A novel restricted single-isocenter stereotactic body radiotherapy (RESIST) method for synchronous multiple lung lesions to minimize setup uncertainties

Treating multiple lung lesions synchronously using a single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can improve treatment efficiency and patient compliance. However, due to set up uncertainty, aligning multiple lung tumors on a single daily cone beam CT (CBCT) image has shown clinically unacceptable loss of target(s) coverage. Herein, we propose a Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST), an alternative treatment that mitigates patient setup uncertainties. Twenty-one patients with two lung lesions were treated with single-isocenter VMAT-SBRT using a 6MV-FFF beam to 54 Gy in 3 fractions (n = 7) or 50 Gy in 5 fractions (n = 14) prescribed to 70-80% isodose line. To minimize setup uncertainties, each plan was re-planned using the RESIST method, utilizing a single-isocenter placed at the patient's mediastinum. It allows for an individual plan to be created for each tumor, using the first plan as the base-dose for the second plan, while still allowing both tumors to be treated in the same session. The technique uses novel features in Eclipse, including dynamic conformal arc (DCA)-based dose and aperture shape controller before each VMAT optimization. RESIST plans provided better target dose conformity (p < 0.001) and gradient indices (p < 0.001) and lower dose to adjacent critical organs. Using RESIST to treat synchronous lung lesions with VMAT-SBRT significantly reduces plan complexity as demonstrated by smaller beam modulation factors (p < 0.001), without unreasonably increasing treatment time. RESIST reduces the chance of a geometric miss due by allowing CBCT matching of one tumor at a time. Placement of isocenter at the mediastinum avoids potential patient/gantry collisions, provides greater flexibility of noncoplanar arcs and eliminates the need for multiple couch movements during CBCT imaging. Efficacy of RESIST has been demonstrated for two lesions and can potentially be used for more lesions. Clinical implementation of this technique is ongoing.     

The standardization of 62Cu and experimental determinations of dose calibrator settings for generator-produced 62CuPTSM.

The Positron Emission Tomography agent 62Cu Pyruvaldehyde Bis(N4-methyl)thiosemicarbazone (PTSM) has been standardized by the National Institute of Standards and Technology (NIST) using 4 pi beta liquid scintillation counting with 3H-standard efficiency tracing. Using a measurement model developed at NIST for the determination of experimental dose calibrator dial settings for short-lived radionuclides, the correct dial settings for 62CuPTSM in a clinically useful geometry (a 35 ml plastic syringe containing 33 ml of solution) as well as the standard NIST 5 ml glass ampoule have been elucidated. This measurement model is fully described, as is the treatment of associated uncertainties. The correct instrument settings for the NIST Capintec CRC-12 re-entrant ionization chamber ('dose calibrator') were found to be '499 +/- 6' and '489 +/- 8', respectively, for the syringe and ampoule geometries. The stated uncertainties are expanded (k = 2) uncertainties. The expanded uncertainties in the measured activity arising from these new dial settings are +/- 0.8% and +/- 1.4%, respectively, for the syringe and ampoule. The measured activities using these settings are lower than those obtained from the manufacture's recommended setting of '448' by 9.7% for the syringe and 7.7% for the ampoule, and underscore the need for experimental verification of the dose calibrator settings for each radionuclide and each geometry used in the clinic.     

Characterization of spatiotemporally complex gait patterns using cross-correlation signatures

We hypothesize that spatiotemporal joint coupling patterns during gait are closely associated with musculoskeletal injury mechanics. Previous studies examining joint coupling, have primarily focused on coupling between single pairs of neighboring body segments or joints; thus falling short of characterizing the full spatiotemporal complexity across the entire gait apparatus. This study proposes the reliance on properties of the temporal cross-correlation of distinct joint variables as a means to characterize and detect differences in multiple segmental coupling pairs and to quantify how these couplings change between different gait conditions or test groups. In particular, for each subject, a characteristic diagram array is obtained whose entries include the maximum values of the cross-correlation between all pairs of joint variables as well as the associated phase shifts at which these maxima are recorded. Paired t-tests are then used to highlight significant differences in the corresponding entries between two gait conditions. In the present study, this technique was applied to angular displacement and velocity histories across 12 lower extremity joint variables, for healthy subjects with and without a brace on the right knee. As expected, the statistical analysis indicated that the temporal cross-correlations associated with the right knee-angle variables differed the most between the two gait conditions. In addition, significant differences (p<0.01) were found in the coupling between other pairs of joint variables, establishing a characteristic spatiotemporal signature for the changes from normative gait that result from reduced mobility at the knee.     

Uncertainties in inverse dynamics solutions: a comprehensive analysis and an application to gait

This paper presents a comprehensive analysis of the uncertainties in joint torque estimates derived through inverse dynamics. The analysis considered most of the quantifiable sources of inaccuracy in the input variables for inverse dynamics solutions (i.e., errors in body segment parameter estimates, joint center of rotation locations, force plate measurements, motion capture system measurements, and segment angle calculations due to skin movement artifacts). Estimates of inaccuracies were synthesized from existing literature and from a complementary set of experimental data. The analysis was illustrated and tested via an inverse dynamic analysis of gait, in which kinematic and force plate data from 10 adult subjects were recorded and used to calculate the planar (flexion/extension) torques at the ankle, knee, hip, elbow, shoulder, and bottom of torso. The results suggested that the uncertainties in torque estimates derived through inverse dynamics can be substantial (6–232% of the estimated torque magnitude); the time-varying uncertainty patterns do not resemble the torque profiles, and the magnitudes are smaller for more distal joints; the main contributors to these uncertainties were identified to be the inaccuracies in estimated segment angles and body segment parameters. The empirical test also showed that the uncertainty predicted by a more conservative (smaller) set of inaccuracy estimates was comparable to the statistical (3σ) bound of the error. Implications in terms of how inverse dynamics solutions should be interpreted and improved, along with the limitations of the current work, are discussed.     

On the calculation of activity concentrations and nuclide ratios from measurements of atmospheric radioactivity

Motivated by the need for consistent use of concepts central to the reporting of results from measurements of atmospheric radioactivity, we discuss some properties of the methods commonly used. Different expressions for decay correction of the activity concentration for parent–daughter decay pairs are presented, and it is suggested that this correction should be performed assuming parent–daughter ingrowth in the sample during the entire measurement process. We note that, as has already been suggested by others, activities rather than activity concentrations should be used when nuclide ratios are calculated. In addition, expressions that can be used to transform activity concentrations to activity ratios are presented. Finally we note that statistical uncertainties for nuclide ratios can be properly calculated using the exact solution to the problem of confidence intervals for a ratio of two jointly normally distributed variables, the so-called Fieller׳s theorem.     

Cost drivers and resource allocation in military health care systems

This study illustrates the feasibility of incorporating technical efficiency considerations in the funding of military hospitals and identifies the primary drivers for hospital costs. Secondary data collected for 24 U.S.-based Army hospitals and medical centers for the years 2001 to 2003 are the basis for this analysis. Technical efficiency was measured by using data envelopment analysis; subsequently, efficiency estimates were included in logarithmic-linear cost models that specified cost as a function of volume, complexity, efficiency, time, and facility type. These logarithmic-linear models were compared against stochastic frontier analysis models. A parsimonious, three-variable, logarithmic-linear model composed of volume, complexity, and efficiency variables exhibited a strong linear relationship with observed costs (R(2) = 0.98). This model also proved reliable in forecasting (R(2) = 0.96). Based on our analysis, as much as $120 million might be reallocated to improve the United States-based Army hospital performance evaluated in this study.     

Magnetic resonance diffusion/perfusion phantom experiments

Recently, several models for determining microcirculatory parameters using magnetic resonance imaging have been proposed. These include the intravoxel incoherent motion (IVIM) model, the intravoxel coherent motion (IVCM) model, and various tracer models. In order to evaluate these models before extension into physiological systems, phantom studies were used to assess model assumptions, measurement uncertainties, and sensitivity to changes in perfusion. Emphasis is placed on the IVIM model, but the techniques discussed could be extended to evaluation of other models as well. An overview of considerations in pulse sequence development, phantom design, and data interpretation is presented for a variety of phantoms ranging in complexity from stationary volumes of fluid and mechanically pumped phantoms to isolated animal kidneys and finally to an in vivo animal model.     

User introduced uncertainties in the measurement of field misalignment by a computer aided technique

While images acquired using an electronic portal imager may be visually compared to other portal or simulator images to assess patient alignment, a more quantitative comparison is desirable. Computer aided alignment tools are available which are based on user placed landmarks. The purpose of this study was to estimate uncertainties introduced by the user to the final measurement of field misalignment using such a tool. Both intra- and inter-user reproducibility were assessed. To complete this task, a number of image pairs including both phantom and patient images were compared by multiple observers. Results of the comparisons (x- and y- translation and rotation) were tabulated for each image pair and their reproducibility assessed by calculating a mean and standard deviation. User introduced uncertainty was found to be independent of the magnitude of rotation or x- or y- translation. In all cases, there was no difference between intra-observer and inter-observer uncertainty. For clinical cases, there is a significant difference between uncertainty in x- and y- translation due to both image quality and patient anatomy. In addition, the magnitude of uncertainty tracks qualitatively with image quality and number of available anatomical landmarks. The decision to make a correction in field alignment must be made considering these uncertainty estimates. Image comparison must be fully automated to eliminate uncertainties introduced by the user.     

Estimating test-retest reliability in functional MR imaging I: Statistical methodology

A common problem in the analysis of functional magnetic resonance imaging (fMRI) data is quantifying the statistical reliability of an estimated activation map. While visual comparison of the classified active regions across replications of an experiment can sometimes be informative, it is typically difficult to draw firm conclusions by inspection; noise and complex patterns in the estimated map make it easy to be misled. Here, several statistical models, of increasing complexity, are developed, under which “test-retest” reliability can be meaningfully defined and quantified. The method yields global measures of reliability that apply uniformly to a specified set of brain voxels. The estimates of these reliability measures and their associated uncertainties under these models can be used to compare statistical methods, to set thresholds for detecting activation, and to optimize the number of images that need to be acquired during an experiment.     

User introduced uncertainties in the measurement of field misalignment by a computer aided technique

While images acquired using an electronic portal imager may be visually compared to other portal or simulator images to assess patient alignment, a more quantitative comparison is desirable. Computer aided alignment tools are available which are based on user placed landmarks. The purpose of this study was to estimate uncertainties introduced by the user to the final measurement of field misalignment using such a tool. Both intra- and inter-user reproducibility were assessed. To complete this task, a number of image pairs including both phantom and patient images were compared by multiple observers. Results of the comparisons (x- and y- translation and rotation) were tabulated for each image pair and their reproducibility assessed by calculating a mean and standard deviation. User introduced uncertainty was found to be independent of the magnitude of rotation or x- or y- translation. In all cases, there was no difference between intra-observer and inter-observer uncertainty. For clinical cases, there is a significant difference between uncertainty in x- and y- translation due to both image quality and patient anatomy. In addition, the magnitude of uncertainty tracks qualitatively with image quality and number of available anatomical landmarks. The decision to make a correction in field alignment must be made considering these uncertainty estimates. Image comparison must be fully automated to eliminate uncertainties introduced by the user.     

Doppler echocardiography for the estimation of cardiac output with exercise

Insights into both normal and pathological cardiac responses to exercise have been hampered by lack of a safe, accurate, feasible means of estimating cardiac output (Q) during high-intensity and maximal exercise. Doppler ultrasound noninvasively measures blood velocity as it exits the heart and can be performed during exhaustive exercise without interference of the subject or need for steady state. From the product of aortic blood velocity and cross-sectional area of the aorta, stroke volume (SV) can be calculated. Despite these advantages of the Doppler technique, a number of potential sources of error have raised concern regarding the accuracy of this method. These include transducer angulation, change in aortic cross-sectional area during exercise, turbulence and alteration of a flat velocity profile in the aorta with increased Q, and uncertainties regarding the proper location for measurement of aortic outflow area. The magnitude of the influence of these potentially confounding variables on the accuracy of SV measurements determined by the Doppler technique is unknown. Estimates of both construct and concurrent validity suggest that the overall error may be small. Test-retest studies have indicated a high level of reliability with this technique.     

Seven years of gamma-ray spectrometry interlaboratory comparisons in Switzerland

Since the 1990s, regular comparisons of gamma-ray spectrometry in Switzerland were organized to improve laboratory abilities to measure the radioactivity in the environment and food stuffs at typical routine levels. The activity concentration of the test samples and the evaluation of the associated uncertainties remained each year the main required test result. Over the years, the comparisons used certified reference solutions as well as environmental samples. The aim of this study is to research the effect of the comparisons on measurement quality. An analysis of the seven last interlaboratory comparisons revealed that the Swiss measurement capability is up to date. In addition, the results showed that the participants now have an improved evaluation of the uncertainties associated with their measurement.     

Radon measurements—discussion of error estimates for selected methods

The main sources of uncertainties for grab sampling, short-term (charcoal canisters) and long term (track detectors) measurements are: systematic bias of reference equipment; random Poisson and non-Poisson errors during calibration; random Poisson and non-Poisson errors during measurements. The origins of non-Poisson random errors during calibration are different for different kinds of instrumental measurements.The main sources of uncertainties for retrospective measurements conducted by surface traps techniques can be divided in two groups: errors of surface ²¹⁰Pb (²¹⁰Po) activity measurements and uncertainties of transfer from ²¹⁰Pb surface activity in glass objects to average radon concentration during this object exposure. It's shown that total measurement error of surface trap retrospective technique can be decreased to 35%.     

Assessment of robustness of institutional applied clinical target volume (CTV) to planning target volume (PTV) margin in cervical cancer using biological models

The aim of this study is to investigate the robustness of our institutionally applied clinical target volume (CTV)-to-planning target volume (PTV) margins in cervical cancer patients in terms of an equivalent uniform dose (EUD) based on tumor control probability (TCP). We simulated target motion using 25 IMRT cervical cancer plans to demonstrate the effect of geometrical uncertainties on the EUD and TCP. The different components of the total geometrical uncertainties budget were estimated. The biological effects were compared by calculating the EUDs from the trial DVHs. The impact of geometric uncertainties was calculated as a percentage of the difference between 〖EUD〗_static and 〖EUD〗_motion, where the 〖EUD〗_static is the EUD calculated from the target DVHs and 〖EUD〗_motion is averaged, over a 1000 calculated EUDs for each of the analyzed IMRT treatment plans. The multivariate nonlinear regression was used to find the predicted difference between the static and motion EUD. The estimate of the systematic and random motion errors were Σ_(total(SI,LR,AP)) (mm)=(2.6; 2.5; 1.8) and σ_(total(SI,LR,AP)) (mm)=(3.4; 1.4; 3.4). For average 〈EUD〉_motion=44.3 Gy (over 25 patients) we have found a TCP decrease of about 1%, %(ΔTCP)≈1% for predefined PTV margin. According to the calculated EUD motion-distributions, for particular patients, the CTV does receive the prescribed EUD of 45 Gy. The predicted difference in EUD showed that our isotropic margin of 10 mm is large enough to absorb geometric uncertainties and ensure dose coverage of the moving CTV in the cervical cancer patients.     

Factor analysis of the functional limitations test in healthy individuals

The NeuroCom's Functional Limitations test evaluates motor performances on various dynamic movements but it is not known how the outcome variables among these movements might be related to each other. An exploratory factor analysis was conducted in healthy young individuals to identify the dimensions that contribute to the overall variance associated with the variables in the test items. Six factors comprising 18 out of 24 variables explained 76% of the overall variance. Variables from within a test item tended to be grouped in the same factor, suggesting that each item evaluates a particular set of motor skills that is required to execute the movement. The results suggest that all six items of the Functional Limitations test should to be used to estimate the overall functional motor control performance of an individual. The normative data gathered in this study using healthy individuals will allow us to compare individuals with movement limitations.     

Reproducibility of 3D proton spectroscopy in the human brain.

The inter- and intrasubject reproducibility of the metabolite levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), obtained with three-dimensional (3D) multivoxel proton spectroscopy (1H-MRS), was analyzed in eight healthy volunteers. Serial, back-to-back measurements on a phantom showed the methodology and instrumentation to be highly reproducible, with a median coefficient of variation (CV) of 3.8%. In the human brain, the metabolite levels' variability was larger, with intrasubject median CVs for a total of 1876 signal voxels of 13.8%, 18.5%, and 20.1% for NAA, Cr, and Cho, respectively. These variations possibly arise from small, unavoidable, +/-1-2 mm volume-of-interest (VOI) repositioning uncertainties, which vary each 0.75-cm(3) voxel's partial fluid/gray/white-matter fractions. Comparing the CVs between eight subjects in a total of 324 selected voxels gave total interindividual CVs of 15.6%, 23.3%, and 24.4%, compared with intraindividual CVs in the same voxels of 14.4%, 14.8%, and 15.3%, for NAA, Cr, and Cho, respectively. Replacing the signal(s) from each voxel by the average of itself with its six canonical neighbors reduces the intrasubject median CVs to 8.3%, 9.5%, and 9.7%. The measurement uncertainties can be reduced at a cost of either spatial resolution (by using larger voxels) or time (by performing serial follow-ups).     

Uncertainties in 63Ni and 55Fe determinations using liquid scintillation counting methods

The implementation of (63)Ni and (55)Fe determination methods in an environmental laboratory implies their validation. In this process, the uncertainties related to these methods should be analysed. In this work, the expression of the uncertainty of the results obtained using separation methods followed by liquid scintillation counting is presented. This analysis includes the consideration of uncertainties coming from the different alternatives which these methods use as well as those which are specific to the individual laboratory and the competency of its operators in applying the standard ORISE (Oak Ridge Institute for Science and Education) methods.     

Asymmetries in ground reaction force patterns in normal human gait

The purpose of this study was to propose a measure of symmetry/asymmetry for normal human gait and to quantify symmetries/asymmetries of normal human gait for selected gait variables using a force platform. Sixty-two subjects performed ten gait trials each, stepping on the force platform five times with each leg. From these gait trials a symmetry index was calculated for 34 gait variables. The upper and lower limits of normal gait were calculated such that 95% of all symmetry indices obtained from this subject population fell within these limits. Upper and lower limits were found to vary from +/- 4% to over +/- 13,000%. Extremely high percentages were found for variables which had absolute magnitudes close to zero and/or variables which occurred at distinctly different instants during the gait cycle. The results of these variables need to be interpreted with caution.