Wave Optical Modeling of the SEM Column From Source to Specimen.

Probe formation in scanning electron microscope (SEM) is often reduced to objective lens action modeling based on a point-spread function or Fourier transforms. In this study, we present the first complete wave optical modeling of the whole SEM column based on plane-by-plane propagation of the electron beam wavefunction without simplifying the optical system. We identify the challenges in plane-by-plane beam propagation and show how sampling limitations produce aliased results. Through a careful selection and combination of propagators, we have developed a general wave optical propagation method that is able to overcome the aliasing problem to achieve the appropriate probe widths. Using a two-step propagator, we show that it is possible to model the electron beam distribution throughout the column from the virtual source plane to the specimen plane. We also show that our results from the wave optical simulations are consistent with the geometrical theory of probe formation. Finally, as a direct application of this method, we demonstrated that the combined effect of aberrations in the condenser lens and the probe forming objective lens cannot be accurately represented using only the objective lens. Designing beam shaping experiments and studying the effect of partial coherence can be some novel applications.

Changes in Telomere Length in Leukocytes and Leukemic Cells after Ultrashort Electron Beam Radiation.

Application of laser-generated electron beams in radiotherapy is a recent development. Accordingly, mechanisms of biological response to radiation damage need to be investigated. In this study, telomere length (TL) as endpoint of genetic damage was analyzed in human blood cells (leukocytes) and K562 leukemic cells irradiated with laser-generated ultrashort electron beam. Metaphases and interphases were analyzed in quantitative fluorescence in situ hybridization (Q-FISH) to assess TL. TLs were shortened compared to non-irradiated controls in both settings (metaphase and interphase) after irradiation with 0.5, 1.5, and 3.0 Gy in blood leukocytes. Radiation also caused a significant TL shortening detectable in the interphase of K562 cells. Overall, a negative correlation between TL and radiation doses was observed in normal and leukemic cells in a dose-dependent manner. K562 cells were more sensitive than normal blood cells to increasing doses of ultrashort electron beam radiation. As telomere shortening leads to genome instability and cell death, the results obtained confirm the suitability of this biomarker for assessing genotoxic effects of accelerated electrons for their further use in radiation therapy. Observed differences in TL shortening between normal and K562 cells provide an opportunity for further development of optimal radiation parameters to reduce side effects in normal cells during radiotherapy.

Adding customized electron energy beams to TrueBeam linear accelerators.

PURPOSE: To better meet clinical needs and facilitate optimal treatment planning, we added two new electron energy beams (7 and 11 MeV) to two Varian TrueBeam linacs. METHODS: We worked with the vendor to create two additional customized electron energies without hardware modifications. For each beam, we set the bending magnet current and then optimized other beam-specific parameters to achieve depths of 50% ionization (I50 ) of 2.9 cm for 7 MeV and 4.2 cm for the 11 MeV beam with the 15 × 15 cm2 cone at 100 cm source-to-surface distance (SSD) by using an ionization chamber profiler (ICP) with a double-wedge (DW) phantom. Beams were steered and balanced to optimize symmetry with the ICP. After all parameters were set, full commissioning was done including measuring beam profiles, percent depth doses (PDDs), output factors (OFs) at standard, and extended SSDs. Measured data were compared between the two linacs and against the values calculated by our RayStation treatment planning system (TPS) following Medical Physics Practice Guideline 5.a (MPPG 5.a) guidelines. RESULTS: The I50 values initially determined with the ICP/DW agreed with those from a PDD-scanned in-water phantom within 0.2 mm for the 7 and 11 MeV on both linacs. Comparison of the beam characteristics from the two linacs indicated that flatness and symmetry agreed within 0.4%, and point-by-point differences in PDD were within 0.01% ± 0.3% for the 7 MeV and 0.01% ± 0.3% for the 11 MeV. The OF ratios between the two linacs were 1.000 ± 0.007 for the 7 MeV and 1.004 ± 0.007 for the 11 MeV. Agreement between TPS-calculated outputs and measurements were -0.1% ± 1.0% for the 7 MeV and 0.2% ± 0.8% for the 11 MeV. All other parameters met the MPPG 5.a's 3%/3-mm criteria. CONCLUSION: We were able to add two new beam energies with no hardware modifications. Tuning of the new beams was facilitated by the ICP/DW system allowing us to have the procedures done in a few hours and achieve highly consistent results across two linacs. PACS numbers: 87.55.Qr, 87.56.Fc.

Planning and delivery of intensity modulated bolus electron conformal therapy.

PURPOSE: Bolus electron conformal therapy (BECT) is a clinically useful, well-documented, and available technology. The addition of intensity modulation (IM) to BECT reduces volumes of high dose and dose spread in the planning target volume (PTV). This paper demonstrates new techniques for a process that should be suitable for planning and delivering IM-BECT using passive radiotherapy intensity modulation for electrons (PRIME) devices. METHODS: The IM-BECT planning and delivery process is an addition to the BECT process that includes intensity modulator design, fabrication, and quality assurance. The intensity modulator (PRIME device) is a hexagonal matrix of small island blocks (tungsten pins of varying diameter) placed inside the patient beam-defining collimator (cutout). Its design process determines a desirable intensity-modulated electron beam during the planning process, then determines the island block configuration to deliver that intensity distribution (segmentation). The intensity modulator is fabricated and quality assurance performed at the factory (.decimal, LLC, Sanford, FL). Clinical quality assurance consists of measuring a fluence distribution in a plane perpendicular to the beam in a water or water-equivalent phantom. This IM-BECT process is described and demonstrated for two sites, postmastectomy chest wall and temple. Dose plans, intensity distributions, fabricated intensity modulators, and quality assurance results are presented. RESULTS: IM-BECT plans showed improved D90-10 over BECT plans, 6.4% versus 7.3% and 8.4% versus 11.0% for the postmastectomy chest wall and temple, respectively. Their intensity modulators utilized 61 (single diameter) and 246 (five diameters) tungsten pins, respectively. Dose comparisons for clinical quality assurance showed that for doses greater than 10%, measured agreed with calculated dose within 3% or 0.3 cm distance-to-agreement (DTA) for 99.9% and 100% of points, respectively. CONCLUSION: These results demonstrated the feasibility of translating IM-BECT to the clinic using the techniques presented for treatment planning, intensity modulator design and fabrication, and quality assurance processes.

Shielding effect of a lead apron on the peripheral radiation dose outside the applicator of electron beams from an Elekta linear accelerator.

PURPOSE: To evaluate the shielding effect of lead aprons (LAs) on peripheral radiation doses outside the applicator of electron beams from a linear accelerator. METHODS: Out-of-field radiation doses of 4-, 6-, 8-, 10-, 12-, and 15-MeV electron beams from an Elekta Synergy linear accelerator (linac) were measured by thermoluminescence dosimeters (TLD) at different depths (0, 0.5, 1.0, and 2.0 cm) and distances from the applicator edge (0-58 cm) in a water-equivalent slab phantom with a different number of layers of LA shielding (0-5 layers). Measurements were performed by 6 × 6, 10 × 10, 14 × 14, and 20 × 20-cm2 applicators at a gantry and collimator angle of 0°. The out-of-field radiation dose profiles were normalized to the maximum dose of every energy and measuring depth. RESULTS: The out-of-field radiation doses (beyond 3 cm away from the field edge) decreased with an increase in the number of LA layers and distance away from the central beam axis (CAX). After shielding with the LA, the out-of-field doses decreased by up to approximately 99% compared with the no shielding group. For 4-MeV electron beams, there was a peak at 24.5 cm from the CAX, which weakened with an increasing number of LA layers. CONCLUSION: The shielding effect of the LA varied for a different number of LA layers as well as different depths and distances away from the CAX. Four LA layers were sufficient for shielding out-of-field doses of 4-15-MeV electron beams.

Nonlinear Interactions between Free Electrons and Nanographenes.

Free electrons act as a source of highly confined, spectrally broad optical fields that are widely used to map photonic modes with nanometer/millielectronvolt space/energy resolution through currently available electron energy-loss and cathodoluminescence spectroscopies. These techniques are understood as probes of the linear optical response, while nonlinear dynamics has escaped observation with similar degree of spatial detail, despite the strong enhancement of the electron evanescent field with decreasing electron energy. Here, we show that the field accompanying low-energy electrons can trigger anharmonic response in strongly nonlinear materials. Specifically, through realistic quantum-mechanical simulations, we find that the interaction between ≲100 eV electrons and plasmons in graphene nanostructures gives rise to substantial optical nonlinearities that are discernible as saturation and spectral shifts in the plasmonic features revealed in the cathodoluminescence emission and electron energy-loss spectra. Our results support the use of low-energy electron-beam spectroscopies for the exploration of nonlinear optical processes in nanostructures.

How electron two-stream instability drives cyclic Langmuir collapse and continuous coherent emission.

Continuous plasma coherent emission is maintained by repetitive Langmuir collapse driven by the nonlinear evolution of a strong electron two-stream instability. The Langmuir waves are modulated by solitary waves in the linear stage and electrostatic whistler waves in the nonlinear stage. Modulational instability leads to Langmuir collapse and electron heating that fills in cavitons. The high pressure is released via excitation of a short-wavelength ion acoustic mode that is damped by electrons and reexcites small-scale Langmuir waves; this process closes a feedback loop that maintains the continuous coherent emission.

Evaluation of prototype of improved electron collimation system for Elekta linear accelerators.

PURPOSE: This study evaluated a new electron collimation system design for Elekta 6-20 MeV beams, which should reduce applicator weights by 25%-30%. Such reductions, as great as 3.9 kg for the largest applicator, should result in considerably easier handling by members of the radiotherapy team. METHODS: Prototype 10 × 10 and 20 × 20-cm2 applicators, used to measure weight, in-field flatness, and out-of-field leakage dose, were constructed according to the previously published design with two minor modifications: (a) rather than tungsten, lead was used for trimmer material; and (b) continuous trimmer outer-edge bevel was approximated by three steps. Because of lead plate softness, a 0.32-cm aluminum plate replaced the equivalent lead thickness on the trimmer's downstream surface for structural support. Models of all applicators (6 × 6-25 × 25 cm2 ) with these modifications were inserted into a Monte Carlo (MC) model for dose calculations using 7, 13, and 20 MeV beams. Planar dose distributions were measured and calculated at 1- and 2-cm water depths to evaluate in-field beam flatness and out-of-field leakage dose. RESULTS: Prototype 10 × 10 and 20 × 20-cm2 applicator measurements agreed with calculated weights, in-field flatness, and out-of-field leakage doses for 7, 13, and 20 MeV beams. Also, MC dose calculations showed that all applicators (6 × 6-25 × 25 cm2 ) and 7, 13, and 20 MeV beams met our stringent in-field flatness specifications (±3% major axes; ±4% diagonals) and IEC out-of-field leakage dose specifications. CONCLUSIONS: Our results validated the new electron collimating system design for Elekta 6-20 MeV electron beams, which could serve as basis for a new clinical electron collimating system with significantly reduced applicator weights.

Improved electron collimation system design for Elekta linear accelerators.

Prototype 10 × 10 and 20 × 20-cm2 electron collimators were designed for the Elekta Infinity accelerator (MLCi2 treatment head), with the goal of reducing the trimmer weight of excessively heavy current applicators while maintaining acceptable beam flatness (±3% major axes, ±4% diagonals) and IEC leakage dose. Prototype applicators were designed initially using tungsten trimmers of constant thickness (1% electron transmission) and cross-sections with inner and outer edges positioned at 95% and 2% off-axis ratios (OARs), respectively, cast by the upstream collimating component. Despite redefining applicator size at isocenter (not 5 cm upstream) and reducing the energy range from 4-22 to 6-20 MeV, the designed 10 × 10 and 20 × 20-cm2 applicator trimmers weighed 6.87 and 10.49 kg, respectively, exceeding that of the current applicators (5.52 and 8.36 kg, respectively). Subsequently, five design modifications using analytical and/or Monte Carlo (MC) calculations were applied, reducing trimmer weight while maintaining acceptable in-field flatness and mean leakage dose. Design Modification 1 beveled the outer trimmer edges, taking advantage of only low-energy beams scattering primary electrons sufficiently to reach the outer trimmer edge. Design Modification 2 optimized the upper and middle trimmer distances from isocenter for minimal trimmer weights. Design Modification 3 moved inner trimmer edges inward, reducing trimmer weight. Design Modification 4 determined optimal X-ray jaw positions for each energy. Design Modification 5 adjusted middle and lower trimmer shapes and reduced upper trimmer thickness by 50%. Design Modifications 1→5 reduced trimmer weights from 6.87→5.86→5.52→5.87→5.43→3.73 kg for the 10 × 10-cm2 applicator and 10.49→9.04→8.62→7.73→7.35→5.09 kg for the 20 × 20-cm2 applicator. MC simulations confirmed these final designs produced acceptable in-field flatness and met IEC-specified leakage dose at 7, 13, and 20 MeV. These results allowed collimation system design for 6 × 6-25 × 25-cm2 applicators. Reducing trimmer weights by as much as 4 kg (25 × 25-cm2 applicator) should result in easier applicator handling by the radiotherapy team.

Introduction to passive electron intensity modulation.

This work introduces a new technology for electron intensity modulation, which uses small area island blocks within the collimating aperture and small area island apertures in the collimating insert. Due to multiple Coulomb scattering, electrons contribute dose under island blocks and lateral to island apertures. By selecting appropriate lateral positions and diameters of a set of island blocks and island apertures, for example, a hexagonal grid with variable diameter circular island blocks, intensity modulated beams can be produced for appropriate air gaps between the intensity modulator (position of collimating insert) and the patient. Such a passive radiotherapy intensity modulator for electrons (PRIME) is analogous to using physical attenuators (metal compensators) for intensity modulated x-ray therapy (IMXT). For hexagonal spacing, the relationship between block (aperture) separation (r) and diameter (d) and the local intensity reduction factor (IRF) is discussed. The PRIME principle is illustrated using pencil beam calculations for select beam geometries in water with half beams modulated by 70%-95% and for one head and neck field of a patient treated with bolus electron conformal therapy. Proof of principle is further illustrated by showing agreement between measurement and calculation for a prototype PRIME. Potential utilization of PRIME for bolus electron conformal therapy, segmented-field electron conformal therapy, modulated electron radiation therapy, and variable surface geometries is discussed. Further research and development of technology for the various applications is discussed. In summary, this paper introduces a practical, new technology for electron intensity modulation in the clinic, demonstrates proof of principle, discusses potential clinical applications, and suggests areas of further research and development.

Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells.

Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10(10) Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone.

Aberration-corrected STEM for atomic-resolution imaging and analysis.

Aberration-corrected scanning transmission electron microscopes are able to form electron beams smaller than 100 pm, which is about half the size of an average atom. Probing materials with such beams leads to atomic-resolution images, electron energy loss and energy-dispersive X-ray spectra obtained from single atomic columns and even single atoms, and atomic-resolution elemental maps. We review briefly how such electron beams came about, and show examples of applications. We also summarize recent developments that are propelling aberration-corrected scanning transmission electron microscopes in new directions, such as complete control of geometric aberration up to fifth order, and ultra-high-energy resolution EELS that is allowing vibrational spectroscopy to be carried out in the electron microscope.

Polymer-free patterning of graphene at sub-10-nm scale by low-energy repetitive electron beam.

A polymer-free technique for generating nanopatterns on both synthesized and exfoliated graphene sheets is proposed and demonstrated. A low-energy (5-30 keV) scanning electron beam with variable repetition rates is used to etch suspended and unsuspended graphene sheets on designed locations. The patterning mechanisms involve a defect-induced knockout process in the initial etching stage and a heat-induced curling process in a later stage. Rough pattern edges appear due to inevitable stochastic knockout of carbon atoms or graphene structure imperfection and can be smoothed by thermal annealing. By using this technique, the minimum feature sizes achieved are about 5 nm for suspended and 7 nm for unsuspended graphene. This study demonstrates a polymer-free direct nanopatterning approach for graphene.

Evaluation of RADIANCE Monte Carlo algorithm for treatment planning in electron based Intraoperative Radiotherapy (IOERT).

PURPOSE: To perform experimental as well as independent Monte Carlo (MC) evaluation of the MC algorithm implemented in RADIANCE version 4.0.8, a dedicated treatment planning system (TPS) for 3D electron dose calculations in intraoperative radiation therapy (IOERT). METHODS AND MATERIALS: The MOBETRON 2000 (IntraOp Medical Corporation, Sunnyvale, CA) IOERT accelerator was employed. PDD and profiles for five cylindrical plastic applicators with 50-90 mm diameter and 0°, 30° beveling were measured in a water phantom, at nominal energies of 6, 9 and 12 MeV. Additional PDD measurements were performed for all the energies without applicator. MC modeling of the MOBETRON was performed with the user code BEAMnrc and egs_chamber of the MC simulation toolkit EGSnrc. The generated phase space files of the two 0°-bevel applicators (50 mm, 80 mm) and three energies in both RADIANCE and BEAMnrc, were used to determine PDD and profiles in various set-ups of virtual water phantoms with air and bone inhomogeneities. 3D dose distributions were also calculated in image data sets of an anthropomorphic tissue-equivalent pelvis phantom. Image acquisitions were realized with a CT scanner (Philips Big Bore CT, Netherlands). Gamma analysis was applied to quantify the deviations of the RADIANCE calculations to the measurements and EGSnrc calculations. Gamma criteria normalized to the global maximum were investigated between 2%, 2 mm and 3%, 3 mm. RESULTS: RADIANCE MC calculations satisfied the gamma criteria of 3%, 3 mm with a tolerance limit of 85% passing rate compared to in- water phantom measurements, except for the dose profiles of the 30° beveled applicators. Mismatches lay in surface doses, in umbra regions and in the beveled end of the 30° applicators. A very good agreement to the EGSnrc calculations in heterogeneous media was observed. Deviations were more pronounced for the larger applicator diameter and higher electron energy. In 3D dose comparisons in the anthropomorphic phantom, gamma passing rates were higher than 96 % for both simulated applicators. CONCLUSIONS: RADIANCE MC algorithm agrees within 3%, 3 mm criteria with in-water phantom measurements and EGSnrc MC dose distributions in heterogeneous media for 0°-bevel applicators. The user should be aware of missing scattering components and the 30° beveled applicators should be used with attention.

Monte Carlo calculated beam quality correction factors for high energy electron beams.

PURPOSE: As the dosimetry protocol TRS 398 is being revised and the ICRU report 90 provides new recommendations for density correction as well as the mean ionization energies of water and graphite, updated beam quality correction factors kQ are calculated for reference dosimetry in electron beams and for independent validation of previously determined values. METHODS: Monte Carlo simulations have been performed using EGSnrc to calculate the absorbed dose to water and the dose to the active volumes of ionization chambers SNC600c, SNC125c and SNC350p (all Sun Nuclear, A Mirion Medical Company, Melbourne, FL). Realistic clinical electron beam spectra were used to cover the entire energy range of therapeutic electron accelerators. The Monte Carlo simulations were validated by measurements on a clinical linear accelerator. With regards to the cylindrical chambers, the simulations were performed according to the setup recommendations of TRS 398 and AAPM TG 51, i.e. with and without consideration of a reference point shift by rcav/2. RESULTS: kQ values as a function of the respective beam quality specifier R50 were fitted by recommended equations for electron beam dosimetry in the range of 5 MeV to 18 MeV. The fitting curves to the calculated values showed a root mean square deviation between 0.0016 and 0.0024. CONCLUSION: Electron beam quality correction factors kQ were calculated by Monte Carlo simulations for the cylindrical ionization chambers SNC600c and SNC125c as well as the plane parallel ionization chamber SNC350p to provide updated data for the TRS 398 and TG 51 dosimetry protocols.

Trends in low temperature and non-thermal technologies for the degradation of persistent organic pollutants.

The daunting effects of persistent organic pollutants on humans, animals, and the environment cannot be overemphasized. Their fate, persistence, long-range transport, and bioavailability have made them an environmental stressor of concern which has attracted the interest of the research community. Concerted efforts have been made by relevant organizations utilizing legislative laws to ban their production and get rid of them completely for the sake of public health. However, they have remained refractive in different compartments of the environment. Their bioavailability is majorly a function of different anthropogenic activities. Landfilling and incineration are among the earliest classical means of environmental remediation of waste; however, they are not sustainable due to the seepage of contaminants in landfills, the release of toxic gases into the atmosphere and energy requirements during incineration. Other advanced waste destruction technologies have been explored for the degradation of these recalcitrant pollutants; although, some are efficient, but are limited by high amounts of energy consumption, the use of organic solvents and hazardous chemicals, high capital and operational cost, and lack of public trust. Thus, this study has systematically reviewed different contaminant degradation technologies, their efficiency, and feasibility. Finally, based on techno-economic feasibility, non-invasiveness, efficiency, and environmental friendliness; radiation technology can be considered a viable alternative for the environmental remediation of contaminants in all environmental matrices at bench-, pilot-, and industrial-scale.

A Highly Versatile X-ray and Electron Beam Diamond Dosimeter for Radiation Therapy and Protection.

Radiotherapy is now recognized as a pillar in the fight against cancer. Two different types are currently used in clinical practice: (1) external beam radiotherapy, using high-energy X-rays or electron beams, both in the MeV-range, and (2) intraoperative radiotherapy, using low-energy X-rays (up to 50 keV) and MeV-range electron beams. Versatile detectors able to measure the radiation dose independently from the radiation nature and energy are therefore extremely appealing to medical physicists. In this work, a dosimeter based on a high-quality single-crystal synthetic diamond sample was designed, fabricated and characterized under low-energy X-rays, as well as under high-energy pulsed X-rays and electron beams, demonstrating excellent linearity with radiation dose and dose-rate. Detector sensitivity was measured to be 0.299 ± 0.002 µC/Gy under 6 MeV X-ray photons, and 0.298 ± 0.004 µC/Gy under 6 MeV electrons, highlighting that the response of the diamond dosimeter is independent of the radiation nature. Moreover, in the case of low-energy X-rays, an extremely low limit of detection (23 nGy/s) was evaluated, pointing out the suitability of the device to radiation protection dosimetry.

Clinical feasibility of combining intraoperative electron radiation therapy with minimally invasive surgery: a potential for electron-FLASH clinical development.

BACKGROUND: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. METHODS: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. RESULTS: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. CONCLUSIONS: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams.

DNA fragmentation by gamma radiation and electron beams using atomic force microscopy.

Double-stranded pBS plasmid DNA was irradiated with gamma rays at doses ranging from 1 to 12 kGy and electron beams from 1 to 10 kGy. Fragment-size distributions were determined by direct visualization, using atomic force microscopy with nanometer-resolution operating in non-tapping mode, combined with an improved methodology. The fragment distributions from irradiation with gamma rays revealed discrete-like patterns at all doses, suggesting that these patterns are modulated by the base pair composition of the plasmid. Irradiation with electron beams, at very high dose rates, generated continuous distributions of highly shattered DNA fragments, similar to results at much lower dose rates found in the literature. Altogether, these results indicate that AFM could supplement traditional methods for high-resolution measurements of radiation damage to DNA, while providing new and relevant information.

FLASH radiotherapy treatment planning and models for electron beams.

The FLASH effect designates normal tissue sparing at ultra-high dose rate (UHDR, >40 Gy/s) compared to conventional dose rate (∼0.1 Gy/s) irradiation while maintaining tumour control and has the potential to improve the therapeutic ratio of radiotherapy (RT). UHDR high-energy electron (HEE, 4-20 MeV) beams are currently a mainstay for investigating the clinical potential of FLASH RT for superficial tumours. In the future very-high energy electron (VHEE, 50-250 MeV) UHDR beams may be used to treat deep-seated tumours. UHDR HEE treatment planning focused at its initial stage on accurate dosimetric modelling of converted and dedicated UHDR electron RT devices for the clinical transfer of FLASH RT. VHEE treatment planning demonstrated promising dosimetric performance compared to clinical photon RT techniques in silico and was used to evaluate and optimise the design of novel VHEE RT devices. Multiple metrics and models have been proposed for a quantitative description of the FLASH effect in treatment planning, but an improved experimental characterization and understanding of the FLASH effect is needed to allow for an accurate and validated modelling of the effect in treatment planning. The importance of treatment planning for electron FLASH RT will augment as the field moves forward to treat more complex clinical indications and target sites. In this review, TPS developments in HEE and VHEE are presented considering beam models, characteristics, and future FLASH applications.