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PubMed1993

Accuracy and precision of quantitative digital coronary arteriography: observer-, short-, and medium-term variabilities.

Coronary arteriograms are increasingly acquired and stored in digital format, which allows instantaneous review of the pictorial data during the cardiac catheterization procedure. To support the angiographer in choosing the optimal sizes of the recanalization devices and studying the efficacy of the recanalization procedures, we have developed a new analytical software package (Automated Coronary Analysis = ACA) on the Philips DCI (-SX) digital cardiac imaging system. The ACA-package allows the objective and reproducible assessment of the morphologic and functional severity of coronary obstructions. Required user interaction is limited to the definition of the start and end points of the coronary segment to be analyzed. Automated contour detection is based on the use of first and second derivative functions along scanlines perpendicular to the automatically computed vessel pathline in the first iteration and perpendicular to the initial contours in the second iteration. These derivative functions have been modified based on the line spread function of the X-ray imaging chain, which is of particular importance for the accurate measurement of small vessel sizes. Phantom studies have indeed demonstrated that vessel sizes down to 0.66 mm can be measured accurately and reproducibly. Inter- and intraobserver variability studies have demonstrated a variability in the obstruction diameter of 0.11 mm and 0.10 mm, respectively, and in the percent diameter stenosis of 5.64% and 3.18%, respectively. These variability studies have been extended to short-term studies with repeated acquisition in the same angiographic views after 5 min and to medium-term studies with repeated acquisition in the initial angiographic views at the end of the catheterization procedures. With these standardized repeated acquisition and analysis procedures, the variabilities in the obstruction diameters increased to 0.19 and 0.18 mm, respectively, and remained below 6% in the percent diameter stenosis (5.61% and 5.28%, respectively). With an analysis time of approximately 15 sec on the DCI-SX, an efficient tool is now available in the catheterization laboratory for the objective and reproducible assessment of vessel dimensions and changes therein as a result of recanalization procedures.

Coronary Angiography↗

PubMed1996

Clinical evaluation of algorithms for ST measurement during exercise test.

HYPOTHESIS: Computer processing of the exercise electrocardiogram (ECG) has many advantages, but the reliability of the analysis algorithms is not easily evaluable. No standard annotated database, nor recommended practice for testing and reporting performance results is available: thus, performance evaluation of such devices can be accomplished only by using a set of unannotated recordings, obtained in clinical practice. We evaluated the accuracy of an original microcomputer-based exercise test analyzer comparing the ST computer output with the measurements obtained by two experienced cardiologists. METHODS: Six hundred ECG strips were randomly selected from the exercise test recordings of 60 patients. The ST shift (at J + 80 ms) was blindly assessed by two observers (with the aid of a calibrated lens) and compared with computer measurements. Correlation coefficients, linear regression equations, percent of discrepant measurements, and 95% confidence limits of the mean error were calculated for all leads, peripheral leads, precordial leads, and "stress-test" leads (II, III, aVF, V4, V5, V6). RESULTS: The computer did not analyze five samples on a total of 600 (0.83%) ECG strips because of excessive noise or signal loss, while 51 (8.5%) were considered unreadable by both observers and 67 (11.2%) were rejected by at least one observer. Correlation between the measurements taken by computer and observer(s) measurements was statistically significant (p < 0.001 for all lead groups), no systematic measurement bias was found, and the mean difference was lower than human eye resolution. CONCLUSIONS: Our algorithms provide results as good as those provided by trained cardiologists in measuring ST changes occurring during exercise test. However, this study did not evaluate whether computer improvement of the signal-to-noise ratio would allow accurate measurements even on cardiologists' uninterpretable ECG. This potential advantage of computer-assisted analysis could be assessed only by using a dedicated exercise test database, in which different patterns of noise are superimposed on noise-free recordings previously annotated for ST level.

Adult↗

PubMed1994

Improved programs for the affected-pedigree-member method of linkage analysis.

The affected-pedigree-member (APM) method is a non-parametric method of linkage analysis, which requires no assumptions about how the trait of interest is inherited [Weeks and Lange, 1988, 1991, 1992; Lange and Weeks, 1990; Weeks et al., 1992]. The APM method uses only the affected members of each pedigree who are typed for the marker(s). Based on the affected members' marker genotypes and the relationships of the affecteds to each other, the APM method computes a statistic which provides a measure of marker similarity. If the affected members are significantly more similar at the marker locus than expected by chance, then one may conclude that the marker is not segregating independently of the disease. Since the APM method tests a hypothesis about marker similarity, and not about recombination between the marker and disease, it makes and requires no assumptions about the mode of inheritance of the disease. For this reason, the APM method has been used for complex diseases such as Alzheimer's, breast cancer, and melanoma [Pericak-Vance et al., 1989, 1990; Haile et al., 1990; Hall et al., 1990; St George-Hyslop et al., 1990; Cannon-Albright et al., 1992]. We would like to announce the availability of a much improved version of the APM program package. This version has been improved in several ways, as outlined below.

Bias↗

PubMed1995

Comparison of analysis of variance and maximum likelihood based path analysis of twin data: partitioning genetic and environmental sources of covariance.

In order to investigate currently used model fitting strategies for twin data, analysis of variance (ANOVA) and path-maximum-likelihood (PATH-ML) methods of analyzing twin data were compared using simulation studies of 50 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs. Phenotypic covariance was partitioned into additive genetic effects (A), environmental effects common to cotwins (C), and environmental variance unique to individuals (E). ANOVA and PATH-ML had identical power to detect total covariance. The PATH-ML AE model was much more powerful than ANOVA comparisons of rMZ and rDZ to detect A. However, to be unbiased, the AE model requires the assumption that C = 0.0. To allow use of the AE model to estimate A, the null hypothesis C = 0.0 is tested by comparing the goodness of fit of the ACE and AE models. Simulation of 50 MZ and 50 DZ pairs revealed that C must be greater than 55% of total variance before the null hypothesis would be rejected (P < 0.05) 80% of the time. Several recent publications were reviewed in which the null hypothesis C = 0.0 was accepted and apparently upwardly biased estimates of A, containing C, were presented with unrealistic P values. It was concluded that use of the AE model to estimate A gives an inflated view of the power of relatively small twin studies. It was recommended that ANOVA or comparison of the ACE and CE PATH-ML models be used to estimate and test the significance of A as neither requires that C = 0.0.

Analysis of Variance↗

PubMedDate not supplied

Computer-assisted identification and quantification of multiple sclerosis lesions in MR imaging volumes in the brain.

Magnetic resonance (MR) imaging is the principal imaging technique for the diagnosis of multiple sclerosis (MS). However, quantifying the number and extent of lesions on MR images manually is arduous. The authors have developed a computerized three-dimensional (3D) quantitative system to assist in the identification and analysis of MS lesions in proton-density (PD)- and T2-weighted volumes of the head. The system provides intuitive, interactive operations that allow flexible extraction of information from the data. Use of the system to analyze MR examinations of a phantom containing regular "lesions" showed that accurate (average error, < 0.21 cm3) and precise (10% or better for lesions > 1 cm3) measurements of objects less than 7 cm3 is possible, and that an estimate of the quantization error predicted the uncertainty in the volume. Analysis of four MR examinations of a chronic-progressive MS patient conducted over an 18-month period was performed. A two-dimensional histogram showing the frequency of voxels with particular PD- and T2-weighted intensities revealed a distinct cluster only in histograms of sections that contained lesions. Measurements and 3D volume rendering of lesions clearly showed changes in lesion shape, position, and size.

Algorithms↗

PubMed1993

Risk ratio and rate ratio estimation in case-cohort designs: hypertension and cardiovascular mortality.

Multivariate analysis in case-base designs depends on approximate methods. In the present study, new pseudo-likelihood methods are developed for this design. With these methods, the case-cohort risk ratio and rate ratio as well as their standard errors are easily estimated using logistic regression and Poisson regression, respectively. This is illustrated by the association between hypertension and cardiovascular mortality in a cohort, estimated by case-cohort analysis, using samples of several sizes. The estimates are compared with those obtaining in full-cohort and nested case-control designs. The results indicate that these methods, which require nothing but widely available computer software, are valid. The case-cohort design, therefore, is a good, sometimes even advantageous alternative to the nested case-control design, in studying a disease that is not very rare. Application of the risk ratio method to the full cohort, using a 'sample' of 100 per cent follows logically; whenever the true risk ratio is desired instead of the odds ratio, a multivariate model for its estimation is therefore available.

Adult↗

PubMed1995

Location-scale cumulative odds models for ordinal data: a generalized non-linear model approach.

Proportional odds regression models for multinomial probabilities based on ordered categories have been generalized in two somewhat different directions. Models having scale as well as location parameters for adjustment of boundaries (on an unobservable, underlying continuum) between categories have been employed in the context of ROC analysis. Partial proportional odds models, having different regression adjustments for different multinomial categories, have also been proposed. This paper considers a synthesis and further generalization of these two families. With use of a number of examples, I discuss and illustrate properties of this extended family of models. Emphasis is on the computation of maximum likelihood estimates of parameters, asymptotic standard deviations, and goodness-of-fit statistics with use of non-linear regression programs in standard statistical software such as SAS.

Humans↗

PubMed1998

Using lazy evaluation to simulate realistic-size repertoires in models of the immune system.

We describe a method of implementing efficient computer simulations of immune systems that have a large number of unique B- and/or T-cell clones. The method uses an implementation technique called lazy evaluation to create the illusion that all clones are being simulated, while only actually simulating a much smaller number of clones that can respond to the antigens in the simulation. The method is effective because only 0.001-0.01% of clones can typically be stimulated by an antigen, and because many simulations involve only a small number of distinct antigens. A lazy simulation of a realistic number of clones and 10 distinct antigens is 1000 times faster and 10,000 times smaller than a conventional simulation--making simulations of immune systems with realistic-size repertoires computationally tractable.

Algorithms↗

PubMed1993

Monitoring free-text data using medical language processing.

In this paper, we describe a software system for automated monitoring of free-text data in a medical information system that we call RadTRAC (Radiology Text Report Analyzer and Classifier). RadTRAC uses a medical language processing tool and rules derived from statistical analysis of a database to process free-text chest X-ray (CXR) reports and identify reports that describe new or expanding neoplasms for the purpose of monitoring the follow-up of these patients. To evaluate the RadTRAC system, we examined a set of 470 consecutive radiology reports at the Veterans Administration Medical Center, Palo Alto, CA. We compared RadTRAC classification of CXR reports with retrospective expert classification of the reports and with clinical classification from CXR films as recorded in a logbook while the films were being read. The RadTRAC system had a sensitivity of 90% and a specificity of 82% using the logbook as the gold standard. This was similar to the performance of expert radiologists (sensitivity, 92%; specificity, 90%). We then reviewed the charts, appointment schedule, and subsequent X-ray reports of cases either in the logbook or that were identified by RadTRAC as needing follow-up. Two cases in the logbook could have potentially benefited from an automatic monitoring system to ensure follow-up. RadTRAC identified six confirmed new tumors or new metastatic lesions that were not in the logbook. Six other cases were identified by the RadTRAC system with suspicious X-ray findings that had either no follow-up or no further mention of the X-ray lesion in medical records. This suggests that a reminder system based on the RadTRAC technology would be potentially useful.

Abstracting and Indexing↗

PubMed1997

Visualization-based analysis of multiparameter models using environment for N-dimensional model analysis.

We present a methodology, based on N-dimensional computer visualization, for analyzing multiparameter models. This approach originally consisted of three steps: behavior analysis, sensitivity analysis, identifiability analysis. We have now developed a new way of calculating sensitivity based on the statistical measure of the coefficient of variation. Furthermore, we extended the methodology through the addition of an extra step, visual regression. Visual regression allows the user to visualize the process of actual parameter identification and presents a combined, empirical view of the first three steps in a single image. Next we applied this methodology to pulmonary capillary-transport models. Finally, we implemented the model analysis process as a stand-alone program. EN-DIMAN, the resulting software, allows researchers to carry out model analysis in a graphical user interface (GUI)-based environment.

Algorithms↗

PubMed2000

An algorithm for clustering cDNA fingerprints.

Clustering large data sets is a central challenge in gene expression analysis. The hybridization of synthetic oligonucleotides to arrayed cDNAs yields a fingerprint for each cDNA clone. Cluster analysis of these fingerprints can identify clones corresponding to the same gene. We have developed a novel algorithm for cluster analysis that is based on graph theoretic techniques. Unlike other methods, it does not assume that the clusters are hierarchically structured and does not require prior knowledge on the number of clusters. In tests with simulated libraries the algorithm outperformed the Greedy method and demonstrated high speed and robustness to high error rate. Good solution quality was also obtained in a blind test on real cDNA fingerprints.

Algorithms↗

PubMed1986

An automated technique for analysis of current transitions in multilevel single-channel recordings.

Detailed kinetic studies of ion channel gating are best carried out using the patch-clamp technique which permits the measurement of the ionic current through individual channels. Typical patch-clamp recordings show the current signal, in the form of a sequence of rectangular pulses (analogous to a random telegraph signal), riding on slow baseline drift, partially obscured by high-frequency noise and distorted by filtering. In order to analyze such recordings, we have developed a set of interactive Pascal programs based on a feature-detection algorithm capable of identifying current transitions in multiple-channel recordings in the presence of substantial levels of noise and drift. Software operation is largely automated but includes provisions for examination and correction of the output. The software was optimized and systematically evaluated using simulated data with variable amounts of noise and drift. Results indicate that satisfactory performance is obtained for signal-to-noise ratio as low as four even with uncommonly large baseline drift. Steady-state processing speeds varied from 1,000 to 4,000 samples per second depending on data complexity.

Automation↗

PubMed1990

Experience with gated cardiac software phantoms for quality control of applications programmes.

Ten gated cardiac software phantoms, representing normal and abnormal clinical conditions, were transferred to 9 different computer systems and tested with 11 cardiac programmes. Problems of inappropriate data format were encountered when analysing the phantoms on other systems. The global left ventricular ejection fraction (LVEF) values resulting from the different programmes were compared. Significant programme differences were found, the programmes falling generally into two groups. Few LVEF outlier values were identified. Full functional assessment of cardiac phantoms requires a set of different views which together form the phantom. Application of software phantoms for programme assessment and training requires prudence and attention to the acquired data format, frame time, and gating method for the appropriate use of phantoms.

Computer Simulation↗

PubMed1991

Designing an outcome-oriented computer decision-support system for cardiovascular ICU--a preliminary report.

This paper describes the conceptual framework and preliminary results of an outcome-oriented decision-support system prototype for the cardiovascular intensive care unit (CVICU). The major characteristics of this design include: (1) its problem-based approach to solving clinical problems; (2) an integrated structure with the hospital information system in terms of its data, model and knowledge bases; (3) proposed alternative modes of interaction that include monitoring and critiquing; (4) and research modules that design, manage, and analyze outcome-based clinical studies. At present, an initial prototype has been implemented on a PC as a set of modules accessible from a main menu. The structural framework of the overall system is fairly well defined but only limited quantitative, statistical and expert knowledge has been captured. The second phase of the project involves porting the prototype to a Unix workstation environment, refining and adding models to the model base, expanding its knowledge bases, reasoning capability, and testing the prototype with actual clinical cases in a real-time fashion.

Alberta↗

PubMed1994

Microsoft Excel Program for creating attractive survival curves.

This paper describes the design of a Microsoft Excel Program which interactively creates attractive and outstanding survival curves. This program enables medical researchers to easily create quality presentation graphs of survival curves and obtain high quality slides and prints, which can be inserted in papers or used directly at medical meetings. Through the use of vertical bars, this program can display the exact points where censored cases occur on survival curves, making it possible to monitor censoring patterns between groups. Furthermore, this program can also create survival curves based on the proportional hazards model for specific patterns of covariate values, given estimated regression coefficients and baseline survival function. This program may be a most useful and effective tool in creating medical research papers containing survival analysis.

Age Factors↗

PubMed1991

A new microcomputer software system evaluation paradigm: the medical perspective.

The new fourth-generation software has enormously eased the burden of computing for users, but they have also created a confusing, difficult problem in software evaluation and selection. Therefore it is argued that a sound and complete evaluation paradigm is a key element in an efficient and effective software system design and use process. While much has been written about software evaluation in general, in the medical field, the guidances and recommendations previously provided are too general to be of practical use. Considering also the other weaknesses of conventional evaluation paradigms we have decided to develop a more adequate one which will have a solid theoretical framework, specific guidances, strict and well-defined taxonomic space, and a fair ranking approach. In the present paper we will therefore introduce our new evaluation paradigm and show its applicability in evaluation and selection of medical software systems according to their usability.

Classification↗

PubMed1991

An assessment of the radiological module of NEONATE as an aid in interpreting chest X-ray findings by nonradiologists.

NEONATE is a prototype of an expert system for the Newborn Intensive Care Unit developed at the Primary Children's Medical Center in Salt Lake City, Utah. A pilot study was undertaken to see if the addition of radiological frames to the NEONATE software could aid attending Neonatologists to interpret chest X-ray films. A set of radiological frames was created from rules generated by a radiologist. The performance of these radiological frames was compared to the performance of other radiologists using the Kappa statistic to measure agreement. There is a good agreement between the computer's decisions and the radiologists' decisions. The radiological frames were also tested to see if they help physicians who are not trained in radiology. A system that compares the residents' interpretation and the computer's interpretation to a gold standard interpretation was developed. It shows that the computer helps the first and second year residents, but not the third year residents. This article suggests that NEONATE's interpretation of chest X-ray findings are close to the radiologists' interpretations. While NEONATE's radiological frames help novice physicians in reaching better chest X-ray interpretation, the current study suggests that they are not likely to help a Neonatologist.

Evaluation Studies as Topic↗

PubMed1991

A distributed approach to integrated inquiry and display for radiology.

Picture archive and communications (PACS) systems should be flexible and modular in design so that new advances in storage, computation, and display technology can be introduced into the system without a significant redesign of existing software. The acquisition, storage, and management of radiologic images must be carefully integrated with a radiology information system. Our architecture is based on a four-level data model: (1) patient information, (2) examination information and reports, (3) image information, and (4) instances of images. The PACS being developed at the Mallinckrodt Institute of Radiology within the Electronic Radiology Laboratory consists of three primary components: application clients, database servers and image servers. One type of application client is an image-capable workstation that supports a radiology image viewing application. The application client queries the database server for information regarding patient and examination data in response to user-level requests. The database server responds to the request by retrieving the appropriate patient demographics and examination information, along with a pointer to the image/instance data from a central database. The client then uses the image data pointer to query the image server for the actual pixel data. The image server responds by transmitting the pixel data to the requesting application client or a designated auxiliary display device. Other clients act as image data acquisition nodes. Queries to the database servers are made via a library of callable subroutines. Software integrity is maintained throughout the system by dynamically loading software from a code-control database. Inquiry and display transactions, supported on a local-area network (Ethernet), have been measured and analyzed. Results and observations are presented.

Computer Communication Networks↗