Citations

PurposeMicrodosimetry is a vital tool for assessing the microscopic patterns of energy deposition by radiation, which ultimately govern biological effect. Solid‐state, silicon‐on‐insulator microdosimeters offer an approach for making microdosimetric measurements with high spatial resolution (on the order of tens of micrometers). These high‐resolution, solid‐state microdosimeters may therefore play a useful role in characterizing proton radiotherapy fields, particularly for making highly resolved measurements within the Bragg peak region. In this work, we obtain microdosimetric measurements with a solid‐state microdosimeter (MicroPlus probe) in a clinical, spot‐scanning proton beam of small spot size.MethodsThe MicroPlus probe had a 3D single sensitive volume on top of silicon oxide. The sensitive volume had an active cross‐sectional area of 250 μm × 10 μm and thickness of 10 μm. The proton facility was a synchrotron‐based, spot‐scanning system with small spot size (σ ≈ 2 mm). We performed measurements with the clinical beam current (≈1 nA) and had no detected pulse pile‐up. Measurements were made in a water‐equivalent phantom in water‐equivalent depth (WED) increments of 0.25 mm or 1.0 mm along pristine Bragg peaks of energies 71.3 MeV and 159.9 MeV, respectively. For each depth, we measured lineal energy distributions and then calculated the dose‐weighted mean lineal energy, . The measurements were repeated for two field sizes: 4 × 4 cm2 and 20 × 20 cm2.ResultsFor both 71.3 MeV and 159.9 MeV and for both field sizes, increased with depth toward the distal edge of the Bragg peak, a result consistent with Monte Carlo calculations and measurements performed elsewhere. For the 71.3 MeV, 4 × 4 cm2 beam (range at 80% distal falloff, R80 = 3.99 cm), we measured keV/μm at WED = 2 cm, and keV/μm at WED = 3.95 cm. For the 71.3 MeV, 20 × 20 cm2 beam, we measured keV/μm at WED = 2.6 cm, and keV/μm at WED = 3 cm. For the 159.9 MeV, 4 × 4 cm2 beam (R80 = 17.7 cm), keV/μm at WED = 5 cm, and keV/μm at WED = 17.6 cm. For the 159.9 MeV, 20 × 20 cm2 beam, keV/μm at WED = 5 cm, and keV/μm at WED = 17.6 cm.ConclusionsWe performed microdosimetric measurements with a novel solid‐state, silicon‐on‐insulator microdosimeter in a clinical spot‐scanning proton beam of small spot size and unmodified beam current. For all of the proton field sizes and energies considered, the measurements of were in agreement with expected trends. Furthermore, we obtained measurements with a spatial resolution of 10 μm in the beam direction. This spatial resolution greatly exceeded that possible with a conventional gaseous tissue‐equivalent proportional counter and allowed us to perform a high‐resolution investigation within the Bragg peak region. The MicroPlus probe is therefore suitable for applications in proton radiotherapy.

PurposeThis work aims to characterize a proton pencil beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon on insulator (SOI) microdosimeter with well‐defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam.MethodsA novel silicon microdosimeter with well‐defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15 keV/μm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread‐out Bragg peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth‐dose distribution from the treatment planning system (TPS) and to compare the simulated dose‐mean lineal energy to the experimental results.ResultsFor a 131 MeV PBS spot (124.6 mm R90 range in water), the measured dose‐mean lineal energy increased from 2 keV/μm at the entrance to 8 keV/μm in the BP, with a maximum value of 10 keV/μm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97 ± 0.14 at the entrance to 1.04 ± 0.09 proximal to the BP, then to 1.1 ± 0.08 in the BP, and steeply rose to 1.57 ± 0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96 ± 0.16 to 1.01 ± 0.16 at shallow depths, and 1.01 ± 0.16 to 1.28 ± 0.17 within the SOBP. The RBE significantly increased from 1.29 ± 0.17 to 1.43 ± 0.18 at the distal edge of the SOBP.ConclusionsThe SOI microdosimeter with its well‐defined 3D SV has applicability in characterizing proton radiation fields and can measure relevant physical parameters to model the RBE with submillimeter spatial resolution. It has been shown that for a physical dose of 1.82 Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy.

Abstract Introduction Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Methods Serial T1‐weighted magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed‐effects models estimated the change‐points when atrophy rates deviate from normal and the rates of change before and after this point. Results Atrophy increased after the change‐point, which occurred 1–1.5 years (assuming a single step change in atrophy rate) or 3–8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change‐point. Discussion Atrophy rates are pathologically increased up to seven years before “expected onset”. During this period, atrophy rates may be useful for inclusion and tracking of disease progression.

AbstractIn endemic regions, coccidioidomycosis causes substantial morbidity and mortality for patients receiving solid organ transplants. We aimed to demonstrate the effect of antifungal coccidioidal prophylaxis in heart transplant (HT) recipients. We retrospectively reviewed the electronic health records of all patients who received HTs between October 19, 2005, and December 13, 2014. We collected information regarding antifungal regimens and determined whether patients subsequently developed infections. Our 174‐person cohort all received antifungal prophylaxis for at least 6 months (mean follow‐up, 53.8 months). One proven and one probable coccidioidal infection (each, 0.6%) occurred during the study period. The incidence of coccidioidomycosis was 0.6% at 1 year and 2.3% at 5 years. No cases of proven coccidioidomycosis occurred within 2 years after transplantation. No patients developed disseminated disease, and no sentinel events were attributed to coccidioidomycosis. Both fluconazole and voriconazole were well tolerated. In the absence of intolerance or contraindication, we suggest continuing a universal antifungal prophylactic regimen with fluconazole for at least 6‐12 months in HT recipients residing in a coccidioidomycosis‐endemic area.

PurposeThe vast majority of body CT exams are performed with automatic exposure control (AEC), which adapts the mean tube current to the patient size and modulates the tube current either angularly, longitudinally or both. However, most radiation dose estimation tools are based on fixed tube current scans. Accurate estimates of patient dose from AEC scans require knowledge of the tube current values, which is usually unavailable. The purpose of this work was to develop and validate methods to accurately estimate the tube current values prescribed by one manufacturer's AEC system to enable accurate estimates of patient dose.MethodsMethods were developed that took into account available patient attenuation information, user selected image quality reference parameters and x‐ray system limits to estimate tube current values for patient scans. Methods consistent with AAPM Report 220 were developed that used patient attenuation data that were: (a) supplied by the manufacturer in the CT localizer radiograph and (b) based on a simulated CT localizer radiograph derived from image data. For comparison, actual tube current values were extracted from the projection data of each patient. Validation of each approach was based on data collected from 40 pediatric and adult patients who received clinically indicated chest (n = 20) and abdomen/pelvis (n = 20) scans on a 64 slice multidetector row CT (Sensation 64, Siemens Healthcare, Forchheim, Germany). For each patient dataset, the following were collected with Institutional Review Board (IRB) approval: (a) projection data containing actual tube current values at each projection view, (b) CT localizer radiograph (topogram) and (c) reconstructed image data. Tube current values were estimated based on the actual topogram (actual‐topo) as well as the simulated topogram based on image data (sim‐topo). Each of these was compared to the actual tube current values from the patient scan. In addition, to assess the accuracy of each method in estimating patient organ doses, Monte Carlo simulations were performed by creating voxelized models of each patient, identifying key organs and incorporating tube current values into the simulations to estimate dose to the lungs and breasts (females only) for chest scans and the liver, kidney, and spleen for abdomen/pelvis scans. Organ doses from simulations using the actual tube current values were compared to those using each of the estimated tube current values (actual‐topo and sim‐topo).ResultsWhen compared to the actual tube current values, the average error for tube current values estimated from the actual topogram (actual‐topo) and simulated topogram (sim‐topo) was 3.9% and 5.8% respectively. For Monte Carlo simulations of chest CT exams using the actual tube current values and estimated tube current values (based on the actual‐topo and sim‐topo methods), the average differences for lung and breast doses ranged from 3.4% to 6.6%. For abdomen/pelvis exams, the average differences for liver, kidney, and spleen doses ranged from 4.2% to 5.3%.ConclusionsStrong agreement between organ doses estimated using actual and estimated tube current values provides validation of both methods for estimating tube current values based on data provided in the topogram or simulated from image data.

ABSTRACT Various types of radiation are utilized in the treatment of cancer. Equal physical doses of different radiation types do not always result in the same amount of biological damage. In order to account for these differences, a scaling factor known as the relative biological effectiveness (RBE) can be used. 137Cesium (137Cs) has been used as a source of radiation in a significant body of radiation therapy research. However, high-energy X-rays, such as 6 MV X-rays, are currently used clinically to treat patients. To date, there is a gap in the literature regarding the RBE comparison of these two types of radiation. Therefore, the purpose of this study was to investigate the RBE of 137Cs relative to that of 6 MV X-rays. To determine the RBE, five cell lines were irradiated [Chinese hamster ovary (CHO); human lung adenocarcinoma (A549); human glioma (U251); human glioma (T98); and human osteosarcoma (U2OS)] by both types of radiation and assessed for cell survival using a clonogenic assay. Three of the five cell lines resulted in RBE values of ~1.00 to within 11% for all survival fractions, showing the physical and biological dose for these two types of radiation were equivalent. The other two cell lines gave RBE values differing from 1.00 by up to 36%. In conclusion, the results show the range in biological effect seen between cell lines, and therefore cell type must be considered when characterizing RBE.