Dupilumab-associated ocular surface disease is characterized by a shift from Th2/Th17 toward Th1/Th17 inflammation.

BACKGROUND: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. METHODS: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non-AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology. RESULTS: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL-12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non-AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome. CONCLUSIONS: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD.

Effect of scattered megavoltage x-rays on markerless tumor tracking using dual energy kilovoltage imaging.

PURPOSE: To determine the effect of megavoltage (MV) scatter on the accuracy of markerless tumor tracking (MTT) for lung tumors using dual energy (DE) imaging and to consider a post-processing technique to mitigate the effects of MV scatter on DE-MTT. METHODS: A Varian TrueBeam linac was used to acquire a series of interleaved 60/120 kVp images of a motion phantom with simulated tumors (10 and 15 mm diameter). Two sets of consecutive high/low energy projections were acquired, with and without MV beam delivery. The MV field sizes (FS) ranged from 2 × 2 cm2 -6 × 6 cm2 in steps of 1 × 1 cm2 . Weighted logarithmic subtraction was performed on sequential images to produce soft-tissue images for kV only (DEkV ) and kV with MV beam on (DEkV+MV ). Wavelet and fast Fourier transformation filtering (wavelet-FFT) was used to remove stripe noise introduced by MV scatter in the DE images ( DE kV + MV Corr ${\rm{DE}}_{{\rm{kV}} + {\rm{MV}}}^{{\rm{Corr}}}$ ). A template-based matching algorithm was then used to track the target on DEkV, DEkV+MV , and DE kV + MV Corr ${\rm{DE}}_{{\rm{kV}} + {\rm{MV}}}^{{\rm{Corr}}}$ images. Tracking accuracy was evaluated using the tracking success rate (TSR) and mean absolute error (MAE). RESULTS: For the 10 and 15 mm targets, the TSR for DEkV images was 98.7% and 100%, and MAE was 0.53 and 0.42 mm, respectively. For the 10 mm target, the TSR, including the effects of MV scatter, ranged from 86.5% (2 × 2 cm2 ) to 69.4% (6 × 6 cm2 ), while the MAE ranged from 2.05 mm to 4.04 mm. The application of wavelet-FFT algorithm to remove stripe noise ( DE kV + MV Corr ${\rm{DE}}_{{\rm{kV}} + {\rm{MV}}}^{{\rm{Corr}}}$ ) resulted in TSR values of 96.9% (2 × 2 cm2 ) to 93.4% (6 × 6 cm2 ) and subsequent MAE values were 0.89 mm to 1.37 mm. Similar trends were observed for the 15 mm target. CONCLUSION: MV scatter significantly impacts the tracking accuracy of lung tumors using DE images. Wavelet-FFT filtering can improve the accuracy of DE-MTT during treatment.

Effect of topical application of platelet-rich plasma on chronic venous leg ulcerations.

Wound products that reliably support healing of chronic leg ulcers remain a huge unmet need in clinical practice. Due to the lack of standardized comparable protocols and different systems for platelet-rich plasma (PRP) preparation, there is limited data on healing rates in chronic venous ulcers. In our case series with a total of seven chronic leg ulcers in four patients, we investigated the healing rates based on standardized digital photographs of chronic venous ulcers after application of topical PRP using a digital imaging software. In 5 out of 7 ulcers, the PRP-treated wound half showed faster healing as compared the control half of the wound. In this case series, PRP-treated sides of chronic venous leg ulcers showed a tendency for accelerated healing as compared to nontreated collateral wound side. Our data support the evaluation of topical PRP treatment in the management of chronic venous leg ulcers.

Effect of different noise reduction techniques and template matching parameters on markerless tumor tracking using dual-energy imaging.

PURPOSE: To evaluate the impact of various noise reduction algorithms and template matching parameters on the accuracy of markerless tumor tracking (MTT) using dual-energy (DE) imaging. METHODS: A Varian TrueBeam linear accelerator was used to acquire a series of alternating 60 and 120 kVp images (over a 180° arc) using fast kV switching, on five early-stage lung cancer patients. Subsequently, DE logarithmic weighted subtraction was performed offline on sequential images to remove bone. Various noise reduction techniques-simple smoothing, anticorrelated noise reduction (ACNR), noise clipping (NC), and NC-ACNR-were applied to the resultant DE images. Separately, tumor templates were generated from the individual planning CT scans, and band-pass parameter settings for template matching were varied. Template tracking was performed for each combination of noise reduction techniques and templates (based on band-pass filter settings). The tracking success rate (TSR), root mean square error (RMSE), and missing frames (percent unable to track) were evaluated against the estimated ground truth, which was obtained using Bayesian inference. RESULTS: DE-ACNR, combined with template band-pass filter settings of σlow  = 0.4 mm and σhigh  = 1.6 mm resulted in the highest TSR (87.5%), RMSE (1.40 mm), and a reasonable amount of missing frames (3.1%). In comparison to unprocessed DE images, with optimized band-pass filter settings of σlow  = 0.6 mm and σhigh  = 1.2 mm, the TSR, RMSE, and missing frames were 85.3%, 1.62 mm, and 2.7%, respectively. Optimized band-pass filter settings resulted in improved TSR values and a lower missing frame rate for both unprocessed DE and DE-ACNR as compared to the use previously published band-pass parameters based on single energy kV images. CONCLUSION: Noise reduction strategies combined with the optimal selection of band-pass filter parameters can improve the accuracy and TSR of MTT for lung tumors when using DE imaging.

Patterns among Patients with Chronic Pruritus: A Retrospective Analysis of 170 Patients.

Chronic pruritus profoundly affects patients' quality of life. The objective of this retrospective cross-sectional study was to characterize patients with chronic pruritus and identify patterns, in order to delineate a better diagnostic approach. Both semantic connectivity map and classical analysis were applied, linking demographic, clinical, laboratory and histopathological data with clinical and aetiological categories of 170 patients with chronic pruritus (median age 72 years, 58.2% women). The semantic map showed clinical categories separated in different hubs associated with distinct patterns concerning sex, aetiology, laboratory findings, and pharmacological treatment. Diabetes, diagnosis of cancer and psychiatric comorbidities were linked with certain clinical categories. Skin eosinophilia was a common finding of chronic pruritus, on both diseased and non-diseased skin. High frequencies of patients with chronic pruritus taking anti-arrhythmics, beta-blockers and AT-II receptor antagonists were noticed among those with underlying systemic, neurological and psychiatric diseases. This study provides a complex analysis of chronic pruritus and thus basic principles for a clinical work-up.

Technical note: TIGRE-DE for the creation of virtual monoenergetic images from dual-energy cone-beam CT.

BACKGROUND: Dual-energy (DE)-CBCT represents a promising imaging modality that can produce virtual monoenergetic (VM) CBCT images. VM images, which provide enhanced contrast and reduced imaging artifacts, can be used to assist in soft-tissue visualization during image-guided radiotherapy. PURPOSE: This work reports the development of TIGRE-DE, a module in the open-source TIGRE toolkit for the performance of DE-CBCT and the production of VM CBCT images. This module is created to make DE-CBCT tools accessible in a wider range of clinical and research settings. METHODS: We developed an add-on (TIGRE-DE) to the TIGRE toolkit that performs DE material decomposition. To verify its performance, sequential CBCT scans at 80 and 140 kV of a Catphan 604 phantom were decomposed into equivalent thicknesses of aluminum (Al) and polymethyl-methylacrylate (PMMA) basis materials. These basis material projections were used to synthesize VM projections for a range of x-ray energies, which were then reconstructed using the Feldkamp-Davis-Kress (FDK) algorithm. Image quality was assessed by computing Hounsfield units (HU) and contrast-to-noise ratios (CNR) for the material inserts of the phantom and comparing with the constituent 80 and 140 kV images. RESULTS: All VM images generated using TIGRE-DE showed good general agreement with the theoretical HU values of the material inserts of the phantom. Apart from the highest-density inserts imaged at the extremes of the energy range, the measured HU values agree with theoretical HUs within the clinical tolerance of ±50 HU. CNR measurements for the various inserts showed that, of the energies selected, 60 keV provided the highest CNR values. Moreover, 60 keV VM images showed average CNR enhancements of 63% and 66% compared to the 80 and 140 kV full-fan protocols. CONCLUSIONS: TIGRE-DE successfully implements DE-CBCT material decomposition and VM image creation in an accessible, open-source platform.

A kV-MV approach to CBCT metal artifact reduction using multi-layer MV-CBCT.

Objective. To demonstrate that complete cone beam CT (CBCT) scans from both MV-energy and kV-energy LINAC sources can reduce metal artifacts in radiotherapy guidance, while maintaining standard-of-care x-ray doses levels.Approach. MV-CBCT and kV-CBCT scans are acquired at half normal dose. The impact of lowered dose on MV-CBCT data quality is mitigated by the use of a 4-layer MV-imager prototype and reduced LINAC energy settings (2.5 MV) to improve photon capture. Additionally, the MV-CBCT is used to determine the 3D position and pose of metal implants, which in turn is used to guide model-based poly-energetic correction and interleaving of the kV-CBCT and MV-CBCT data. Certain edge-preserving regularization steps incorporated into the model-based correction algorithm further reduce MV data noise.Main results. The method was tested in digital phantoms and a real pelvis phantom with large 2.5″ spherical inserts, emulating hip replacements of different materials. The proposed method demonstrated an appealing compromise between the high contrast of kV-CBCT and low artifact content of MV-CBCT. Contrast-to-noise improved 3-fold compared to MV-CBCT with a clinical 1-layer architecture at matched dose (37 mGy) and edge blur levels. Visual delineation of the bladder and prostate improved noteably over kV- or MV-CBCT alone.Significance. The proposed method demonstrates that a full MV-CBCT scan can be combined with kV-CBCT to reduce metal artifacts without resorting to complicated beam collimation strategies to limit the MV-CBCT dose contribution. Additionally, significant improvements in CNR can be achieved as compared to metal artifact reduction through current clinical MV-CBCT practices.

[COVID 19 - Hospital Admission in the First and Second Wave in Germany]. / COVID 19 ­ Hospitalisierung in der ersten und zweiten Welle.

PURPOSE: We analyzed patients' characteristics and hospital admission in Germany's first and second COVID 19 wave. METHODS: We include all patients hospitalized with the proven diagnosis COVID 19 admitted to the HELIOS Hospital Krefeld, Germany, in the first wave (n = 84; from 11.03.2020-30.06.2020) and the second wave (n = 344; from 01.07.2020-31.01.2021). RESULTS: Patients' age, gender and comorbidities were similar with the exception of venous thrombosis in medical history which was more frequent in the first wave (6 % vs 0.3 %, p = p = 0,001). At admission, there were no differences in the results of the initial lab values (c-reactive protein, leucocytes) and blood gas analyses between both groups. Treatment differed in the application of dexamethasone and anticoagulation. In the first wave, nobody received dexamethasone. However, this changed to 52.6 % of patients in the second wave for a mean length of 3.6 ±â€Š4.1 days. Anticoagulation with double standard prophylaxis (2 × 40 mg low molecular heparin, subcutaneous) was applied in 7.1 % of patients in the first wave but 30.2 % (p = 0.002) in the second wave. In the first wave more thromboembolic events were diagnosed after admission (19.0 % vs 7.0 %, p = 0.001). In-hospital death was 26.2 % in the first wave and 15.4 % in the second wave (p = 0.0234). Most deaths were attributed to acute respiratory distress syndrome (ARDS). CONCLUSION: Patients' characteristics did not vary in Germany's first and second COVID 19 wave, but anticoagulation and dexamethasone were applied more frequently in the second wave. In addition, there were fewer thromboembolic complications in the second wave.

Monte Carlo model of a prototype flat-panel detector for multi-energy applications in radiotherapy.

BACKGROUND: The incorporation of multi-energy capabilities into radiotherapy flat-panel detectors offers advantages including enhanced soft tissue visualization by reduction of signal from overlapping anatomy such as bone in 2D image projections; creation of virtual monoenergetic images for 3D contrast enhancement, metal artefact reduction and direct acquisition of relative electron density. A novel dual-layer on-board imager offering dual energy processing capabilities is being designed. As opposed to other dual-energy implementation techniques which require separate acquisition with two different x-ray spectra, the dual-layer detector design enables simultaneous acquisition of high and low energy images with a single exposure. A computational framework is required to optimize the design parameters and evaluate detector performance for specific clinical applications. PURPOSE: In this study, we report on the development of a Monte Carlo (MC) model of the imager including model validation. METHODS: The stack-up of the dual-layer imager (DLI) was implemented in GEANT4 Application for Tomographic Emission (GATE). The DLI model has an active area of 43×43 cm2 , with top and bottom Cesium Iodide (CsI) scintillators of 600 and 800 µm thickness, respectively. Measurement of spatial resolution and imaging of dedicated multi-material dual-energy (DE) phantoms were used to validate the model. The modulation transfer function (MTF) of the detector was calculated for a 120 kVp x-ray spectrum using a 0.5 mm thick tantalum edge rotated by 2.5o . For imaging validation, the DE phantom was imaged using a 140 kVp x-ray spectrum. For both validation simulations, corresponding measurements were done using an initial prototype of the imager. Agreement between simulations and measurement was assessed using normalized root mean square error (NRMSE) and 1D profile difference for the MTF and phantom images respectively. Further comparison between measurement and simulation was made using virtual monoenergetic images (VMIs) generated from basis material images derived using precomputed look-up tables. RESULTS: The MTF of the bottom layer of the dual-layer model shows values decreasing more quickly with spatial frequency, compared to the top layer, due to the thicker bottom scintillator thickness and scatter from the top layer. A comparison with measurement shows NRMSE of 0.013 and 0.015 as well as identical MTF50 of 0.8 mm1 and 1.0 mm1 for the top and bottom layer respectively. For the DE imaging of the DE-phantom, although a maximum deviation of 3.3% is observed for the 10 mm aluminum and Teflon inserts at the top layer, the agreement for all other inserts is less than 2.2% of the measured value at both layers. Material decomposition of simulated scatter-free DE images gives an average accuracy in PMMA and aluminum composition of 4.9% and 10.3% for 11-30 mm PMMA and 1-10 mm aluminum objects respectively. A comparison of decomposed values using scatter containing measured and simulated DE images shows good agreement within statistical uncertainty. CONCLUSION: Validation using both MTF and phantom imaging shows good agreement between simulation and measurements. With the present configuration of the digital prototype, the model can generate material decomposed images and virtual monoenergetic images.

Chlorine/methyl exchange reactions in silylated aminostibanes: a new route to stibinostibonium cations.

The Lewis acid assisted triflate/methyl, azide/methyl, and chlorine/methyl exchange reactions between silicon and antimony have been studied in the reaction of R(Me(3)Si)N-SbCl(2) (R = Ter) with AgOTf, AgN(3), KOtBu, GaCl(3), and Me(3)SiN(3)/GaCl(3), resulting in the formation of different methylantimony compounds. Furthermore, R(Me(3)Si)N-SbCl(2) (R = SiMe(3)) was reacted with GaCl(3) at low temperatures to yield a hitherto unreported amino(chloro)stibenium cation, the proposed intermediate in methyl exchange reactions. Tetrachloridogallate salts bearing different stibinostibonium cations such as [(Me(3)Sb)SbMe(2)](+) and [(Me(3)Sb)(2)SbMe](2+) along with the GaCl(3) adduct of SbMe(3) were isolated from such R(Me(3)Si)N-SbCl(2)/GaCl(3) mixtures (R = SiMe(3)) at ambient temperatures, depending on the reaction parameters.

Synthesis of blue imino(pentafluorophenyl)phosphane.

The reaction of AgC(6)F(5) with monomeric iminophosphanes of Mes*-N═P-X (X = Cl, I) in CH(2)Cl(2) at ambient temperature gives imino(pentafluorophenyl)phosphane, Mes*N═P(C(6)F(5)) (1), in almost quantitative yield (96%), which could be isolated as a highly viscous blue oil. The same reaction with LiC(6)F(5) results in the formation of imino(amino)phosphane (C(6)F(5))(2)P-N(Mes*)-P═NMes* (2) (yield 93%). In the second series of experiments the analogous reaction of MC(6)F(5) (M = Ag, Li) with dimeric [Cl-P(µ-N-Dipp)](2) was studied, leading to the formation of [R-P(µ-N-Dipp)](2) (R = C(6)F(5)) (3) for M = Ag, while only decomposition products such as P(C(6)F(5))(3) were observed in the reaction with the Li salt. Highly labile Mes*-N═P-C(6)F(5) (1) decomposes at ambient temperatures, forming among other products the diphosphane (C(6)F(5))(2)P-P(C(6)F(5))(2) (4). Reaction of 1 with Fe(2)(CO)(9) yields the iron carbonyl complexes Mes*-N═P(C(6)F(5))·Fe(CO)(4) (5) and [Mes*-N═P(C(6)F(5))](2)·Fe(CO)(3) (6). The structure, bonding, and potential energy surface are discussed on the basis of B3LYP/6-31G(d,p) computations. According to time-dependent B3LYP calculations, the blue color of 1 arises from an n → π* electronic transition.

Reducing residual-motion artifacts in iterative 3D CBCT reconstruction in image-guided radiation therapy.

PURPOSE: Recent evaluations of a 3D iterative cone-beam computed tomography (iCBCT) reconstruction method available on Varian radiation treatment devices demonstrated that iCBCT provides superior image quality when compared to analytical Feldkamp-Davis-Kress (FDK) method. However, iCBCT employs statistical penalized likelihood (PL) that is known to be highly sensitive to inconsistencies due to physiological motion occurring during the acquisition. We propose a computationally inexpensive extension of iCBCT addressing this deficiency. METHODS: During the iterative process, the gradients of PL are modified to avoid the generation of motion-related artifacts. To assess the impact of this modification, we propose a motion simulation generating CBCT projections of a moving anatomy together with artifact-free images used as ground truth. Contrast-to-noise ratio and power spectra of difference images are computed to quantify the impact of the motion on reconstructed CBCT volumes as well as the effect of the proposed modification. RESULTS: Using both simulated and clinical data, it is shown that the motion of patient's abdominal wall during the acquisition results in artifacts that can be quantified as low-frequency components in volumes reconstructed with iCBCT. Further, a quantitative evaluation demonstrates that the proposed modification of PL reduces these low-frequency components. While preserving the advantages of PL, it effectively suppresses the propagation of motion-related artifacts into clinically important regions, thus increasing the motion resiliency of iCBCT. CONCLUSIONS: The proposed modified iterative reconstruction method significantly improves the quality of CBCT images of anatomies suffering from residual motion.

Frequency-dependent optimal weighting approach for megavoltage multilayer imagers.

Multi-layer imaging (MLI) devices improve the detective quantum efficiency (DQE) while maintaining the spatial resolution of conventional mega-voltage (MV) x-ray detectors for applications in radiotherapy. To date, only MLIs with identical detector layers have been explored. However, it may be possible to instead use different scintillation materials in each layer to improve the final image quality. To this end, we developed and validated a method for optimally combining the individual images from each layer of MLI devices that are built with heterogeneous layers. Two configurations were modeled within the GATE Monte Carlo package by stacking different layers of a terbium doped gadolinium oxysulfide Gd2O2S:Tb (GOS) phosphor and a LKH-5 glass scintillator. Detector response was characterized in terms of the modulation transfer function (MTF), normalized noise power spectrum (NNPS) and DQE. Spatial frequency-dependent weighting factors were then analytically derived for each layer such that the total DQE of the summed combination image would be maximized across all spatial modes. The final image is obtained as the weighted sum of the sub-images from each layer. Optimal weighting factors that maximize the DQE were found to be the quotient of MTF and NNPS of each layer in the heterogeneous MLI detector. Results validated the improvement of the DQE across the entire frequency domain. For the LKH-5 slab configuration, DQE(0) increases between 2%-3% (absolute), while the corresponding improvement for the LKH-5 pixelated configuration was 7%. The performance of the weighting method was quantitatively evaluated with respect to spatial resolution, contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) of simulated planar images of phantoms at 2.5 and 6 MV. The line pair phantom acquisition exhibited a twofold increase in CNR and SNR, however MTF was degraded at spatial frequencies greater than 0.2 lp mm-1. For the Las Vegas phantom, the weighting improved the CNR by around 30% depending on the contrast region while the SNR values are higher by a factor of 2.5. These results indicate that the imaging performance of MLI systems can be enhanced using the proposed frequency-dependent weighting scheme. The CNR and SNR of the weighted combined image are improved across all spatial scales independent of the detector combination or photon beam energy.

Abbreviated on-treatment CBCT using roughness penalized mono-energization of kV-MV data and a multi-layer MV imager.

Simultaneous acquisition of cone beam CT (CBCT) projections using both the kV and MV imagers of an image guided radiotherapy system reduces set-up scan times-a benefit to lung cancer radiation oncology patients-but increases noise in the 3D reconstruction. In this article, we present a kV-MV scan time reduction technique that uses two noise-reducing measures to achieve superior performance. The first is a high-DQE multi-layer MV imager prototype. The second is a beam hardening correction algorithm which combines poly-energetic modeling with edge-preserving, regularized smoothing of the projections. Performance was tested in real acquisitions of the Catphan 604 and a thorax phantom. Percent noise was quantified from voxel values in a soft tissue volume of interest (VOI) while edge blur was quantified from a VOI straddling a boundary between air and soft material. Comparisons in noise/resolution performance trade-off were made between our proposed approach, a dose-equivalent kV-only scan, and a kV-MV reconstruction technique previously published by Yinet al(2005Med. Phys.329). The proposed technique demonstrated lower noise as a function of spatial resolution than the baseline kV-MV method, notably a 50% noise reduction at typical edge blur levels. Our proposed method also exhibited fainter non-uniformity artifacts and in some cases superior contrast. Overall, we find that the combination of a multi-layer MV imager, acquiring at a LINAC source energy of 2.5 MV, and a denoised beam hardening correction algorithm enables noise, resolution, and dose performance comparable to standard kV-imager only set-up CBCT, but with nearly half the gantry rotation time.

Characterization of Markerless Tumor Tracking Using the On-Board Imager of a Commercial Linear Accelerator Equipped With Fast-kV Switching Dual-Energy Imaging.

PURPOSE: To describe and characterize fast-kV switching, dual-energy (DE) imaging implemented within the on-board imager of a commercial linear accelerator for markerless tumor tracking (MTT). METHODS AND MATERIALS: Fast-kV switching, DE imaging provides for rapid switching between programmed tube voltages (ie, 60 and 120 kVp) from one image frame to the next. To characterize this system, the weighting factor used for logarithmic subtraction and signal difference-to-noise ratio were analyzed as a function of time and frame rate. MTT was evaluated using a thorax motion phantom and fast kV, DE imaging was compared versus single energy (SE) imaging over 360 degrees of rotation. A template-based matching algorithm was used to track target motion on both DE and SE sequences. Receiver operating characteristics were used to compare tracking results for both modalities. RESULTS: The weighting factor was inversely related to frame rate and stable over time. After applying the frame rate-dependent weighting factor, the signal difference-to-noise ratio was consistent across all frame rates considered for simulated tumors ranging from 5 to 25 mm in diameter. An analysis of receiver operating characteristics curves showed improved tracking with DE versus SE imaging. The area under the curve for the 10-mm target ranged from 0.821 to 0.858 for SE imaging versus 0.968 to 0.974 for DE imaging. Moreover, the residual tracking errors for the same target size ranged from 2.02 to 2.18 mm versus 0.79 to 1.07 mm for SE and DE imaging, respectively. CONCLUSIONS: Fast-kV switching, DE imaging was implemented on the on-board imager of a commercial linear accelerator. DE imaging resulted in improved MTT accuracy over SE imaging. Such an approach may have application for MTT of patients with lung cancer receiving stereotactic body radiation therapy, particularly for small tumors where MTT with SE imaging may fail.

GPU-accelerated Monte Carlo simulation of MV-CBCT.

Monte Carlo simulation (MCS) is one of the most accurate computation methods for dose calculation and image formation in radiation therapy. However, the high computational complexity and long execution time of MCS limits its broad use. In this paper, we present a novel strategy to accelerate MCS using a graphic processing unit (GPU), and we demonstrate the application in mega-voltage (MV) cone-beam computed tomography (CBCT) simulation. A new framework that generates a series of MV projections from a single simulation run is designed specifically for MV-CBCT acquisition. A Geant4-based GPU code for photon simulation is incorporated into the framework for the simulation of photon transport through a phantom volume. The FastEPID method, which accelerates the simulation of MV images, is modified and integrated into the framework. The proposed GPU-based simulation strategy was tested for its accuracy and efficiency in a Catphan 604 phantom and an anthropomorphic pelvis phantom with beam energies at 2.5 MV, 6 MV, and 6 MV FFF. In all cases, the proposed GPU-based simulation demonstrated great simulation accuracy and excellent agreement with measurement and CPU-based simulation in terms of reconstructed image qualities. The MV-CBCT simulation was accelerated by factors of roughly 900-2300 using an NVIDIA Tesla V100 GPU card against a 2.5 GHz AMD Opteron™ Processor 6380.

A rapid, accurate image simulation strategy for mega-voltage cone-beam computed tomography.

Intensive computation time is required to simulate images of electronic portal imaging device (EPID) using Monte Carlo (MC) technique, limiting the development of applications associated with EPID, such as mega-voltage cone-beam computed tomography (MV-CBCT). In this study, a fast, accurate simulation strategy for MV-CBCT utilizing the FastEPID technique has been developed and validated. During FastEPID simulation, photon detection was determined by pre-calculated photon energy deposition efficiency (η) and particle transport within the EPID was replaced with a pre-calculated optical photon spread function. This method is capable of reducing the time required for EPID image simulation by a factor of 90-140, without compromising image quality. MV-CBCT images reconstructed from the FastEPID simulated projections have been validated against measurement in terms of mean Hounsfield unit (HU), noise, and cupping artifact. These images were obtained with both a Catphan 604 phantom and an anthropomorphic pelvis phantom, under treatment beam energies of 2.5 MV, 6 MV, and 6 MV flattening filter free. The agreement between measurement and simulation was excellent in all cases. This novel strategy was capable of reducing the run time of a full scan simulation of MV-CBCT performed on a CPU cluster to a matter of hours, rather than weeks or months required by a conventional approach. Multiple applications associated with MV-CBCT (e.g. imager design optimization) are anticipated to gain from the implementation of this novel simulation strategy.

Low-dose megavoltage cone-beam computed tomography using a novel multi-layer imager (MLI).

PURPOSE: The feasibility of low-dose megavoltage cone-beam acquisition (MVCBCT) using a novel, high detective quantum efficiency (DQE) multi-layer imager (MLI) was investigated. The aim of this work was to reconstruct MVCBCT images using the MLI at different total dose levels, and assess Hounsfield Unit (HU) accuracy, noise and contrast-to-noise ratio (CNR) for low-dose megavoltage cone-beam acquisition. METHODS: The MLI has four stacked layers; each layer contains a combination of copper filter/converter, gadolinium oxysulfide (GOS) scintillator and a-Si detector array. In total, 720 projections of a CATPHAN® phantom were acquired over 360° at 2.5, 6, and 6 MV flattening filter free (FFF) beam energies on a Varian TrueBeam LINAC. The dose per projection was 0.01, 0.0167, and 0.05 MU for 2.5, 6, and 6 MV FFF, respectively. MVCBCT images were reconstructed with varying numbers of projections to provide a range of doses for evaluation. Hounsfield Unit uniformity, accuracy, noise and CNR were estimated. Improvements were quantified relative to the standard AS1200 single-layer imager. RESULTS: Average HU uniformity for the MLI reconstructions was within a range of 95%-99% for all of the energies studied. Relative electron density estimation from HU values was within 0.4% ± 1.8% from nominal values. The CNR for MVCBCT based on MLI projections was 2-4× greater than from AS1200 projections. The 2.5 MV beam acquisition with the MLI exhibited the lowest noise and the best balance between CNR and dose for low-dose reconstructions. CONCLUSIONS: Megavoltage cone-beam acquisition imaging with a novel MLI prototype mounted on a clinical linear accelerator demonstrated substantial improvement over the standard AS1200 EPID. Further optimization of MVCBCT reconstruction, particularly for 2.5 MV acquisitions, will improve image metrics. Overall, the MLI improves CNR at substantially lower doses than currently required by conventional detectors. This new high DQE detector could provide high-quality MVCBCT at clinically acceptable doses.

Fast-switching dual energy cone beam computed tomography using the on-board imager of a commercial linear accelerator.

To evaluate fast-kV switching (FS) dual energy (DE) cone beam computed tomography (CBCT) using the on-board imager (OBI) of a commercial linear accelerator to produce virtual monoenergetic (VM) and relative electron density (RED) images. Using an polynomial attenuation mapping model, CBCT phantom projections obtained at 80 and 140 kVp with FS imaging, were decomposed into equivalent thicknesses of aluminum (Al) and polymethyl methacrylate (PMMA). All projections were obtained with the titanium foil and bowtie filter in place. Basis material projections were then recombined to create VM images by using the linear attenuation coefficients at the specified energy for each material. Similarly, RED images were produced by replacing the linear attenuation values of Al and PMMA by their respective RED values in the projection space. VM and RED images were reconstructed using Feldkamp-Davis-Kress (FDK) and an iterative algorithm (iCBCT, Varian Medical Systems). Hounsfield units (HU), contrast-to-noise ratio (CNR) and RED values were compared against known values. The results after VM-CBCT production showed good material decomposition and consistent HUVM values, with measured root mean square errors (RMSE) from theoretical values, after FDK reconstruction, of 20.5, 5.7, 12.8 and 21.7 HU for 50, 80, 100 and 150 keV, respectively. The largest CNR improvements, when compared to polychromatic images, were observed for the 50 keV VM images. Image noise was reduced up to 28% in the VM-CBCT images after iterative image reconstruction. RED values measured for our method resulted in a mean percentage error of 0.0% ± 1.8%. This study describes a method to generate VM-CBCT and RED images using FS-DE scans obtained using the OBI of a linac, including the effects of the bowtie filter. The creation of VM and RED images increases the dynamic range of CBCT images, and provides additional data that may be used for adaptive radiotherapy, and on table verification for radiotherapy treatments.

A novel method for fast image simulation of flat panel detectors.

We have developed a novel method for fast image simulation of flat panel detectors, based on the photon energy deposition efficiency and the optical spread function (OSF). The proposed method, FastEPID, determines the photon detection using photon energy deposition and replaces particle transport within the detector with precalculated OSFs. The FastEPID results are validated against experimental measurement and conventional Monte Carlo simulation in terms of modulation transfer function (MTF), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contrast, and relative difference of pixel value, obtained with a slanted slit image, Las Vegas phantom, and anthropomorphic pelvis phantom. Excellent agreement is observed between simulation and measurement in all cases. Without degrading image quality, the FastEPID method is capable of reducing simulation time up to a factor of 150. Multiple applications, such as imager design optimization for planar and volumetric imaging, are expected to benefit from the implementation of the FastEPID method.