Trends of twinning rates in ten countries, 1972-1996

The data quality and completeness of acquired images, which we refer to as integrity, is considered as the most important requirement in the image acquisition design of the Picture Archiving and Communication System (PACS). The Digital Imaging and Communications in Medicine (DICOM) standard significantly simplifies the task of acquiring radiological images from a DICOM compliant imaging system into the PACS. However, human interaction with the imaging system by changing the DICOM communication settings can result in missing images during the PACS image acquisition. A scheme based on the DICOM Query and Retrieve (Q/R) service class was developed to automatically identify and recover missing images. In addition, grouping sequential scanned images such as a CT and MR image series is another potential process that can miss images because of no indication of the end of series. Two methods are presented for determining the end of series and the pros and cons of each method are discussed in detail. Two experiments in a real clinical environment were conducted; one with and one without the Q/R implementation. The statistical results indicate two highlights from this work. First, the Q/R scheme faithfully recovered all missing images caused by human interaction with the DICOM compliant imaging system. Second, there was no single image slice missed when grouping slices into a series using the presented grouping algorithm in the two experimental periods.     

Simulation of two-dimensional tagged MRI

MR tagging is a recent imaging development that, in cardiac applications, makes possible the tracking of points in the myocardium during the cardiac cycle. Researchers have developed semiautomated, computer-based methods for analyzing tagged images, but the images are complex and present a challenge to automated tracking systems. Simulation can provide an inexhaustible supply of images for testing and validation of tag tracking software and preview the effect of parameter changes in acquisition. SIMTAG is an interactive computer program that simulates two-dimensional tagged-MR experiments. The mathematic model used in the simulation and algorithms for simulating image noise and object deformation are described. Examples of the use of simulated images in SPAMM parameter selection, a comparison of tag contrast in signal-averaged SPAMM and CSPAMM, and simulated images as test sets for tag-tracking software are presented.     

p53 mutations and overexpressions in Japanese breast cancer

In this paper, we explore the use of a variety of familial transmission tests (and case-control analyses) to screen for allelic associations in simulated marker data of a quality (2 cM map) that will feasibly arise from genomic scans within the next 5-10 years. We demonstrate a form of the transmission-disequilibrium test extended to multiallele systems. The methods used were log-linear and related models implemented largely using standard statistical packages.     

Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2

Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets.     

Hodgkin''s disease and anaplastic large cell lymphoma in 1998

The purpose of this study was to investigate the effects of cohort size on maximum likelihood estimates of mortality parameters. Recent experimental investigations have stressed the importance of large cohorts for detecting leveling off of mortality rates at older ages. In the present study, emphasis was placed on evaluation of relatively small cohorts (about 150-300 individuals). Deaths were simulated under the assumption of the frailty mortality model. Two different parameter sets that resulted in differences in mean life span of more than twofold were used for simulations. Our smallest cohorts yielded parameter estimates that had generally good statistical properties, but relatively large standard errors. For tests of hypotheses concerning equality of parameters among populations or experimental treatments, empirical standard errors (obtained from several cohorts) were preferable to asymptotic standard errors (obtained for single cohorts). In particular, empirical standard errors yielded reliable type I error rates.     

Quantitative imaging in electron and confocal microscopies for applications in biology

Among the large number of topics related to the quantification of images in electron and confocal microscopies for applications in biology, we selected four subjects that we consider to be representative of some recent tendencies. The first is the quantification of three-dimensional data sets recorded routinely in scanning confocal microscopy. The second is the quantification of the textural and fractal appearance of images. The two other topics are related to image series, which are more and more often provided by imaging instruments. The first kind of series concerns electron energy-filtered images. We show that the parametric (modelling) approach can be complemented by non-parametric approaches (e.g., different variants of multivariate statistical techniques). The other kind of series consists of multiple mappings of a specimen. We describe several new tools for the study and quantification of the co-location, with potential application to multiple mappings in microanalysis or in fluorescence microscopy.     

A simple algorithm for planar image registration in radiation therapy

A simple algorithm is presented for planar image registration and the method is applied to the simulator and portal image registration for patient setup verification in radiation therapy. Basically, the algorithm follows the concept proposed by Balter et al. [Med. Phys. 19, 329-334 (1992)], which converts the problem of open curve registration into matching a series of points along the curves. Balter's algorithm consists of three steps: (1) to determine a common starting point for each curve pair, (2) acquire two corresponding point sets along each curve, and (3) obtain a global transform matrix by matching two point sets. We integrate all three steps into one simple procedure which fits the sampled points along the intended curve pair by taking the relative path length shift as an independent fitting parameter. After being modified, the algorithm is able to take the different magnification factors of images into account, and it avoids curvature calculations. Numerical simulation as well as clinical and phantom images have been utilized to test the accuracy of the algorithm. The typical errors are less than 1 mm in translation and 1 degree in rotation. We also made a comparison study with the chamfer method. The results of the two methods agree to within 0.5 mm in translation and 0.5 degree in rotation.     

Load Testing and Settlement Prediction of Shallow Foundation

The purpose of this study was to critically examine insitu test methods as a means for predicting settlement of shallow foundations. Accordingly, a 1.8?m (6?ft) diameter concrete footing was statically load tested. Prior to construction, insitu [standard penetration test (SPT), cone penetration test (CPT), dilatometer (DMT), and pressuremeter (PMT)] and laboratory tests were performed to determine engineering properties of the soil. Predictions of the footing settlement were made by traditional as well as finite element methods. The results of the static load test showed settlements were over predicted by all methods. However, the traditional methods provided reasonable settlement estimates using either SPT-N or back computed CPT(N) as input. Finite element analyses using either DMT or CPT derived input parameters provided reasonable settlement estimates. Finite element analyses using SPT or PMT derived input parameters provided poor settlement estimates. The Mohr–Coulomb (elastoplastic) model, accounting for overconsolidation, provided better estimates than the hardening soil (hyperbolic-cap) model for all insitu test derived parameters.     

Real-time homogeneous assay of rapid cycle polymerase chain reaction product for identification of Leptonema illini

The validation study is described of a new modelling method that has been developed, using tracer kinetic modelling with positron emission tomography (PET) to achieve non-invasive measurement of myocardial metabolic rate of glucose (MMRGlc). Eight data sets obtained from dynamic cardiac PET 2-[18F]fluoro-2-deoxy-D-glucose (FDG) studies on human subjects are employed, and the estimation of MMRGlc using both the new and traditional methods is compared. The results from all eight human FDG studies are consistent with those from previous computer simulations. With the new method, the estimated mean of K (a parameter directly proportional to MMRGlc) increases by about 8%, and that of k 4 (the rate constant of FDG dephosphorylation) decreases by about 48%. The approach should be more suitable for use in dynamic cardiac PET studies when non-invasive means are used to obtain the plasma time-activity curve from left-ventricle PET images.     

Statistical distribution of factors and factor images in factor analysis of medical image sequences

From a time or energy image sequence, factor analysis of medical image sequences (FAMIS) estimates factors, representing kinetics or spectra in a given physiological compartment, and associated factor images, showing the compartments corresponding to each curve. In this paper, we show that the statistical properties of factor images and associated factors can be determined using a well known result from elementary probability theory. Numerical experiments are conducted to demonstrate that the variance observed in factor images can be predicted when the statistical properties of the original data are known. It is shown how these theoretical results can be used to relax the non-negativity constraints during FAMIS oblique analysis and to improve the quantitative interpretation of the factor images by associating a confidence interval with each pixel value.     

Accurate tests of statistical significance for rWG and average deviation interrater agreement indexes.

The authors demonstrated that the most common statistical significance test used with rWG-type interrater agreement indexes in applied psychology, based on the chi-square distribution, is flawed and inaccurate. The chi-square test is shown to be extremely conservative even for modest, standard significance levels (e.g., .05). The authors present an alternative statistical significance test, based on Monte Carlo procedures, that produces the equivalent of an approximate randomization test for the null hypothesis that the actual distribution of responding is rectangular and demonstrate its superiority to the chi-square test. Finally, the authors provide tables of critical values and offer downloadable software to implement the approximate randomization test for rWG type and for average deviation (AD)-type interrater agreement indexes. The implications of these results for studying a broad range of interrater agreement problems in applied psychology are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute vision loss resulting from complications of ethanol abuse

A dynamic digital brain phantom was created from the MRI to evaluate visually the relationship between the noise and the error in the parameter estimates in the PET kinetic analysis. This phantom incorporates the noise level depending on administration dose, camera efficiency and the data acquisition schedule. We simulated a serial dynamic scan with 18F-FDG or 11C-flumazenil, assuming 2-tissue 3-parameter model and 1-tissue 2-parameter model, respectively, and the sampling schedule was determined according to the clinical examination. The noise in the tissue time activity curve in FDG had a peak in the first minute and decreased thereafter, whereas the noise increased gradually in the flumazenil study after the initial peak due to radioactivity decay. We examined the relationship between the noise level and the error in the parameter estimates. Both mean absolute differences between true and estimated values and standard deviation became large, and the quality of the parametric images became poor with increasing noise level. This simulation was compared with human tissue time activity curves and parametric images, which were obtained with 100 MBq administration dose in FDG study and 430 MBq in flumazenil study. We inferred that the noise level in the human study was 10-20% in FDG, and 20-40% in flumazenil, and the error in the estimated parameter of K-complex in FDG study was about 20%, that of DV in flumazenil study was 2%.     

Human biodistribution and dosimetry of the PET perfusion agent copper-62-PTSM

Copper-62-pyruvaldehyde bis(N4-methyl)thiosemicarbazone (PTSM) has been proposed as a generator-produced radiopharmaceutical for perfusion imaging using PET. Several clinical studies have demonstrated the ability of 62Cu-PTSM to quantitate myocardial and cerebral perfusion in humans. Because 62Cu-PTSM is generator-produced, it can be provided to clinical centers without cyclotron availability and, therefore, represents a cost-effective, practical PET perfusion tracer for clinical applications. To assess the safety, time-dependent biodistribution, and whole-body and organ-specific absorbed radiation dose estimates of this tracer, a Phase I study of 62Cu-PTSM was performed using whole-body imaging with PET in 10 healthy volunteers and with the radiopharmaceutical delivered by a compact modular generator unit. METHODS: Five male and five female subjects underwent a series of clinical tests and head-to-midthigh, whole-body PET scans at three time points over 1 hr after intravenous injection of 62Cu-PTSM. Before injection of the tracer, PET transmission scans were performed and used to correct the emission data for attenuation. Final image data were expressed in units of mCi/cc. Using standard organ weights, the percent injected dose per organ was calculated. Biodistribution data were obtained at three different time points and from these data biological half-lives in different organs were determined for calculation of radiation absorbed dose estimates. RESULTS: The liver was seen as the critical organ receiving a dose of 0.0886 rad/mCi. This organ defined the maximum single injected dose at 56 mCi using the limit of 5 rads to a critical organ per study per year. The whole-body dose is 0.0111 rad/mCi, resulting in a 0.622 rad exposure with a maximum single injection dose. Only trace levels of activity were found in the urine, which suggests low levels of urinary excretion and bladder exposure. No significant clinical, electrocardiographic or laboratory abnormalities were seen after the injection of 62Cu-PTSM. CONCLUSION: Copper-62-PTSM is a clinically safe radiopharmaceutical with favorable dosimetry for human studies at injected doses significantly above those projected for use in clinical studies.     

Validation of an MRI/PET landmark registration method using 3D simulated PET images and point simulations

Three-dimensional (3D) simulated PET images generated from MRI were used to validate a multimodality registration technique based on the identification of internal anatomical landmarks. In addition, point-based simulations were compared with registration datasets acquired over 3 yr of routine use of the technique. Registration errors were found to range from 1.0 mm at the brain centre to 2.8 mm in each dimension at the brain surface.     

Logistic regression models with missing covariate values for complex survey data

Maximum likelihood methods are used to incorporate partially observed covariate values in fitting logistic regression models. We extend these methods to data collected through complex surveys using the pseudo-likelihood approach. One can obtain parameter estimates of the logistic regression model using standard statistical software and their standard errors by Taylor series expansion or the jackknife method. We apply the approach to data from a two-phase survey screening for dementia in a community sample of African Americans age 65 and older living in Indianapolis. The binary response variable is dementia and the covariate with missing values is a daily functioning score collected from interviews with a relative of the study subject.     

Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma

BACKGROUND: An extensive literature describes structural lesions in apraxia, but few studies have used functional neuroimaging. We used positron emission tomography (PET) to characterize relative cerebral glucose metabolism in a 65-year-old, right-handed woman with progressive decline in ability to manipulate objects, write, and articulate speech. OBJECTIVE: To characterize functional brain organization in apraxia. DESIGN AND METHODS: The patient underwent a neurological examination, neuropsychological testing, magnetic resonance imaging, and fludeoxyglucose F 18 PET. The patient's magnetic resonance image was coregistered to her PET image, which was compared with the PET images of 7 right-handed, healthy controls. Hemispheric regions of interest were normalized by calcrine cortex. RESULTS: Except for apraxia and mild grip weakness, results of the neurological examination were normal. There was ideomotor apraxia of both hands (command, imitation, and object) and buccofacial apraxia. The patient could recognize meaningful gestures performed by the examiner and discriminate between his accurate and awkward pantomime. The magnetic resonance image showed moderate generalized atrophy and mild ischemic changes. Positron emission tomographic scans showed abnormal fludeoxyglucose F 18 uptake in the posterior frontal, supplementary motor, and parietal regions, the left affected more than the right. Focal metabolic deficit was present in the angular gyrus, an area hypothesized to store conceptual knowledge of skilled movement. CONCLUSIONS: Greater parietal than frontal physiological dysfunction and preserved gesture recognition are not consistent with the theory that knowledge of limb praxis is stored in the dominant parietal cortex. Gesture comprehension may be more diffusely distributed.     

Intermodality, retrospective image registration in the thorax

The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.     

Randomization test for coupled data

Coupled data arise in perceptual research when subjects are contributing two scores to the data pool. These two scores, it can be reasonably argued, cannot be assumed to be independent of one another; therefore, special treatment is needed when performing statistical inference. This paper shows how the Type I error rate of randomization-based inference is affected by coupled data. It is demonstrated through Monte Carlo simulation that a randomization test behaves much like its parametric counterpart except that, for the randomization test, a negative correlation results in an inflation in the Type I error rate. A new randomization test, the couplet-referenced randomization test, is developed and shown to work for sample sizes of 8 or more observations. An example is presented to demonstrate the computation and interpretation of the new randomization test.