectively. Depth-dose profiles and temporal profiles at individual pulse resolution were compared to the film and scintillation measurements, respectively. The radiation-induced change in response sensitivity was quantified via irradiation of ∼5kGy. RESULTS: The EDGE Detector agreed with film measurements in the measured range with varying dose (up to 70 Gy), dose rate (nearly 200 Gy/s), and dose per pulse (up to 0.63 Gy/pulse) on average to within 2%, 5%, and 1%, respectively. The detector also agreed with W1 scintillation detector on average to within 2% for dose per pulse (up to 0.78 Gy/pulse). The EDGE Detector signal was proportional to ion chamber (IC) measured dose, and mean dose rate in the bremsstrahlung tail to within 0.4% and 0.2% respectively. The EDGE Detector measured percent depth dose (PDD) agreed with film to within 3% and per pulse output agreed with W1 scintillator to within -6% to +5%. The radiation-induced response decrease was 0.4% per kGy. CONCLUSIONS: The EDGE Detector demonstrated dose linearity, mean dose rate independence, and dose per pulse independence for UHDR electron beams. It can quantify the beam spatially, and temporally at sub millisecond resolution. It's robustness and individual pulse detectability of treatment deliveries can potentially lead to its implementation for in vivo FLASH dosimetry, and dose monitoring.

The role of EPID in vivo dosimetry in the risk management of stereotactic lung treatments.

BACKGROUND AND OBJECTIVE: In this work we report our experience with the use of in vivo dosimetry (IVD) in the risk management of stereotactic lung treatments. METHODS: A commercial software based on the electronic portal imaging device (EPID) signal was used to reconstruct the actual planning target volume (PTV) dose of stereotactic lung treatments. The study was designed in two phases: i) in the observational phase, the IVD results of 41 consecutive patients were reviewed and out-of-tolerance cases were studied for root cause analysis; ii) in the active phase, the IVD results of 52 patients were analyzed and corrective actions were taken when needed. Moreover, proactive preventions were further introduced to reduce the risk of future failures. The error occurrence rate was analyzed to evaluate the effectiveness of proactive actions. RESULTS: A total of 330 fractions were analyzed. In the first phase, 13 errors were identified. In the active phase, 12 errors were detected, 5 of which needed corrective actions; in 4 patients the actions taken corrected the error. Several preventions and barriers were introduced to reduce the risk of future failures: the planning checklist was updated, the procedure for vacuum pillows was improved, and use of the respiratory compression belt was optimized. A decrease in the failure rate was observed, showing the effectiveness of procedural adjustment. CONCLUSION: The use of IVD allowed the quality of lung stereotactic body radiation therapy (SBRT) treatments to be improved. Patient-specific and procedural corrective actions were successfully taken as part of risk management, leading to an overall improvement in the dosimetric accuracy.

Towards quantitative in vivo dosimetry using x-ray acoustic computed tomography.

BACKGROUND: Radiation dosimetry is essential for radiation therapy (RT) to ensure that radiation dose is accurately delivered to the tumor. Despite its wide use in clinical intervention, the delivered radiation dose can only be planned and verified via simulation. This makes precision radiotherapy challenging while in-line verification of the delivered dose is still absent in the clinic. X-ray-induced acoustic computed tomography (XACT) has recently been proposed as an imaging tool for in vivo dosimetry. PURPOSE: Most of the XACT studies focus on localizing the radiation beam. However, it has not been studied for its potential for quantitative dosimetry. The aim of this study was to investigate the feasibility of using XACT for quantitative in vivo dose reconstruction during radiotherapy. METHODS: Varian Eclipse system was used to generate simulated uniform and wedged 3D radiation field with a size of 4 cm × $ \times \ $ 4 cm. In order to use XACT for quantitative dosimetry measurements, we have deconvoluted the effects of both the x-ray pulse shape and the finite frequency response of the ultrasound detector. We developed a model-based image reconstruction algorithm to quantify radiation dose in vivo using XACT imaging, and universal back-projection (UBP) reconstruction is used as comparison. The reconstructed dose was calibrated before comparing it to the percent depth dose (PDD) profile. Structural similarity index matrix (SSIM) and root mean squared error (RMSE) are used for numeric evaluation. Experimental signals were acquired from 4 cm × $ \times \ $ 4 cm radiation field created by Linear Accelerator (LINAC) at depths of 6, 8, and 10 cm beneath the water surface. The acquired signals were processed before reconstruction to achieve accurate results. RESULTS: Applying model-based reconstruction algorithm with non-negative constraints successfully reconstructed accurate radiation dose in 3D simulation study. The reconstructed dose matches well with the PDD profile after calibration in experiments. The SSIMs between the model-based reconstructions and initial doses are over 85%, and the RMSEs of model-based reconstructions are eight times lower than the UBP reconstructions. We have also shown that XACT images can be displayed as pseudo-color maps of acoustic intensity, which correspond to different radiation doses in the clinic. CONCLUSION: Our results show that the XACT imaging by model-based reconstruction algorithm is considerably more accurate than the dose reconstructed by UBP algorithm. With proper calibration, XACT is potentially applicable to the clinic for quantitative in vivo dosimetry across a wide range of radiation modalities. In addition, XACT's capability of real-time, volumetric dose imaging seems well-suited for the emerging field of ultrahigh dose rate "FLASH" radiotherapy.

Selective de-implementation of routine in vivo dosimetry.

As cone-beam computed tomography (CBCT) has become the localization method for a majority of cases, the indications for diode-based confirmation of accurate patient set-up and treatment are now limited and must be balanced between proper resource allocation and optimizing efficiency without compromising safety. We undertook a de-implementation quality improvement project to discontinue routine diode use in non-intensity modulated radiotherapy (IMRT) cases in favor of tailored selection of scenarios where diodes may be useful. After analysis of safety reports from the last 5 years, literature review, and stakeholder discussions, our safety and quality (SAQ) committee introduced a recommendation to limit diode use to specific scenarios in which in vivo verification may add value to standard quality assurance (QA) processes. To assess changes in patterns of use, we reviewed diode use by clinical indication 4 months prior and after the implementation of the revised policy, which includes use of diodes for: 3D conformal photon fields set up without CBCT; total body irradiation (TBI); electron beams; cardiac devices within 10 cm of the treatment field; and unique scenarios on a case-by-case basis. We identified 4459 prescriptions and 1038 unique instances of diode use across five clinical sites from 5/2021 to 1/2022. After implementation of the revised policy, we observed an overall decrease in diode use from 32% to 13.2%, with a precipitous drop in 3D cases utilizing CBCT (from 23.2% to 4%), while maintaining diode utilization in the 5 selected scenarios including 100% of TBI and electron cases. By identifying specific indications for diode use and creating a user-friendly platform for case selection, we have successfully de-implemented routine diode use in favor of a selective process that identifies cases where the diode is important for patient safety. In doing so, we have streamlined patient care and decreased cost without compromising patient safety.

Development of a real-time in vivo dosimetry tool for electron beam therapy using a flexible thin film solar cell coated with scintillator powder.

PURPOSE: A real-time solar cell based in vivo dosimetry system (SC-IVD) was developed using a flexible thin film solar cell and scintillating powder. The present study evaluated the clinical feasibility of the SC-IVD in electron beam therapy. METHODS: A thin film solar cell was coated with 100 mg of scintillating powder using an optical adhesive to enhance the sensitivity of the SC-IVD. Calibration factors were obtained by dividing the dose, measured at a reference depth for 6-20 MeV electron beam energy, by the signal obtained using the SC-IVD. Dosimetric characteristics of SC-IVDs containing variable quantities of scintillating powder (0-500 mg) were evaluated, including energy, dose rate, and beam angle dependencies, as well as dose linearity. To determine the extent to which the SC-IVD affected the dose to the medium, doses at R90 were compared depending on whether the SC-IVD was on the surface. Finally, the accuracy of surface doses measured using the SC-IVD was evaluated by comparison with surface doses measured using a Markus chamber. RESULTS: Charge measured using the SC-IVD increased linearly with dose and was within 1% of the average signal according to the dose rate. The signal generated by the SC-IVD increased as the beam angle increased. The presence of the SC-IVD on the surface of a phantom resulted in a 0.5%-2.2% reduction in dose at R90 for 6-20 MeV electron beams compared with the bare phantom. Surface doses measured using the SC-IVD system and Markus chamber differed by less than 5%. CONCLUSIONS: The dosimetric characteristics of the SC-IVD were evaluated in this study. The results showed that it accurately measured the surface dose without a significant difference of dose in the medium when compared with the Markus chamber. The flexibility of the SC-IVD allows it to be attached to a patient's skin, enabling real-time and cost-effective measurement.

A phamtom study: In vivo rectal dosimetry of high dose rate brachytherapy in cervical cancer.

The purpose of this study was to perform in-vivo dosimetry using a diode rectal dosimeter in phantom and compare the dose delivered to the rectum between the dose measured by the diode dosimeter and the dose calculated by the treatment planning system in cervical cancer. The PTW T9112 diode detector calibrations were performed to find the correction factor. Then the calibrated diode detector was used to measure the radiation dose received in the rectum area in the in-house pelvic phantom. An Iridium-192 source was loaded into the phantom with 7 Gy, the measurements were 3 times per treatment plan, with 15 total plans studied. The average cumulative charge (nC) of each plan was converted to the absorbed dose (mGy) for comparison with the treatment planning system. Finally, to test the hypothesis that an absorbed dose from the detector and the treatment planning system were not significantly different, dependent t-test statistical analysis was applied with p-value <0.05. For distance and direction correction factors, we found that the factors were approximately 1 at 5 cm and 180°. The percentage differences of radiation dose between the diode dosimeter and the treatment planning system were between -3.3 and 4.1%. Statistical analysis revealed that the doses from the detector and the treatment planning system were not statistically significant different. The comparison showed that the percent difference between diode dosimeter and treatment planning system was acceptable to perform the in vivo dosimetry in brachytherapy. Therefore, the diode detector may be a suitable candidate for a treatment verification system in cervical cancer brachytherapy to prevent the dose delivery errors that directly affect the prognosis and may cause complications for the patient.

Clinical pilot study for EPID-based in vivo dosimetry using EPIgray™ for head and neck VMAT.

This work details the clinical pilot study methodology used at Wellington Blood and Cancer Centre (WBCC) before the clinical release of in vivo dosimetry (IVD) system EPIgray™ for head and neck (H&N) volumetric modulated arc therapy (VMAT) treatments. Clinical pilot studies make it possible to select appropriate, department-specific tolerance ranges for the treatment type and site under investigation. An IVD clinical pilot study of H&N VMAT treatments was conducted over 3 months at WBCC using EPIgray™ dose reconstruction software and included 12 patients and 32 individual treatment fractions. Statistical analysis of the dose deviations between the treatment planning system (TPS) dose and EPIgray™ reconstructed dose confirmed that a deviation tolerance range of ± 7.0% was an appropriate choice for H&N VMAT at WBCC.

3D in vivo dosimetry of HDR gynecological brachytherapy using micro silica bead TLDs.

PURPOSE: This study aimed to evaluate the feasibility of defining an in vivo dosimetry (IVD) protocol as a patient-specific quality assurance (PSQA) using the bead thermoluminescent dosimeters (TLDs) for point and 3D IVD during brachytherapy (BT) of gynecological (GYN) cancer using 60 Co high-dose-rate (HDR) source. METHODS: The 3D in vivo absorbed dose verification within the rectum and bladder as organs-at-risk was performed by bead TLDs for 30 GYN cancer patients. For rectal wall dosimetry, 80 TLDs were placed in axial arrangements around a rectal tube covered with a layer of gel. Ten beads were placed inside the Foley catheter to get the bladder-absorbed dose. Beads TLDs were localized and defined as control points in the treatment planning system (TPS) using CT images of the patients. Patients were planned and treated using the routine BT protocol. The experimentally obtained absorbed dose map of the rectal wall and the point dose of the bladder were compared to the TPSs predicted absorbed dose at these control points. RESULTS: Relative difference between TPS and TLDs results were -8.3% ± 19.5% and -7.2% ± 14.6% (1SD) for rectum- and bladder-absorbed dose, respectively. Gamma analysis was used to compare the calculated with the measured absorbed dose maps. Mean gamma passing rates of 84.1%, 90.8%, and 92.5% using the criteria of 3%/2 mm, 3%/3 mm, and 4%/2 mm were obtained, respectively. Eventually, a "considering level" of at least 85% as pass rate with 4%/2-mm criteria was recommended. CONCLUSIONS: A 3D IVD protocol employing bead TLDs was presented to measure absorbed doses delivered to the rectum and bladder during GYN HDR-BT as a reliable PSQA method. 3D rectal absorbed dose measurements were performed. Differences between experimentally measured and planned absorbed dose maps were presented in the form of a gamma index, which may be used as a warning for corrective action.

Combined in vitro-in vivo dosimetry enables the extrapolation of in vitro doses to human exposure levels: A proof of concept based on a meta-analysis of in vitro and in vivo titanium dioxide toxicity data.

Evaluating the potential risks of nanomaterials on human health is fundamental to assure their safety. To do so, Human Health Risk Assessment (HHRA) relies mostly on animal studies to provide information about nanomaterials toxicity. The scarcity of such data, due to the shift of the nanotoxicology field away from a phenomenological, animal-based approach and towards a mechanistic understanding based on in vitro studies, represents a challenge for HHRA. Implementing in vitro data in the HHRA methodology requires an extrapolation strategy; combining in vitro dosimetry and lung dosimetry can be an option to estimate the toxic effects on lung cells caused by inhaled nanomaterials. Since the two dosimetry models have rarely been used together, we developed a combined dosimetry model (CoDo) that estimates the air concentrations corresponding to the in vitro doses, extrapolating in this way in vitro doses to human doses. Applying the model to a data set of in vitro and in vivo toxicity data about titanium dioxide, we demonstrated CoDo's multiple applications. First, we confirmed that most in vitro doses are much higher than realistic human exposures, considering the Swiss Occupational Exposure Limit as benchmark. The comparison of the Benchmark Doses (BMD) extrapolated from in vitro and in vivo data, using the surface area dose metric, showed that despite both types of data had a quite wide range, animal data were overall more precise. The high variability of the results may be due both to the dis-homogeneity of the original data (different cell lines, particle properties, etc.) and to the high level of uncertainty in the extrapolation procedure caused by both model assumptions and experimental conditions. Moreover, while the surface area BMDs from studies on rodents and rodent cells were comparable, human co-cultures showed less susceptibility and had higher BMDs regardless of the titanium dioxide type. Last, a Support Vector Machine classification model built on the in vitro data set was able to predict the BMD-derived human exposure level range for viability effects based on the particle properties and experimental conditions with an accuracy of 85%, while for cytokine release in vitro and neutrophil influx in vivo the model had a lower performance.

In vivo dosimetry in pelvic brachytherapy.

ADVANCES IN KNOWLEDGE: This paper describes the potential role for in vivo dosimetry in the reduction of uncertainties in pelvic brachytherapy, the pertinent factors for consideration in clinical practice, and the future potential for in vivo dosimetry in the personalisation of brachytherapy.

Mouthpiece polymer-gel dosimeter for in vivo oral dosimetry during head and neck radiotherapy.

In this study, we developed a mouthpiece-type gel dosimeter to prevent the oral mucositis caused by the perturbation effect of dental alloys in the radiotherapy of the head and neck regions and to enable in vivo dosimetry. Understanding the dose distribution in the oral cavity during radiotherapy helps identify the possible site for oral mucositis during treatment. Here agarose, which has a higher melting point than gelatin, was added as a coagulant to stabilize the shape of the dosimeter. The strength and dose response of the dosimeter were investigated. The strength was measured at room temperature, 20°C-40 °C, which is higher than the intraoral temperature. The dose-response curves were obtained by magnetic resonance imaging with R2 ranging from 0 to 25 Gy. The strength and dose response of the mouthpiece-type gel dosimeter were approximately 4 and 2.1 times higher than those of polyacrylamide gel and tetrakis hydroxymethyl phosphonium chloride dosimeters commonly used in the prescribed doses per fraction of treatment. The dosimeter is composed of 4 wt% MgCl2 and 1.5 wt% agarose; thus, it can retain the water equivalence. Through in vivo oral dosimetry in three dimensions for head and neck radiotherapy with dental alloys using the mouthpiece-type gel dosimeter, we obtained three-dimensional dose distributions in the dosimeter. The properties of the dosimeter show that it can be used in the clinic, depending on the prescribed dose.

Monte Carlo characterization of high atomic number inorganic scintillators for in vivo dosimetry in 192 Ir brachytherapy.

BACKGROUND: There is increased interest in in vivo dosimetry for 192 Ir brachytherapy (BT) treatments using high atomic number (Z) inorganic scintillators. Their high light output enables construction of small detectors with negligible stem effect and simple readout electronics. Experimental determination of absorbed-dose energy dependence of detectors relative to water is prevalent, but it can be prone to high detector positioning uncertainties and does not allow for decoupling of absorbed-dose energy dependence from other factors affecting detector response . PURPOSE: To investigate which measurement conditions and detector properties could affect their absorbed-dose energy dependence in BT in vivo dosimetry. METHODS: We used a general-purpose Monte Carlo (MC) code PENELOPE for the characterization of high-Z inorganic scintillators with the focus on ZnSe ( Z ¯ = 32 $\bar{Z}=32$ ) Z. Two other promising media CsI ( Z ¯ = 54 $\bar{Z}=54$ ) and Al2 O3 ( Z ¯ = 11 $\bar{Z}=11$ ) were included for comparison in selected scenarios. We determined absorbed-dose energy dependence of crystals relative to water under different scatter conditions (calibration phantom 12 × 12 × 30 cm3 , characterization phantoms 20 × 20 × 20 cm3 , 30 × 30 × 30 cm3 , 40 × 40 × 40 cm3 , and patient-like elliptic phantom 40 × 30 × 25 cm3 ). To mimic irradiation conditions during prostate treatments, we evaluated whether the presence of pelvic bones and calcifications affect ZnSe response. ZnSe detector design influence was also investigated. RESULTS: In contrast to low-Z organic and medium-Z inorganic scintillators, ZnSe and CsI media have substantially greater absorbed-dose energy dependence relative to water. The response was phantom-size dependent and changed by 11% between limited- and full-scatter conditions for ZnSe, but not for Al2 O3 . For a given phantom size, a part of the absorbed-dose energy dependence of ZnSe is caused not due to in-phantom scatter but due to source anisotropy. Thus, the absorbed-dose energy dependence of high-Z scintillators is a function of not only the radial distance but also the polar angle. Pelvic bones did not affect ZnSe response, whereas large and intermediate size calcifications reduced it by 9% and 5%, respectively, when placed midway between the source and the detector. CONCLUSIONS: Unlike currently prevalent low- and medium-Z scintillators, high-Z crystals are sensitive to characterization and in vivo measurement conditions. However, good agreement between MC data for ZnSe in the present study and experimental data for ZnSe:O by Jørgensen et al. (2021) suggests that detector signal is proportional to the average absorbed dose to the detector cavity. This enables an easy correction for non-TG43-like scenarios (e.g., patient sizes and calcifications) through MC simulations. Such information should be provided to the clinic by the detector vendors.

Pre-clinical and clinical evaluation of the HYPERSCINT plastic scintillation dosimetry research platform for in vivo dosimetry during radiotherapy.

PURPOSE: The purpose of this work is to evaluate the Hyperscint-RP100 scintillation dosimetry research platform (Hyperscint-RP100, Medscint Inc., Quebec, QC, Canada) designed for clinical quality assurance (QA) for use in in vivo dosimetry measurements. METHODS: The pre-clinical evaluation of the scintillator was performed using a Varian TrueBeam linear accelerator. Dependency on field size, depth, dose, dose rate, and temperature were evaluated in a water tank and compared to calibration data from commissioning and annual QA. Angularity was evaluated with a 3D printed phantom. The clinical evaluation was first performed in two cadaver dogs, and then in three companion animal dogs receiving radiation therapy for nasal tumors. A treatment planning CT scan was performed for cadavers and clinical patients. Prior to treatment, the probe was inserted into the radiation field. Radiation was then delivered and measured with the scintillator. For cadavers, the treatment was repeated after making an intentional shift in patient position to simulate a treatment error. RESULTS: In the preclinical measurements the dose differed from annual measurements as follows: field size -0.77 to 0.43%, depth dose -0.36 to 1.14%, dose -0.54 to 2.93%, dose rate 0.3 to 3.6%, and angularity -1.18 to 0.01%. Temperature dependency required a correction factor of 0.11%/°C. In the two cadavers, the dose differed by -1.17 to 0.91%. The device correctly detected the treatment error when the heads were intentionally laterally shifted. In three canine clinical patients treated in multiple fractions, the detected dose ranged from 98.33 to 103.15%. CONCLUSION: Results of this new device are promising although more work is necessary to fully validate it for clinical dosimetry.

3D dose reconstruction based on in vivo dosimetry for determining the dosimetric impact of geometric variations in high-dose-rate prostate brachytherapy.

INTRODUCTION: In vivo dosimetry (IVD) can be used for source tracking (ST), i.e., estimating source positions, during brachytherapy. The aim of this study was to exploit IVD-based ST to perform 3D dose reconstruction for high-dose-rate prostate brachytherapy and to evaluate the robustness of the treatments against observed geometric variations. MATERIALS AND METHODS: Twenty-three fractions of high-dose-rate prostate brachytherapy were analysed. The treatment planning was based on MRI. Time-resolved IVD was performed using a fibre-coupled scintillator. ST was retrospectively performed using the IVD measurements. The ST identified 2D positional shifts of each treatment catheter and thereby inferred updated source positions. For each fraction, the dose was recalculated based on the source-tracked catheter positions and compared with the original plan dose using differences in dose volume histogram indices. RESULTS: Of 352 treatment catheters, 344 had shifts of less than 5 mm. Shifts between 5 and 10 mm were observed for 3 catheters, and shifts greater than 10 mm for 2 catheters. The ST failed for 3 catheters. The maximum relative difference in clinical target volume (prostate + 3 mm isotropic margin) D90% was 5%. In one fraction, the bladder D2cm3 dose increased by 18% (1.4 Gy) due to a single source position being inside the bladder rather than nearby as planned. The max increase in urethra dose was 1.5 Gy (15%). CONCLUSION: IVD-based 3D dose reconstruction for high-dose-rate prostate brachytherapy is feasible. The dosimetric impact of the observed catheter shifts was limited. Dose reconstruction can therefore aid in determining the dosimetric impact of geometric variations and errors in brachytherapy.