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PubMed1997

Method-based differences in the automated analysis of the three-dimensional morphology of trabecular bone.

The three-dimensional (3D) morphology of trabecular bone is frequently quantified using computer programs. However, there are no standardized implementations of morphology programs and many variations are possible. Even though programs may use the same basic method, results can be significantly different because of differences in implementation. Morphology data from different laboratories therefore may not be comparable. The method of directed secants, with parallel plate assumptions, is commonly used to quantify 3D morphology. We examined the effect of several variations in the implementation of this method on measurements of trabecular plate number (Tb.N), trabecular thickness, and trabecular spacing. Three-dimensional micromagnetic resonance images of 10 bovine trabecular bone specimens were analyzed using several variations of the directed secant method. An analysis of covariance with repeated measures suggested that variations in the algorithm used to count test line intersections, variations in the criteria used to classify a test coordinate as bone or marrow, and variations in the number of test grid rotations had significant effects on Tb.N (p < 0.0001). The largest difference in Tb.N (52%) was due to the method used to count test line intersections with the bone-marrow interface. Variations in the classification algorithm and variations in the number of test line grid rotations resulted in a 6% difference in Tb.N. The spacing of the test line grids did not affect Tb.N (p = 0.28), and all differences were independent of volume fraction (p = 0.67). These data show that there can be significant differences in trabecular bone morphology measurements due only to the method used for the measurements. To facilitate comparisons between laboratories, we have made validated computer programs to measure trabecular bone morphology available over the Internet.

Algorithms↗
PubMed1994

Rate-related and autonomic effects on atrioventricular conduction assessed through beat-to-beat PR interval and cycle length variability.

INTRODUCTION: Atrioventricular (AV) conduction time varies on a beat-by-beat basis in response to the influences of cardiac efferent autonomic activity and rate-dependent electrical recovery processes. The goals of this study were to distinguish these effects on AV conduction time and to compare the variability in sinoatrial and AV nodal function. METHODS AND RESULTS: The PR interval on the surface ECG served as an index of AV conduction time in this study of 14 adult human subjects undergoing a random interval breathing protocol. P and R waves were located by a template-matching algorithm. Spectral analysis allowed frequency-domain comparisons between PR and RR interval variability. Spectra of PR and RR intervals had similar power distributions, although the power of the RR interval spectra was much greater. Autonomic blockade with atropine plus propranolol reduced the power of both spectra. Standing significantly decreased the spectral power from 0.15 to 0.5 Hz for PR and RR spectra, and introduced a peak near 0.1 Hz in the mean PR and RR spectra, although the latter finding was significant only for the RR interval spectra. Propranolol had no significant effects on the PR and RR interval spectra. Linear regression analysis allowed quantification of the autonomic and recovery effects on AV conduction and showed which effect predominated. Simple linear regression confirmed in adults a previous finding in children that conduction time may be either positively or negatively correlated with cycle length. By multiple regression and transfer function analysis, the inverse relation seen in some subjects was attributed to the effect of recovery from the preceding cycle. With the preceding recovery period accounted for, the conduction time and cycle length of the current beat were positively correlated, presumably due to the parallel autonomic effects on the sinoatrial and AV nodes. The magnitude of the recovery effect predicted by the regression analysis was similar to published values. CONCLUSION: A noninvasive evaluation of the surface ECG can be used to compare variability in AV conduction time and cycle length and characterize the effects of autonomic efferent activity and rate-related recovery on AV nodal function.

Adult↗
PubMed1989

The analysis of titration studies in phase III clinical trials.

Clinical trials commonly employ the titration design for certain drugs such as antihypertensives. In a Phase III trial the design has purposes distinct from those of a Phase I or II trial, as well as from those of a trial with a parallel design. In this paper we compare the titration design with the usual parallel design in their respective purposes for Phase III trials, explore the relevant questions addressed, and examine typical data from such trials. We also discuss work which focuses primarily on the Phase I or II titration trials. We formulate the problem in the framework of one-way contingency table augmented with incomplete data and obtain the maximum likelihood estimates of the parameters and their estimated variances/covariances via the EM algorithm. An example of a Phase III study of an antihypertensive agent illustrates the proposed procedure.

Analysis of Variance↗
PubMed1997

The b matrix in diffusion tensor echo-planar imaging.

In diffusion tensor imaging (DTI) an effective diffusion tensor in each voxel is measured by using a set of diffusion-weighted images (DWIs) in which diffusion gradients are applied in a multiplicity of oblique directions. However, to estimate the diffusion tensor accurately, one must account for the effects of all imaging and diffusion gradient pulses on each signal echo, which are embodied in the b matrix. For DTI to be practical clinically, one must also acquire DWIs rapidly and free of motion artifacts, which is now possible with diffusion-weighted echo-planar imaging (DW-EPI). An analytical expression for the b matrix of a general DW-EPI pulse sequence is presented and then validated experimentally by measuring the diffusion tensor in an isotropic phantom whose diffusivity is already known. The b matrix is written in a convenient tabular form as a sum of individual pair-wise contributions arising from gradient pulses applied along parallel and perpendicular directions. While the contributions from readout and phase-encode gradient pulse trains are predicted to have a negligible effect on the echo, the contributions from other imaging and diffusion gradient pulses applied in both parallel and orthogonal directions are shown to be significant in our sequence. In general, one must understand and account for the multiplicity of interactions between gradient pulses and the echo signal to ensure that diffusion tensor imaging is quantitative.

Algorithms↗
PubMed1996

Segmentation of brain tissue from magnetic resonance images.

Segmentation of medical imagery is a challenging problem due to the complexity of the images, as well as to the absence of models of the anatomy that fully capture the possible deformations in each structure. The brain is a particularly complex structure, and its segmentation is an important step for many problems, including studies in temporal change detection of morphology, and 3-D visualizations for surgical planning. We present a method for segmentation of brain tissue from magnetic resonance images that is a combination of three existing techniques from the computer vision literature: expectation/maximization segmentation, binary mathematical morphology, and active contour models. Each of these techniques has been customized for the problem of brain tissue segmentation such that the resultant method is more robust than its components. Finally, we present the results of a parallel implementation of this method on IBM's supercomputer Power Visualization System for a database of 20 brain scans each with 256 x 256 x 124 voxels and validate those results against segmentations generated by neuroanatomy experts.

Algorithms↗
PubMed1991

Computer design and fabrication of custom-contoured seating.

This article describes the development of a computer-controlled system for measuring anatomical contours and forces at the interface with seat surfaces. The system was designed to eliminate the cause of pressure sores, which are a major problem for wheelchair-bound individuals. A parallel and compatible system also has been developed for the rapid, precise, and cost-effective fabrication of custom-contoured seat cushions and other body supports from a range of open- and closed-cell foam materials.

Algorithms↗
PubMed1994

Instruction in the techniques and concept of supportive care in oncology.

Cancer education merits a coordinated, vertical curriculum and an integrated planning strategy. It has become clear that it is as important to teach the techniques of supportive care in oncology as it is to teach the concepts of cancer biology, pathology, epidemiology, prevention, detection and aggressive treatments. Our aim is to determine whether the medical school and nursing school curricula give the students an introduction to the concepts of supportive care of the cancer patient. The spectrum of such supportive care encompasses a wide range of issues working towards a common goal of providing overall comfort with an emphasis on quality of life, and runs parallel with specific therapeutic strategies and associated problems. Do the graduate medical student and nursing student understand that cancer management is multidisciplinary and team-based? That the approach to pain management not only includes the administration of pain medications, but should also evaluate pain assessment and anesthetic, neurosurgical and behavioral approaches? That nausea and vomiting associated with chemotherapy can be ameliorated to a certain extent? That infections are common but algorithms exist for prevention and therapy? That certain metabolic complications are unique to cancer patients? That transfusions are vital procedures in patients with neoplasms undergoing aggressive treatments but are associated with certain risks and complications? That there are serious psychosocial, ethical and legal needs to be considered? To address these issues, the American Cancer Society Professors of Clinical Oncology, the American Cancer Society Professors of Oncology Nursing and the United States Cancer Center Directors were surveyed.(ABSTRACT TRUNCATED AT 250 WORDS)

Curriculum↗
PubMedDate not supplied

Multiple regression and vector analyses of laser in situ keratomileusis for myopia and astigmatism.

PURPOSE: To construct a quantitative model relating refractive results to laser settings and other factors. METHODS: A prospective clinical trial was performed, including 14 surgeons and 523 eyes of 278 patients who desired correction of myopia from -1.00 to -16.00 D (mean, -6.20 D) and astigmatism up to 6.00 D (mean, 1.10 D). Myopia and astigmatism were corrected by laser in situ keratomileusis (LASIK) with sequential spherical and cylindrical ablations using a 5.5-mm ablation zone and a transition zone to 7.0 mm. The Nidek EC-5000 excimer laser and the Chiron Automated Corneal Shaper were used. RESULTS: Surgically induced refractive changes 3 months after surgery were measured. Spherical ablation by LASIK produced a 19% greater refractive change than that predicted by the Nidek PRK algorithm. The laser setting needed to achieve each 1.00 D of cylinder correction induced 1.30 D change in spherical equivalent refraction (0.80 D more than expected). Patient age and nonlinear effects had small but statistically significant influences on refractive outcome. Sex, left/right eye, and surgeon were not significant factors. Residual variations in spherical equivalent refraction included a 0.50-D constant plus 9% of the predicted spherical equivlanet change. Residual variations in the parallel and orthogonal components of cylinder correction were, respectively, 28% and 13% of the predicted cylinder change plus a 0.30-D constant component. The standard deviation of axis alignment error for cylinder ablation was 3.7 degrees. CONCLUSIONS: Cylindrical ablation produced a spherical change that was larger than expected. To compensate for this, spherical ablation should be reduced in eyes with astigmatism. Variability in the correction of astigmatism was proportionally larger than that for spherical correction and was primarily due to magnitude rather than axis error.

Adult↗
PubMed1995

Evaluation of SPECT quantification of radiopharmaceutical distribution in canine myocardium.

UNLABELLED: This study evaluates the quantitative accuracy of SPECT for in vivo distributions of 99mTc radiopharmaceuticals using fanbeam (FB) and parallel-beam (PB) collimators and compares uniform and nonuniform attenuation correction methods in terms of quantitative accuracy. METHODS: SPECT quantification of canine myocardial radioactivity was performed followed by well counter measurements of extracted myocardial tissue samples. Transmission scans using a line source and an FB collimator were performed to generate nonuniform attenuation maps of the canine thorax. Emission scans with two energy windows were acquired. Images were reconstructed using a filtered backprojection algorithm, with a dual-window scatter subtraction combined with either no attenuation compensation or single iteration Chang attenuation compensation based on an uniform attenuation map (mu = 0.152 cm-1) or the nonuniform transmission map. RESULTS: The measured mean counts from the SPECT images were converted to radionuclide concentrations (MBq/g) using a standard source calibration and were compared with those obtained using the well counter. CONCLUSION: The experimental results demonstrate that, compared with well counter values, the in vivo distributions of 99mTc were most accurately determined in FB and PB SPECT reconstructions with nonuniform attenuation compensation, under-estimated without attenuation compensation and overestimated with uniform attenuation compensation.

Animals↗
PubMed1996

Detection of non-topological motifs in protein structures.

We present an efficient technique for the comparison of protein structures. The algorithm uses a vector representation of the secondary structure elements and searches for spatial configurations of secondary structure elements in proteins. In such recurring protein folds, the order of the secondary structure elements in the protein chains is disregarded. The method is based on the geometric hashing paradigm and implements approaches originating in computer vision. It represents and matches the secondary structure element vectors in a 3-D translation and rotation invariant manner. The matching of a pair of proteins takes on average under 3 s on a Silicon Graphics Indigo2 workstation, allowing extensive all-against-all comparisons of the data set of non-redundant protein structures. Here we have carried out such a comparison for a data set of over 500 protein molecules. The detection of recurring topological and non-topological, secondary structure element order-independent protein folds may provide further insight into evolution. Moreover, as these recurring folding units are likely to be conformationally favourable, the availability of a data set of such topological motifs can serve as a rich input for threading routines. Below, we describe this rapid technique and the results it has obtained. While some of the obtained matches conserve the order of the secondary structure elements, others are entirely order independent. As an example, we focus on the results obtained for Che Y, a signal transduction protein, and on the profilin-beta-actin complex. The Che Y molecule is composed of a five-stranded, parallel beta-sheet flanked by five helices. Here we show its similarity with the Escherichia coli elongation factor, with L-arabinose binding protein, with haloalkane dehalogenase and with adenylate kinase. The profilin-beta-actin contains an antiparallel beta-pleated sheet with alpha-helical termini. Its similarities to lipase, fructose disphosphatase and beta-lactamase are displayed.

Algorithms↗
PubMed1999

An algorithm for evaluating human cytotoxic T lymphocyte responses to candidate AIDS vaccines.

Development of an effective vaccine against HIV-1 will likely require the induction of a broad array of immune responses, including virus-specific CTLs and neutralizing antibodies. One promising vaccine approach involves live recombinant canarypox (CP)-based vectors (ALVAC) containing multiple HIV-1 genes. In phase I clinical trials in HIV-1-seronegative volunteers, the cumulative rate of detection of HIV-1-specific CTLs has been as high as 60-70%. In the present study, the factors associated with CTL responsiveness were evaluated in a subset of vaccinees immunized with a CP vector expressing portions of the gag, pro, and env genes of HIV-1 (ALVAC-HIV). CTL responses were detected in one of seven examined. While the responding individual had both CD4+ and CD8+ CTLs directed at multiple HIV-1 antigens, this response was not detectable 1 year after the last vaccination. In-depth characterization of "CTL nonresponders" showed that nonresponsiveness was not associated with defects in antigen processing or presentation. A generalized defect in CTL responsiveness was ruled out by parallel assays to detect CMV-specific CTLs from these same volunteers. Furthermore, HIV-1-specific memory CTLs were not detectable by peptide stimulation or by a novel technique for flow cytometric visualization of Gag epitope-specific T lymphocytes while HIV-1-seropositive donors frequently had 0.1-3% of CD8+ cells stain positively for this epitope (SLYNTVATL). Taken together, these results suggest that the lack of detectable HIV-1 CTLs in these volunteers was not due to classic MHC-linked nonresponsiveness.

AIDS Vaccines↗
PubMed1988

Three-dimensional structure of acyl carrier protein in solution determined by nuclear magnetic resonance and the combined use of dynamical simulated annealing and distance geometry.

The solution conformation of acyl carrier protein from Escherichia coli (77 residues) has been determined on the basis of 423 interproton-distance restraints and 32 hydrogen-bonding restraints derived from NMR measurements. A total of nine structures were computed using a hybrid approach combining metric matrix distance geometry and dynamic simulated annealing. The polypeptide fold is well defined with an average backbone atomic root-mean-square difference of 0.20 +/- 0.03 nm between the final nine converged structures and the mean structure obtained by averaging their coordinates. The principal structural motif is composed of three helices: 1 (residues 3-12), 2 (residues 37-47) and 4 (residues 65-75) which line a hydrophobic cavity. Helices 2 and 4 are approximately parallel to each other and anti-parallel at an angle of approximately equal to 150 degrees to helix 1. The smaller helix 3 (residues 56-63) is at an angle of approximately equal to 100 degrees to helix 4.

Acyl Carrier Protein↗
PubMed1999

Information technology applications in biomedical functional imaging.

In parallel with rapid advances in computer technology, biomedical functional imaging is having an ever-increasing impact on healthcare. Functional imaging allows us to see dynamic processes quantitatively in the living human body. However, as we need to deal with four-dimensional time-varying images, space requirements and computational complexity are extremely high. This makes information management, processing, and communication difficult. Using the minimum amount of data to represent the required information, developing fast algorithms to process the data, organizing the data in such a way as to facilitate information management, and extracting the maximum amount of useful information from the recorded data have become important research tasks in biomedical information technology. For the last ten years, the Biomedical and Multimedia Information Technology (BMIT) Group and, recently, the Center for Multimedia Signal Processing have conducted systematic studies on these topics. Some of the results relating to functional imaging data acquisition, compression, storage, management, processing, modeling, and simulation are briefly reported in this paper.

Algorithms↗
PubMed1994

A physician-based architecture for the construction and use of statistical models.

Physicians need specially tailored computer tools to take advantage of published research results. We present a knowledge-based computer framework--the physician-based (PB) architecture--for constructing such tools, and we use the problem of physicians' interpretation of two-arm parallel randomized clinical trials (TAPRCT) as a working example. Statistical models are represented by influence diagrams. The interpretation of influence-diagram elements are mapped into users' language in a domain-specific, physician-based user interface, called a patient-flow diagram. Statistical-model transformations that maintain the semantic relationships of the model and that embody clinical-epidemiological knowledge are encoded in a mediating structure called the cohort-state diagram. The algorithm that coordinates the interactions among the knowledge representations uses modular actions called construction steps. This architecture has been implemented in a Bayesian system, called THOMAS, that supports physician decision making in light of TAPRCT data. This support entails assessing clinical significance, prior beliefs, and methodological concerns. We suggest that the PB architecture applies to a wide range of statistical tools and users.

Algorithms↗
PubMed1993

The influence of air cavities on interface doses for photon beams.

PURPOSE: As the quantification of dose in homogeneous media is now better understood, it is necessary to further quantify effects from heterogeneous media. The most extreme case is related to air cavities. Although dose corrections at large distances beyond a cavity are accountable by attenuation differences, perturbations at air-tissue interfaces are complex to measure or calculate. These measurements helps understand the physical processes that govern these perturbations. METHODS AND MATERIALS: A thin window parallel-plate chamber and a special diode were used for measurements with various air cavity geometries (layer, channel, cubic cavity, triangle) in x-ray beams of 4 and 15 MV. RESULTS: Underdosing effects occur at both the distal and proximal air cavity interfaces. The magnitude depends on geometry, energy, and field sizes. As the cavity thickness increases, the central axis dose at the distal interface decreases. Increasing field size remedied the underdosing, as did the introduction of lateral walls. Following a 2.0 cm wide air channel for a 4 MV, 4 x 4 cm2 field there was an 11% underdose at the distal interface, while a 2.0 cm cubic cavity yielded only a 3% loss. Measurements at the proximal interface showed losses of 5% to 8%. For a 4 MV parallel opposed beam irradiation the losses at the interfaces were 10% for a channel cavity (in comparison with the homogeneous case) and 1% for a cube. The losses were slightly larger for the 15 MV beam. Underdosage at the lateral interface was 4% and 8% for the 4 MV and 15 MV beams, respectively. CONCLUSION: Although reports suggest better clinical results using lower photon energies with the presence of air cavities, there is no reliable dose calculation algorithm to predict interface doses accurately. The measurements reported here can be used to guide the development of new calculation models under nonequilibrium conditions. This situation is of clinical concern when lesions such as larynx carcinoma beyond air cavities are irradiated.

Absorption↗
PubMed1982

Karyometry of pseudostratified, metaplastic and dysplastic nasal epithelium by morphometry and stereology. 1. A general model for automated image analysis of epithelia.

Nuclear enlargement, usually due to the existence of abnormally high DNA (ploidy) values, is one of the alterations most often encountered in pathological epithelia, especially in cancerous and precancerous states. Direct DNA measurements on microscopic sections are impossible, and karyometric studies must take the difficult stereologic problem of spheroid sectioning into account. A mathematical model is proposed to describe an aggregate of separate parallel anisotropic prolate spheroids of variable size and eccentricity. This model appears suitable for the study of epithelial nuclei. After a tentative estimation of the biopsy angle, the application of the model to nuclear profile measurements produces the stereologic data of the mean spheroid nucleus: major and minor axes (and their ratio), volume, surface area (and the V/S ratio), and numerical density. Considerable time may be saved by the use of an image analyser with a specific algorithm. Most of the steps are entirely automated, but the user retains the interactive choice of the nuclei to be studied, for instance by separating the different epithelial layers. The profile data are computer-filed and several programs can yield the stereologic estimations and plots of nuclear profile areas. Poolings of cases of similar histologic staging and nearly the same sectioning angle can be used for the profile area plots. The model has been applied to pseudostratified and altered nasal mucosa of nickel workers. The stereologic estimates, mainly the nuclear volume, correlate well with histologic gradings. The nuclear profile area plots are considered useful for an assessment of the nuclear polyploidism. The complete model should be applicable to many other types of functionally or pathologically altered epithelia, particularly for cancer and precancer screenings, when the use of sectioned material is a prerequisite.

Electronic Data Processing↗
PubMed1978

A new method of multiplanar emission tomography using a seven pinhole collimator and an Anger scintillation camera.

A new method of multiplanar emission tomography is described; it uses a wide-field Anger scintillation camera (37.5 cm crystal diameter) and a seven-pinhole collimator. The pinholes (5.5 mm) acquire data simultaneously from the emissing source and project the data onto seven independent regions of the camera crystal. Multiple planes are reconstructed from the initial seven-view data acquisition through the use of a computerized addition-multiplication algorithm and variation of the superposition relationships among the projected views. These planes are then altered iteratively by a least-error criterion following ray-sum comparison with the original views. Planar resolution (full-width-half-maximum) is 1.0 cm and depth resolution is 1.5 cm. In 42 patients with angiographically demonstrated coronary-artery disease, studies of myocardial Tl-201 perfusion, under exercise, have shown improved detection sensitivity in comparison with scintigraphy using parallel-hole collimation.

Coronary Disease↗
PubMed1998

Distributed parallel processing for multidimensional maximum entropy reconstruction.

We have developed a two-dimensional maximum entropy spectrum reconstruction program designed to run in parallel on workstation clusters. Test reconstructions of planes extracted from a three-dimensional NMR data set indicate that the parallel speedup is nearly equal to the number of processors provided that the individual processors have comparable performance and that there are at least as many planes as processors. The program also works well in a typical laboratory setting consisting of heterogeneous workstations.

Algorithms↗