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Image analysis and glare sensitivity in human age-related cataracts.

BACKGROUND: A new glare disability test and a diagnostic instrument, the Halometer, were proposed for measuring intraocular light scattering in the presence of human cataracts. The objectives of this work were to introduce new methods of computer-generated analysis of lens images and a glare disability test to validate the use of two new tests to measure the severity of cataract and to document and quantify changes in lens clarity at diagnosis in a group of patients with age-related cataract with minimal to advanced opacities. METHODS: The authors followed 28 patients (46 eyes) with an average age of 66.9 +/- 6 years. Tests included ophthalmoscopy, visual acuity, the halometer glare disability test, stereocinematographic slit-image and retro-illumination photography with subsequent interactive digital image analysis and three-dimensional (3-D) computer graphics of the areas of lens light scattering/absorbing. RESULTS: The intra-reader reproducibility of measuring techniques for cataractous changes was good. The Halometer instrument measures the angular distance from the glare source from which a specific target can be recognised. The source and the target are in the same vertical and tangential planes and to measure the angular distribution of the glare light, it is necessary to measure the incident light angle between the source and the target, by measuring the distance between the source and the target. The clinical Halometry readings assessed the index of the forward scattered light that reaches the retina and produces a veiling luminance (glare). The glare sensitivity score was determined from the angle of the glare source using both red and green optotypes, so that the effects of light absorption were separated from those of light scatter. DISCUSSION: The interactive and automated computerised system discriminated the photographic image features of the back light-scattering/absorb centres within different grey thresholds and documented objective lens findings such as optical density, areas of equidensities, geometric surfaces, opacity grading. Digital image analysis gave a topographic and 3-D assembling and visualisation for nuclear, cortical and posterior subcapsular opacities in human lenses revealed from the optical scanning tomographic study of the anterior eye segment. The results indicate on agreement between clinical findings and applied quantitative techniques of analysis. This system has the potential to be a useful objective clinical assessment of cataract.

Aged↗

Three-dimensional fetal echocardiography: gated versus nongated techniques.

The purpose of this study was to compare gated with nongated three-dimensional fetal echocardiography in terms of the ability to demonstrate fetal cardiac anatomy. We examined nine fetuses in utero using conventional two-dimensional sonographic imaging equipment, an electromagnetic position sensor, and a computer-graphics workstation. Free-hand sweeps were performed through the fetal heart and great vessels in either transverse or sagittal orientations with respect to the fetal heart. Seven transverse and five sagittal sweeps were selected for reconstruction and analysis. Cardiac gating was performed by using a temporal Fourier transform to determine the fundamental frequency of cardiac motion. Two-dimensional data from each sweep were reprojected to a series of volume data sets. Each series was then condensed to a single volume, so that each two-dimensional sweep could be compared with its respective gated and nongated volume data sets. The two-dimensional data were reviewed utilizing a display with forward and backward cineloop capability. The gated and nongated volume data sets were displayed interactively as a series of three orthogonal planes, with the ability of the observer to control the location of each image plane within the volume. The gated data were animated with variable display frame rates. Conventional two-dimensional imaging provided a fairly complete evaluation of the fetal heart when scanning included the four-chamber view with a sweep across the outflow tracts. Nongated three-dimensional fetal echocardiography allowed visualization of some structures and views not demonstrated with two-dimensional ultrasonography. Gated three-dimensional fetal echocardiography provided significantly better visualization and comprehension of cardiac anatomy than nongated three-dimensional fetal echocardiography. The superiority of gated over nongated three-dimensional fetal echocardiography appears to come from both improved image quality and the anatomic clues that derive from the ability to view cardiac motion.

Echocardiography, Three-Dimensional↗

Virtual reality in the operating room of the future.

In cooperation with the Max-Delbrück-Centrum/Robert-Rössle-Klinik (MDC/RRK) in Berlin, the Fraunhofer Institute for Computer Graphics is currently designing and developing a scenario for the operating room of the future. The goal of this project is to integrate new analysis, visualization and interaction tools in order to optimize and refine tumor diagnostics and therapy in combination with laser technology and remote stereoscopic video transfer. Hence, a human 3-D reference model is reconstructed using CT, MR, and anatomical cryosection images from the National Library of Medicine's Visible Human Project. Applying segmentation algorithms and surface-polygonization methods a 3-D representation is obtained. In addition, a "fly-through" the virtual patient is realized using 3-D input devices (data glove, tracking system, 6-DOF mouse). In this way, the surgeon can experience really new perspectives of the human anatomy. Moreover, using a virtual cutting plane any cut of the CT volume can be interactively placed and visualized in realtime. In conclusion, this project delivers visions for the application of effective visualization and VR systems. Commonly known as Virtual Prototyping and applied by the automotive industry long ago, this project shows, that the use of VR techniques can also prototype an operating room. After evaluating design and functionality of the virtual operating room, MDC plans to build real ORs in the near future. The use of VR techniques provides a more natural interface for the surgeon in the OR (e.g., controlling interactions by voice input). Besides preoperative planning future work will focus on supporting the surgeon in performing surgical interventions. An optimal synthesis of real and synthetic data, and the inclusion of visual, aural, and tactile senses in virtual environments can meet these requirements. This Augmented Reality could represent the environment for the surgeons of tomorrow.

Computer Simulation↗

A robust method for registration of three-dimensional knee implant models to two-dimensional fluoroscopy images.

A method was developed for registering three-dimensional knee implant models to single plane X-ray fluoroscopy images. We use a direct image-to-image similarity measure, taking advantage of the speed of modern computer graphics workstations to quickly render simulated (predicted) images. As a result, the method does not require an accurate segmentation of the implant silhouette in the image (which can be prone to errors). A robust optimization algorithm (simulated annealing) is used that can escape local minima and find the global minimum (true solution). Although we focus on the analysis of total knee arthroplasty (TKA) in this paper, the method can be (and has been) applied to other implanted joints, including, but not limited to, hips, ankles, and temporomandibular joints. Convergence tests on an in vivo image show that the registration method can reliably find poses that are very close to the optimal (i.e., within 0.4 degrees and 0.1 mm), even from starting poses with large initial errors. However, the precision of translation measurement in the Z (out-of-plane) direction is not as good. We also show that the method is robust with respect to image noise and occlusions. However, a small amount of user supervision and intervention is necessary to detect cases when the optimization algorithm falls into a local minimum. Intervention is required less than 5% of the time when the initial starting pose is reasonably close to the correct answer, but up to 50% of the time when the initial starting pose is far away. Finally, extensive evaluations were performed on cadaver images to determine accuracy of relative pose measurement. Comparing against data derived from an optical sensor as a "gold standard," the overall root-mean-square error of the registration method was approximately 1.5 degrees and 0.65 mm (although Z translation error was higher). However, uncertainty in the optical sensor data may account for a large part of the observed error.

Algorithms↗

SPI: a tool for incorporating gene expression data into a four-dimensional database of Caenorhabditis elegans embryogenesis.

MOTIVATION: A comprehensive gene expression database is essential for computer modeling and simulation of biological phenomena, including development. Development is a four-dimensional (4D; 3D structure and time course) phenomenon. We are constructing a 4D database of gene expression for the early embryogenesis of the nematode Caenorhabditis elegans. As a framework of the 4D database, we have constructed computer graphics (CG), into which we will incorporate the expression data of a number of genes at the subcellular level. However, the assignment of 3D distribution of gene products (protein, mRNA), of embryos at various developmental stages, is both difficult and tedious. We need to automate this process. For this purpose, we developed a new system, named SPI after superimposing fluorescent confocal microscopic data onto a CG framework. RESULTS: The scheme of this system comprises the following: (1) acquirement of serial sections (40 slices) of fluorescent confocal images of three colors (4',6'-diamino-2-phenylindole (DAPI) for nuclei, indodicarbocyanine (Cy-3) for the internal marker, which is a germline-specific protein POS-1 and indocarbocyanine (Cy-5) for the gene product to be examined); (2) identification of several features of the stained embryos, such as contour, developmental stage and position of the internal marker; (3) selection of CG images of the corresponding stage for template matching; (4) superimposition of serial sections onto the CG; (5) assignment of the position of superimposed gene products. The Snakes algorithm identified the embryo contour. The detection accuracy of embryo contours was 92.1% when applied to 2- to 28-cell-stage embryos. The accuracy of the developmental stage prediction method was 81.2% for 2- to 8-cell-stage embryos. We manually judged only the later stage embryos because the accuracy for embryos at the later stages was unsatisfactory due to experimental noise effects. Finally, our system chose the optimal CG and performed the superposition and assignment of gene product distribution. We established an initial 4D gene expression database with 56 maternal gene products. AVAILABILITY: This system is available at http://anti.lab.nig.ac.jp/spi/ and http://anti.lab.nig.ac.jp/4ddb/

Animals↗

Advanced interactive planning techniques for conformal therapy: high level beam descriptions and volumetric mapping techniques.

PURPOSE: To aid in design of conformal radiation therapy treatment plans involving many conformally shaped fields, this work investigates the use of two methodologies to enhance the ease of interactive treatment planning: high-level beam constructs and beam's-eye view volumetric mapping. METHODS AND MATERIALS: High-performance computer graphics running on various workstations using a graphical visualization system (AVS) have been used in this work. Software specific to this application has been written in standard FORTRAN and C languages. A new methodology is introduced by defining radiation therapy "fields" to be composed of multiple beam "segments." Fields can then be defined as higher-level entities such as arcs, cones, and other shapes. A "segmental cone" field, for example, is defined by a symmetry axis and a cone angle, and can be used to rapidly place a series of beam segments that converge at the target volume, while reducing the degree of overlap elsewhere. A new beam's-eye view (BEV) volumetric mapping technique is presented to aid in selecting the placement of conformal radiation fields. With this technique, the relative average dose within an organ of interest is calculated for a sampling of isocentric, conformally shaped beams and displayed either as a "globe," which can be combined with the display of anatomical surfaces, or as a two-dimensionally mapped projection. The dose maps from multiple organs can be generated, stacked, or composited with relative weightings to aid in the placement of fields that minimize overlap with critical structures. RESULTS: The use of these new methodologies is demonstrated for prostate and lung treatment sites and compared to conventional planning techniques. DISCUSSION: The use of many beams for conformal treatment delivery is difficult with current interactive planning. The use of high-level beam constructs provides a means to quickly specify, place, and configure multiple beam arrangements. The BEV volumetrics aids in the placing of fields, which minimize involvement with critical normal tissues. CONCLUSIONS: Early experience with the new methodologies suggest that the new methods help to enhance (or at least speed up) the ability of a treatment planner to create optimal radiation treatment field arrangements.

Evaluation Studies as Topic↗

Comparison of three classes of human liver alcohol dehydrogenase. Emphasis on different substrate binding pockets.

Conformational models of the three characterized classes of mammalian liver alcohol dehydrogenase were constructed using computer graphics based on the known three-dimensional structure of the E subunit of the horse enzyme (class I) and the primary structures of the three human enzyme classes. This correlates the substrate-binding pockets of the class I subunits (alpha, beta and gamma in the human enzyme) with those of the class II and III subunits (pi and chi, respectively) for three enzymes that differ in substrate specificity, inhibition pattern and many other properties. The substrate-binding sites exhibit pronounced differences in both shape and properties. Comparing human class I subunits with those of class II and III subunits there are no less than 8 and 10 replacements, respectively, out of 11 residues in the substrate pocket, while in the human class I isozyme variants, only 1-3 of these 11 positions differ. A single residue, Val294, is conserved throughout. The liver alcohol dehydrogenases, with different substrate-specificity pockets, resemble the patterns of other enzyme families such as the pancreatic serine proteases. The inner part of the substrate cleft in the class II and III enzymes is smaller than in the horse class I enzyme, because both Ser48 and Phe93 are replaced by larger residues, Thr and Tyr, respectively. In class II, the residues in the substrate pocket are larger in about half of the positions. It is rich in aromatic residues, four Phe and one Tyr, making the substrate site distinctly smaller than in the class I subunits. In class III, the inner part of the substrate cleft is narrow but the outer part considerably wider and more polar than in the class I and II enzymes. In addition, Ser (or Thr) and Tyr in class II and III instead of His51 may influence proton abstraction/donation at the active site.

Alcohol Dehydrogenase↗

Architecture of the microtubule component of mitotic spindles from Dictyostelium discoideum.

Ten mitotic spindles from Dictyostelium discoideum have been studied by electron microscopy of serial sections. We have used computer graphics to track individual microtubules (MTs) in three dimensions and to compare seven spindles at different stages of anaphase and telophase. The central spindle of early anaphase is formed by the interdigitation of two sets of pole-associated MTs. The distribution of MT lengths at this stage is hetero-disperse. During anaphase total MT length decreases by a factor of about 2 as a result of two opposing changes in MT length: the longer MTs that interdigitate become even longer, while the short MTs, including those attached to kinetochores, become shorter still and decrease in number. The extent of MT interdigitation is less in longer spindles than in short ones. In metaphase and early anaphase, the MTs are not in an ordered arrangement as seen in spindle cross-sections, but as anaphase proceeds the MTs cluster into a square-packed, paracrystalline bundle in which most of the nearest neighbours come from opposite poles. This arrangement and the condensation-like increase in order suggest the existence of specific interactions between antiparallel MTs. A quantitative analysis of MT positions supports this interpretation, but direct evidence for convincing bridges between MTs is lacking. The pole-distal ends of the MTs that interdigitate show an irregular termination (C-shaped ends in transverse view), as is characteristic of MTs that are either adding or losing subunits. Since it is these interdigitating MTs that elongate, and since the shortening MTs show the customary blunt endings, we conclude that subunits add to the interdigitating MTs at their pole-distal ends. This inference, combined with other structural data, suggests that the interdigitating MTs of Dictyostelium are sliding over one another as they polymerize in anaphase. It also suggests a simple model for why the spindle becomes thinner as it elongates. We propose that MT interdigitation defines a region where MTs bind a factor that will associate only with antiparallel MTs. This factor biases the MT assembly equilibrium toward polymer. As the shorter MTs slide out of this region, they lose their polymerization advantage and depolymerize, releasing subunits to contribute to the further elongation of the already longer MTs. The properties of the Dictyostelium spindle are compared with those of both higher and lower eukaryotes.

Anaphase↗

Vitreous surgery simulator.

OBJECTIVE: To reduce the surgical risks to patients and expose surgeons to surgical experience and complications, we have developed a practical system of vitreous surgery using virtual-reality technology. METHODS: The system is composed of high-resolution color stereo binoculars, haptic devices, foot switches, and a high-speed graphics computer. To simulate vitreous surgery, we created several virtual patient eyes with retinal diseases such as preretinal membranes and subretinal neovascular tissue at the fovea. RESULTS: The simulator provided the trainees with an operating environment similar to an actual one, and allowed them to learn to maneuver surgical instruments and remove proliferative tissue on the retina, under the retina, or both. This system allowed surgeons to avoid iatrogenic complications through visual signs such as retinal hemorrhage when the instrument contacted the retinal surface. CONCLUSIONS: This simulator may not only be suitable for residents to learn ocular surgical techniques but may also allow veteran surgeons to develop new surgical methods and skills.

Computer Simulation↗

The first twelve cases of computer assisted periacetabular osteotomy.

Image guided freehand navigation of surgical instruments has been applied to the Bernese periacetabular osteotomy, a complex surgical technique for the treatment of dysplastic hips. This navigation system has been introduced into the operating room and has so far been used for 12 patients. Image data from computed tomography (CT) scans are presented in various ways to support the preoperative plan and to provide optimized control of surgical action. Special attention has been paid to the implementation of a sophisticated surgeon-machine interface. This paper describes the features of this novel surgical navigation system and its introduction into the clinical environment.

Acetabulum↗

Augmented reality visualization system for intravascular neurosurgery.

We aimed to construct an augmented reality-based visualization system to support intravascular neurosurgery and evaluate it in clinical environments. Three-dimensional (3D) vascular models are overlaid on motion pictures from X-ray fluoroscopy by 2D/3D registration using fiducial markers. The models are reconstructed from 3D data obtained from X-ray computed tomographic angiography or from magnetic resonance angiography using the marching-cube algorithm. Intraoperative X-ray images are mapped as texture patterns on a screen object which is displayed with the vascular models. Distortion of X-ray fluoroscopy is eliminated by a new technique of screen mesh deformation. A quantity called reprojection distance was introduced to evaluate the reliability of the displayed images. It predicts the maximum registration error around the registered objects. Analyses of reprojection distances were performed using synthetic data consisting of marker coordinates with 2D or 3D errors. The tolerance of reprojection distance for the clinical environment was determined to be 3.0 mm. The system was tested in two clinical cases in which reprojection distances of 2.6 and 2.09 mm were obtained. Construction and evaluation of our prototype system were successfully carried out. Further development is planned employing a range sensor to permit markerless registration.

Computer Graphics↗

Volume rendering using seed-filling acceleration: supporting cut planes by fast reseeding.

OBJECTIVE: Seed filling in view lattice is a method for accelerating volume rendering. Our previously published results on using seed filling had the limitation that they did not support cut planes. Cut planes are one of the main advantages of using volume rendering over surface rendering. In this article we describe the seed-filling acceleration technique and propose two fast reseeding processes that may be performed for each frame. MATERIALS AND METHODS: The reseeding process performs a connected component search on the cut plane within the volume data set. The amount of processing done by a connected component search algorithm is proportional to N(2), assuming the data set size is N(3). We implemented two connected component search algorithms: one for orthogonal cut planes and another for oblique cut planes. We measured the time taken by the cutting and estimated the effect on the rendering performance when the cut plane was moved interactively. RESULTS: Our measurements show that rendering rates of several frames per second can be achieved with a 266-MHz Pentium II PC, even when the object is interactively modified with cut planes during the rendering. CONCLUSIONS: We have shown that the seed-filling algorithm is also applicable in situations where the displayed data is modified interactively using cut planes or objects. Applications in this regard include, for example, computer-aided surgery systems, where the instrument may be used to interactively perform the simulated cut in the data set.

Algorithms↗

Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors.

Multivariable regression models are powerful tools that are used frequently in studies of clinical outcomes. These models can use a mixture of categorical and continuous variables and can handle partially observed (censored) responses. However, uncritical application of modelling techniques can result in models that poorly fit the dataset at hand, or, even more likely, inaccurately predict outcomes on new subjects. One must know how to measure qualities of a model's fit in order to avoid poorly fitted or overfitted models. Measurement of predictive accuracy can be difficult for survival time data in the presence of censoring. We discuss an easily interpretable index of predictive discrimination as well as methods for assessing calibration of predicted survival probabilities. Both types of predictive accuracy should be unbiasedly validated using bootstrapping or cross-validation, before using predictions in a new data series. We discuss some of the hazards of poorly fitted and overfitted regression models and present one modelling strategy that avoids many of the problems discussed. The methods described are applicable to all regression models, but are particularly needed for binary, ordinal, and time-to-event outcomes. Methods are illustrated with a survival analysis in prostate cancer using Cox regression.

Clinical Trials as Topic↗

Protecting confidentiality in small population health and environmental statistics.

Public policy decisions are fuelled by information. Often, this information is in the form of statistical data. Questions stemming from public health and environmental concerns often arise or are studied within small subgroups of a population. Continuing improvements in the performance and availability of computing resources, including geographic information systems, and the need to better understand environmental exposures and consequent health effects create increasing demand for small population health and environmental data. These demands are at odds with the need to preserve the privacy and data confidentiality of persons, groups or organizations covered by the data. Although confidentiality issues for demographic and economic data are well-studied and are gaining maturity for health data, these issues are only beginning to emerge for environmental data and combined environmental-health data. The aim of this paper is to provide a framework for that examination. Herein we examine confidentiality problems posed by small population health and environmental data, summarize available statistical methods, and propose avenues for the solution of new problems.

Computer Graphics↗

Human anatomical science and illustration: the origin of two inseparable disciplines.

From the early wall paintings of ancient Egyptians to the recent advent of computer graphics, medical illustrators have employed a variety of techniques and materials to enrich the art of medicine. Over the centuries, medical illustrators have captured the variety of physical findings observed in the clinical, surgical, or postmortem settings and transferred them to a permanent medium. Specifically, the study of human anatomy has enjoyed a historically popular courtship with medical artistry since 1543, when Andreas Vesalius published his now legendary work entitled De Humani Corporis Fabrica. However, the development and subsequent advancement of human anatomical illustration are indebted to individuals whose lifetimes span several centuries prior to Vesalius. The scientific achievements in anatomy manifest not only an advancement of knowledge, but also are a reflection of cultural, political, and religious beliefs. With respect to the development of human anatomic illustration, three elements were essential: the recognition of anatomy as a distinct branch of medical science, the acceptance of human dissection as a scientific method to advance understanding of anatomical structure, and the advancement in printing such that illustrations could be included alongside descriptive text. This brief study will examine these milestones while highlighting the origin of anatomical illustration in its historical context and its relationship to the development of human anatomy as a recognized medical science.

Anatomy↗

Enhanced image detail using continuity in the MIP Z-buffer: applications to magnetic resonance angiography.

In this paper a new algorithm is presented for the segmentation and display of blood vessels from images obtained with magnetic resonance angiography (MRA) and other three-dimensional (3D) angiographic imaging techniques. The algorithm developed is based on the observation that vessels are strongly evident in the maximum intensity projection (MIP) Z-buffer as regions of high continuity and low local roughness. Roughness is measured here by the minimum chi2 value of a low-order local least-squares fit in the principal directions through each point in the MIP Z-buffer. Although some background pixels in the Z-buffer exhibit low local roughness, the size of the connected region is nearly always much smaller than even the very smallest vessels that appear in the MIP image. It is shown that by applying connectivity to the regions of low roughness, there is nearly complete separation between vascular detail and background. When connectivity is further applied in the original 3D image, vascular bed segmentation becomes nearly complete. The algorithm consists of three basic steps: a) determination of the minimum local roughness at each point in the MIP Z-buffer; b) connection of all neighboring points of low local roughness; and c) connection of all points in the original 3D image matrix that are connected to the points determined in the MIP Z-buffer and that are above an intensity threshold. The algorithm as presented is not optimized but demonstrates a very strong potential for improved portrayal of vascular detail.

Algorithms↗

Computer-assisted knee anterior cruciate ligament reconstruction: first clinical tests.

Anterior cruciate ligament reconstruction is a delicate task. The procedure of choice is the patellar tendon bone autograft, but an anisometric position of this tendon often leads to failure. We allows positioning of the central part of the ligament graft at the least anisometric sites. The system uses a workstation and a three-dimensional optical localizer to create images that represent knee kinematics. The surgeon uses these images to guide the surgery. This technique has been validated on eight cadavers and 12 patients.

Anterior Cruciate Ligament↗

Computer-assisted spine surgery: a technique for accurate transpedicular screw fixation using CT data and a 3-D optical localizer.

The computer-assisted spine surgery system presented in this paper follows the basic ideas which have been developed for computer-assisted medical interventions (CAMI) in our lab since 1985. There are three steps to insert a linear tool inside vertebral pedicles. First, the surgeon defines an optimal trajectory on pre-operative computed tomography. Second, this trajectory is reported in the operating room coordinate system using an intra-operative sensor and a registration algorithm. Third, a guiding system helps the surgeon follow the selected trajectory. In this paper, we present an implementation of this method that uses only a 3-dimensional optical localizer. Results on cadaver specimens and on the first seven patients are presented.

Bone Screws↗