A phantom based evaluation of the clinical imaging performance of electronic portal imaging devices.

Purpose: In this study an evaluation of the imaging performance of an electronic portal imaging device (EPID) is presented. The evaluation performed employing the QC-3V image quality phantom. Methods: An EPID system of a 6 MV LINAC, was used to obtain images of a QC-3V EPID phantom. The X-ray source to phantom distance was 100 cm and the field size was 15x15 cm2. The irradiation conditions comprised Dose Rates (DR) of 200, 400 and 600 for a 2 MU-100 MU range. The Contrast Transfer Function (CTF), the Noise Power Spectrum (NPS), the Normalized Noise Power Spectrum (NNPS) and the Contrast-to-Noise Ratio (CNR) were studied. In addition, an alternative factor showing a frequency related output signal-to-noise ratio (SNR), the Signal-to-Noise-Frequency Response (SNFR), has been introduced. SNFR is a comprehensive quality index, easily determined in clinical environment. Results: The CTF curves were found comparable to each other. The lowest values were measured at 2 MU and 200 MU/min. Concerning the NPS and NNPS graphs it was found that the values decrease up to approximately 0.3 lp/mm and demonstrate a white noise shape afterwards. SNFR values were found reducing with spatial frequency. Highest CNR were found between the region 7 and 11 of the phantom. Conclusions: The influence of MU and DR on EPID performance were investigated. Image quality was assessed using the QC-3V phantom. The presented results can lead to image quality amelioration and act supportively to current image quality control routine protocols.

A MC-based anthropomorphic test case for commissioning model-based dose calculation in interstitial breast 192-Ir HDR brachytherapy.

PURPOSE: To provide the first clinical test case for commissioning of 192 Ir brachytherapy model-based dose calculation algorithms (MBDCAs) according to the AAPM TG-186 report workflow. ACQUISITION AND VALIDATION METHODS: A computational patient phantom model was generated from a clinical multi-catheter 192 Ir HDR breast brachytherapy case. Regions of interest (ROIs) were contoured and digitized on the patient CT images and the model was written to a series of DICOM CT images using MATLAB. The model was imported into two commercial treatment planning systems (TPSs) currently incorporating an MBDCA. Identical treatment plans were prepared using a generic 192 Ir HDR source and the TG-43-based algorithm of each TPS. This was followed by dose to medium in medium calculations using the MBDCA option of each TPS. Monte Carlo (MC) simulation was performed in the model using three different codes and information parsed from the treatment plan exported in DICOM radiation therapy (RT) format. Results were found to agree within statistical uncertainty and the dataset with the lowest uncertainty was assigned as the reference MC dose distribution. DATA FORMAT AND USAGE NOTES: The dataset is available online at http://irochouston.mdanderson.org/rpc/BrachySeeds/BrachySeeds/index.html,https://doi.org/10.52519/00005. Files include the treatment plan for each TPS in DICOM RT format, reference MC dose data in RT Dose format, as well as a guide for database users and all files necessary to repeat the MC simulations. POTENTIAL APPLICATIONS: The dataset facilitates the commissioning of brachytherapy MBDCAs using TPS embedded tools and establishes a methodology for the development of future clinical test cases. It is also useful to non-MBDCA adopters for intercomparing MBDCAs and exploring their benefits and limitations, as well as to brachytherapy researchers in need of a dosimetric and/or a DICOM RT information parsing benchmark. Limitations include specificity in terms of radionuclide, source model, clinical scenario, and MBDCA version used for its preparation.

On the potential of 2D ion chamber arrays for high-dose rate remote afterloading brachytherapy quality assurance.

Objective. To investigate the potential of 2D ion chamber arrays to serve as a standalone tool for the verification of source strength, positioning and dwell time, within the framework of192Ir high-dose rate brachytherapy device quality assurance (QA).Approach.A commercially available ion chamber array was used. Fitting of a 2D Lorentzian peak function to experimental data from a multiple source dwell position irradiation on a frame-by-frame basis, facilitated tracking of the source center orthogonal projection on the array plane. For source air kerma strength verification, Monte Carlo simulation was employed to obtain a chamber array- and source-specific correction factor of calibration with a 6 MV photon beam. This factor converted the signal measured by each ion chamber element to air kerma in free space. A source positioning correction was also applied to lift potential geometry mismatch between experiment and Monte Carlo simulation.Main results.Spatial and temporal accuracy of source movement was verified within 0.5 mm and 0.02 s, respectively, in compliance with the test endpoints recommended by international professional societies. The source air kerma strength was verified experimentally within method uncertainties estimated as 1.44% (k = 1). The source positioning correction method employed did not introduce bias to experimental results of irradiations where source positioning was accurate. Development of a custom jig attachable to the chamber array for accurate and reproducible experimental set up would improve testing accuracy and obviate the need for source positioning correction in air kerma strength verification.Significance.Delivery of a single irradiation plan, optimized based on results of this work, to a 2D ion chamber array can be used for concurrent testing of source position, dwell time and air kerma strength, and the procedure can be expedited through automation. Chamber arrays merit further study in treatment planning QA and real time,in vivodose verification.

Pleural effusion osmolality correlation with pH and glucose level of pleural fluid and its effects on the pleural membrane permeability.

BACKGROUND AND AIM: Pleural effusions (PE) are a common clinical entity resulting from pathologies that affect the pleural space such as congestive heart failure, malignancy and pneumonia. The osmolality of the pleural fluid has never been studied as well as the effects of its changes on the pleural membrane. The purpose of this study was to identify the osmolality levels of PEs of different etiologies and to assess the potential effects of osmolality imbalance on the pleural permeability. MATERIALS AND METHODS: We measured the osmolality of the PEs of 64 consecutive patients (6 with transudative, 11 with parapneumonic and 47 with malignant pleural effusions) that were hospitalized in the University Hospital of Larissa. Subsequently, we selected clinically relevant hyper- and hypo- osmolality levels and performed assessment of the permeability of sheep parietal pleura by means of Ussing chamber experiments. RESULTS: The mean pleural fluid osmolality was 291.7 ± 24.89 mOms/Kg (95 % CI: 285.4-297.9), and it varied among the three groups of PEs (p = 0.05). Transformed osmolality values were associated with pH and glucose levels in the PEs. After exposure of the sheep parietal pleura to 240 mOsm/kg (hyposmolar) the transmesothelial resistance (RTM) significantly increased (p < 0.05) while at 340 mOsm/kg (hyperosmolar) the RTM was not significantly altered. CONCLUSIONS: PEs osmolality differs depending on the underlying pathology and is linked to PE pH and glucose. Hypo-osmotic PEs can lead to decreased pleural permeability. These results warrant further study of the PEs osmolality levels on the function of the pleural mesothelial cells.

Comparison and Evaluation of Different Radiotherapy Techniques Using Biodosimetry Based on Cytogenetics.

While rapid technological advances in radiotherapy techniques have led to a more precise delivery of radiation dose and to a decreased risk of side effects, there is still a need to evaluate the efficacy of the new techniques estimating the biological dose and to investigate the radiobiological impact of the protracted radiotherapy treatment duration. The aim of this study is to compare, at a cytogenetic level, advanced radiotherapy techniques VMAT and IMRT with the conventional 3D-CRT, using biological dosimetry. A dicentric biodosimetry assay based on the frequency of dicentrics chromosomes scored in peripheral blood lymphocytes from prostate cancer patients and PC3 human prostate cancer cell line was used. For each patient blood sample and each subpopulation of the cultured cell line, three different irradiations were performed using the 3D-CRT, IMRT, and VMAT technique. The absorbed dose was estimated with the biodosimetry method based on the induced dicentric chromosomes. The results showed a statistically significant underestimation of the biological absorbed dose of ~6% for the IMRT and VMAT compared to 3D-CRT irradiations for peripheral blood lymphocytes, whereas IMRT and VMAT results were comparable without a statistically significant difference, although slightly lower values were observed for VMAT compared to IMRT irradiation. Similar results were obtained using the PC3 cell line. The observed biological dose underestimation could be associated with the relative decreased dose rate and increase irradiation time met in modulated techniques compared to the conventional 3D-CRT irradiations.

On the use of a novel Ferrous Xylenol-orange gelatin dosimeter for HDR brachytherapy commissioning and quality assurance testing.

PURPOSE: To evaluate a commercially available Ferrous-Xylenol Orange-Gel (FXG) dosimeter (TrueView™) coupled with Optical-Computed Tomography (OCT) read out, for 3D dose verification in an Ir-192 superficial brachytherapy application. METHODS: Two identical polyethylene containers filled with gel from the same batch were used. One was irradiated with an 18 MeV electron field to examine the dose-response linearity and obtain a calibration curve. A flap surface applicator was attached to the other to simulate treatment of a skin lesion. The dose distribution in the experimental set up was calculated with the TG-43 and the model based dose calculation (MBCA) algorithms of a commercial treatment planning system (TPS), as well as Monte Carlo (MC) simulation using the MCNP code. Measured and calculated dose distributions were spatially registered and compared. RESULTS: Apart from a region close to the container's neck, where gel measurements exhibited an over-response relative to MC calculations (probably due to stray light perturbation), an excellent agreement was observed between measurements and simulations. More than 97% of points within the 10% isodose line (80 cGy) met the gamma index criteria established from uncertainty analysis (5%/2 mm). The corresponding passing rates for the comparison of experiment to calculations using the TG-43 and MBDCA options of the TPS were 57% and 92%, respectively. CONCLUSION: TrueView™ is suitable for the quality assurance of demanding radiotherapy applications. Experimental results of this work confirm the advantage of the studied MBDCA over TG-43, expected from the improved account of scatter radiation in the treatment geometry.

Time resolved dose rate distributions in brachytherapy.

PURPOSE: To investigate the biological significance of introducing time-resolved dose rate distributions (TR-DRD) in brachytherapy. MATERIALS AND METHODS: The treatment plan of a head and neck patient treated with pulsed-dose-rate (PDR) brachytherapy was considered. The TR-DRD was calculated on the basis of a Monte Carlo generated single source dose rate matrix taking into account the dose rate per source dwell position. Biologically Effective Dose (BED) was obtained considering either the mean dose rate per pulse (analytical method) or the TR-DRD (numerical method). Corresponding Tumor Control Probabilities (TCP) were calculated and compared for various PDR schemes and repair half-times from the literature. The dose of the biologically equivalent high-dose-rate (HDR) treatment schedule was also evaluated. RESULTS: The analytical method presents an overall BED underestimation (up to 2%) relative to TR-DRD results. This is associated with an analytical-based TCP underestimation which increases with dose/pulse, pulse duration and period time and decreases with total dose. The half-time of repair seems to have the largest impact on the TCP calculations, with significant differences (up to 39.1%) corresponding to the shorter repair half-times. Regarding the equivalent HDR treatment schedule, the analytical method resulted to a HDR isoeffective dose underestimation lower than 2.2% and thus does not warrant any change in the derivation of the equivalent HDR scheme. CONCLUSION: TR-DRD data should be taken into account for PDR biological effectiveness estimations, especially for short tissue repair half-times. This does not appear however to influence dose prescription of the equivalent HDR treatment schedule for mobile tongue carcinoma.

On the experimental validation of model-based dose calculation algorithms for 192Ir HDR brachytherapy treatment planning.

There is an acknowledged need for the design and implementation of physical phantoms appropriate for the experimental validation of model-based dose calculation algorithms (MBDCA) introduced recently in 192Ir brachytherapy treatment planning systems (TPS), and this work investigates whether it can be met. A PMMA phantom was prepared to accommodate material inhomogeneities (air and Teflon), four plastic brachytherapy catheters, as well as 84 LiF TLD dosimeters (MTS-100M 1 × 1 × 1 mm3 microcubes), two radiochromic films (Gafchromic EBT3) and a plastic 3D dosimeter (PRESAGE). An irradiation plan consisting of 53 source dwell positions was prepared on phantom CT images using a commercially available TPS and taking into account the calibration dose range of each detector. Irradiation was performed using an 192Ir high dose rate (HDR) source. Dose to medium in medium, [Formula: see text], was calculated using the MBDCA option of the same TPS as well as Monte Carlo (MC) simulation with the MCNP code and a benchmarked methodology. Measured and calculated dose distributions were spatially registered and compared. The total standard (k = 1) spatial uncertainties for TLD, film and PRESAGE were: 0.71, 1.58 and 2.55 mm. Corresponding percentage total dosimetric uncertainties were: 5.4-6.4, 2.5-6.4 and 4.85, owing mainly to the absorbed dose sensitivity correction and the relative energy dependence correction (position dependent) for TLD, the film sensitivity calibration (dose dependent) and the dependencies of PRESAGE sensitivity. Results imply a LiF over-response due to a relative intrinsic energy dependence between 192Ir and megavoltage calibration energies, and a dose rate dependence of PRESAGE sensitivity at low dose rates (<1 Gy min-1). Calculations were experimentally validated within uncertainties except for MBDCA results for points in the phantom periphery and dose levels <20%. Experimental MBDCA validation is laborious, yet feasible. Further work is required for the full characterization of dosimeter response for 192Ir and the reduction of experimental uncertainties.

On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy.

PURPOSE: To study the effect of finite patient dimensions and tissue heterogeneities in head and neck high dose rate brachytherapy. METHODS AND MATERIALS: The current practice of TG-43 dosimetry was compared to patient specific dosimetry obtained using Monte Carlo simulation for a sample of 22 patient plans. The dose distributions were compared in terms of percentage dose differences as well as differences in dose volume histogram and radiobiological indices for the target and organs at risk (mandible, parotids, skin, and spinal cord). RESULTS: Noticeable percentage differences exist between TG-43 and patient specific dosimetry, mainly at low dose points. Expressed as fractions of the planning aim dose, percentage differences are within 2% with a general TG-43 overestimation except for the spine. These differences are consistent resulting in statistically significant differences of dose volume histogram and radiobiology indices. Absolute differences of these indices are however small to warrant clinical importance in terms of tumor control or complication probabilities. CONCLUSIONS: The introduction of dosimetry methods characterized by improved accuracy is a valuable advancement. It does not appear however to influence dose prescription or call for amendment of clinical recommendations for the mobile tongue, base of tongue, and floor of mouth patient cohort of this study.

A user-oriented procedure for the commissioning and quality assurance testing of treatment planning system dosimetry in high-dose-rate brachytherapy.

PURPOSE: To develop a user-oriented procedure for testing treatment planning system (TPS) dosimetry in high-dose-rate brachytherapy, with particular focus to TPSs using model-based dose calculation algorithms (MBDCAs). METHODS AND MATERIALS: Identical plans were prepared for three computational models using two commercially available systems and the same (192)Ir source. Reference dose distributions were obtained for each plan using the MCNP v.6.1 Monte Carlo (MC) simulation code with input files prepared via automatic parsing of plan information using a custom software tool. The same tool was used for the comparison of reference dose distributions with corresponding MBDCA exports. RESULTS: The single source test case yielded differences due to the MBDCA spatial discretization settings. These affect points at relatively increased distance from the source, and they are abated in test cases with multiple source dwells. Differences beyond MC Type A uncertainty were also observed very close to the source(s), close to the test geometry boundaries, and within heterogeneities. Both MBDCAs studied were found equivalent to MC within 5 cm from the target volume for a clinical breast brachytherapy test case. These are in agreement with previous findings of MBDCA benchmarking in the literature. CONCLUSIONS: The data and the tools presented in this work, that are freely available via the web, can serve as a benchmark for advanced clinical users developing their own tests, a complete commissioning procedure for new adopters of currently available TPSs using MBDCAs, a quality assurance testing tool for future updates of already installed TPSs, or as an admission prerequisite in multicentric clinical trials.

Animal models in peritoneal dialysis.

Peritoneal dialysis (PD) has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease (ESRD). In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use.

VEGF increases the permeability of sheep pleura ex vivo through VEGFR2 stimulation.

Vascular endothelial growth factor (VEGF), a cytokine that increases vascular permeability to water and proteins and induces angiogenesis, has been implicated in the development of pleural effusions. Inflammatory and malignant pleural effusions are rich in VEGF content while mesothelial cells produce and excrete VEGF. In this report we aimed at investigating by means of electrophysiology the direct effects of VEGF on the parietal and visceral sheep pleura as well as the type of receptors that mediate this effect. Our findings show that VEGF has a direct effect on the pleural mesothelium rendering it more permeable and this effect is mediated through the stimulation of VEGF receptor 2. Our findings shed more light to the role of VEGF in the pathogenesis of pleural effusions and provide functional evidence for a role of VEGFR2 on the pleural mesothelium that has never been studied before.