Dosimetric characterization of a novel UHDR megavoltage X-ray source for FLASH radiobiological experiments.

A first irradiation platform capable of delivering 10 MV X-ray beams at ultra-high dose rates (UHDR) has been developed and characterized for FLASH radiobiological research at TRIUMF. Delivery of both UHDR (FLASH mode) and low dose-rate conventional (CONV mode) irradiations was demonstrated using a common source and experimental setup. Dose rates were calculated using film dosimetry and a non-intercepting beam monitoring device; mean values for a 100 µA pulse (peak) current were nominally 82.6 and 4.40 × 10-2 Gy/s for UHDR and CONV modes, respectively. The field size for which > 40 Gy/s could be achieved exceeded 1 cm down to a depth of 4.1 cm, suitable for total lung irradiations in mouse models. The calculated delivery metrics were used to inform subsequent pre-clinical treatments. Four groups of 6 healthy male C57Bl/6J mice were treated using thoracic irradiations to target doses of either 15 or 30 Gy using both FLASH and CONV modes. Administration of UHDR X-ray irradiation to healthy mouse models was demonstrated for the first time at the clinically-relevant beam energy of 10 MV.

Design optimization of an electron-to-photon conversion target for ultra-high dose rate x-ray (FLASH) experiments at TRIUMF.

OBJECTIVE: To develop a bremsstrahlung target and megavoltage (MV) x-ray irradiation platform for ultrahigh dose-rate (UHDR) irradiation of small-animals on the Advanced Rare Isotope Laboratory (ARIEL) electron linac (e-linac) at TRIUMF. APPROACH: An electron-to-photon converter design for UHDR radiotherapy (RT) was centered around optimization of a tantalum-aluminum (Ta-Al) explosion-bonded target. Energy deposition within a homogeneous water-phantom and the target itself were evaluated using EGSnrc and FLUKA MC codes, respectively, for various target thicknesses (0.5-1.5 mm), beam energies (Ee-= 8, 10 MeV) and electron (Gaussian) beam sizes (2σ= 2-10 mm). Depth dose-rates in a 3D-printed mouse phantom were also calculated to infer the compatibility of the 10 MV dose distributions for FLASH-RT in small-animal models. Coupled thermo-mechanical FEA simulations in ANSYS were subsequently used to inform the stress-strain conditions and fatigue life of the target assembly. MAIN RESULTS: Dose-rates of up to 128 Gy s-1at the phantom surface, or 85 Gy s-1at 1 cm depth, were obtained for a 1 × 1 cm2field size, 1 mm thick Ta target and 7.5 cm source-to-surface distance using the FLASH-mode beam (Ee-= 10 MeV, 2σ= 5 mm,P = 1 kW); furthermore, removal of the collimation assembly and using a shorter (3.5 cm) SSD afforded dose-rates >600 Gy s-1, albeit at the expense of field conformality. Target temperatures were maintained below the tantalum, aluminum and cooling-water thresholds of 2000 °C, 300 °C and 100 °C, respectively, while the aluminum strain behavior remained everywhere elastic and helped ensure   the converter survives its prescribed 5 yr operational lifetime. SIGNIFICANCE: Effective design iteration, target cooling and failure mitigation have culminated in a robust target compatible with intensive transient (FLASH) and steady-state (diagnostic) applications. The ARIEL UHDR photon source will facilitate FLASH-RT experiments concerned with sub-second, pulsed or continuous beam irradiations at dose rates in excess of 40 Gy s-1.

Direct observation of Mg2+ complexes in ionic liquid solutions by 31Mg ß-NMR spectroscopy.

NMR spectra of Mg2+ ions in ionic liquids were recorded using a highly sensitive variant of NMR spectroscopy known as ß-NMR. The ß-NMR spectra of MgCl2 in EMIM-Ac and EMIM-DCA compare favourably with conventional NMR, and exhibit linewidths of ∼3 ppm, allowing for discrimination of species with oxygen and nitrogen coordination.

Direct Observation of Nanosecond Water Exchange Dynamics at a Protein Metal Site.

Nanosecond ligand exchange dynamics at metal sites within proteins is essential in catalysis, metal ion transport, and regulatory metallobiochemistry. Herein we present direct observation of the exchange dynamics of water at a Cd2+ binding site within two de novo designed metalloprotein constructs using 111mCd perturbed angular correlation (PAC) of γ-rays and 113Cd NMR spectroscopy. The residence time of the Cd2+-bound water molecule is tens of nanoseconds at 20 °C in both proteins. This constitutes the first direct experimental observation of the residence time of Cd2+ coordinated water in any system, including the simple aqua ion. A Leu to Ala amino acid substitution ∼10 Å from the Cd2+ site affects both the equilibrium constant and the residence time of water, while, surprisingly, the metal site structure, as probed by PAC spectroscopy, remains essentially unaltered. This implies that remote mutations may affect metal site dynamics, even when structure is conserved.

Billion-fold enhancement in sensitivity of nuclear magnetic resonance spectroscopy for magnesium ions in solution.

ß-nuclear magnetic resonance (NMR) spectroscopy is highly sensitive compared to conventional NMR spectroscopy, and may be applied for several elements across the periodic table. ß-NMR has previously been successfully applied in the fields of nuclear and solid-state physics. In this work, ß-NMR is applied, for the first time, to record an NMR spectrum for a species in solution. (31)Mg ß-NMR spectra are measured for as few as 10(7) magnesium ions in ionic liquid (EMIM-Ac) within minutes, as a prototypical test case. Resonances are observed at 3882.9 and 3887.2 kHz in an external field of 0.3 T. The key achievement of the current work is to demonstrate that ß-NMR is applicable for the analysis of species in solution, and thus represents a novel spectroscopic technique for use in general chemistry and potentially in biochemistry.