Purpose To use a portable 4°C cooled MR‐compatible water calorimeter to measure absorbed dose in a magnetic resonance‐guided radiation therapy (MRgRT) system. Furthermore, to use the calorimetric dose results and direct cross‐calibration to experimentally measure the combined beam quality and magnetic field correction factor (kQmag) of a clinically used reference‐class ionization chamber placed under the same radiation field. Methods An Elekta Unity MR‐linac (7 MV FFF, B = 1.5 T) was used in this study. Measurements were taken using the in‐house designed and built water calorimeter. Following preparation and cooling of the system, the MR‐compatible calorimeter was positioned using a combination of MR and EPID imaging and the dose to water was measured by monitoring the radiation‐induced temperature change. Immediately after the calorimetric measurements, an A1SL ionization chamber was placed inside the calorimeter for direct cross‐calibration. The results allowed for a direct and absolute experimental measurement of kQmag for this chamber and comparison against existing Monte Carlo values. Results The calorimeter was successfully positioned using imaging in under an hour. The 1‐hour setup time is from the time the calorimeter leaves storage to the first calorimetric measurement. Absorbed dose was successfully measured with a relative combined standard uncertainty of 0.71 % (k = 1). Through a cross‐calibration, the kQmag for an Exradin A1SL ionization chamber, set up perpendicular to the incident photon beam and opposite to the direction of the Lorentz force, was directly determined in water in absolute terms to be 0.977 ± 0.010. The currently published kQmag results, obtained via Monte Carlo calculations, agree with experimental measurements in this work within combined uncertainties. Conclusions A novel design of an MR‐compatible water calorimeter was successfully used to measure absorbed dose in an MR‐linac and determine an experimental value of kQmag for a clinically used ionization chamber.

We used two-electrode voltage-clamp electrophysiology to measure channel activation by classical GABA receptor agonists on Hco-UNC-49 expressed in Xenopus laevis oocytes, along with site-directed mutagenesis and in silico homology modelling. KEY RESULTSThe sulphonated molecules P4S and taurine had no effect on Hco-UNC-49. Other classical Cys-loop GABAA receptor agonists tested on the Hco-UNC-49B/C heteromeric channel had a rank order efficacy of GABA > trans-4-aminocrotonic acid > isoguvacine > imidazole-4-acetic acid (IMA) > ( R)-(−)-4-amino-3-hydroxybutyric acid [R(−)-GABOB] > (S)-(+)-4-amino-3-hydroxybutyric acid [S(+)-GABOB]> guanidinoacetic acid > isonipecotic acid > 5-aminovaleric acid (DAVA) (partial agonist) > β-alanine (partial agonist). In silico ligand docking revealed some variation in binding between agonists. Mutagenesis of a key serine residue in binding loop C to threonine had minimal effects on GABA and IMA but significantly increased the maximal response to DAVA and decreased twofold the EC50 for R(−)-and S(+)-GABOB.

Purpose Through the addition of high‐Z dopants, the sensitivity of plastic scintillators to low‐energy radiation can be increased. This study quantifies this change in sensitivity as a function of dopant concentration. Methods Measurements were conducted using four different lead‐doped scintillators (0%, 1%, 1.5%, and 5% Pb) in high‐energy electrons (6 to 15 MeV) and low‐energy photon (100 to 300 kVp) radiation fields. High‐energy and low‐energy irradiations were done using a clinical linear accelerator and an orthovoltage unit, respectively. Light emitted by the scintillator was quantified using a photosensor module. The experimental setup was replicated in Geant4.10.3 Monte Carlo and scintillator parameters (Quenching parameter: kB and the light yield: L0) were varied until agreement between measured and simulated results was reached. Monoenergetic electrons were used to simulate the high‐energy electron beam while a spectrum generated using SpekCalc® software was used in the low‐energy simulations. Light produced by the scintillator was quantified using a flux scorer sensitive only to photons in the visible wavelength range. In order to compare measured and simulated results, the light produced by the scintillator was normalized to the absorbed dose‐to‐water at the point of measurement. Results At high lead dopant concentrations, the scintillator's sensitivity to the 100 kVp beam increased by 474% relative to the 15 MeV electron beam; the scintillator's kB parameter increased from 0.126 to 0.27 mm/MeV. A model quantifying the change in kB and L0 as a function of Zeff was derived; presenting a modified Birks' Law for metal‐doped plastic scintillators. Conclusion The impact of high‐Z doping on plastic scintillator response was quantified; this can allow for the controlled induction of energy dependence in plastic scintillator detectors.

Low energy scattered particles cause the average energy at the treatment field edge to be lower relative to the center of the beam. These particles have a higher LET, making them more biologically damaging. With a single beam (large field-size (FS)), the amount of these highly damaging electrons is low relative to within the treatment beam. However, when multiple beam angles and smaller FS are used (IMRT/VMAT), the relative contribution of scattered radiation increases and biological consequences may vary. The purpose of this study was to evaluate the theoretical impact of increased scattered radiation in single and composite field beams. Monte Carlo Geant4.10.3 was used to score the electron energy spectra at different depths in water with a 6 MV photon beam incident. The energy spectra were then used to calculate the maximum RBE, RBE M . Beams examined were phase-spaces of a Varian Clinac 600C 6 MV linac (10×10 cm 2 beam, 1×1 cm 2 beam), and a composite 10×10 cm 2 beam. The composite 10×10 cm 2 treatment field (simple IMRT) was created by summating one hundred 1×1 cm 2 beams to form a relatively uniform 10×10 cm 2 field. For smaller FS (1.5 cm depth), an increase in RBE M was seen 5.2 cm outside the beam (17%). The 10×10 cm 2 beam showed an increase of 14%, 9.2 cm away from beam's edge (1.5 cm depth). The composite 10×10 cm 2 beam exhibited similar RBE M enhancement to the 10×10 cm 2 phase-space, however, the region of increased damage occurred closer to the beam (5.6 cm away). The results indicate that although the region inside the primary beam is not affected, the contribution of damaging particles happens much closer to the beam's edge in the composite field case relative to an open field. This may have potential implications regarding the effective dose to organs at risk during radiotherapy.

The purpose of this study is to design a water calorimeter with three goals in mind: (a) To be fully magnetic resonance (MR)-compatible; (b) To be imaged using kV cone beam computed tomography (CBCT), MV portal imaging or MRI for accurate positioning; (c) To accommodate both vertical and horizontal beam incidence, as well as volumetric deliveries or Gamma Knife ®. Following this, the calorimeter performance will be measured using an accelerator-based high-energy photon beam. Methods: A portable 4°C cooled stagnant water calorimeter was built using MR-compatible materials. The walls consist of layers of acrylic plastic, aerogel-based material acting as thermal insulation, as well as tubing for coolant to flow to keep the calorimeter temperature stable at 4°C. The lid contains additional pathways for coolant to flow through as well as two hydraulically driven stirrers. The water calorimeter was positioned in an Elekta Versa using kV CBCT imaging as well as orthogonal MV image pairs. Absolute absorbed dose to water was then determined under a 6 MV flattening filter-free (FFF) beam. This was compared against reference dosimetry results that were measured under identical conditions with an Exradin A1SL ionization chamber with a calibration coefficient directly traceable to the National Research Council Canada. Results: The dose to water determined with the calorimeter (n = 30) agreed with the A1SL ionization chamber reference dose measurements (n = 15) to within 0.25%. The uncertainty associated with the water calorimeter absorbed dose measurement was estimated to be 0.54% (k = 1). Conclusions: An MR-compatible water calorimeter was successfully built and absolute absorbed dose to water under a conventional 6 MV FFF beam was determined successfully as a first-stage validation of the system.