Roadmap to clinical use of gold nanoparticles for radiation sensitization

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Evaluating laser-driven Bremsstrahlung radiation sources for imaging and analysis of nuclear waste packages

A small scale sample nuclear waste package, consisting of a 28 mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500 keV), with a source size of <0.5 mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips. The uranium penny was clearly resolved to sub-mm accuracy over a 30 cm2 scan area from a single shot acquisition. In addition, neutron generation was demonstrated in situ with the X-ray beam, with a single shot, thus demonstrating the potential for multi-modal criticality testing of waste materials. This feasibility study successfully demonstrated non-destructive radiography of encapsulated, high density, nuclear material. With recent developments of high-power laser systems, to 10 Hz operation, a laser-driven multi-modal beamline for waste monitoring applications is envisioned.

Experimental measurements of the collisional absorption of XUV radiation in warm dense aluminium

The collisional (or free-free) absorption of soft x rays in warm dense aluminium remains an unsolved problem. Competing descriptions of the process exist, two of which we compare to our experimental data here. One of these is based on a weak scattering model, another uses a corrected classical approach. These two models show distinctly different behaviors with temperature. Here we describe experimental evidence for the absorption of 26-eV photons in solid density warm aluminium (Te≈1 eV). Radiative x-ray heating from palladium-coated CH foils was used to create the warm dense aluminium samples and a laser-driven high-harmonic beam from an argon gas jet provided the probe. The results indicate little or no change in absorption upon heating. This behavior is in agreement with the prediction of the corrected classical approach, although there is not agreement in absolute absorption value. Verifying the correct absorption mechanism is decisive in providing a better understanding of the complex behavior of the warm dense state.

Bespoke Radiology e-Learning

Introduction: Foundation doctors are expected to assess and interpret plain x-ray studies of the chest/abdomen before a definitive report is issued by senior staff. The Royal College of Radiologists have published guidelines (RCR curriculum) on the scope of plain film findings medical students should be familiar with.1 Studies have shown that the x-ray interpretation without feedback does not significantly improve diagnostic ability. 2 Queen’s University, Belfast Trust Radiology and Experior Medical developed an online system to assess individual student ability to interpret X-ray findings. Over a series of assessments each student’s profile is built up, identifying strengths and weakness. The system can then create bespoke individual assessments re-evaluating previously identified weak areas and quantifying interpretative skill improvement. Aim: To determine how readily an online system is adopted by senior medical students, investigating if increasing exposure to x-ray interpretation combined with cyclical formative feedback enhances performance. Methods: The system was offered to all 270 final year medical students as an online resource. The system comprised a series of 20 weekly 30 minute assessments, containing normal and abnormal x-rays within the RCR curriculum. After each assessment students were given formative feedback, including their own result, annotated answers, peer group comparison and a breakdown of areas of strength and weakness. Focus groups of 4-5 students addressed student perspectives of the system, including ease of use, image resolution, system performance across different operating platforms, perceived value of formative feedback loops, breakdown of performance and the value of bespoke personalised assessments. Research Ethics Approval was granted for the study. Data analysis was via two-sided one-sample t-test; initial minimal recruitment was estimated as 60 students, to detect a mean 10% change in performance, with a standard deviation of 20%. Results and Discussion: Over 80% (n = XXX/270) of the student cohort engaged with the study. Student baseline average was 39%, increasing to 62% by the exit test. The steadily sustained improvement (57% relative performance in interpretative diagnostic accuracy) was despite increasing test difficulty. Student feedback via focus groups was universally positive throughout the examined domains. Conclusion: The online resource proved to be valuable, with high levels of student engagement, improving performance despite increasingly difficulty testing and positive learner experience with the system. References: 1. Undergraduate Radiology Curriculum, The Royal College of Ra, April 2012. Ref No. BFCR(12)4 The Royal College of Radiologists, April 2012 2. I Satia, S Bashagha, A Bibi, R Ahmed, S Mellor, F Zaman. Assessing the accuracy and certainty in interpretating chest x-rays in the medical division. Clin Med August 2013 Vol.13 no. 4 349-352

Detector for imaging and dosimetry of laser-driven epithermal neutrons by alpha conversion

An epithermal neutron imager based on detecting alpha particles created via boron neutron capture mechanism is discussed. The diagnostic mainly consists of a mm thick Boron Nitride (BN) sheet (as an alpha converter) in contact with a non-borated cellulose nitride film (LR115 type-II) detector. While the BN absorbs the neutrons in the thermal and epithermal ranges, the fast neutrons register insignificantly on the detector due to their low neutron capture and recoil cross-sections. The use of solid-state nuclear track detectors (SSNTD), unlike image plates, micro-channel plates and scintillators, provide safeguard from the x-rays, gamma-rays and electrons. The diagnostic was tested on a proof-of-principle basis, in front of a laser driven source of moderated neutrons, which suggests the potential of using this diagnostic (BN+SSNTD) for dosimetry and imaging applications.

Photodiodes array as potential diagnostic for measuring short bursts of K-alpha radiation from Ti targets irradiated with 45 fs laser pulses

We report on a study comparing absolute K-alpha yield from Ti foils measured with a calibrated system of an X-ray CCD coupled to a curved LiF Von-Hamos crystal spectrometer to the difference in the signals measured simultaneously with two similar photodiodes fitted with two different filters. Our data indicate that a combination of photodiodes with different filters could be developed into an alternative and inexpensive diagnostic for monitoring single shot pulsed emission in a narrow band of X-ray region.

A filamentation instability for streaming cosmic rays

We demonstrate that cosmic rays form filamentary structures in the precursors of supernova remnant shocks due to their self-generated magnetic fields. The cosmic ray filamentation results in the growth of a long-wavelength instability, and naturally couples the rapid non-linear amplification on small scales to larger length-scales. Hybrid magnetohydrodynamics-particle simulations are performed to confirm the effect. The resulting large-scale magnetic field may facilitate the scattering of high-energy cosmic rays as required to accelerate protons beyond the knee in the cosmic ray spectrum at supernova remnant shocks. Filamentation far upstream of the shock may also assist in the escape of cosmic rays from the accelerator.

The transport of cosmic rays in self-excited magnetic turbulence

The process of diffusive shock acceleration relies on the efficacy with which hydromagnetic waves can scatter charged particles in the precursor of a shock. The growth of self-generated waves is driven by both resonant and non-resonant processes. We perform high-resolution magnetohydrodynamic simulations of the non-resonant cosmic ray driven instability, in which the unstable waves are excited beyond the linear regime. In a snapshot of the resultant field, particle transport simulations are carried out. The use of a static snapshot of the field is reasonable given that the Larmor period for particles is typically very short relative to the instability growth time. The diffusion rate is found to be close to, or below, the Bohm limit for a range of energies. This provides the first explicit demonstration that self-excited turbulence reduces the diffusion coefficient and has important implications for cosmic-ray transport and acceleration in supernova remnants.

Table-Top Laser-Based Source of Femtosecond, Collimated, Ultrarelativistic Positron Beams

The generation of ultrarelativistic positron beams with short duration (τ_e⁺≃30 fs), small divergence (θ_e⁺≃3 mrad), and high density (n _e⁺≃1014-1015 cm^-3) from a fully optical setup is reported. The detected positron beam propagates with a high-density electron beam and γ rays of similar spectral shape and peak energy, thus closely resembling the structure of an astrophysical leptonic jet. It is envisaged that this experimental evidence, besides the intrinsic relevance to laser-driven particle acceleration, may open the pathway for the small-scale study of astrophysical leptonic jets in the laboratory. 

Bright Subcycle Extreme Ultraviolet Bursts from a Single Dense Relativistic Electron Sheet

Double-foil targets separated by a low density plasma and irradiated by a petawatt-class laser are shown to be a copious source of coherent broadband radiation. Simulations show that a dense sheet of relativistic electrons is formed during the interaction of the laser with the tenuous plasma between the two foils. The coherent motion of the electron sheet as it transits the second foil results in strong broadband emission in the extreme ultraviolet, consistent with our experimental observations.

A twist in the tale of γ-ray bursts

An unusually long burst of γ-rays zapped Earth in December 2011, lasting 4 hours. The cause of this burst is now proposed to be a peculiar supernova produced by a spinning magnetic neutron star. See Letter p.189

SN2014J gamma rays from the 56Ni decay chain

Context. The detection and measurement of gamma-ray lines from the decaychain of 56Ni provides unique information about the explosionin supernovae. SN2014J at 3.3 Mpc is a sufficiently-nearby supernova oftype Ia so that such measurements have been feasible with the gamma-rayspectrometer SPI on ESA's INTEGRAL gamma-ray observatory.

Aims:The 56Ni freshly produced in the supernova is understood topower the optical light curve, because it emits gamma rays upon itsradioactive decay first to 56Co and then to 56Fe.Gamma-ray lines from 56Co decay are expected to becomedirectly visible through the white dwarf material several weeks afterthe explosion, as they progressively penetrate the overlying material ofthe supernova envelope, which is diluted as it expands. The lines areexpected to be Doppler-shifted or broadened from the kinematics of the56Ni ejecta. We aim to exploit high-resolution gamma-rayspectroscopy with the SPI spectrometer on INTEGRAL toward constrainingthe 56Ni distribution and kinematics in this supernova.

Methods: We use the observations with the SPI spectrometer onINTEGRAL, together with an improved instrumental background method.

Results: We detect the two main lines from 56Co decay at847 and 1238 keV, which are significantly Doppler-broadened, and atintensities (3.65 ± 1.21) × 10-4 and (2.27± 0.69) × 10-4 ph cm-2s-1, respectively, at their brightness maximum. We measuretheir rise toward a maximum after about 60-100 days and a declinethereafter. The intensity ratio of the two lines is found to beconsistent with expectations from 56Co decay (0.62 ±0.28 at brightness maximum, the expected ratio is 0.68). We find thatthe broad lines seen in the late, gamma-ray transparent phase are notrepresentative of the early gamma-ray emission, and notice instead thatthe emission spectrum is complex and irregular until the supernova isfully transparent to gamma rays, with progressive uncovering of the bulkof 56Ni. We infer that the explosion morphology is notspherically symmetric, both in the distribution of 56Ni andin the unburnt material which occults the 56Co emission.After we compare light curves from different plausible models, theresulting 56Ni mass is determined to be 0.49 ± 0.09M⊙.