Blood amyloid levels and risk of dementia in the Ginkgo Evaluation of Memory Study (GEMS): A longitudinal analysis.

INTRODUCTION: Both high or low plasma amyloid levels have been associated with risk of dementia in nondemented subjects. METHODS: We examined baseline plasma ß-amyloid (Aß) levels in relationship to incident dementia during a period of 8.5 years in 2840 subjects age >75 years; 2381 were cognitively normal (CN) and 450 mild cognitive impairment. RESULTS: Increased plasma Aß1-40 and Aß1-42 levels were associated with gender (women), age, low education, creatinine levels, history of stroke, and hypertension. CN participants who developed dementia had lower levels of Aß1-42 and Aß1-42/Aß1-40 ratio compared with those who did not. Aß levels did not predict dementia in mild cognitive impairment participants. DISCUSSION: There was an inverse association between Aß1-42 and Aß1-42/Aß1-40 ratio to risk of dementia in CN participants. Cerebral and cardiovascular disease and renal function are important determinants of increased Aß levels and must be considered in evaluations of relationship of plasma Aß and subsequent risk of dementia.

Multi-GPU Acceleration of Branchless Distance Driven Projection and Backprojection for Clinical Helical CT.

Model-based image reconstruction (MBIR) techniques have the potential to generate high quality images from noisy measurements and a small number of projections which can reduce the x-ray dose in patients. These MBIR techniques rely on projection and backprojection to refine an image estimate. One of the widely used projectors for these modern MBIR based technique is called branchless distance driven (DD) projection and backprojection. While this method produces superior quality images, the computational cost of iterative updates keeps it from being ubiquitous in clinical applications. In this paper, we provide several new parallelization ideas for concurrent execution of the DD projectors in multi-GPU systems using CUDA programming tools. We have introduced some novel schemes for dividing the projection data and image voxels over multiple GPUs to avoid runtime overhead and inter-device synchronization issues. We have also reduced the complexity of overlap calculation of the algorithm by eliminating the common projection plane and directly projecting the detector boundaries onto image voxel boundaries. To reduce the time required for calculating the overlap between the detector edges and image voxel boundaries, we have proposed a pre-accumulation technique to accumulate image intensities in perpendicular 2D image slabs (from a 3D image) before projection and after backprojection to ensure our DD kernels run faster in parallel GPU threads. For the implementation of our iterative MBIR technique we use a parallel multi-GPU version of the alternating minimization (AM) algorithm with penalized likelihood update. The time performance using our proposed reconstruction method with Siemens Sensation 16 patient scan data shows an average of 24 times speedup using a single TITAN X GPU and 74 times speedup using 3 TITAN X GPUs in parallel for combined projection and backprojection.

Clinical and demographic correlates of medication and visit adherence in a large randomized controlled trial.

BACKGROUND: Patient characteristics are associated with adherence, which has implications for planning clinical research or designing payment systems that reward superior outcomes. It is unclear to what extent clinician efforts to improve adherence can attenuate these associations. METHODS: To identify factors predicting visit and medication adherence in settings designed to optimize adherence, we did a retrospective analysis of participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT recruited participants at 632 sites in North America, Puerto Rico, and the U.S. Virgin Islands for random assignment to antihypertensive treatment with amlodipine, chlorthalidone, or lisinopril. Site investigators reported clinic characteristics at the time they applied to participate in the study and research coordinators used standardized methods to measure patient characteristics. We defined adequate visit adherence as attending at least 80 % of scheduled visits; adequate medication adherence was defined as taking 80 % or more of the randomly assigned medication at all study visits. RESULTS: The 31,250 ALLHAT participants eligible for the visit adherence analysis attended 78.5 % of scheduled study visits; 68.9 % attended more than 80 % of scheduled visits. Clinic setting was predictive of both forms of adherence; adherence was worst at private clinics; clinics that enrolled more study participants had superior adherence. Adjusting for clinic characteristics and clinical factors, women, younger participants, Blacks and smokers were less likely to have adequate visit adherence. Among the 28,967 participants eligible for the medication adherence analysis, 21,261 (73.4 %) reported adequate medication adherence. In adjusted analyses, younger and less educated participants, Blacks, and smokers were less likely to report adequate adherence. CONCLUSIONS: Participant demographics were associated with adherence despite strenuous efforts to optimize adherence. Our results could inform decisions by researchers planning trials and policymakers designing payment systems. TRIAL REGISTRATION: NCT00000542 . Registered 27 October 1999.

Infection hospitalization increases risk of dementia in the elderly.

OBJECTIVES: Severe infections, often requiring ICU admission, have been associated with persistent cognitive dysfunction. Less severe infections are more common and whether they are associated with an increased risk of dementia is unclear. We determined the association of pneumonia hospitalization with risk of dementia in well-functioning older adults. DESIGN: Secondary analysis of a randomized multicenter trial to determine the effect of Gingko biloba on incident dementia. SETTING: Five academic medical centers in the United States. SUBJECTS: Healthy community volunteers (n = 3,069) with a median follow-up of 6.1 years. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We identified pneumonia hospitalizations using International Classification of Diseases, 9th Edition-Coding Manual codes and validated them in a subset. Less than 3% of pneumonia cases necessitated ICU admission, mechanical ventilation, or vasopressor support. Dementia was adjudicated based on neuropsychological evaluation, neurological examination, and MRI. Two hundred twenty-one participants (7.2%) incurred at least one hospitalization with pneumonia (mean time to pneumonia = 3.5 yr). Of these, dementia was developed in 38 (17%) after pneumonia, with half of these cases occurring 2 years after the pneumonia hospitalization. Hospitalization with pneumonia was associated with increased risk of time to dementia diagnosis (unadjusted hazard ratio = 2.3; CI, 1.6-3.2; p < 0.0001). The association remained significant when adjusted for age, sex, race, study site, education, and baseline mini-mental status examination (hazard ratio = 1.9; CI, 1.4-2.8; p < 0.0001). Results were unchanged when additionally adjusted for smoking, hypertension, diabetes, heart disease, and preinfection functional status. Results were similar using propensity analysis where participants with pneumonia were matched to those without pneumonia based on age, probability of developing pneumonia, and similar trajectories of cognitive and physical function prior to pneumonia (adjusted prevalence rates, 91.7 vs 65 cases per 1,000 person-years; adjusted prevalence rate ratio = 1.6; CI, 1.06-2.7; p = 0.03). Sensitivity analyses showed that the higher risk also occurred among those hospitalized with other infections. CONCLUSION: Hospitalization with pneumonia is associated with increased risk of dementia.

Cerebral white matter hyperintensity in African Americans and European Americans with type 2 diabetes.

Previous studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs) compared with European Americans (EAs). This finding might be attributable to the higher prevalence of cardiovascular disease (CVD) risk factors and poorer access to healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and good access to healthcare would have comparable or lower levels of WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and to test for association between WMH and race. The unadjusted mean WMH score from the Diabetes Heart Study-Mind was 1.9 in AAs and 2.3 in EAs (P = .3244). Among those with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9 in AAs and 3.9 in EAs (P = .0503). Adjustment for age and sex produced no statistically significant differences in WMH score between AAs and EAs. These independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden of WMH in AAs.

MB-DECTNet: a model-based unrolling network for accurate 3D dual-energy CT reconstruction from clinically acquired helical scans.

Objective.Over the past several decades, dual-energy CT (DECT) imaging has seen significant advancements due to its ability to distinguish between materials. DECT statistical iterative reconstruction (SIR) has exhibited potential for noise reduction and enhanced accuracy. However, its slow convergence and substantial computational demands render the elapsed time for 3D DECT SIR often clinically unacceptable. The objective of this study is to accelerate 3D DECT SIR while maintaining subpercentage or near-subpercentage accuracy.Approach.We incorporate DECT SIR into a deep-learning model-based unrolling network for 3D DECT reconstruction (MB-DECTNet), which can be trained end-to-end. This deep learning-based approach is designed to learn shortcuts between initial conditions and the stationary points of iterative algorithms while preserving the unbiased estimation property of model-based algorithms. MB-DECTNet comprises multiple stacked update blocks, each containing a data consistency layer (DC) and a spatial mixer layer, with the DC layer functioning as a one-step update from any traditional iterative algorithm.Main results.The quantitative results indicate that our proposed MB-DECTNet surpasses both the traditional image-domain technique (MB-DECTNet reduces average bias by a factor of 10) and a pure deep learning method (MB-DECTNet reduces average bias by a factor of 8.8), offering the potential for accurate attenuation coefficient estimation, akin to traditional statistical algorithms, but with considerably reduced computational costs. This approach achieves 0.13% bias and 1.92% mean absolute error and reconstructs a full image of a head in less than 12 min. Additionally, we show that the MB-DECTNet output can serve as an initializer for DECT SIR, leading to further improvements in results.Significance.This study presents a model-based deep unrolling network for accurate 3D DECT reconstruction, achieving subpercentage error in estimating virtual monoenergetic images for a full head at 60 and 150 keV in 30 min, representing a 40-fold speedup compared to traditional approaches. These findings have significant implications for accelerating DECT SIR and making it more clinically feasible.

Motion-compensated scheme for sequential scanned statistical iterative dual-energy CT reconstruction.

Objective.Dual-energy computed tomography (DECT) has been widely used to reconstruct numerous types of images due its ability to better discriminate tissue properties. Sequential scanning is a popular dual-energy data acquisition method as it requires no specialized hardware. However, patient motion between two sequential scans may lead to severe motion artifacts in DECT statistical iterative reconstructions (SIR) images. The objective is to reduce the motion artifacts in such reconstructions.Approach.We propose a motion-compensation scheme that incorporates a deformation vector field into any DECT SIR. The deformation vector field is estimated via the multi-modality symmetric deformable registration method. The precalculated registration mapping and its inverse or adjoint are then embedded into each iteration of the iterative DECT algorithm.Main results.Results from a simulated and clinical case show that the proposed framework is capable of reducing motion artifacts in DECT SIRs. Percentage mean square errors in regions of interest in the simulated and clinical cases were reduced from 4.6% to 0.5% and 6.8% to 0.8%, respectively. A perturbation analysis was then performed to determine errors in approximating the continuous deformation by using the deformation field and interpolation. Our findings show that errors in our method are mostly propagated through the target image and amplified by the inverse matrix of the combination of the Fisher information and Hessian of the penalty term.Significance.We have proposed a novel motion-compensation scheme to incorporate a 3D registration method into the joint statistical iterative DECT algorithm in order to reduce motion artifacts caused by inter-scan motion, and successfully demonstrate that interscan motion corrections can be integrated into the DECT SIR process, enabling accurate imaging of radiological quantities on conventional SECT scanners, without significant loss of either computational efficiency or accuracy.

Night temperature and source-sink effects on overall growth, cell number and cell size in bell pepper ovaries.

BACKGROUND AND AIMS: Ovary swelling, and resultant fruit malformation, in bell pepper flowers is favoured by low night temperature or a high source-sink ratio. However, the interaction between night temperature and source-sink ratio on ovary swelling and the contribution of cell size and cell number to ovary swelling are unknown. The present research examined the interactive effects of night temperature and source-sink ratio on ovary size, cell number and cell size at anthesis in bell pepper flowers. METHODS: Bell pepper plants were grown in growth chambers at night temperatures of either 20 °C (HNT) or 12 °C (LNT). Within each temperature treatment, plants bore either 0 (non-fruiting) or two developing fruits per plant. Ovary fresh weight, cell size and cell number were measured. KEY RESULTS: Ovary fresh weights in non-fruiting plants grown at LNT were the largest, while fresh weights were smallest in plants grown at HNT with fruits. In general, mesocarp cell size in ovaries was largest in non-fruiting plants grown at either LNT or HNT and smallest in fruiting plants at HNT. Mesocarp cell number was greater in non-fruiting plants under LNT than in the rest of the night temperature/fruiting treatments. These responses were more marked in ovaries sampled after 18 d of treatment compared with those sampled after 40 d of treatment. CONCLUSIONS: Ovary fresh weight of flowers at anthesis increased 65 % in non-fruiting plants grown under LNT compared with fruiting plants grown under HNT. This increase was due primarily to increases in mesocarp cell number and size. These results indicate that the combined effects of LNT and high source-sink ratio on ovary swelling are additive. Furthermore, the combined effects of LNT and low source-sink ratio or HNT and high source-sink ratio can partially overcome the detrimental effects of LNT and high source-sink ratio.

Impact of flat panel-imager veiling glare on scatter-estimation accuracy and image quality of a commercial on-board cone-beam CT imaging system.

PURPOSE: The purposes of this study is to measure the low frequency drop (LFD) of the modulation transfer function (MTF), associated with the long tails of the detector point spread function (PSF) of an on-board flat panel imager and study its impact on cone-beam CT (CBCT) image quality and scatter measurement accuracy. METHODS: Two different experimental methods were used to characterize LFD and its associated PSF of a Varian OBI flat-panel detector system: the edge response function (ERF) method and the disk transfer function (DTF) method. PSF was estimated by fitting parametric models to these measurements for four values of the applied voltage (kVp). The resultant PSF was used to demonstrate the effect of LFD on image contrast and CT number accuracy in CBCT images reconstructed from synthetic datasets, as well as, accuracy of scatter measurements with the beam-stop method. RESULTS: The MTFs derived from the measured ERF data revealed LFDs varying from 8% (at 60 kVp) to 10.5% (at 120 kVp), while the intensity of the long PSF tails was found to increase with increasing kVp. The veiling glare line spread functions derived from the ERF and DTF methods were in excellent agreement. Uncorrected veiling glare reduced contrast and the image intensity in CBCT reconstruction, near the phantom periphery (by 67 Hounsfield units in a 20 cm-in-diameter water phantom) and (to a smaller degree) near inhomogeneities. Use of the bow-tie filter mitigated these effects. Veiling glare also resulted in about 10%-15% overestimation of the scatter-to-primary ratio when measured with the beam-stop or beam-stop array method. CONCLUSIONS: The long tails of the detector PSF were found to have a modest dependence of beam spectrum, which is reflected on the MTF curve LFD. Our findings show that uncorrected veiling glare can affect quantitative accuracy and contrast in CBCT imaging, based on flat panel imager. In addition, it results in overestimation of the scatter-to-primary ratio, measured with the beam-stop methods.

Fast patient-specific Monte Carlo brachytherapy dose calculations via the correlated sampling variance reduction technique.

PURPOSE: To demonstrate potential of correlated sampling Monte Carlo (CMC) simulation to improve the calculation efficiency for permanent seed brachytherapy (PSB) implants without loss of accuracy. METHODS: CMC was implemented within an in-house MC code family (PTRAN) and used to compute 3D dose distributions for two patient cases: a clinical PSB postimplant prostate CT imaging study and a simulated post lumpectomy breast PSB implant planned on a screening dedicated breast cone-beam CT patient exam. CMC tallies the dose difference, ΔD, between highly correlated histories in homogeneous and heterogeneous geometries. The heterogeneous geometry histories were derived from photon collisions sampled in a geometrically identical but purely homogeneous medium geometry, by altering their particle weights to correct for bias. The prostate case consisted of 78 Model-6711 (125)I seeds. The breast case consisted of 87 Model-200 (103)Pd seeds embedded around a simulated lumpectomy cavity. Systematic and random errors in CMC were unfolded using low-uncertainty uncorrelated MC (UMC) as the benchmark. CMC efficiency gains, relative to UMC, were computed for all voxels, and the mean was classified in regions that received minimum doses greater than 20%, 50%, and 90% of D(90), as well as for various anatomical regions. RESULTS: Systematic errors in CMC relative to UMC were less than 0.6% for 99% of the voxels and 0.04% for 100% of the voxels for the prostate and breast cases, respectively. For a 1 × 1 × 1 mm(3) dose grid, efficiency gains were realized in all structures with 38.1- and 59.8-fold average gains within the prostate and breast clinical target volumes (CTVs), respectively. Greater than 99% of the voxels within the prostate and breast CTVs experienced an efficiency gain. Additionally, it was shown that efficiency losses were confined to low dose regions while the largest gains were located where little difference exists between the homogeneous and heterogeneous doses. On an AMD 1090T processor, computing times of 38 and 21 sec were required to achieve an average statistical uncertainty of 2% within the prostate (1 × 1 × 1 mm(3)) and breast (0.67 × 0.67 × 0.8 mm(3)) CTVs, respectively. CONCLUSIONS: CMC supports an additional average 38-60 fold improvement in average efficiency relative to conventional uncorrelated MC techniques, although some voxels experience no gain or even efficiency losses. However, for the two investigated case studies, the maximum variance within clinically significant structures was always reduced (on average by a factor of 6) in the therapeutic dose range generally. CMC takes only seconds to produce an accurate, high-resolution, low-uncertainly dose distribution for the low-energy PSB implants investigated in this study.

Dose calculation for photon-emitting brachytherapy sources with average energy higher than 50 keV: report of the AAPM and ESTRO.

PURPOSE: Recommendations of the American Association of Physicists in Medicine (AAPM) and the European Society for Radiotherapy and Oncology (ESTRO) on dose calculations for high-energy (average energy higher than 50 keV) photon-emitting brachytherapy sources are presented, including the physical characteristics of specific (192)Ir, (137)Cs, and (60)Co source models. METHODS: This report has been prepared by the High Energy Brachytherapy Source Dosimetry (HEBD) Working Group. This report includes considerations in the application of the TG-43U1 formalism to high-energy photon-emitting sources with particular attention to phantom size effects, interpolation accuracy dependence on dose calculation grid size, and dosimetry parameter dependence on source active length. RESULTS: Consensus datasets for commercially available high-energy photon sources are provided, along with recommended methods for evaluating these datasets. Recommendations on dosimetry characterization methods, mainly using experimental procedures and Monte Carlo, are established and discussed. Also included are methodological recommendations on detector choice, detector energy response characterization and phantom materials, and measurement specification methodology. Uncertainty analyses are discussed and recommendations for high-energy sources without consensus datasets are given. CONCLUSIONS: Recommended consensus datasets for high-energy sources have been derived for sources that were commercially available as of January 2010. Data are presented according to the AAPM TG-43U1 formalism, with modified interpolation and extrapolation techniques of the AAPM TG-43U1S1 report for the 2D anisotropy function and radial dose function.

Report of the Task Group 186 on model-based dose calculation methods in brachytherapy beyond the TG-43 formalism: current status and recommendations for clinical implementation.

The charge of Task Group 186 (TG-186) is to provide guidance for early adopters of model-based dose calculation algorithms (MBDCAs) for brachytherapy (BT) dose calculations to ensure practice uniformity. Contrary to external beam radiotherapy, heterogeneity correction algorithms have only recently been made available to the BT community. Yet, BT dose calculation accuracy is highly dependent on scatter conditions and photoelectric effect cross-sections relative to water. In specific situations, differences between the current water-based BT dose calculation formalism (TG-43) and MBDCAs can lead to differences in calculated doses exceeding a factor of 10. MBDCAs raise three major issues that are not addressed by current guidance documents: (1) MBDCA calculated doses are sensitive to the dose specification medium, resulting in energy-dependent differences between dose calculated to water in a homogeneous water geometry (TG-43), dose calculated to the local medium in the heterogeneous medium, and the intermediate scenario of dose calculated to a small volume of water in the heterogeneous medium. (2) MBDCA doses are sensitive to voxel-by-voxel interaction cross sections. Neither conventional single-energy CT nor ICRU∕ICRP tissue composition compilations provide useful guidance for the task of assigning interaction cross sections to each voxel. (3) Since each patient-source-applicator combination is unique, having reference data for each possible combination to benchmark MBDCAs is an impractical strategy. Hence, a new commissioning process is required. TG-186 addresses in detail the above issues through the literature review and provides explicit recommendations based on the current state of knowledge. TG-43-based dose prescription and dose calculation remain in effect, with MBDCA dose reporting performed in parallel when available. In using MBDCAs, it is recommended that the radiation transport should be performed in the heterogeneous medium and, at minimum, the dose to the local medium be reported along with the TG-43 calculated doses. Assignments of voxel-by-voxel cross sections represent a particular challenge. Electron density information is readily extracted from CT imaging, but cannot be used to distinguish between different materials having the same density. Therefore, a recommendation is made to use a number of standardized materials to maintain uniformity across institutions. Sensitivity analysis shows that this recommendation offers increased accuracy over TG-43. MBDCA commissioning will share commonalities with current TG-43-based systems, but in addition there will be algorithm-specific tasks. Two levels of commissioning are recommended: reproducing TG-43 dose parameters and testing the advanced capabilities of MBDCAs. For validation of heterogeneity and scatter conditions, MBDCAs should mimic the 3D dose distributions from reference virtual geometries. Potential changes in BT dose prescriptions and MBDCA limitations are discussed. When data required for full MBDCA implementation are insufficient, interim recommendations are made and potential areas of research are identified. Application of TG-186 guidance should retain practice uniformity in transitioning from the TG-43 to the MBDCA approach.

A protocol to extend the longitudinal coverage of on-board cone-beam CT.

The longitudinal coverage of a LINAC-mounted CBCT scan is limited to the corresponding dimensional limits of its flat panel detector, which is often shorter than the length of the treatment field. These limits become apparent when fields are designed to encompass wide regions, as when providing nodal coverage. Therefore, we developed a novel protocol to acquire double orbit CBCT images using a commercial system, and combine the images to extend the longitudinal coverage for image-guided adaptive radiotherapy (IGART). The protocol acquires two CBCT scans with a couch shift similar to the "step-and-shoot" cine CT acquisition, allowing a small longitudinal overlap of the two reconstructed volumes. An in-house DICOM reading/writing software was developed to combine the two image sets into one. Three different approaches were explored to handle the possible misalignment between the two image subsets: simple stacking, averaging the overlapped volumes, and a 3D-3D image registration with the three translational degrees of freedom. Using thermoluminescent dosimeters and custom-designed holders for a CTDI phantom set, dose measurements were carried out to assess the resultant imaging dose of the technique and its geometric distribution. Deformable registration was tested on patient images generated with the double-orbit protocol, using both the planning FBCT and the artificially deformed CBCT as source images. The protocol was validated on phantoms and has been employed clinically for IRB-approved IGART studies for head and neck and prostate cancer patients.

A tribute to Karen Greenwood and her contributions to the American Medical Informatics Association.

After 25 years of service to the American Medical Informatics Association (AMIA), Ms Karen Greenwood, the Executive Vice President and Chief Operating Officer, is leaving the organization. In this perspective, we reflect on her accomplishments and her effect on the organization and the field of informatics nationally and globally. We also express our appreciation and gratitude for Ms Greenwood's role at AMIA.

25 × 5 Symposium to Reduce Documentation Burden: Report-out and Call for Action.

BACKGROUND: The widespread adoption of electronic health records and a simultaneous increase in regulatory demands have led to an acceleration of documentation requirements among clinicians. The corresponding burden from documentation requirements is a central contributor to clinician burnout and can lead to an increased risk of suboptimal patient care. OBJECTIVE: To address the problem of documentation burden, the 25 by 5: Symposium to Reduce Documentation Burden on United States Clinicians by 75% by 2025 (Symposium) was organized to provide a forum for experts to discuss the current state of documentation burden and to identify specific actions aimed at dramatically reducing documentation burden for clinicians. METHODS: The Symposium consisted of six weekly sessions with 33 presentations. The first four sessions included panel presentations discussing the challenges related to documentation burden. The final two sessions consisted of breakout groups aimed at engaging attendees in establishing interventions for reducing clinical documentation burden. Steering Committee members analyzed notes from each breakout group to develop a list of action items. RESULTS: The Steering Committee synthesized and prioritized 82 action items into Calls to Action among three stakeholder groups: Providers and Health Systems, Vendors, and Policy and Advocacy Groups. Action items were then categorized into as short-, medium-, or long-term goals. Themes that emerged from the breakout groups' notes include the following: accountability, evidence is critical, education and training, innovation of technology, and other miscellaneous goals (e.g., vendors will improve shared knowledge databases). CONCLUSION: The Symposium successfully generated a list of interventions for short-, medium-, and long-term timeframes as a launching point to address documentation burden in explicit action-oriented ways. Addressing interventions to reduce undue documentation burden placed on clinicians will necessitate collaboration among all stakeholders.

Towards subpercentage uncertainty proton stopping-power mapping via dual-energy CT: Direct experimental validation and uncertainty analysis of a statistical iterative image reconstruction method.

PURPOSE: To assess the potential of a joint dual-energy computerized tomography (CT) reconstruction process (statistical image reconstruction method built on a basis vector model (JSIR-BVM)) implemented on a 16-slice commercial CT scanner to measure high spatial resolution stopping-power ratio (SPR) maps with uncertainties of less than 1%. METHODS: JSIR-BVM was used to reconstruct images of effective electron density and mean excitation energy from dual-energy CT (DECT) sinograms for 10 high-purity samples of known density and atomic composition inserted into head and body phantoms. The measured DECT data consisted of 90 and 140 kVp axial sinograms serially acquired on a Philips Brilliance Big Bore CT scanner without beam-hardening corrections. The corresponding SPRs were subsequently measured directly via ion chamber measurements on a MEVION S250 superconducting synchrocyclotron and evaluated theoretically from the known sample compositions and densities. Deviations of JSIR-BVM SPR values from their theoretically calculated and directly measured ground-truth values were evaluated for our JSIR-BVM method and our implementation of the Hünemohr-Saito (H-S) DECT image-domain decomposition technique for SPR imaging. A thorough uncertainty analysis was then performed for five different scenarios (comparison of JSIR-BVM stopping-power ratio/stopping power (SPR/SP) to International Commission on Radiation Measurements and Units benchmarks; comparison of JSIR-BVM SPR to measured benchmarks; and uncertainties in JSIR-BVM SPR/SP maps for patients of unknown composition) per the Joint Committee for Guides in Metrology and the Guide to Expression of Uncertainty in Measurement, including the impact of uncertainties in measured photon spectra, sample composition and density, photon cross section and I-value models, and random measurement uncertainty. Estimated SPR uncertainty for three main tissue groups in patients of unknown composition and the weighted proportion of each tissue type for three proton treatment sites were then used to derive a composite range uncertainty for our method. RESULTS: Mean JSIR-BVM SPR estimates deviated by less than 1% from their theoretical and directly measured ground-truth values for most inserts and phantom geometries except for high-density Delrin and Teflon samples with SPR error relative to proton measurements of 1.1% and -1.0% (head phantom) and 1.1% and -1.1% (body phantom). The overall root-mean-square (RMS) deviations over all samples were 0.39% and 0.52% (head phantom) and 0.43% and 0.57% (body phantom) relative to theoretical and directly measured ground-truth SPRs, respectively. The corresponding RMS (maximum) errors for the image-domain decomposition method were 2.68% and 2.73% (4.68% and 4.99%) for the head phantom and 0.71% and 0.87% (1.37% and 1.66%) for the body phantom. Compared to H-S SPR maps, JSIR-BVM yielded 30% sharper and twofold sharper images for soft tissues and bone-like surrogates, respectively, while reducing noise by factors of 6 and 3, respectively. The uncertainty (coverage factor k = 1) of the DECT-to-benchmark values comparison ranged from 0.5% to 1.5% and is dominated by scanning-beam photon-spectra uncertainties. An analysis of the SPR uncertainty for patients of unknown composition showed a JSIR-BVM uncertainty of 0.65%, 1.21%, and 0.77% for soft-, lung-, and bony-tissue groups which led to a composite range uncertainty of 0.6-0.9%. CONCLUSIONS: Observed JSIR-BVM SPR estimation errors were all less than 50% of the estimated k = 1 total uncertainty of our benchmarking experiment, demonstrating that JSIR-BVM high spatial resolution, low-noise SPR mapping is feasible and is robust to variations in the geometry of the scanned object. In contrast, the much larger H-S SPR estimation errors are dominated by imaging noise and residual beam-hardening artifacts. While the uncertainties characteristic of our current JSIR-BVM implementation can be as large as 1.5%, achieving < 1% total uncertainty is feasible by improving the accuracy of scanner-specific scatter-profile and photon-spectrum estimates. With its robustness to beam-hardening artifact, image noise, and variations in phantom size and geometry, JSIR-BVM has the potential to achieve high spatial-resolution SPR mapping with subpercentage accuracy and estimated uncertainty in the clinical setting.

Estimation of CT cone-beam geometry using a novel method insensitive to phantom fabrication inaccuracy: implications for isocenter localization accuracy.

PURPOSE: Mechanical instabilities that occur during gantry rotation of on-board cone-beam computed tomography (CBCT) imaging systems limit the efficacy of image-guided radiotherapy. Various methods for calibrating the CBCT geometry and correcting errors have been proposed, including some that utilize dedicated fiducial phantoms. The purpose of this work was to investigate the role of phantom fabrication imprecision on the accuracy of a particular CT cone-beam geometry estimate and to test a new method to mitigate errors in beam geometry arising from imperfectly fabricated phantoms. METHODS: The authors implemented a fiducial phantom-based beam geometry estimation following the one described by Cho et al. [Med Phys 32(4), 968-983 (2005)]. The algorithm utilizes as input projection images of the phantom at various gantry angles and provides a full nine parameter beam geometry characterization of the source and detector position and detector orientation versus gantry angle. A method was developed for recalculating the beam geometry in a coordinate system with origin at the source trajectory center and aligned with the axis of gantry rotation, thus making the beam geometry estimation independent of the placement of the phantom. A second CBCT scan with the phantom rotated 180 degrees about its long axis was averaged with the first scan to mitigate errors from phantom imprecision. Computer simulations were performed to assess the effect of 2D fiducial marker positional error on the projections due to image discretization, as well as 3D fiducial marker position error due to phantom fabrication imprecision. Experimental CBCT images of a fiducial phantom were obtained and the algorithm used to measure beam geometry for a Varian Trilogy with an on-board CBCT. RESULTS: Both simulations and experimental results reveal large sinusoidal oscillations in the calculated beam geometry parameters with gantry angle due to displacement of the phantom from CBCT isocenter and misalignment with the gantry axis, which are eliminated by recalculating the beam geometry in the source coordinate system. Simulations and experiments also reveal an additional source of oscillations arising from fiducial marker position error due to phantom fabrication imprecision that are mitigated by averaging the results with those of a second CBCT scan with phantom rotated. With a typical fiducial marker position error of 0.020 mm (0.001 in.), source and detector position are found in simulations to be within 250 microm of the true values, and detector and gantry angles less than 0.2 degrees. Detector offsets are within 100 microm of the known value. Experimental results verify the efficacy of the second scan in mitigating beam geometry errors, as well as large apparent source/detector isocenter offsets arising from phantom fabrication imprecision. CONCLUSIONS: The authors have developed and validated a novel fiducial phantom-based CBCT beam geometry estimation algorithm that does not require precise positioning of the phantom at machine isocenter and is insensitive to positional imprecision of fiducial markers within the phantom due to fabrication errors. The method can accurately locate source and detector isocenters even when using an imprecise phantom, which is very important for measurement of isocenter coincidence of the therapy and on-board imaging systems.

Reconstruction of brachytherapy seed positions and orientations from cone-beam CT x-ray projections via a novel iterative forward projection matching method.

PURPOSE: To generalize and experimentally validate a novel algorithm for reconstructing the 3D pose (position and orientation) of implanted brachytherapy seeds from a set of a few measured 2D cone-beam CT (CBCT) x-ray projections. METHODS: The iterative forward projection matching (IFPM) algorithm was generalized to reconstruct the 3D pose, as well as the centroid, of brachytherapy seeds from three to ten measured 2D projections. The gIFPM algorithm finds the set of seed poses that minimizes the sum-of-squared-difference of the pixel-by-pixel intensities between computed and measured autosegmented radiographic projections of the implant. Numerical simulations of clinically realistic brachytherapy seed configurations were performed to demonstrate the proof of principle. An in-house machined brachytherapy phantom, which supports precise specification of seed position and orientation at known values for simulated implant geometries, was used to experimentally validate this algorithm. The phantom was scanned on an ACUITY CBCT digital simulator over a full 660 sinogram projections. Three to ten x-ray images were selected from the full set of CBCT sinogram projections and postprocessed to create binary seed-only images. RESULTS: In the numerical simulations, seed reconstruction position and orientation errors were approximately 0.6 mm and 5 degrees, respectively. The physical phantom measurements demonstrated an absolute positional accuracy of (0.78 +/- 0.57) mm or less. The theta and phi angle errors were found to be (5.7 +/- 4.9) degrees and (6.0 +/- 4.1) degrees, respectively, or less when using three projections; with six projections, results were slightly better. The mean registration error was better than 1 mm/6 degrees compared to the measured seed projections. Each test trial converged in 10-20 iterations with computation time of 12-18 min/iteration on a 1 GHz processor. CONCLUSIONS: This work describes a novel, accurate, and completely automatic method for reconstructing seed orientations, as well as centroids, from a small number of radiographic projections, in support of intraoperative planning and adaptive replanning. Unlike standard back-projection methods, gIFPM avoids the need to match corresponding seed images on the projections. This algorithm also successfully reconstructs overlapping clustered and highly migrated seeds in the implant. The accuracy of better than 1 mm and 6 degrees demonstrates that gIFPM has the potential to support 2D Task Group 43 calculations in clinical practice.

Localizing intracavitary brachytherapy applicators from cone-beam CT x-ray projections via a novel iterative forward projection matching algorithm.

PURPOSE: To present a novel method for reconstructing the 3D pose (position and orientation) of radio-opaque applicators of known but arbitrary shape from a small set of 2D x-ray projections in support of intraoperative brachytherapy planning. METHODS: The generalized iterative forward projection matching (gIFPM) algorithm finds the six degree-of-freedom pose of an arbitrary rigid object by minimizing the sum-of-squared-intensity differences (SSQD) between the computed and experimentally acquired autosegmented projection of the objects. Starting with an initial estimate of the object's pose, gIFPM iteratively refines the pose parameters (3D position and three Euler angles) until the SSQD converges. The object, here specialized to a Fletcher-Weeks intracavitary brachytherapy (ICB) applicator, is represented by a fine mesh of discrete points derived from complex combinatorial geometric models of the actual applicators. Three pairs of computed and measured projection images with known imaging geometry are used. Projection images of an intrauterine tandem and colpostats were acquired from an ACUITY cone-beam CT digital simulator. An image postprocessing step was performed to create blurred binary applicators only images. To quantify gIFPM accuracy, the reconstructed 3D pose of the applicator model was forward projected and overlaid with the measured images and empirically calculated the nearest-neighbor applicator positional difference for each image pair. RESULTS: In the numerical simulations, the tandem and colpostats positions (x,y,z) and orientations (alpha, beta, gamma) were estimated with accuracies of 0.6 mm and 2 degrees, respectively. For experimentally acquired images of actual applicators, the residual 2D registration error was less than 1.8 mm for each image pair, corresponding to about 1 mm positioning accuracy at isocenter, with a total computation time of less than 1.5 min on a 1 GHz processor. CONCLUSIONS: This work describes a novel, accurate, fast, and completely automatic method to localize radio-opaque applicators of arbitrary shape from measured 2D x-ray projections. The results demonstrate approximately 1 mm accuracy while compared against the measured applicator projections. No lateral film is needed. By localizing the applicator internal structure as well as radioactive sources, the effect of intra-applicator and interapplicator attenuation can be included in the resultant dose calculations. Further validation tests using clinically acquired tandem and colpostats images will be performed for the accurate and robust applicator/sources localization in ICB patients.

Bow-tie wobble artifact: effect of source assembly motion on cone-beam CT.

PURPOSE: To investigate the cause of a bow-tie wobble artifact (BWA) discovered on Varian OBI CBCT images and to develop practical correction strategies. METHOD AND MATERIALS: The dependence of the BWA on phantom geometry, phantom position, specific system, and reconstruction algorithm was investigated. Simulations were conducted to study the dependence of the BWA on scatter and beam hardening corrections. Geometric calibration was performed to rule out other gantry-angle dependent mechanical non-idealities as BWA causes. Air scans were acquired with ball-bearing markers to study the motions of the x-ray head assembly as functions of gantry angle. Based on measurements, we developed hypothesis regarding the BWA cause. Simulations were performed to validate our hypothesis. Two correction strategies were implemented: a measurement-based method, which acquires gantry-dependent normalization projections (NPs); and a model-based method that involves numerically shifting the single-angle NP to compensate for the previously-measured bow-tie-filter (BTF) motion. RESULTS: The BWA has a diameter of approximately 15 cm, is centered at the isocenter, and is reproducible independent of phantom, position, system, reconstruction, and standard corrections, but only when the BTF is used. Measurements identified a 2D sinusoidal gantry-angle-dependent motion of the x-ray head assembly, and it was the BTF motion (>3 mm amplitude projected onto the detector) resulting an intensity mismatch between the all-angle CBCT projections and a single-angle NP that caused the BWA. Both correction strategies were demonstrated effective. CONCLUSIONS: A geometric mismatch between the BTF modulation patterns on CBCT projections and on the NP causes the BWA. The BTF wobble requires additional degrees of freedom in CBCT geometric calibration to characterize.