Commissioning and quality assurance for VMAT delivery systems: An efficient time-resolved system using real-time EPID imaging.

PURPOSE: An ideal commissioning and quality assurance (QA) program for Volumetric Modulated Arc Therapy (VMAT) delivery systems should assess the performance of each individual dynamic component as a function of gantry angle. Procedures within such a program should also be time-efficient, independent of the delivery system and be sensitive to all types of errors. The purpose of this work is to develop a system for automated time-resolved commissioning and QA of VMAT control systems which meets these criteria. METHODS: The procedures developed within this work rely solely on images obtained, using an electronic portal imaging device (EPID) without the presence of a phantom. During the delivery of specially designed VMAT test plans, EPID frames were acquired at 9.5 Hz, using a frame grabber. The set of test plans was developed to individually assess the performance of the dose delivery and multileaf collimator (MLC) control systems under varying levels of delivery complexities. An in-house software tool was developed to automatically extract features from the EPID images and evaluate the following characteristics as a function of gantry angle: dose delivery accuracy, dose rate constancy, beam profile constancy, gantry speed constancy, dynamic MLC positioning accuracy, MLC speed and acceleration constancy, and synchronization between gantry angle, MLC positioning and dose rate. Machine log files were also acquired during each delivery and subsequently compared to information extracted from EPID image frames. RESULTS: The largest difference between measured and planned dose at any gantry angle was 0.8% which correlated with rapid changes in dose rate and gantry speed. For all other test plans, the dose delivered was within 0.25% of the planned dose for all gantry angles. Profile constancy was not found to vary with gantry angle for tests where gantry speed and dose rate were constant, however, for tests with varying dose rate and gantry speed, segments with lower dose rate and higher gantry speed exhibited less profile stability. MLC positional accuracy was not observed to be dependent on the degree of interdigitation. MLC speed was measured for each individual leaf and slower leaf speeds were shown to be compensated for by lower dose rates. The test procedures were found to be sensitive to 1 mm systematic MLC errors, 1 mm random MLC errors, 0.4 mm MLC gap errors and synchronization errors between the MLC, dose rate and gantry angle controls systems of 1°. In general, parameters measured by both EPID and log files agreed with the plan, however, a greater average departure from the plan was evidenced by the EPID measurements. CONCLUSION: QA test plans and analysis methods have been developed to assess the performance of each dynamic component of VMAT deliveries individually and as a function of gantry angle. This methodology relies solely on time-resolved EPID imaging without the presence of a phantom and has been shown to be sensitive to a range of delivery errors. The procedures developed in this work are both comprehensive and time-efficient and can be used for streamlined commissioning and QA of VMAT delivery systems

A placebo-controlled proof-of-concept study of alirocumab on postprandial lipids and vascular elasticity in insulin-treated patients with type 2 diabetes mellitus

Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear. Material and Methods: Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. Results: Alirocumab treatment reduced fasting plasma TG levels (between group median change −24.7%; P = 0.018) and fasting apoB48 serum levels (−35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (−26.4%; P = 0.006) and apoB48 AUC (−55.7%; P = 0.046), as well as plasma TG incremental AUC (−21.4%; P = 0.04) and apoB48 incremental AUC (−26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. Conclusions: In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants

Supercontinuum generation in higher order modes of photonic crystal fibre

Soliton behaviour in higher order electromagnetic (EM) modes in commercial highly nonlinear photonic crystal fibre (PCF) was investigated by mapping spatial and spectral emission. A femtosecond mode-locked Titanium:Sapphire laser was used to generate supercontinua within a set of higher-order electromagnetic modes by piezoelectric control of the spatial field input to the PCF. Coupling pump wavelengths within the normal dispersion regime for the fundamental EM mode into higher EM modes resulted in the emission of blue light, characteristic of higher order soliton fission, in higher order EM modes. Detailed spectral measurements across the spatial mode field output from the PCF, showed different spectral components of the generated continua occupying different spatial electromagnetic modes. In particular, the blue emission was found to be structured with spectral wavelengths at 440 nm and 450 nm associated with different spatial EM modes. These new measurements are the first to detail high order solitonic interactions in higher order electromagnetic modes and to record different spectral emission wavelengths associated with different higher order spatial modes. These results are not well matched to current theoretical models for supercontinuum generation developed for the fundamental EM mode. The lower zero dispersion wavelengths associated with higher EM modes in PCF enable previously undetected engagement of these modes in supercontinuum generation and propagation

Spatio-spectral analysis of supercontinuum generation in higher order electromagnetic modes of photonic crystal fiber

The far-field spatial distributions of higher order electro-magnetic mode supercontinua were resolved spectrally and recorded. The supercontinua were created by precise control and direction of input pump energy offset axially from the photonic crystal fiber core. By processing the measured spectra, the spatial mode shape at each wavelength was determined. Discrete spectral features are associated with symmetrical spatial patterns arising from the host fiber geometry and suggest the electromagnetic mode pairing between the longer wavelength solitons and associated visible dispersive waves. Clear differences between supercontinua generated in fundamental and higher order electromagnetic modes exist. These data should inform theoretical studies as the solitons and the dispersive wave generated by fission may be matched by spatial orientation of the electromagnetic mode that both occupy

Dose-to-water conversion for the backscatter-shielded EPID: a frame-based method to correct for EPID energy response to MLC transmitted radiation

Purpose: To develop a frame-by-frame correction for the energy response of amorphous silicon electronic portal imaging devices (a-Si EPIDs) to radiation that has transmitted through the multileaf collimator (MLC) and to integrate this correction into the backscatter shielded EPID (BSS-EPID) dose-to-water conversion model. Methods: Individual EPID frames were acquired using a Varian frame grabber and iTools acquisition software then processed using in-house software developed in MATLAB. For each EPID image frame, the region below the MLC leaves was identified and all pixels in this region were multiplied by a factor of 1.3 to correct for the under-response of the imager to MLC transmitted radiation. The corrected frames were then summed to form a corrected integrated EPID image. This correction was implemented as an initial step in the BSS-EPID dose-to-water conversion model which was then used to compute dose planes in a water phantom for 35 IMRT fields. The calculated dose planes, with and without the proposed MLC transmission correction, were compared to measurements in solid water using a two-dimensional diode array. Results: It was observed that the integration of the MLC transmission correction into the BSS-EPID dose model improved agreement between modeled and measured dose planes. In particular, the MLC correction produced higher pass rates for almost all Head and Neck fields tested, yielding an average pass rate of 99.8% for 2%/2 mm criteria. A two-sample independent-test and fisher F-test were used to show that the MLC transmission correction resulted in a statistically significant reduction in the mean and the standard deviation of the gamma values, respectively, to give a more accurate and consistent dose-to-water conversion. Conclusions: The frame-by-frame MLC transmission response correction was shown to improve the accuracy and reduce the variability of the BSS-EPID dose-to-water conversion model. The correction may be applied as a preprocessing step in any pretreatment portal dosimetry calculation and has been shown to be beneficial for highly modulated IMRT fields

Low order solitons in higher order electromagnetic modes of photonic crystal fibre

Comparative measurements of supercontinua generated in various photonic crystal fibres (PCFs) reveal unique low-order solitons occupying higher-order electromagnetic modes in each PCF. Matching modes allows correlation of soliton and associated dispersive wave, informing energy transfer processes

Remote dosimetric auditing for intensity modulated radiotherapy: A pilot study

Background and Purpose: Electronic portal imaging devices (EPIDs) can be used to reconstruct dose inside a virtual phantom. This work aims to study the feasibility of using this method for remote dosimetry auditing of clinical trials. Materials and Methods: Six centres participated in an intensity modulated radiotherapy (IMRT) pilot study of this new audit approach. Each centre produced a head and neck (HN) and post-prostatectomy (PP) trial plan and transferred the plans to virtual phantoms to calculate a reference dose distribution. They acquired in-air images of the treatment fields along with calibration images using their EPID. These data were sent to the central site where the images were converted to 2D field-by-field doses in a flat virtual water phantom and to 3D combined field doses in a cylindrical virtual phantom for comparison with corresponding reference dose distributions. Additional test images were used to assess the accuracy of the method when using different EPIDs. Results: Field-by-field 2D analysis yielded mean gamma pass-rates of 99.6% (±0.3%) and 99.6% (±0.6%) for HN and PP plans respectively (3%/3 mm, doses greater than 10% global max). 3D combined field analysis gave mean pass-rates of 97.9% (±2.6%) and 97.9% (±1.8%) for the HN and PP plans. Dosimetry tests revealed some field size limitations of the EPIDs. Conclusions: The remote auditing methodology using EPIDs is feasible and potentially an inexpensive method