Clinical Implementation and Evaluation of Auto-Segmentation Tools for Multi-Site Contouring in Radiotherapy.

Background and purpose: Tools for auto-segmentation in radiotherapy are widely available, but guidelines for clinical implementation are missing. The goal was to develop a workflow for performance evaluation of three commercial auto-segmentation tools to select one candidate for clinical implementation. Materials and Methods: One hundred patients with six treatment sites (brain, head-and-neck, thorax, abdomen, and pelvis) were included. Three sets of AI-based contours for organs-at-risk (OAR) generated by three software tools and manually drawn expert contours were blindly rated for contouring accuracy. The dice similarity coefficient (DSC), the Hausdorff distance, and a dose/volume evaluation based on the recalculation of the original treatment plan were assessed. Statistically significant differences were tested using the Kruskal-Wallis test and the post-hoc Dunn Test with Bonferroni correction. Results: The mean DSC scores compared to expert contours for all OARs combined were 0.80 ± 0.10, 0.75 ± 0.10, and 0.74 ± 0.11 for the three software tools. Physicians' rating identified equivalent or superior performance of some AI-based contours in head (eye, lens, optic nerve, brain, chiasm), thorax (e.g., heart and lungs), and pelvis and abdomen (e.g., kidney, femoral head) compared to manual contours. For some OARs, the AI models provided results requiring only minor corrections. Bowel-bag and stomach were not fit for direct use. During the interdisciplinary discussion, the physicians' rating was considered the most relevant. Conclusion: A comprehensive method for evaluation and clinical implementation of commercially available auto-segmentation software was developed. The in-depth analysis yielded clear instructions for clinical use within the radiotherapy department.

Review and recommendations on deformable image registration uncertainties for radiotherapy applications.

Deformable image registration (DIR) is a versatile tool used in many applications in radiotherapy (RT). DIR algorithms have been implemented in many commercial treatment planning systems providing accessible and easy-to-use solutions. However, the geometric uncertainty of DIR can be large and difficult to quantify, resulting in barriers to clinical practice. Currently, there is no agreement in the RT community on how to quantify these uncertainties and determine thresholds that distinguish a good DIR result from a poor one. This review summarises the current literature on sources of DIR uncertainties and their impact on RT applications. Recommendations are provided on how to handle these uncertainties for patient-specific use, commissioning, and research. Recommendations are also provided for developers and vendors to help users to understand DIR uncertainties and make the application of DIR in RT safer and more reliable.

Evaluation of a novel CBCT conversion method implemented in a treatment planning system.

BACKGROUND: To evaluate a novel CBCT conversion algorithm for dose calculation implemented in a research version of a treatment planning system (TPS). METHODS: The algorithm was implemented in a research version of RayStation (v. 11B-DTK, RaySearch, Stockholm, Sweden). CBCTs acquired for each ten head and neck (HN), gynecology (GYN) and lung cancer (LNG) patients were collected and converted using the new algorithm (CBCTc). A bulk density overriding technique implemented in the same version of the TPS was used for comparison (CBCTb). A deformed CT (dCT) was created by using deformable image registration of the planning CT (pCT) to the CBCT to reduce anatomical changes. All treatment plans were recalculated on the pCT, dCT, CBCTc and the CBCTb. The resulting dose distributions were analyzed using the MICE toolkit (NONPIMedical AB Sweden, Umeå) with local gamma analysis, with 1% dose difference and 1 mm distance to agreement criteria. A Wilcoxon paired rank sum test was applied to test the differences in gamma pass rates (GPRs). A p value smaller than 0.05 considered statistically significant. RESULTS: The GPRs for the CBCTb method were systematically lower compared to the CBCTc method. Using the 10% dose threshold and the dCT as reference the median GPRs were for the CBCTc method were 100% and 99.8% for the HN and GYN cases, respectively. Compared to that the GPRs of the CBCTb method were lower with values of 99.8% and 98.0%, for the HN and GYN cases, respectively. The GPRs of the LNG cases were 99.9% and 97.5% for the CBCTc and CBCTb method, respectively. These differences were statistically significant. The main differences between the dose calculated on the CBCTs and the pCTs were found in regions near air/tissue interfaces, which are also subject to anatomical variations. CONCLUSION: The dose distribution calculated using the new CBCTc method showed excellent agreement with the dose calculated using dCT and pCT and was superior to the CBCTb method. The main reasons for deviations of the calculated dose distribution were caused by anatomical variations between the pCT and the corrected CBCT.

Generating deliverable DICOM RT treatment plans for prostate VMAT by predicting MLC motion sequences with an encoder-decoder network.

BACKGROUND: Deep learning-based auto-planning is an active research field; however, for some tasks a treatment planning system (TPS) is still required. PURPOSE: To introduce a deep learning-based model generating deliverable DICOM RT treatment plans that can be directly irradiated by a linear accelerator (LINAC). The model was based on an encoder-decoder network and can predict multileaf collimator (MLC) motion sequences for prostate VMAT radiotherapy. METHODS: A total of 619 treatment plans from 460 patients treated for prostate cancer with single-arc VMAT were included in this study. An encoder-decoder network was trained using 465 clinical treatment plans and validated on 77 plans. The performance was analyzed on a separate test set of 77 treatment plans. Separate L1 losses were computed for the leaf and jaw positions as well as the monitor units, with the leaf loss being weighted by a factor of 100 before being added to the other losses. The generated treatment plans were recalculated in a treatment planning system and the dose-volume metrics and gamma passing rates were compared to the original dose. RESULTS: All generated treatment plans showed good agreement with the original data, with an average gamma passing rate (3%/3 mm) of 91.9 ± 7.1%. However, the coverage of the PTVs. was slightly lower for the generated plans (D98%  = 92.9 ± 2.6%) in comparison to the original plans (D98%  = 95.7 ± 2.2%). There was no significant difference in mean dose to the bladder between the predicted and original plan (Dmean of 28.0 ± 13.5 vs. 28.1 ± 13.3% of prescribed dose) or rectum (Dmean of 42.3 ± 7.4 vs. 42.6 ± 7.5%). The maximum dose to bladder was only slightly higher in the predicted plans (D2% of 100.7 ± 5.3 vs. 99.8 ± 4.0%) and for the rectum it was even lower (D2% of 100.5 ± 3.7 vs. 100.1 ± 4.3). CONCLUSIONS: The deep learning-based model could predict MLC motion sequences in prostate VMAT plans, eliminating the need for sequencing inside a TPS, thus revolutionizing autonomous treatment planning workflows. This research completes the loop in deep learning-based treatment planning processes, enabling more efficient workflows for real-time or online adaptive radiotherapy.

Rydberg-Blockade-Based Parity Quantum Optimization.

We present a scalable architecture for solving higher-order constrained binary optimization (HCBO) problems on current neutral-atom hardware operating in the Rydberg blockade regime. In particular, we formulate the recently developed parity encoding of arbitrary connected HCBO problems as a maximum-weight independent set (MWIS) problem on disk graphs, that are directly encodable on such devices. Our architecture builds from small MWIS modules in a problem-independent way, crucial for practical scalability.

Impact of log file source and data frequency on accuracy of log file-based patient specific quality assurance.

Performing phantom measurements for patient-specific quality assurance (PSQA) adds a significant amount of time to the adaptive radiotherapy procedure. Log file based PSQA can be used to increase the efficiency of this process. This study compared the dosimetric accuracy of high-frequency linear accelerator (Linac) log files and low-frequency log data stored in the oncology information system (OIS). Thirty patients were included, that were recently treated in the head and neck (HN), brain, and prostate region with volumetric modulated arc therapy (VMAT) and an additional ten patients treated using stereotactic body radiation therapy (SBRT) with 3D-conformal radiotherapy (3D-CRT) technique. Log data containing a single fraction were used to calculate the dose distributions. The dosimetric differences between Linac log files and OIS logs were evaluated with a gamma analysis with 2%/2 mm criterion and dose threshold of 30%. The original treatment plan was used as a reference. Moreover, DVH parameters of D98%, D50%, and D2% of the planning-target volume (PTV) and dose to several organs at risk (OARs) were reported. Significant differences in dose distributions between the two log types and the original dose were observed for PTV D98% and D2% (r < 0.001) for HN cases, PTV D98% (r = 0.005) for brain cases, and PTV D50% (r = 0.015) for prostate cases. No significant differences were found between the two log types with respect to D50%. The root mean square (RMS) error of the leaf positions of the OIS log was approximately twice the RMS error of the Linac log file for VMAT plans, but identical for 3D-CRT plans. The relationship between the gamma pass rate and the RMS error showed a moderate correlation for the Linac log files (r = -0.58, p < 0.001) and strong correlation for OIS logs (r = -0.71, p < 0.001). Furthermore, all doses calculated using Linac log files and OIS log data had a GPR >90% for an RMS error < 3.3 mm. Based on these findings, a tolerance limit of RMS error of 3.3 mm for considering OIS log based PSQA was established. Nevertheless, the OIS log data quality should be improved to achieve adequate PSQA.

Universal evaluation of MLC models in treatment planning systems based on a common set of dynamic tests.

PURPOSE: To demonstrate the feasibility of characterising MLCs and MLC models implemented in TPSs using a common set of dynamic beams. MATERIALS AND METHODS: A set of tests containing synchronous (SG) and asynchronous sweeping gaps (aSG) was distributed among twenty-five participating centres. Doses were measured with a Farmer-type ion chamber and computed in TPSs, which provided a dosimetric characterisation of the leaf tip, tongue-and-groove, and MLC transmission of each MLC, as well as an assessment of the MLC model in each TPS. Five MLC types and four TPSs were evaluated, covering the most frequent combinations used in radiotherapy departments. RESULTS: Measured differences within each MLC type were minimal, while large differences were found between MLC models implemented in clinical TPSs. This resulted in some concerning discrepancies, especially for the HD120 and Agility MLCs, for which differences between measured and calculated doses for some MLC-TPS combinations exceeded 10%. These large differences were particularly evident for small gap sizes (5 and 10 mm), as well as for larger gaps in the presence of tongue-and-groove effects. A much better agreement was found for the Millennium120 and Halcyon MLCs, differences being within ± 5% and ± 2.5%, respectively. CONCLUSIONS: The feasibility of using a common set of tests to assess MLC models in TPSs was demonstrated. Measurements within MLC types were very similar, but TPS dose calculations showed large variations. Standardisation of the MLC configuration in TPSs is necessary. The proposed procedure can be readily applied in radiotherapy departments and can be a valuable tool in IMRT and credentialing audits.

Scalable set of reversible parity gates for integer factorization.

Classical microprocessors operate on irreversible gates, that, when combined with AND, half-adder and full-adder operations, execute complex tasks such as multiplication of integers. We introduce parity versions of all components of a multiplication circuit. The parity gates are reversible quantum gates based on the recently introduced parity transformation and build on ground-space encoding of the corresponding gate logic. Using a quantum optimization heuristic, e.g., an adiabatic quantum computing protocol, allows one to quantum mechanically reverse the process of multiplication and thus factor integers, which has applications in cryptography. Our parity approach builds on nearest-neighbor constraints equipped with local fields, able to encode the logic of a binary multiplication circuit in a modular and scalable way.

Scalable quantum processors empowered by the Fermi scattering of Rydberg electrons.

Quantum computing promises exponential speed-up compared to its classical counterpart. While the neutral atom processors are the pioneering platform in terms of scalability, the dipolar Rydberg gates impose the main bottlenecks on the scaling of these devices. This article presents an alternative scheme for neutral atom quantum processing, based on the Fermi scattering of a Rydberg electron from ground-state atoms in spin-dependent lattice geometries. Instead of relying on Rydberg pair-potentials, the interaction is controlled by engineering the electron cloud of a sole Rydberg atom. The present scheme addresses the scaling obstacles in Rydberg processors by exponentially suppressing the population of short-lived states and by operating in ultra-dense atomic lattices. The restoring forces in molecule type Rydberg-Fermi potential preserve the trapping over a long interaction period. Furthermore, the proposed scheme mitigates different competing infidelity criteria, eliminates unwanted cross-talks, and significantly suppresses the operation depth in running complicated quantum algorithms.

Universal Parity Quantum Computing.

We propose a universal gate set for quantum computing with all-to-all connectivity and intrinsic robustness to bit-flip errors based on parity encoding. We show that logical controlled phase gate and R_{z} rotations can be implemented in parity encoding with single-qubit operations. Together with logical R_{x} rotations, implemented via nearest-neighbor controlled-NOT gates and an R_{x} rotation, these form a universal gate set. As the controlled phase gate requires only single-qubit rotations, the proposed scheme has advantages for several cornerstone quantum algorithms, e.g., the quantum Fourier transform. We present a method to switch between different encoding variants via partial on-the-fly encoding and decoding.

Impact of SSTR PET on Inter-Observer Variability of Target Delineation of Meningioma and the Possibility of Using Threshold-Based Segmentations in Radiation Oncology.

Aim: The aim of this study was to assess the effects of including somatostatin receptor agonist (SSTR) PET imaging in meningioma radiotherapy planning by means of changes in inter-observer variability (IOV). Further, the possibility of using threshold-based delineation approaches for semiautomatic tumor volume definition was assessed. Patients and Methods: Sixteen patients with meningioma undergoing fractionated radiotherapy were delineated by five radiation oncologists. IOV was calculated by comparing each delineation to a consensus delineation, based on the simultaneous truth and performance level estimation (STAPLE) algorithm. The consensus delineation was used to adapt a threshold-based delineation, based on a maximization of the mean Dice coefficient. To test the threshold-based approach, seven patients with SSTR-positive meningioma were additionally evaluated as a validation group. Results: The average Dice coefficients for delineations based on MRI alone was 0.84 ± 0.12. For delineation based on MRI + PET, a significantly higher dice coefficient of 0.87 ± 0.08 was found (p < 0.001). The Hausdorff distance decreased from 10.96 ± 11.98 mm to 8.83 ± 12.21 mm (p < 0.001) when adding PET for the lesion delineation. The best threshold value for a threshold-based delineation was found to be 14.0% of the SUVmax, with an average Dice coefficient of 0.50 ± 0.19 compared to the consensus delineation. In the validation cohort, a Dice coefficient of 0.56 ± 0.29 and a Hausdorff coefficient of 27.15 ± 21.54 mm were found for the threshold-based approach. Conclusions: SSTR-PET added to standard imaging with CT and MRI reduces the IOV in radiotherapy planning for patients with meningioma. When using a threshold-based approach for PET-based delineation of meningioma, a relatively low threshold of 14.0% of the SUVmax was found to provide the best agreement with a consensus delineation.

Accelerating and improving radiochromic film calibration by utilizing the dose ratio in photon and proton beams.

PURPOSE: Radiochromic films are versatile 2D dosimeters with high-resolution and near tissue equivalence. To assure high precision and accuracy, a time-consuming calibration process is required. To improve the time efficiency, a novel calibration method utilizing the ratio of the same dose profile measured at different monitor units (MUs) is introduced and tested in a proton and photon beam. METHODS: The calibration procedure employs the dose ratio of film measurements of the same relative profile for different absolute dose values. Hence, the ratio of the dose is constant at any point of the profile, but the ratio of the net optical densities is not constant. The key idea of the method is to optimize the calibration function until the ratio of the calculated doses is constant. The proposed method was tested in the dose range between 0.25-12 and 1-6 Gy in a proton and photon beam, respectively. A radial symmetric profile and a rectangular profile were created, both having a central plateau region of about 3 cm diameter and a dose falloff of about 1.5 cm at larger distances. The dose falloff region was used as input for the optimization method and the central plateau region served as dose reference points. Only the plateau region of the highest dose entered the optimization as an additional objective. The measured data were randomly split into differently sized training and test sets. The optimization was repeated 1000 times with random start value initialization using the same start values for the standard and the gradient method. Finally, a proton plan with four dose levels was created, which were separated spatially, to test the possibility of a full calibration within a single measurement. RESULTS: Parameter estimation was possible with as low as one dose ratio used for optimization in both the photon and the proton case, yet exhibiting a high sensitivity on the dose level. The root mean squared deviation (RMSD) of the dose was less than 1% when the dose ratio was in the order of 20, whereas the median RMSD of all optimizations was 1.7%. Using four dose levels for optimization resulted in a median RMSD of 1% when randomly selecting the dose levels. Having at least one dose ratio of about 20 included in the optimization considerably improved the RMSD of the calibration function. Using six or eight dose levels reduced the sensitivity on the dose level selection and the median RMSD was 0.8%. A full calibration was possible in a single measurement having four dose levels in one plan but spatially separated. CONCLUSIONS: The number of measurements required to obtain an EBT3 film calibration function could be reduced using the proposed dose ratio method while maintaining the same accuracy as with the standard method.

A multi-institutional evaluation of small field output factor determination following the recommendations of IAEA/AAPM TRS-483.

PURPOSE: The aim of this work was to test the implementation of small field dosimetry following TRS-483 and to develop quality assurance procedures for the experimental determination of small field output factors (SFOFs). MATERIALS AND METHODS: Twelve different centers provided SFOFs determined with various detectors. Various linac models using the beam qualities 6 MV and 10 MV with flattening filter and without flattening filter were utilized to generate square fields down to a nominal field size of 0.5 cm × 0.5 cm. The detectors were positioned at 10 cm depth in water. Depending on the local situation, the source-to-surface distance was either set to 90 cm or 100 cm. The SFOFs were normalized to the output of the 10 cm × 10 cm field. The spread of SFOFs measured with different detectors was investigated for each individual linac beam quality and field size. Additionally, linac-type specific SFOF curves were determined for each beam quality and the SFOFs determined using individual detectors were compared to these curves. Example uncertainty budgets were established for a solid state detector and a micro ionization chamber. RESULTS: The spread of SFOFs for each linac and field was below 5% for all field sizes. With the exception of one linac-type, the SFOFs of all investigated detectors agreed within 10% with the respective linac-type SFOF curve, indicating a potential inter-detector and inter-linac variability. CONCLUSION: Quality assurance on the SFOF measurements can be done by investigation of the spread of SFOFs measured with multiple detectors and by comparison to linac-type specific SFOFs. A follow-up of a measurement session should be conducted if the spread of SFOFs is larger than 5%, 3%, and 2% for field sizes of 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 2 cm × 2 cm, respectively. Additionally, deviations of measured SFOFs to the linac-type-curves of more than 7%, 3%, and 2% for field sizes 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 1 cm × 1 cm, respectively, should be followed up.

Quantum Optimization via Four-Body Rydberg Gates.

A large ongoing research effort focuses on obtaining a quantum advantage in the solution of combinatorial optimization problems on near-term quantum devices. A particularly promising platform implementing quantum optimization algorithms are arrays of trapped neutral atoms, laser coupled to highly excited Rydberg states. However, encoding combinatorial optimization problems in atomic arrays is challenging due to limited interqubit connectivity of the native finite-range interactions. Here, we present a four-body Rydberg parity gate, enabling a direct and straightforward implementation of the parity architecture, a scalable architecture for encoding arbitrarily connected interaction graphs. Our gate relies on adiabatic laser pulses and is fully programmable by adjusting two hold times during operation. We numerically demonstrate implementations of the quantum approximate optimization algorithm (QAOA) for small-scale test problems. Variational optimization steps can be implemented with a constant number of system manipulations, paving the way for experimental investigations of QAOA beyond the reach of numerical simulations.

Qualifying quantum approaches for hard industrial optimization problems. A case study in the field of smart-charging of electric vehicles.

In order to qualify quantum algorithms for industrial NP-Hard problems, comparing them to available polynomial approximate classical algorithms and not only to exact exponential ones is necessary. This is a great challenge as, in many cases, bounds on the reachable approximation ratios exist according to some highly-trusted conjectures of Complexity Theory. An interesting setup for such qualification is thus to focus on particular instances of these problems known to be "less difficult" than the worst-case ones and for which the above bounds can be outperformed: quantum algorithms should perform at least as well as the conventional approximate ones on these instances, up to very large sizes. We present a case study of such a protocol for two industrial problems drawn from the strongly developing field of smart-charging of electric vehicles. Tailored implementations of the Quantum Approximate Optimization Algorithm (QAOA) have been developed for both problems, and tested numerically with classical resources either by emulation of Pasqal's Rydberg atom based quantum device or using Atos Quantum Learning Machine. In both cases, quantum algorithms exhibit the same approximation ratios as conventional approximation algorithms or improve them. These are very encouraging results, although still for instances of limited size as allowed by studies on classical computing resources. The next step will be to confirm them on larger instances, on actual devices, and for more complex versions of the problems addressed.

Reply to comment on 'Lateral response heterogeneity of Bragg peak ionization chambers for narrow-beam photon and proton dosimetry'.

Gomà (2020Phys. Med. Biol.) commented on our paper 'Lateral response heterogeneity of Bragg peak ionization chambers for narrow-beam photon and proton dosimetry' (Kuesset al2017Phys. Med. Biol.629189-206) which describes a method to determine the response pattern of large-area ionization chambers using a collimated x-ray beam. Gomà performed a simple Monte Carlo simulation to investigate the energy transferred by secondary electrons within the detector, deducing that our conclusion, that the chamber has a non-uniform response, is not supported by our results. We appreciate the work performed by Gomà very much and believe that the transport of secondary electrons in the chamber is an important contribution to understand the non-uniformity response of large-area chambers in narrow beams. However, we disagree with the conclusions drawn by Gomà that the radial response is homogenous. His simulation actually demonstrates that the response is non-uniform in an x-ray beam.

Cone beam CT based validation of neural network generated synthetic CTs for radiotherapy in the head region.

PURPOSE: In the past years, many different neural network-based conversion techniques for synthesizing computed tomographys (sCTs) from MR images have been published. While the model's performance can be checked during the training against the test set, test datasets can never represent the whole population. Conversion errors can still occur for special cases, for example, for unusual anatomical situations. Therefore, the performance of sCT conversion needs to be verified on a patient specific level, especially in the absence of a planning CT (pCT). In this study, the capability of cone-beam CTs (CBCTs) for the validation of sCTs generated by a neural network was investigated. METHODS: 41 patients with tumors in the head region were selected. 20 of them were used for model training and 10 for validation. Different implementations of CycleGAN (with/without identity and feature loss) were used to generate sCTs. The pixel (MAE, RMSE, PSNR) and geometric error (DICE, Sensitivity, Specificity) values were reported to identify the best model. VMAT plans were created for the remaining 11 patients on the pCTs. These plans were re-calculated on sCTs and CBCTs. An automatic density overriding method ( C B C T RS ) and a population-based dose calculation method ( C B C T Pop ) were employed for CBCT-based dose calculation. The dose distributions were analysed using 3D global gamma analysis, applying a threshold of 10% with respect to the prescribed dose. Differences in DVH metrics for the PTV and the organs-at-risk were compared among the dose distributions based on pCTs, sCTs, and CBCTs. RESULTS: The best model was the CycleGAN without identity and feature matching loss. Including the identity loss led to a metric decrease of 10% for DICE and a metric increase of 20-60 HU for MAE. Using the 2%/2 mm gamma criterion and pCT as reference, the mean gamma pass rates were 99.0  ±  0.4% for sCTs. Mean gamma pass rate values comparing pCT and CBCT were 99.0  ±  0.8% and 99.1  ±  0.8% for the C B C T RS and C B C T Pop , respectively. The mean gamma pass rates comparing sCT and CBCT resulted in 98.4  ±  1.6% and 99.2  ±  0.6% for C B C T RS and C B C T Pop , respectively. The differences between the gamma-pass-rates of the sCT and two CBCT-based methods were not significant. The majority of deviations of the investigated DVH metrices between sCTs and CBCTs were within 2%. CONCLUSION: The dosimetric results demonstrate good agreement between sCT, CBCT, and pCT based calculations. A properly applied CBCT conversion method can serve as a tool for quality assurance procedures in an MR only radiotherapy workflow for head patients. Dosimetric deviations of DVH metrics between sCT and CBCTs of larger than 2% should be followed up. A systematic shift of approximately 1% should be taken into account when using the C B C T RS approach in an MR only workflow.

Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors.

Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation sources, such as artificially generated ß- or electron-irradiation, is encouraged by authorities. Since the effect of the less hazardous electron-radiation on the production and functions of paracrine factors has not been tested so far, we compared the effects of γ- and electron-irradiation on PBMCs and determined the efficacy of both radiation sources for producing regenerative secretomes. Exposure to 60 Gy γ-rays from a radioactive nuclide and 60 Gy electron-irradiation provided by a linear accelerator comparably induced cell death and DNA damage. The transcriptional landscapes of PBMCs exposed to either radiation source shared a high degree of similarity. Secretion patterns of proteins, lipids, and extracellular vesicles displayed similar profiles after γ- and electron-irradiation. Lastly, we detected comparable biological activities in functional assays reflecting the regenerative potential of the secretomes. Taken together, we were able to demonstrate that electron-irradiation is an effective, alternative radiation source for producing therapeutic, cell-free secretomes. Our study paves the way for future clinical trials employing secretomes generated with electron-irradiation in tissue-regenerative medicine.

Comparison of CBCT conversion methods for dose calculation in the head and neck region.

The purpose of this study was to compare different methods of CBCT conversion respect to dose calculation accuracy. Twelve head and neck cancer patients treated with VMAT using simultaneous integrated boost technique were selected for the study. For each patient a planning CT (pCT), a control. CT acquired in the fourth week of treatment and a CBCT scan acquired on the closest day with the control CT were used. In order to re-calculate dose directly on CBCT image sets, a population based approach (CBCTPop) and a Histogram Matching (HM) approach based on rigid (CBCTHM-R) and deformable registration (CBCTHM-D) were used. Additionally, virtual CTs (vCTs) were generated using two deformable image registration algorithms (CTELX and CTANC) of the planning CT to the CBCT by using two different deformable image registration (DIR) algorithms. The corresponding control CTs were selected as ground truth and dose distributions on CBCT were analyzed using 3D global gamma index analysis applying a threshold of 10% with respect to the prescribed dose. Using the 2%/2mm gamma criterion, the results were 89.9%(±8.3%), 94.1%(±5.0%), 94.3%(±5.7%), 96.1%(±3.9%), 93.4%(±6.3%) for the CBCTPop, CBCTHM-R, CBCTHM-D, CTELX and CTANC, respectively. On average, the HM and DIR techniques showed a higher accuracy compared to the population based approach, but Kruskal-Wallis test did not show significant difference among the investigated dose calculation techniques assuming p<0.05. More sophisticated CBCT dose calculation methods seem to improve the dose calculation accuracy, but statistical significance remains to be demonstrated.

Perspectives of quantum annealing: methods and implementations.

Quantum annealing is a computing paradigm that has the ambitious goal of efficiently solving large-scale combinatorial optimization problems of practical importance. However, many challenges have yet to be overcome before this goal can be reached. This perspectives article first gives a brief introduction to the concept of quantum annealing, and then highlights new pathways that may clear the way towards feasible and large scale quantum annealing. Moreover, since this field of research is to a strong degree driven by a synergy between experiment and theory, we discuss both in this work. An important focus in this article is on future perspectives, which complements other review articles, and which we hope will motivate further research.