Time structures of proton pencil beam scanning delivery on a microsecond scale measured with a pixelated semiconductor detector Timepix3.

PURPOSE: The time structures of proton spot delivery in proton pencil beam scanning (PBS) radiation therapy are essential in many clinical applications. This study aims to characterize the time structures of proton PBS delivered by both synchrotron and synchrocyclotron accelerators using a non-invasive technique based on scattered particle tracking. METHODS: A pixelated semiconductor detector, AdvaPIX-Timepix3, with a temporal resolution of 1.56 ns, was employed to measure time of arrival of secondary particles generated by a proton beam. The detector was placed laterally to the high-flux area of the beam in order to allow for single particle detection and not interfere with the treatment. The detector recorded counts of radiation events, their deposited energy and the timestamp associated with the single events. Individual recorded events and their temporal characteristics were used to analyze beam time structures, including energy layer switch time, magnet switch time, spot switch time, and the scanning speeds in the x and y directions. All the measurements were repeated 30 times on three dates, reducing statistical uncertainty. RESULTS: The uncertainty of the measured energy layer switch times, magnet switch time, and the spot switch time were all within 1% of average values. The scanning speeds uncertainties were within 1.5% and are more precise than previously reported results. The measurements also revealed continuous sub-milliseconds proton spills at a low dose rate for the synchrotron accelerator and radiofrequency pulses at 7 µs and 1 ms repetition time for the synchrocyclotron accelerator. CONCLUSION: The AdvaPIX-Timepix3 detector can be used to directly measure and monitor time structures on microseconds scale of the PBS proton beam delivery. This method yielded results with high precision and is completely independent of the machine log files.

Simulation-based education for transfusion medicine.

BACKGROUND: The administration of blood products is frequently determined by physicians without subspecialty training in transfusion medicine (TM). Education in TM is necessary for appropriate utilization of resources and maintaining patient safety. Our institution developed an efficient simulation-based TM course with the goal of identifying key topics that could be individualized to learners of all levels in various environments while also allowing for practice in an environment where the patient is not placed at risk. STUDY DESIGN AND METHODS: A 2.5-hour simulation-based educational activity was designed and taught to undergraduate medical students rotating through anesthesiology and TM elective rotations and to all Clinical Anesthesia Year 1 (CA-1) residents. Content and process evaluation of the activity consisted of multiple-choice tests and course evaluations. RESULTS: Seventy medical students and seven CA-1 residents were enrolled in the course. There was no significant difference on pretest results between medical students and CA-1 residents. The posttest results for both medical students and CA-1 residents were significantly higher than pretest results. The results of the posttest between medical students and CA-1 residents were not significantly different. CONCLUSION: The TM knowledge gap is not a trivial problem as transfusion of blood products is associated with significant risks. Innovative educational techniques are needed to address the ongoing challenges with knowledge acquisition and retention in already full curricula. Our institution developed a feasible and effective way to integrate TM into the curriculum. Educational activities, such as this, might be a way to improve the safety of transfusions.

Particle tracking, recognition and LET evaluation of out-of-field proton therapy delivered to a phantom with implants.

Objective.This study aims to assess the composition of scattered particles generated in proton therapy for tumors situated proximal to some titanium (Ti) dental implants. The investigation involves decomposing the mixed field and recording Linear Energy Transfer (LET) spectra to quantify the influence of metallic dental inserts located behind the tumor.Approach.A therapeutic conformal proton beam was used to deliver the treatment plan to an anthropomorphic head phantom with two types of implants inserted in the target volume (made of Ti and plastic, respectively). The scattered radiation resulted during the irradiation was detected by a hybrid semiconductor pixel detector MiniPIX Timepix3 that was placed distal to the Spread-out Bragg peak. Visualization and field decomposition of stray radiation were generated using algorithms trained in particle recognition based on artificial intelligence neural networks (AI NN). Spectral sensitive aspects of the scattered radiation were collected using two angular positions of the detector relative to the beam direction: 0° and 60°.Results.Using AI NN, 3 classes of particles were identified: protons, electrons & photons, and ions & fast neutrons. Placing a Ti implant in the beam's path resulted in predominantly electrons and photons, contributing 52.2% of the total number of detected particles, whereas for plastic implants, the contribution was 65.4%. Scattered protons comprised 45.5% and 31.9% with and without metal inserts, respectively. The LET spectra were derived for each group of particles identified, with values ranging from 0.01 to 7.5 keVµm-1for Ti implants/plastic implants. The low-LET component was primarily composed of electrons and photons, while the high-LET component corresponded to protons and ions.Significance.This method, complemented by directional maps, holds the potential for evaluating and validating treatment plans involving stray radiation near organs at risk, offering precise discrimination of the mixed field, and enhancing in this way the LET calculation.

Characterizing devices for validation of dose, dose rate, and LET in ultra high dose rate proton irradiations.

BACKGROUND: Ultra high dose rate (UHDR) radiotherapy using ridge filter is a new treatment modality known as conformal FLASH that, when optimized for dose, dose rate (DR), and linear energy transfer (LET), has the potential to reduce damage to healthy tissue without sacrificing tumor killing efficacy via the FLASH effect. PURPOSE: Clinical implementation of conformal FLASH proton therapy has been limited by quality assurance (QA) challenges, which include direct measurement of UHDR and LET. Voxel DR distributions and LET spectra at planning target margins are paramount to the DR/LET-related sparing of organs at risk. We hereby present a methodology to achieve experimental validation of these parameters. METHODS: Dose, DR, and LET were measured for a conformal FLASH treatment plan involving a 250-MeV proton beam and a 3D-printed ridge filter designed to uniformly irradiate a spherical target. We measured dose and DR simultaneously using a 4D multi-layer strip ionization chamber (MLSIC) under UHDR conditions. Additionally, we developed an "under-sample and recover (USRe)" technique for a high-resolution pixelated semiconductor detector, Timepix3, to avoid event pile-up and to correct measured LET at high-proton-flux locations without undesirable beam modifications. Confirmation of these measurements was done using a MatriXX PT detector and by Monte Carlo (MC) simulations. RESULTS: MC conformal FLASH computed doses had gamma passing rates of >95% (3 mm/3% criteria) when compared to MatriXX PT and MLSIC data. At the lateral margin, DR showed average agreement values within 0.3% of simulation at 100 Gy/s and fluctuations ∼10% at 15 Gy/s. LET spectra in the proximal, lateral, and distal margins had Bhattacharyya distances of <1.3%. CONCLUSION: Our measurements with the MLSIC and Timepix3 detectors shown that the DR distributions for UHDR scenarios and LET spectra using USRe are in agreement with simulations. These results demonstrate that the methodology presented here can be used effectively for the experimental validation and QA of FLASH treatment plans.

Thermal neutron detection and track recognition method in reference and out-of-field radiotherapy FLASH electron fields using Timepix3 detectors.

Objective.This work presents a method for enhanced detection, imaging, and measurement of the thermal neutron flux.Approach. Measurements were performed in a water tank, while the detector is positioned out-of-field of a 20 MeV ultra-high pulse dose rate electron beam. A semiconductor pixel detector Timepix3 with a silicon sensor partially covered by a6LiF neutron converter was used to measure the flux, spatial, and time characteristics of the neutron field. To provide absolute measurements of thermal neutron flux, the detection efficiency calibration of the detectors was performed in a reference thermal neutron field. Neutron signals are recognized and discriminated against other particles such as gamma rays and x-rays. This is achieved by the resolving power of the pixel detector using machine learning algorithms and high-resolution pattern recognition analysis of the high-energy tracks created by thermal neutron interactions in the converter.Main results. The resulting thermal neutrons equivalent dose was obtained using conversion factor (2.13(10) pSv·cm2) from thermal neutron fluence to thermal neutron equivalent dose obtained by Monte Carlo simulations. The calibrated detectors were used to characterize scattered radiation created by electron beams. The results at 12.0 cm depth in the beam axis inside of the water for a delivered dose per pulse of 1.85 Gy (pulse length of 2.4µs) at the reference depth, showed a contribution of flux of 4.07(8) × 103particles·cm-2·s-1and equivalent dose of 1.73(3) nSv per pulse, which is lower by ∼9 orders of magnitude than the delivered dose.Significance. The presented methodology for in-water measurements and identification of characteristic thermal neutrons tracks serves for the selective quantification of equivalent dose made by thermal neutrons in out-of-field particle therapy.

Out-of-field measurements and simulations of a proton pencil beam in a wide range of dose rates using a Timepix3 detector: Dose rate, flux and LET.

Stray radiation produced by ultra-high dose-rates (UHDR) proton pencil beams is characterized using ASIC-chip semiconductor pixel detectors. A proton pencil beam with an energy of 220 MeV was utilized to deliver dose rates (DR) ranging from conventional radiotherapy DRs up to 270 Gy/s. A MiniPIX Timepix3 detector equipped with a silicon sensor and integrated readout electronics was used. The chip-sensor assembly and chipboard on water-equivalent backing were detached and immersed in the water-phantom. The deposited energy, particle flux, DR, and the linear energy transfer (LET(Si)) spectra were measured in the silicon sensor at different positions both laterally, at different depths, and behind the Bragg peak. At low-intensity beams, the detector is operated in the event-by-event data-driven mode for high-resolution spectral tracking of individual particles. This technique provides precise energy loss response and LET(Si) spectra with radiation field composition resolving power. At higher beam intensities a rescaling of LET(Si) can be performed as the distribution of the LET(Si) spectra exhibits the same characteristics regardless of the delivered DR. The integrated deposited energy and the absorbed dose can be thus measured in a wide range. A linear response of measured absorbed dose was obtained by gradually increasing the delivered DR to reach UHDR beams. Particle tracking of scattered radiation in data-driven mode could be performed at DRs up to 0.27 Gy/s. In integrated mode, the saturation limits were not reached at the measured out-of-field locations up to the delivered DR of over 270 Gy/s. A good agreement was found between measured and simulated absorbed doses.

Measurement of the time structure of FLASH beams using prompt gamma rays and secondary neutrons as surrogates.

Objective. The aim of this study was to investigate the feasibility of online monitoring of irradiation time (IRT) and scan time for FLASH proton radiotherapy using a pixelated semiconductor detector.Approach. Measurements of the time structure of FLASH irradiations were performed using fast, pixelated spectral detectors based on the Timepix3 (TPX3) chips with two architectures: AdvaPIX-TPX3 and Minipix-TPX3. The latter has a fraction of its sensor coated with a material to increase sensitivity to neutrons. With little or no dead time and an ability to resolve events that are closely spaced in time (tens of nanoseconds), both detectors can accurately determine IRTs as long as pulse pile-up is avoided. To avoid pulse pile-up, the detectors were placed well beyond the Bragg peak or at a large scattering angle. Prompt gamma rays and secondary neutrons were registered in the detectors' sensors and IRTs were calculated based on timestamps of the first charge carriers (beam-on) and the last charge carriers (beam-off). In addition, scan times inx,y, and diagonal directions were measured. The experiment was carried out for various setups: (i) a single spot, (ii) a small animal field, (iii) a patient field, and (iv) an experiment using an anthropomorphic phantom to demonstratein vivoonline monitoring of IRT. All measurements were compared to vendor log files.Main results. Differences between measurements and log files for a single spot, a small animal field, and a patient field were within 1%, 0.3% and 1%, respectively.In vivomonitoring of IRTs (95-270 ms) was accurate within 0.1% for AdvaPIX-TPX3 and within 6.1% for Minipix-TPX3. The scan times inx,y, and diagonal directions were 4.0, 3.4, and 4.0 ms, respectively.Significance. Overall, the AdvaPIX-TPX3 can measure FLASH IRTs within 1% accuracy, indicating that prompt gamma rays are a good surrogate for primary protons. The Minipix-TPX3 showed a somewhat higher discrepancy, likely due to the late arrival of thermal neutrons to the detector sensor and lower readout speed. The scan times (3.4 ± 0.05 ms) in the 60 mm distance ofy-direction were slightly less than (4.0 ± 0.06 ms) in the 24 mm distance ofx-direction, confirming the much faster scanning speed of the Y magnets than that of X. Diagonal scan speed was limited by the slower X magnets.

Single proton LET characterization with the Timepix detector and artificial intelligence for advanced proton therapy treatment planning.

Objective.Protons have advantageous dose distributions and are increasingly used in cancer therapy. At the depth of the Bragg peak range, protons produce a mixed radiation field consisting of low- and high-linear energy transfer (LET) components, the latter of which is characterized by an increased ionization density on the microscopic scale associated with increased biological effectiveness. Prediction of the yield and LET of primary and secondary charged particles at a certain depth in the patient is performed by Monte Carlo simulations but is difficult to verify experimentally.Approach.Here, the results of measurements performed with Timepix detector in the mixed radiation field produced by a therapeutic proton beam in water are presented and compared to Monte Carlo simulations. The unique capability of the detector to perform high-resolution single particle tracking and identification enhanced by artificial intelligence allowed to resolve the particle type and measure the deposited energy of each particle comprising the mixed radiation field. Based on the collected data, biologically important physics parameters, the LET of single protons and dose-averaged LET, were computed.Main results.An accuracy over 95% was achieved for proton recognition with a developed neural network model. For recognized protons, the measured LET spectra generally agree with the results of Monte Carlo simulations. The mean difference between dose-averaged LET values obtained from measurements and simulations is 17%. We observed a broad spectrum of LET values ranging from a fraction of keVµm-1to about 10 keVµm-1for most of the measurements performed in the mixed radiation fields.Significance.It has been demonstrated that the introduced measurement method provides experimental data for validation of LETDor LET spectra in any treatment planning system. The simplicity and accessibility of the presented methodology make it easy to be translated into a clinical routine in any proton therapy facility.

Monte Carlo modelling of pixel clusters in Timepix detectors using the MCNP code.

The track structure of the signal measured by the semiconductor pixel detector Timepix3 was modelled in the Monte Carlo MCNP® code. A detailed model at the pixel-level (256 × 256 pixels, 55 × 55 µm2 pixel size) was developed and used to generate and store clusters of adjacent hit pixels observed in the measured data because of particle energy deposition path, charge sharing, and drift processes. An analytical model of charge sharing effect and the detector energy resolution was applied to the simulated data. The method will help the user sort the measured clusters and distinguish radiation components of mixed fields by determining the response of Timepix3 detector to particular particle types, energies, and incidence angles that cannot be measured separately.

Predicting improvement in urinary and bowel incontinence for home health patients using electronic health record data.

PURPOSE: The purpose of the study was to discover which patient and support system characteristics and interventions documented by home health clinicians were associated with improvement in urinary and bowel incontinence contrasting logistic regression and data mining approaches. SUBJECTS AND SETTING: Seventeen hundred ninety-three patients in this study experienced 2072 episodes of care. The study sample comprised all nonmaternity patients aged 18 years or older receiving skilled home health services in 2004. Subjects were drawn from a convenience sample of 15 home health agencies . DESIGN: We completed a secondary analysis of data from 15 home health agencies' electronic health records. Data for this study were documented by home care clinicians using the Outcome and Assessment Information Set (OASIS) structured assessment form and the Omaha System interventions, which is a standardized terminology. RESULTS: There were 684 patients with urinary incontinence and 187 with bowel incontinence. By discharge 38% improved in urinary incontinence and 45% improved their bowel incontinence. Using logistic regression, no patient or support system characteristics were identified that associated with improvement in either urinary or bowel incontinence, only a limited number of interventions were significant. A data mining decision tree was producible only for bowel incontinence, demonstrating a combination of patient and support system factors as well as selected interventions were important in determining whether patients would improve in bowel incontinence. CONCLUSIONS: Home health patients have complex comorbid conditions requiring home care nurses to have broad, generalized knowledge. Future research is needed to determine if the inclusion of a certified WOC nurse would improve outcomes.

A novel proton counting detector and method for the validation of tissue and implant material maps for Monte Carlo dose calculation.

The presence of artificial implants complicates the delivery of proton therapy due to inaccurate characterization of both the implant and the surrounding tissues. In this work, we describe a method to characterize implant and human tissue mimicking materials in terms of relative stopping power (RSP) using a novel proton counting detector. Each proton is tracked by directly measuring the deposited energy along the proton track using a fast, pixelated spectral detector AdvaPIX-TPX3 (TPX3). We considered three scenarios to characterize the RSPs. First, in-air measurements were made in the presence of metal rods (Al, Ti and CoCr) and bone. Then, measurements of energy perturbations in the presence of metal implants and bone in an anthropomorphic phantom were performed. Finally, sampling of cumulative stopping power (CSP) of the phantom were made at different locations of the anthropomorphic phantom. CSP and RSP information were extracted from energy spectra at each beam path. To quantify the RSP of metal rods we used the shift in the most probable energy (MPE) of CSP from the reference CSP without a rod. Overall, the RSPs were determined as 1.48, 2.06, 3.08, and 5.53 from in-air measurements; 1.44, 1.97, 2.98, and 5.44 from in-phantom measurements, for bone, Al, Ti and CoCr, respectively. Additionally, we sampled CSP for multiple paths of the anthropomorphic phantom ranging from 18.63 to 25.23 cm deriving RSP of soft tissues and bones in agreement within 1.6% of TOPAS simulations. Using minimum error of these multiple CSP, optimal mass densities were derived for soft tissue and bone and they are within 1% of vendor-provided nominal densities. The preliminary data obtained indicates the proposed novel method can be used for the validation of material and density maps, required by proton Monte Carlo Dose calculation, provided by competing multi-energy computed tomography and metal artifact reduction techniques.

The feasibility of integrating the Omaha system data across home care agencies and vendors.

Federal and state initiatives are aligning around the goal that by 2014 all Americans will have electronic health records to support access to their health information any time and anywhere. As a key healthcare provider, nursing data must be included to enhance patient safety, effectiveness, and efficiency of care that is patient-centric. The purpose of this study was to test the feasibility of abstracting, integrating, and comparing the effective use of a standardized terminology, the Omaha System, across software vendors and 15 home care agencies. Results showed that the 2900 patients in this study had an average of four problems on care plans, with interventions most frequently addressing surveillance (39%) and teaching (30%). Findings in this study support the feasibility of integrating data across software vendors and agencies as well as the usefulness for describing care provided in home care. However, before exchanging data across systems, data quality issues found in this study need attention. There were missing data for 10.8% of patients as well as concerns about the validity of using the problem rating scale for outcomes. Strategies for effective use of standardized nursing terminologies are recommended.

Variation in detection of adenomas and polyps by colonoscopy and change over time with a performance improvement program.

BACKGROUND & AIMS: There has been no prospective, community-based study to track changes in adenoma detection by individual physicians over time and to determine the effectiveness of targeted educational interventions. METHODS: We prospectively collected information on 47,253 screening colonoscopies in average-risk individuals 50 years and older performed by a community-based practice in the Twin Cities of Minnesota. During a period of 3 years, 5 specific interventions were implemented; each was designed to improve adenoma detection rates. Controlling for patient-related and procedure-related factors, rates of adenoma detection and 3-year trends for individual physicians were plotted, and intraclass correlation coefficients were calculated. Generalized estimating equations were used to identify factors associated with detection of adenomas and polyps. RESULTS: At least 1 polyp and 1 adenoma were found in 36% and 22% of examinations, respectively. Adenoma detection rates by endoscopists ranged from 10%-39%. There was no significant improvement during the study period despite planned, systematic interventions. Factors associated with adenoma detection included age of the patient (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.02), male sex (OR, 1.53; 95% CI, 1.34-1.74), and adequate preparation quality (OR, 2.26; 95% CI, 1.64-3.12). CONCLUSIONS: The detection of adenomas by individual physicians during a 3-year period varied and did not appear to change between individual endoscopists, despite planned, systematic interventions. This indicates that other targeted interventions might be required to improve adenoma detection rates among experienced, community gastroenterologists.

Inadequate antibiotic therapy in solid organ transplant recipients is associated with a higher mortality rate.

BACKGROUND: Inadequate antibiotic therapy and failure to administer antibiotics in a timely fashion have been associated with substantial mortality rates in patients in the intensive care unit (ICU). We analyzed the infection pattern in solid organ transplant recipients as well as the impact of antibiotic resistance and inadequate antibiotic treatment on mortality rates and morbidity outcomes. METHODS: Charts of adult solid organ transplant recipients in 2006 from a single institution were reviewed. Data on patients with bacterial and fungal infections acquired within one year after transplantation were compared with the primary outcome of death within 28 days. Statistical analysis included nonparametric tests (Wilcoxon rank sum, Fisher exact, and chi-square) and multivariable logistic regression with p < 0.05 considered significant. RESULTS: Of the 366 patients, 114 (31%) had a total of 208 bacterial or fungal infections, and 44 of them (39%) were admitted to the ICU. Our primary endpoint, the 28-day mortality rate, was 8% overall, whereas the six-month mortality rate was 11%. Patients treated inadequately with antibiotics had a significantly higher mortality rate. The leading causes of infection were multiple organisms, coagulase-negative Staphylococcus, and E. coli, of which 76% were resistant to antibiotics. Antibiotic-resistant infections were associated with longer hospital stays (p = 0.04), intravenous antibiotic use prior to infection (p = 0.04), nucleotide synthesis inhibitor use (p = 0.02), ICU admission (p < 0.01), and respiratory failure (p = 0.03). Most infections were treated inadequately initially (69%) but treated adequately at 24 h (56%). Inadequate antibiotic treatment was significantly associated with younger age (p = 0.04), prior intravenous antibiotic use (p = 0.04), longer stay prior to infection (p = 0.05), and cardiovascular shock (p = 0.014). Inadequate antibiotic therapy at 24 h was associated with a higher mortality rate (14% vs. 2%; p = 0.03) and a trend toward longer ICU and in-hospital stays. CONCLUSIONS: Most bacterial and fungal infections were resistant to antibiotics and were treated inadequately initially. Prior intravenous antibiotic use and longer stay prior to infection were associated with antibiotic resistance and inadequate antibiotic therapy. Failure to provide adequate antibiotic treatment within 24 h had a significant impact on the 28-day mortality rate and was associated with other detrimental clinical outcomes.

Predictive modeling for improving incontinence and pressure ulcers in homecare patients.

A comparison of traditional statistical techniques and knowledge discovery in database techniques is presented for examining risk factors and interventions predictive of incontinence and pressure ulcers for homecare patients. The data set consists of OASIS (Outcome and Assessment Information Set) and intervention data from the Omaha System from 15 homecare agencies.

Defining medication complexity and its effect on outcomes in community dwelling elders receiving home care.

Complexity of medication regimens in community dwelling elders is examined in relationship to emergent care use, hospitalization and self management of medications in this secondary data analysis of OASIS data and medication data from all 2004 open admissions to 15 home health care agencies. Preliminary findings and the use of innovative techniques are discussed highlighting the predictive potential for medication complexity in other settings, risk stratification, and design implications for both clinical tools and databases.

Decline in esophageal candidiasis and use of antimycotics in European patients with HIV.

BACKGROUND: Esophageal candidiasis (EC) remains one of the most common AIDS defining illnesses in patients with human immunodeficiency virus (HIV) in the era of highly active antiretroviral therapy (HAART), but little is known about factors associated with EC after starting HAART. OBJECTIVES: To describe changes in the use of antimycotic medication, the incidence of EC and factors associated with EC before and after starting HAART. METHODS: Patients from EuroSIDA, a pan-European longitudinal, prospective observational study. Generalized linear models and poisson regression models were used to investigate the relationships. RESULTS: A total of 9,873 patients did not have EC at recruitment, subsequently 537 (15.8%) developed EC. The proportion of patients taking any antimycotic dropped from 18% at January 1995 to 2% at January 2004 (p < 0.0001); the duration of treatment declined from 10 to 3 months over the same period (p < 0.0001). There was a 32% annual decline in the incidence of EC (95% CI 30-35%, p < 0.0001). There was a significant annual decline in the incidence of EC pre-HAART in time-updated, adjusted models, (incidence rate ratio (IRR) 0.80, 95% CI 0.76-0.85, p < 0.0001) but not post-HAART (IRR 0.97; 95% CI 0.90-1.06, p= 0.54). Older patients and those with low CD4 counts had the greatest incidence of EC in the post-HAART era. CONCLUSIONS: There has been a marked decline in the incidence of EC between 1994 and 2004. This was accompanied by a decline in markers associated with fungal disease, including use of antimycotics and a decline in duration of treatment.