A Pilot Study of Simulation-Free Hippocampal-Avoidance Whole Brain Radiation Therapy Using Diagnostic MRI-Based and Online Adaptive Planning.

PURPOSE: We aimed to demonstrate the clinical feasibility and safety of simulation-free hippocampal avoidance whole brain radiation therapy (HA-WBRT) in a pilot study (National Clinical Trial 05096286). METHODS AND MATERIALS: Ten HA-WBRT candidates were enrolled for treatment on a commercially available computed tomography (CT)-guided linear accelerator with online adaptive capabilities. Planning structures were contoured on patient-specific diagnostic magnetic resonance imaging (MRI), which were registered to a CT of similar head shape, obtained from an atlas-based database (AB-CT). These patient-specific diagnostic MRI and AB-CT data sets were used for preplan calculation, using NRG-CC001 constraints. At first fraction, AB-CTs were used as primary data sets and deformed to patient-specific cone beam CTs (CBCT) to give patient-matched density information. Brain, ventricle, and brain stem contours were matched through rigid translation and rotation to the corresponding anatomy on CBCT. Lens, optic nerve, and brain contours were manually edited based on CBCT visualization. Preplans were then reoptimized through online adaptation to create final, simulation-free plans, which were used if they met all objectives. Workflow tasks were timed. In addition, patients underwent CT-simulation to create immobilization devices and for prospective dosimetric comparison of simulation-free and simulation-based plans. RESULTS: Median time from MRI importation to completion of "preplan" was 1 weekday (range, 1-4). Median on-table workflow duration was 41 minutes (range, 34-70). NRG-CC001 constraints were achieved by 90% of the simulation-free plans. One patient's simulation-free plan failed a planning target volume coverage objective (89% instead of 90% coverage); this was deemed acceptable for first-fraction delivery, with an offline replan used for subsequent fractions. Both simulation-free and simulation CT-based plans otherwise met constraints, without clinically meaningful differences. CONCLUSIONS: Simulation-free HA-WBRT using online adaptive radiation therapy is feasible, safe, and results in dosimetrically comparable treatment plans to simulation CT-based workflows while providing convenience and time savings for patients.

A Collaborative Platform for Advancing Automatic Interpretation in ECG Signals.

Numerous papers report the efficiency of the automatic interpretation capabilities of commercial algorithms. Unfortunately, these algorithms are proprietary, and academia has no means of directly contributing to these results. In fact, nothing at the same stage of development exists in academia. Despite the extensive research in ECG signal processing, from signal conditioning to expert systems, a cohesive single application for clinical use is not ready yet. This is due to a serious lack of coordination in the academic efforts, which involve not only algorithms for signal processing, but also the signal acquisition equipment itself. For instance, the different sampling rates and the different noise levels frequently found in the available signal databases can cause severe incompatibility problems when the integration of different algorithms is desired. Therefore, this work aims to solve this incompatibility problem by providing the academic community with a diagnostic-grade electrocardiograph. The intention is to create a new standardized ECG signals database in order to address the automatic interpretation problem and create an electrocardiography system that can fully assist clinical practitioners, as the proprietary systems do. Achieving this objective is expected through an open and coordinated collaboration platform for which a webpage has already been created.

Functional network disorganization and cognitive decline following fractionated whole-brain radiation in mice.

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of temporally evolving neural dynamics as they relate to cerebral hemodynamics for bridging with human studies. In order to adequately study the underlying mechanisms of RT-induced cognitive dysfunction, the development of clinically mimetic RT protocols in animal models is needed. To address these challenges, we developed a fractionated whole-brain RT protocol (3Gy/day for 10 days) and applied longitudinal wide field optical imaging (WFOI) of neural and hemodynamic brain activity at 1, 2, and 3 months post RT. At each time point, mice were subject to repeated behavioral testing across a variety of sensorimotor and cognitive domains. Disruptions in cortical neuronal and hemodynamic activity observed 1 month post RT were significantly worsened by 3 months. While broad changes were observed in functional brain organization post RT, brain regions most impacted by RT occurred within those overlapping with the mouse default mode network and other association areas similar to prior reports in human subjects. Further, significant cognitive deficits were observed following tests of novel object investigation and responses to auditory and contextual cues after fear conditioning. Our results fill a much-needed gap in understanding the effects of whole-brain RT on systems level brain organization and how RT affects neuronal versus hemodynamic signaling in the cortex. Having established a clinically-relevant injury model, future studies can examine therapeutic interventions designed to reduce neuroinflammation-based injury following RT. Given the overlap of sequelae that occur following RT with and without chemotherapy, these tools can also be easily incorporated to examine chemotherapy-related cognitive impairment.

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

BACKGROUND: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. METHODS: In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. FINDINGS: In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. CONCLUSIONS: These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. FUNDING: NIH, ASTRO, AHA, Longer Life Foundation.

In silico trial of simulation-free hippocampal-avoidance whole brain adaptive radiotherapy.

Background and Purpose: Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) can be a time-consuming process compared to conventional whole brain techniques, thus potentially limiting widespread utilization. Therefore, we evaluated the in silico clinical feasibility, via dose-volume metrics and timing, by leveraging a computed tomography (CT)-based commercial adaptive radiotherapy (ART) platform and workflow in order to create and deliver patient-specific, simulation-free HA-WBRT. Materials and methods: Ten patients previously treated for central nervous system cancers with cone-beam computed tomography (CBCT) imaging were included in this study. The CBCT was the adaptive image-of-the-day to simulate first fraction on-board imaging. Initial contours defined on the MRI were rigidly matched to the CBCT. Online ART was used to create treatment plans at first fraction. Dose-volume metrics of these simulation-free plans were compared to standard-workflow HA-WBRT plans on each patient CT simulation dataset. Timing data for the adaptive planning sessions were recorded. Results: For all ten patients, simulation-free HA-WBRT plans were successfully created utilizing the online ART workflow and met all constraints. The median hippocampi D100% was 7.8 Gy (6.6-8.8 Gy) in the adaptive plan vs 8.1 Gy (7.7-8.4 Gy) in the standard workflow plan. All plans required adaptation at first fraction due to both a failing hippocampal constraint (6/10 adaptive fractions) and sub-optimal target coverage (6/10 adaptive fractions). Median time for the adaptive session was 45.2 min (34.0-53.8 min). Conclusions: Simulation-free HA-WBRT, with commercially available systems, was clinically feasible via plan-quality metrics and timing, in silico.

Initial clinical experience building a dual CT- and MR-guided adaptive radiotherapy program.

Introduction: Our institution was the first in the world to clinically implement MR-guided adaptive radiotherapy (MRgART) in 2014. In 2021, we installed a CT-guided adaptive radiotherapy (CTgART) unit, becoming one of the first clinics in the world to build a dual-modality ART clinic. Herein we review factors that lead to the development of a high-volume dual-modality ART program and treatment census over an initial, one-year period. Materials and Methods: The clinical adaptive service at our institution is enabled with both MRgART (MRIdian, ViewRay, Inc, Mountain View, CA) and CTgART (ETHOS, Varian Medical Systems, Palo Alto, CA) platforms. We analyzed patient and treatment information including disease sites treated, radiation dose and fractionation, and treatment times for patients on these two platforms. Additionally, we reviewed our institutional workflow for creating, verifying, and implementing a new adaptive workflow on either platform. Results: From October 2021 to September 2022, 256 patients were treated with adaptive intent at our institution, 186 with MRgART and 70 with CTgART. The majority (106/186) of patients treated with MRgART had pancreatic cancer, and the most common sites treated with CTgART were pelvis (23/70) and abdomen (20/70). 93.0% of treatments on the MRgART platform were stereotactic body radiotherapy (SBRT), whereas only 72.9% of treatments on the CTgART platform were SBRT. Abdominal gated cases were allotted a longer time on the CTgART platform compared to the MRgART platform, whereas pelvic cases were allotted a shorter time on the CTgART platform when compared to the MRgART platform. Our adaptive implementation technique has led to six open clinical trials using MRgART and seven using CTgART. Conclusions: We demonstrate the successful development of a dual platform ART program in our clinic. Ongoing efforts are needed to continue the development and integration of ART across platforms and disease sites to maximize access and evidence for this technique worldwide.

EOG Signal Classification with Wavelet and Supervised Learning Algorithms KNN, SVM and DT.

The work carried out in this paper consists of the classification of the physiological signal generated by eye movement called Electrooculography (EOG). The human eye performs simultaneous movements, when focusing on an object, generating a potential change in origin between the retinal epithelium and the cornea and modeling the eyeball as a dipole with a positive and negative hemisphere. Supervised learning algorithms were implemented to classify five eye movements; left, right, down, up and blink. Wavelet Transform was used to obtain information in the frequency domain characterizing the EOG signal with a bandwidth of 0.5 to 50 Hz; training results were obtained with the implementation of K-Nearest Neighbor (KNN) 69.4%, a Support Vector Machine (SVM) of 76.9% and Decision Tree (DT) 60.5%, checking the accuracy through the Jaccard index and other metrics such as the confusion matrix and ROC (Receiver Operating Characteristic) curve. As a result, the best classifier for this application was the SVM with Jaccard Index.

Clinical application of a template-guided automated planning routine.

PURPOSE: Determine the dosimetric quality and the planning time reduction when utilizing a template-based automated planning application. METHODS: A software application integrated through the treatment planning system application programing interface, QuickPlan, was developed to facilitate automated planning using configurable templates for contouring, knowledge-based planning structure matching, field design, and algorithm settings. Validations are performed at various levels of the planning procedure and assist in the evaluation of readiness of the CT image, structure set, and plan layout for automated planning. QuickPlan is evaluated dosimetrically against 22 hippocampal-avoidance whole brain radiotherapy patients. The required times to treatment plan generation are compared for the validations set as well as 10 prospective patients whose plans have been automated by QuickPlan. RESULTS: The generations of 22 automated treatment plans are compared against a manual replanning using an identical process, resulting in dosimetric differences of minor clinical significance. The target dose to 2% volume and homogeneity index result in significantly decreased values for automated plans, whereas other dose metric evaluations are nonsignificant. The time to generate the treatment plans is reduced for all automated plans with a median difference of 9' 50″ ± 4' 33″. CONCLUSIONS: Template-based automated planning allows for reduced treatment planning time with consistent optimization structure creation, treatment field creation, plan optimization, and dose calculation with similar dosimetric quality. This process has potential expansion to numerous disease sites.

Minimización de costos de sedación usando anestesia inhalada. Análisis en la UTI durante la pandemia por COVID-19 / Minimization of sedation costs using inhaled anesthesia. Analysis in the ICU during the COVID-19 pandemic / Minimização dos custos de sedação usando anestesia inalatória. Análise na UTI durante a pandemia de COVID-19

Resumen: Introducción: los sedantes de uso no convencional y aquéllos fuera de recomendación como los anestésicos inhalados se usaron ante la escasez de medicamentos durante la pandemia por SARS-CoV-2. Objetivos: comparar el costo y resultados obtenidos con el uso de anestésicos inhalados versus sedantes intravenosos en COVID-19. Material y métodos: estudio retrospectivo en una unidad de terapia intensiva (UTI) de un hospital público de referencia. Se hizo un cálculo de costos de sedación de los dos primeros días de estancia en la UTI. Las dosis de fármacos fueron tomadas del expediente clínico y los costos de adquisición directamente de CompraNet. Se comparan medias de costos por medicamento y por grupo. Resultados: de 151 pacientes, 81 recibieron sedación intravenosa y 70 anestesia inhalada con o sin sedantes intravenosos. No hubo diferencia en mortalidad, días de ventilación mecánica, estancia en la UTI y estancia hospitalaria entre grupos. Se observó una reducción significativa de costos derivados del menor uso de midazolam, propofol y dexmedetomidina (p < 0.0001) cuando se usó anestesia inhalada y una diferencia entre medias de costos totales de sedación de $4,108.42 M.N. por día por paciente. Conclusiones: la anestesia inhalada durante la pandemia por COVID-19 permitió una reducción de costos comparada con sedación intravenosa en los primeros dos días de estancia en la UTI.

Abstract: Introduction: non-conventional sedatives and those off-label, such as inhaled anesthetics, were used due to the shortage of medicines during the SARS-CoV-2 pandemic. Objectives: to compare the cost and results obtained with the use of inhaled anesthetics versus intravenous sedatives in COVID-19. Material and methods: retrospective study in a public reference hospital ICU. A calculation of sedation costs was made of the first two days of ICU stay. Drug doses were taken from the clinical records and acquisition costs directly from CompraNet. Mean costs per medication and per group are compared. Results: of 151 patients, 81 received intravenous sedation and 70 received inhaled anesthesia with or without intravenous sedatives. There was no difference in mortality, days of mechanical ventilation, ICU stay, and hospital stay between groups. A significant reduction in costs derived from the less use of midazolam, propofol and dexmedetomidine (p < 0.0001), and a difference between means of total sedation costs of $4,108.42 Mexican pesos per patient per day was observed with inhaled anesthesia. Conclusions: inhaled anesthesia during the COVID-19 pandemic compared to intravenous sedation allowed a cost reduction in the first two days of ICU stay.

Resumo: Introdução: sedativos de uso não convencional e não recomendados, como anestésicos inalatórios, foram utilizados devido à escassez de medicamentos durante a pandemia de SARS-CoV-2. Objetivos: comparar o custo e os resultados obtidos com o uso de anestésicos inalatórios versus sedativos intravenosos na COVID-19. Material e métodos: estudo retrospectivo em uma UTI de um hospital público de referência. Foi feito um cálculo dos custos de sedação para os dois primeiros dias de internação na UTI. As doses dos medicamentos foram retiradas do prontuário clínico e os custos de aquisição diretamente do CompraNet. Os custos médios por medicamento e por grupo são comparados. Resultados: dos 151 pacientes, 81 receberam sedação intravenosa e 70 anestesia inalatória com ou sem sedativos intravenosos. Não houve diferença na mortalidade, dias em ventilação mecânica, permanência na UTI e internação entre os grupos. Uma redução significativa nos custos derivados do menor uso de midazolam, propofol e dexmedetomidina (p < 0.0001) foi observada quando a anestesia inalatória foi usada e uma diferença entre as médias dos custos totais de sedação de $4,108.42 M.N. por dia por paciente. Conclusões: a anestesia inalatória durante a pandemia de COVID-19 permitiu redução de custos em comparação com a sedação endovenosa nos primeiros dois dias de internação na UTI.

Eco-Friendly Approach for Graphene Oxide Synthesis by Modified Hummers Method.

The aim of this study is to produce graphene oxide using a modified Hummers method without using sodium nitrate. This modification eliminates the production of toxic gases. Two drying temperatures, 60 °C and 90 °C, were used. Material was characterized by X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, Raman Spectroscopy and Scanning Electron Microscopy. FTIR study shows various functional groups such as hydroxyl, carboxyl and carbonyl. The XRD results show that the space between the layers of GO60 is slightly larger than that for GO90. SEM images show a homogeneous network of graphene oxide layers of ≈6 to ≈9 nm. The procedure described has an environmentally friendly approach.

Heart Sparing Radiotherapy Techniques in Breast Cancer: A Focus on Deep Inspiration Breath Hold.

Adjuvant radiation therapy is a critical component of breast cancer management. However, when breast cancer patients receive incidental radiation to the heart, there is an increased risk of cardiac disease and mortality. This is most common for patients with left-sided breast cancers and those receiving nodal irradiation as part of treatment. The overall risk of cardiac toxicity increases 4-16% with each Gray increase in mean heart radiation dose, with data suggesting that no lower limit exists which would eliminate cardiac risk entirely. Radiation techniques have improved over time, leading to lower cardiac radiation exposure than in the past. This decline is expected to reduce the incidence of radiation-induced heart dysfunction in patients. Deep inspiration breath hold (DIBH) is one such technique that was developed to reduce the risk of cardiac death and coronary events. DIBH is a non-invasive approach that capitalizes on the natural physiology of the respiratory cycle to increase the distance between the heart and the therapeutic target throughout the course of radiation therapy. DIBH has been shown to decrease the mean incidental radiation doses to the heart and left anterior descending coronary artery by approximately 20-70%. In this review, we summarize different techniques for DIBH and discuss recent data on this technique.

RapidPlan hippocampal sparing whole brain model version 2-how far can we reduce the dose?

Whole-brain radiotherapy has been the standard palliative treatment for patients with brain metastases due to its effectiveness, availability, and ease of administration. Recent clinical trials have shown that limiting radiation dose to the hippocampus is associated with decreased cognitive toxicity. In this study, we updated an existing Knowledge Based Planning model to further reduce dose to the hippocampus and improve other dosimetric plan quality characteristics. Forty-two clinical cases were contoured according to guidelines. A new dosimetric scorecard was created as an objective measure for plan quality. The new Hippocampal Sparing Whole Brain Version 2 (HSWBv2) model adopted a complex recursive training process and was validated with five additional cases. HSWBv2 treatment plans were generated on the Varian HalcyonTM and TrueBeamTM systems and compared against plans generated from the existing (HSWBv1) model released in 2016. On the HalcyonTM platform, 42 cases were re-planned. Hippocampal D100% from HSWBv2 and HSWBv1 models had an average dose of 5.75 Gy and 6.46 Gy, respectively (p < 0.001). HSWBv2 model also achieved a hippocampal Dmean of 7.49 Gy, vs 8.10 Gy in HSWBv1 model (p < 0.001). Hippocampal D0.03CC from HSWBv2 model was 9.86 Gy, in contrast to 10.57 Gy in HSWBv1 (p < 0.001). For PTV_3000, D98% and D2% from HSWBv2 model were 28.27 Gy and 31.81 Gy, respectively, compared to 28.08 Gy (p = 0.020) and 32.66 Gy from HSWBv1 (p < 0.001). Among several other dosimetric quality improvements, there was a significant reduction in PTV_3000 V105% from 35.35% (HSWBv1) to 6.44% (HSWBv2) (p < 0.001). On 5 additional validation cases, dosimetric improvements were also observed on TrueBeamTM. In comparison to published data, the HSWBv2 model achieved higher quality hippocampal avoidance whole brain radiation therapy treatment plans through further reductions in hippocampal dose while improving target coverage and dose conformity/homogeneity. HSWBv2 model is shared publicly.

Pattern Recognition of EMG Signals by Machine Learning for the Control of a Manipulator Robot.

Human Machine Interfaces (HMI) principles are for the development of interfaces for assistance or support systems in physiotherapy or rehabilitation processes. One of the main problems is the degree of customization when applying some rehabilitation therapy or when adapting an assistance system to the individual characteristics of the users. To solve this inconvenience, it is proposed to implement a database of surface Electromyography (sEMG) of a channel in healthy individuals for pattern recognition through Neural Networks of contraction in the muscular region of the biceps brachii. Each movement is labeled using the One-Hot Encoding technique, which activates a state machine to control the position of an anthropomorphic manipulator robot and validate the response time of the designed HMI. Preliminary results show that the learning curve decreases when customizing the interface. The developed system uses muscle contraction to direct the position of the end effector of a virtual robot. The classification of Electromyography (EMG) signals is obtained to generate trajectories in real time by designing a test platform in LabVIEW.

A reconstruction approach for proton computed tomography by modeling the integral depth dose of the scanning proton pencil beam.

PURPOSE: To present a proton computed tomography (pCT) reconstruction approach that models the integral depth dose (IDD) of the clinical scanning proton beam into beamlets. Using a multilayer ionization chamber (MLIC) as the imager, the proposed pCT system and the reconstruction approach can minimize extra ambient neutron dose and simplify the beamline design by eliminating an additional collimator to confine the proton beam. METHODS: Monte Carlo simulation was applied to digitally simulate the IDDs of the exiting proton beams detected by the MLIC. A forward model was developed to model each IDD into a weighted sum of percentage depth doses of the constituent beamlets separated laterally by 1 mm. The water equivalent path lengths (WEPLs) of the beamlets were determined by iteratively minimizing the squared L2-norm between the forward projected and simulated IDDs. The final WEPL values were reconstructed to pCT images, that is, proton stopping power ratio (SPR) maps, through simultaneous algebraic reconstruction technique with total variation regularization. The reconstruction process was tested with a digital cylindrical water-based phantom and an ICRP adult reference computational phantom. The mean of SPR within regions of interest (ROIs) and the WEPL along a 4 mm-wide beam ( WEP L 4 mm ${\rm{WEP}}{{\rm{L}}_{4{\rm{mm}}}}$ ) were compared with the reference values. The spatial resolution was analyzed at the edge of a cortical insert of the cylindrical phantom. RESULTS: The percentage deviations from reference SPR were within ±1% in all selected ROIs. The mean absolute error of the reconstructed SPR was 0.33%, 0.19%, and 0.27% for the cylindrical phantom, the adult phantom at the head and lung region, respectively. The corresponding percentage deviations from reference WEP L 4 mm ${\rm{WEP}}{{\rm{L}}_{4{\rm{mm}}}}$ were 0.48 ± 0.64%, 0.28 ± 0.48%, and 0.22 ± 0.49%. The full width at half maximum of the line spread function (LSF) derived from the radial edge spread function (ESF) of a cortical insert was 0.13 cm. The frequency at 10% of the modulation transfer function (MTF) was 6.38 cm-1 . The mean signal-to-noise ratio (SNR) of all the inserts was 2.45. The mean imaging dose was 0.29 and 0.25 cGy at the head and lung region of the adult phantom, respectively. CONCLUSION: A new pCT reconstruction approach was developed by modeling the IDDs of the uncollimated scanning proton beams in the pencil beam geometry. SPR accuracy within ±1%, spatial resolution of better than 2 mm at 10% MTF, and imaging dose at the magnitude of mGy were achieved. Potential side effects caused by neutron dose were eliminated by removing the extra beam collimator.

Technical Report: Development and Implementation of an Open Source Template Interpretation Class Library for Automated Treatment Planning.

PURPOSE: Widespread implementation of automated treatment planning in radiation therapy remains elusive owing to variability in clinic and physician preferences, making it difficult to ensure consistent plan parameters. We have developed an open-source class library with the aim to improve efficiency and consistency for automated treatment planning in radiation therapy. METHODS AND MATERIALS: An open-source class library has been developed that interprets clinical templates within a commercial treatment planning system into a treatment plan for automated planning. This code was leveraged for the automated planning of 39 patients and retrospectively compared with the 78 clinically approved manual plans. RESULTS: From the initial 39 patients, 74 of 78 plans were successfully generated without manual intervention. The target dose was more homogeneous for automated plans, with an average homogeneity index of 3.30 for manual plans versus 3.11 for automated plans (P = .107). The generalized equivalent uniform dose (gEUD) was decreased in the femurs and rectum for automated plans, with a mean gEUD of 3746 cGy versus 3338 cGy (P ≤ 0.001) and 5761 cGy versus 5634 cGy (P ≤ 0.001) for the femurs and rectum, respectively. Dose metrics for the bladder and rectum (V6500 cGy and V4000 cGy) showed recognizable but insignificant improvements. All automated plans delivered for quality assurance passed a gamma analysis (>95%), with an average composite pass rate of 99.3% for pelvis plans and 98.8% for prostate plans. Deliverability parameters such as total monitor units and aperture complexity indicated deliverable plans. CONCLUSIONS: Prostate cancer and pelvic node radiation therapy can be automated using volumetric modulated arc therapy planning and clinical templates based on a standardized clinical workflow. The class library developed in this study conveniently interfaced between the plan template and the treatment planning system to automatically generate high-quality plans on customizable templates.

Quantification of gold nanoparticle photon radiosensitization from direct and indirect effects using a complete human genome single cell model based on Geant4.

PURPOSE: To investigate the radiosensitization properties of gold nanoparticles (GNPs) and better understand the intricate deoxyribonucleic acid (DNA) damage induction mechanisms involved in GNP-aided radiotherapy, a single cell model with complete human genome based on the Geant4 Monte Carlo toolkit was applied. MATERIALS AND METHODS: A Geant4-DNA model was implemented to simulate direct and indirect DNA damage generated in the physical and chemical stages. In the physical stage, a mixed-physics approach was taken by using Geant4-DNA in water and Livermore in gold. Water radiolysis was created posteriorly in the physicochemical and chemical stages to simulate indirect damage from reactions between DNA molecules and OH• radicals. A mono-energetic photon beam (100 keV) and two clinical photon sources (250-kVp, 6-MV flattening-filter free) were simulated for modeling the irradiation of a single cell with or without GNPs. In order to study the effects of GNP size on radiosensitization, 15, 30, and 100 nm GNPs were simulated. The effects of intracellular distribution were simulated using 90-nm GNPs with different characteristics of distribution within the cell. The time dependence of DNA damage enhancement was also studied with chemistry stage simulation end-time no larger than 10 ns. RESULTS: Double strand break (DSB) enhancement due to direct and indirect action was quantified under different scenarios. Under realistic cellular uptake condition, the 100-nm GNPs had the most significant increase in DSBs: 40.9% and 28.5% for 100 keV and 250-kVp photon irradiation, respectively. The intracellular localization showed differing levels of radiosensitization with a maximum of 64%, 27%, and 6% DSB enhancements for 100 keV, 250-kVp, and 6-MV respectively, when 90-nm GNPs congregate around the nucleus. CONCLUSION: The results indicate that photon energy, GNP size, and intracellular distribution play an important role in the enhancement of DSB from direct and indirect damage under scenarios close to cell experiments. The radiosensitization effects due to indirect damage are significant and should be considered carefully.

Human-Machine Interface: Multiclass Classification by Machine Learning on 1D EOG Signals for the Control of an Omnidirectional Robot.

People with severe disabilities require assistance to perform their routine activities; a Human-Machine Interface (HMI) will allow them to activate devices that respond according to their needs. In this work, an HMI based on electrooculography (EOG) is presented, the instrumentation is placed on portable glasses that have the task of acquiring both horizontal and vertical EOG signals. The registration of each eye movement is identified by a class and categorized using the one hot encoding technique to test precision and sensitivity of different machine learning classification algorithms capable of identifying new data from the eye registration; the algorithm allows to discriminate blinks in order not to disturb the acquisition of the eyeball position commands. The implementation of the classifier consists of the control of a three-wheeled omnidirectional robot to validate the response of the interface. This work proposes the classification of signals in real time and the customization of the interface, minimizing the user's learning curve. Preliminary results showed that it is possible to generate trajectories to control an omnidirectional robot to implement in the future assistance system to control position through gaze orientation.

Spatially fractionated stereotactic body radiation therapy (Lattice) for large tumors.

PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated clinical benefits for patients with metastatic and/or unresectable cancer. Technical considerations of treatment delivery and nearby organs at risk can limit the use of SBRT in large tumors or those in unfavorable locations. Spatially fractionated radiation therapy (SFRT) may address this limitation because this technique can deliver high-dose radiation to discrete subvolume vertices inside a tumor target while restricting the remainder of the target to a safer lower dose. Indeed, SFRT, such as GRID, has been used to treat large tumors with reported dramatic tumor response and minimal side effects. Lattice is a modern approach to SFRT delivered with arc-based therapy, which may allow for safe, high-quality SBRT for large and/or deep tumors. METHODS AND MATERIALS: Herein, we report the results of a dosimetry and quality assurance feasibility study of Lattice SBRT in 11 patients with 12 tumor targets, each ≥10 cm in an axial dimension. Prior computed tomography simulation scans were used to generate volumetric modulated arc therapy Lattice SBRT plans that were then delivered on clinically available Linacs. Quality assurance testing included external portal imaging device and ion chamber analyses. RESULTS: All generated plans met the standard SBRT dose constraints, such as those from the American Association of Physicists in Medicine Task Group 101. Additionally, we provide a step-by-step approach to generate and deliver Lattice SBRT plans using commercially available treatment technology. CONCLUSIONS: Lattice SBRT is currently being tested in a prospective trial for patients with metastatic cancer who need palliation of large tumors (NCT04553471, NCT04133415).

Spread-out Bragg peak proton FLASH irradiation using a clinical synchrocyclotron: Proof of concept and ion chamber characterization.

PURPOSE: The purpose of this work is to (a) demonstrate the feasibility of delivering a spread-out Bragg peak (SOBP) proton beam in ultra-high dose rate (FLASH) using a proton therapy synchrocyclotron as a major step toward realizing an experimental platform for preclinical studies, and (b) evaluate the response of four models of ionization chambers in such a radiation field. METHODS: A clinical Mevion HYPERSCAN® synchrocyclotron was adjusted for ultra-high dose rate proton delivery. Protons with nominal energy of 230 MeV were delivered in pulses with temporal width ranging from 12.5 µs to 24 µs spanning from conventional to FLASH dose rates. A boron carbide absorber and a range modulator block were placed in the beam path for range modulation and creating an SOBP dose profile. The radiation field was defined by a brass aperture with 11 mm diameter. Two Faraday cups were used to determine the number of protons per pulse at various dose rates. The dosimetric response of two cylindrical (IBA CC04 and CC13) and two plane-parallel (IBA PPC05 and PTW Advanced Markus® ) ionization chambers were evaluated. The dose rate was measured using the plane-parallel ionization chambers. The integral depth dose (IDD) was measured with a PTW Bragg Peak® ionization chamber. The lateral beam profile was measured with EBT-XD radiochromic film. Monte Carlo simulation was performed in TOPAS as the secondary check for the measurements and as a tool for further optimization of the range modulators' design. RESULTS: Faraday cups measurement showed that the maximum protons per pulse is 39.9 pC at 24 µs pulse width. A good agreement between the measured and simulated IDD and lateral beam profiles was observed. The cylindrical ionization chambers showed very high ion recombination and deemed not suitable for absolute dosimetry at ultra-high dose rates. The average dose rate measured using the PPC05 ionization chamber was 163 Gy/s at the pristine Bragg peak and 126 Gy/s at 1 cm depth for the SOBP beam. The SOBP beam range and modulation were measured 24.4 mm and 19 mm, respectively. The pristine Bragg peak beam had 25.6 mm range. Simulation results showed that the IDD and profile flatness can be improved by the cavity diameter of the range modulator and the number of scanned spots, respectively. CONCLUSIONS: Feasibility of delivering protons in an SOBP pattern with >100 Gy/s average dose rate using a clinical synchrocyclotron was demonstrated. The dose heterogeneity can be improved through optimization of the range modulator and number of delivered spots. Plane-parallel chambers with smaller gap between electrodes are more suitable for FLASH dosimetry compared to the other ion chambers used in this work.

Application programming interface guided QA plan generation and analysis automation.

PURPOSE: Linear accelerator quality assurance (QA) in radiation therapy is a time consuming but fundamental part of ensuring the performance characteristics of radiation delivering machines. The goal of this work is to develop an automated and standardized QA plan generation and analysis system in the Oncology Information System (OIS) to streamline the QA process. METHODS: Automating the QA process includes two software components: the AutoQA Builder to generate daily, monthly, quarterly, and miscellaneous periodic linear accelerator QA plans within the Treatment Planning System (TPS) and the AutoQA Analysis to analyze images collected on the Electronic Portal Imaging Device (EPID) allowing for a rapid analysis of the acquired QA images. To verify the results of the automated QA analysis, results were compared to the current standard for QA assessment for the jaw junction, light-radiation coincidence, picket fence, and volumetric modulated arc therapy (VMAT) QA plans across three linacs and over a 6-month period. RESULTS: The AutoQA Builder application has been utilized clinically 322 times to create QA patients, construct phantom images, and deploy common periodic QA tests across multiple institutions, linear accelerators, and physicists. Comparing the AutoQA Analysis results with our current institutional QA standard the mean difference of the ratio of intensity values within the field-matched junction and ball-bearing position detection was 0.012 ± 0.053 (P = 0.159) and is 0.011 ± 0.224 mm (P = 0.355), respectively. Analysis of VMAT QA plans resulted in a maximum percentage difference of 0.3%. CONCLUSION: The automated creation and analysis of quality assurance plans using multiple APIs can be of immediate benefit to linear accelerator quality assurance efficiency and standardization. QA plan creation can be done without following tedious procedures through API assistance, and analysis can be performed inside of the clinical OIS in an automated fashion.