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Super-resolution registration using tissue-classified distance fields.

We present a method for registering the position and orientation of bones across multiple computed-tomography (CT) volumes of the same subject. The method is subvoxel accurate, can operate on multiple bones within a set of volumes, and registers bones that have features commensurate in size to the voxel dimension. First, a geometric object model is extracted from a reference volume image. We use then unsupervised tissue classification to generate from each volume to be registered a super-resolution distance field--a scalar field that specifies, at each point, the signed distance from the point to a material boundary. The distance fields and the geometric bone model are finally used to register an object through the sequence of CT images. In the case of multiobject structures, we infer a motion-directed hierarchy from the distance-field information that allows us to register objects that are not within each other's capture region. We describe a validation framework and evaluate the new technique in contrast with grey-value registration. Results on human wrist data show average accuracy improvements of 74% over grey-value registration. The method is of interest to any intrasubject, same-modality registration applications where subvoxel accuracy is desired.

Algorithms↗

The use of a priori information in the detection of mammographic microcalcifications to improve their classification.

In this work, we present a calcification-detection scheme that automatically localizes calcifications in a previously detected cluster in order to generate the input for a cluster-classification scheme developed in the past. The calcification-detection scheme makes use of three pieces of a priori information: the location of the center of the cluster, the size of the cluster, and the approximate number of calcifications in the cluster. This information can be obtained either automatically from a cluster-detection scheme or manually by a radiologist. It is used to analyze only the portion of the mammogram that contains a cluster and to identify the individual calcifications more accurately, after enhancing them by means of a "Difference of Gaussians" filter. Classification performances (patient-based Az=0.92; cluster-based Az=0.72) comparable to those obtained by using manually-identified calcifications (patient-based Az=0.92; cluster-based Az=0.82) can be achieved.

Algorithms↗

Design of a cybernetic hand for perception and action.

Strong motivation for developing new prosthetic hand devices is provided by the fact that low functionality and controllability-in addition to poor cosmetic appearance-are the most important reasons why amputees do not regularly use their prosthetic hands. This paper presents the design of the CyberHand, a cybernetic anthropomorphic hand intended to provide amputees with functional hand replacement. Its design was bio-inspired in terms of its modular architecture, its physical appearance, kinematics, sensorization, and actuation, and its multilevel control system. Its underactuated mechanisms allow separate control of each digit as well as thumb-finger opposition and, accordingly, can generate a multitude of grasps. Its sensory system was designed to provide proprioceptive information as well as to emulate fundamental functional properties of human tactile mechanoreceptors of specific importance for grasp-and-hold tasks. The CyberHand control system presumes just a few efferent and afferent channels and was divided in two main layers: a high-level control that interprets the user's intention (grasp selection and required force level) and can provide pertinent sensory feedback and a low-level control responsible for actuating specific grasps and applying the desired total force by taking advantage of the intelligent mechanics. The grasps made available by the high-level controller include those fundamental for activities of daily living: cylindrical, spherical, tridigital (tripod), and lateral grasps. The modular and flexible design of the CyberHand makes it suitable for incremental development of sensorization, interfacing, and control strategies and, as such, it will be a useful tool not only for clinical research but also for addressing neuroscientific hypotheses regarding sensorimotor control.

Algorithms↗

Implicit learning of a recursive rule in an artificial grammar.

Participants performed an artificial grammar learning task, in which the standard finite state grammar (J. Verb. Learn. Verb. Behavior 6 (1967) 855) was extended with a recursive rule generating self-embedded sequences. We studied the learnability of such a rule in two experiments. The results verify the general hypothesis that recursivity can be learned in an artificial grammar learning task. However this learning seems to be rather based on recognising chunks than on abstract rule induction. First, performance was better for strings with more than one level of self-embedding in the sequence, uncovering more clearly the self-embedding pattern. Second, the infinite repeatability of the recursive rule application was not spontaneously induced from the training, but it was when an additional cue about this possibility was given. Finally, participants were able to verbalise their knowledge of the fragments making up the sequences-especially in the crucial front and back positions-, whereas knowledge of the underlying structure, to the extent it was acquired, was not articulatable. The results are discussed in relation to previous studies on the implicit learnability of complex and abstract rules.

Adolescent↗

Theodor Bücher Lecture. Metabolomics, modelling and machine learning in systems biology - towards an understanding of the languages of cells. Delivered on 3 July 2005 at the 30th FEBS Congress and the 9th IUBMB conference in Budapest.

The newly emerging field of systems biology involves a judicious interplay between high-throughput 'wet' experimentation, computational modelling and technology development, coupled to the world of ideas and theory. This interplay involves iterative cycles, such that systems biology is not at all confined to hypothesis-dependent studies, with intelligent, principled, hypothesis-generating studies being of high importance and consequently very far from aimless fishing expeditions. I seek to illustrate each of these facets. Novel technology development in metabolomics can increase substantially the dynamic range and number of metabolites that one can detect, and these can be exploited as disease markers and in the consequent and principled generation of hypotheses that are consistent with the data and achieve this in a value-free manner. Much of classical biochemistry and signalling pathway analysis has concentrated on the analyses of changes in the concentrations of intermediates, with 'local' equations - such as that of Michaelis and Menten v=(Vmax x S)/(S+K m) - that describe individual steps being based solely on the instantaneous values of these concentrations. Recent work using single cells (that are not subject to the intellectually unsupportable averaging of the variable displayed by heterogeneous cells possessing nonlinear kinetics) has led to the recognition that some protein signalling pathways may encode their signals not (just) as concentrations (AM or amplitude-modulated in a radio analogy) but via changes in the dynamics of those concentrations (the signals are FM or frequency-modulated). This contributes in principle to a straightforward solution of the crosstalk problem, leads to a profound reassessment of how to understand the downstream effects of dynamic changes in the concentrations of elements in these pathways, and stresses the role of signal processing (and not merely the intermediates) in biological signalling. It is this signal processing that lies at the heart of understanding the languages of cells. The resolution of many of the modern and postgenomic problems of biochemistry requires the development of a myriad of new technologies (and maybe a new culture), and thus regular input from the physical sciences, engineering, mathematics and computer science. One solution, that we are adopting in the Manchester Interdisciplinary Biocentre (http://www.mib.ac.uk/) and the Manchester Centre for Integrative Systems Biology (http://www.mcisb.org/), is thus to colocate individuals with the necessary combinations of skills. Novel disciplines that require such an integrative approach continue to emerge. These include fields such as chemical genomics, synthetic biology, distributed computational environments for biological data and modelling, single cell diagnostics/bionanotechnology, and computational linguistics/text mining.

Artificial Intelligence↗

Adjuvants and delivery issues related to immunization: a survey of the recent patent literature.

Vaccines have provided generations of individuals with protection against a number of devastating childhood diseases and, in the case of smallpox, have eradicated the disease. Arguably, this preventive approach to health care may have saved more lives than all other therapeutic approaches combined. Being commonly composed of killed-whole or live-attenuated organisms, successful vaccines have been capable of not only presenting crucial epitopes required for protective immunity but also components which stimulate the immune system provide a response of sufficient intensity to provide sustained protection. It is unlikely, however, that these same vaccines would be approved in today's regulatory climate where manufacturers must validate a highly reproducible manufacturing process and demonstrate the exact composition of the final product through stringent quality control (Gupta, 1997). Therefore, companies involved in the identification of new vaccines and their production appear to be moving away from the ill-defined and poorly-controlled immunogens of the past. Instead, they have started employing recombinant biotechnology to produce large quantities of specific antigens with the hope that these antigens will provide protective immunity. Antigen identification can take years of investigation. This process could be speeded up, however, by understanding the mechanisms which pathogens such as viruses and bacteria use to infect the host, their replication cycle and the steps they frequently take to evade the host immune system. Such a rational approach to immunogen design results in what has been termed an "intelligent" vaccine (Plough, 1998). "Intelligent" vaccines will likely be completely composed of artificial or synthetically derived products using recombinant and cell culture technologies and hopefully will allow manufacturers to develop products with the desired efficacy and safety profiles required by regulatory authorities. But unlike the complex and ill-defined immunogens of the past, these specific antigens are frequently poorly antigenic by themselves when compared to whole organisms. Co-delivery with a variety of agents, known as adjuvants, has been shown to increase the antigenicity of these poorly antigenic immunogens. In this editorial, I review the recent patent literature as it pertains to targeting of specific antigens and the role played by various classes of adjuvants to enable or enhance such targeted deliveries.

Adjuvants, Immunologic↗

Getting to the point: developing IT for the sharp end of healthcare.

Healthcare demonstrates the same properties of risk, complexity, uncertainty, dynamic change, and time-pressure as other high hazard sectors including aviation, nuclear power generation, the military, and transportation. Unlike those sectors, healthcare has particular traits that make it unique such as wide variability, ad hoc configuration, evanescence, resource constraints, and governmental and professional regulation. While healthcare's blunt (management) end is more easily understood, the sharp (operator) end is more difficult to research the closer one gets to the sharp end's point. Understanding sharp end practice and cognitive work can improve computer-based systems resilience, which is the ability to perform despite change and challenges. Research into actual practice at the sharp end of healthcare will provide the basis to understand how IT can support clinical practice. That understanding can be used to develop computer-based systems that will act as team players, able to support both individual and distributed cognitive work at healthcare's sharp end.

Artificial Intelligence↗

Identification of humans using gait.

We propose a view-based approach to recognize humans from their gait. Two different image features have been considered: the width of the outer contour of the binarized silhouette of the walking person and the entire binary silhouette itself. To obtain the observation vector from the image features, we employ two different methods. In the first method, referred to as the indirect approach, the high-dimensional image feature is transformed to a lower dimensional space by generating what we call the frame to exemplar (FED) distance. The FED vector captures both structural and dynamic traits of each individual. For compact and effective gait representation and recognition, the gait information in the FED vector sequences is captured in a hidden Markov model (HMM). In the second method, referred to as the direct approach, we work with the feature vector directly (as opposed to computing the FED) and train an HMM. We estimate the HMM parameters (specifically the observation probability B) based on the distance between the exemplars and the image features. In this way, we avoid learning high-dimensional probability density functions. The statistical nature of the HMM lends overall robustness to representation and recognition. The performance of the methods is illustrated using several databases.

Algorithms↗

Dictionary learning algorithms for sparse representation.

Algorithms for data-driven learning of domain-specific overcomplete dictionaries are developed to obtain maximum likelihood and maximum a posteriori dictionary estimates based on the use of Bayesian models with concave/Schur-concave (CSC) negative log priors. Such priors are appropriate for obtaining sparse representations of environmental signals within an appropriately chosen (environmentally matched) dictionary. The elements of the dictionary can be interpreted as concepts, features, or words capable of succinct expression of events encountered in the environment (the source of the measured signals). This is a generalization of vector quantization in that one is interested in a description involving a few dictionary entries (the proverbial "25 words or less"), but not necessarily as succinct as one entry. To learn an environmentally adapted dictionary capable of concise expression of signals generated by the environment, we develop algorithms that iterate between a representative set of sparse representations found by variants of FOCUSS and an update of the dictionary using these sparse representations. Experiments were performed using synthetic data and natural images. For complete dictionaries, we demonstrate that our algorithms have improved performance over other independent component analysis (ICA) methods, measured in terms of signal-to-noise ratios of separated sources. In the overcomplete case, we show that the true underlying dictionary and sparse sources can be accurately recovered. In tests with natural images, learned overcomplete dictionaries are shown to have higher coding efficiency than complete dictionaries; that is, images encoded with an overcomplete dictionary have both higher compression (fewer bits per pixel) and higher accuracy (lower mean square error).

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Parallelization of multicategory support vector machines (PMC-SVM) for classifying microarray data.

BACKGROUND: Multicategory Support Vector Machines (MC-SVM) are powerful classification systems with excellent performance in a variety of data classification problems. Since the process of generating models in traditional multicategory support vector machines for large datasets is very computationally intensive, there is a need to improve the performance using high performance computing techniques. RESULTS: In this paper, Parallel Multicategory Support Vector Machines (PMC-SVM) have been developed based on the sequential minimum optimization-type decomposition method for support vector machines (SMO-SVM). It was implemented in parallel using MPI and C++ libraries and executed on both shared memory supercomputer and Linux cluster for multicategory classification of microarray data. PMC-SVM has been analyzed and evaluated using four microarray datasets with multiple diagnostic categories, such as different cancer types and normal tissue types. CONCLUSION: The experiments show that the PMC-SVM can significantly improve the performance of classification of microarray data without loss of accuracy, compared with previous work.

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Assessing the effectiveness of a computerized blood order "consultation" system.

To optimize blood ordering and accurately assess transfusion practice, in 1987, an "on line" computerized, knowledge-based, blood order critiquing system was integrated into the HELP Hospital Information System (HIS) at LDS Hospital. Evaluations of the computerized ordering system demonstrated its benefits and limitations on transfusion practice. Based on this experience, a second generation blood ordering system using a consultation mode was developed. A pilot test of this blood order consultant system, using historical data in the HELP system's database, was performed. This pilot test demonstrated that the consultation system provided accurate recommendations for red blood cell (RBC) and platelet orders. Comparing the appropriateness of blood orders with the recommendations made by the director of the blood bank, the orders recommended by the computer "consultant" agreed 95.5% of the time. The computer consultation system also recommended fewer RBC units for transfusion. Preliminary results obtained using the consultant approach suggest that we may be able to simplify blood ordering practice and also reduce the number of units of blood products ordered. Based on these findings we are now preparing to compare the "critiquing" and "consultation" approaches using a clinical trial.

Artificial Intelligence↗

Intensity non-uniformity correction in MRI: existing methods and their validation.

Magnetic resonance imaging is a popular and powerful non-invasive imaging technique. Automated analysis has become mandatory to efficiently cope with the large amount of data generated using this modality. However, several artifacts, such as intensity non-uniformity, can degrade the quality of acquired data. Intensity non-uniformity consists in anatomically irrelevant intensity variation throughout data. It can be induced by the choice of the radio-frequency coil, the acquisition pulse sequence and by the nature and geometry of the sample itself. Numerous methods have been proposed to correct this artifact. In this paper, we propose an overview of existing methods. We first sort them according to their location in the acquisition/processing pipeline. Sorting is then refined based on the assumptions those methods rely on. Next, we present the validation protocols used to evaluate these different correction schemes both from a qualitative and a quantitative point of view. Finally, availability and usability of the presented methods is discussed.

Algorithms↗

A computerized laboratory alerting system.

A computerized laboratory alerting system (CLAS) has been developed as part of an ongoing effort to improve the quality of care at LDS Hospital. The system identifies potentially life-threatening conditions on the basis of laboratory findings and then generates appropriate warnings and transmits them to clinicians. Use of the system has led to a significant increase in the proportion of patients in life-threatening situations who have received appropriate care (50.8% before implementation vs. 62.5% afterward, P less than 0.05). Among patients with hypokalemia, falling potassium levels, hyperkalemia, hypokalemia during treatment with digoxin, hyponatremia, falling sodium levels, hypernatremia, hypoglycemia, or hyperglycemia, the average length of time spent in the life-threatening situation has decreased from 30.4 to 15.7 hours (P less than 0.05) and the average length of stay has decreased from 14.6 to 8.8 days (P less than 0.05). There has been little change in the proportion of patients with findings indicating metabolic acidosis who have received appropriate care (32.3 vs. 34.6%). We conclude that CLAS has an important role in patient care at our hospital.

Artificial Intelligence↗

Lidar detection of underwater objects using a neuro-SVM-based architecture.

This paper presents a neural network architecture using a support vector machine (SVM) as an inference engine (IE) for classification of light detection and ranging (Lidar) data. Lidar data gives a sequence of laser backscatter intensities obtained from laser shots generated from an airborne object at various altitudes above the earth surface. Lidar data is pre-filtered to remove high frequency noise. As the Lidar shots are taken from above the earth surface, it has some air backscatter information, which is of no importance for detecting underwater objects. Because of these, the air backscatter information is eliminated from the data and a segment of this data is subsequently selected to extract features for classification. This is then encoded using linear predictive coding (LPC) and polynomial approximation. The coefficients thus generated are used as inputs to the two branches of a parallel neural architecture. The decisions obtained from the two branches are vector multiplied and the result is fed to an SVM-based IE that presents the final inference. Two parallel neural architectures using multilayer perception (MLP) and hybrid radial basis function (HRBF) are considered in this paper. The proposed structure fits the Lidar data classification task well due to the inherent classification efficiency of neural networks and accurate decision-making capability of SVM. A Bayesian classifier and a quadratic classifier were considered for the Lidar data classification task but they failed to offer high prediction accuracy. Furthermore, a single-layered artificial neural network (ANN) classifier was also considered and it failed to offer good accuracy. The parallel ANN architecture proposed in this paper offers high prediction accuracy (98.9%) and is found to be the most suitable architecture for the proposed task of Lidar data classification.

Algorithms↗

Feature generation using genetic programming with application to fault classification.

One of the major challenges in pattern recognition problems is the feature extraction process which derives new features from existing features, or directly from raw data in order to reduce the cost of computation during the classification process, while improving classifier efficiency. Most current feature extraction techniques transform the original pattern vector into a new vector with increased discrimination capability but lower dimensionality. This is conducted within a predefined feature space, and thus, has limited searching power. Genetic programming (GP) can generate new features from the original dataset without prior knowledge of the probabilistic distribution. In this paper, a GP-based approach is developed for feature extraction from raw vibration data recorded from a rotating machine with six different conditions. The created features are then used as the inputs to a neural classifier for the identification of six bearing conditions. Experimental results demonstrate the ability of GP to discover autimatically the different bearing conditions using features expressed in the form of nonlinear functions. Furthermore, four sets of results--using GP extracted features with artificial neural networks (ANN) and support vector machines (SVM), as well as traditional features with ANN and SVM--have been obtained. This GP-based approach is used for bearing fault classification for the first time and exhibits superior searching power over other techniques. Additionaly, it significantly reduces the time for computation compared with genetic algorithm (GA), therefore, makes a more practical realization of the solution.

Algorithms↗

Simple decision rules for classifying human cancers from gene expression profiles.

MOTIVATION: Various studies have shown that cancer tissue samples can be successfully detected and classified by their gene expression patterns using machine learning approaches. One of the challenges in applying these techniques for classifying gene expression data is to extract accurate, readily interpretable rules providing biological insight as to how classification is performed. Current methods generate classifiers that are accurate but difficult to interpret. This is the trade-off between credibility and comprehensibility of the classifiers. Here, we introduce a new classifier in order to address these problems. It is referred to as k-TSP (k-Top Scoring Pairs) and is based on the concept of 'relative expression reversals'. This method generates simple and accurate decision rules that only involve a small number of gene-to-gene expression comparisons, thereby facilitating follow-up studies. RESULTS: In this study, we have compared our approach to other machine learning techniques for class prediction in 19 binary and multi-class gene expression datasets involving human cancers. The k-TSP classifier performs as efficiently as Prediction Analysis of Microarray and support vector machine, and outperforms other learning methods (decision trees, k-nearest neighbour and naïve Bayes). Our approach is easy to interpret as the classifier involves only a small number of informative genes. For these reasons, we consider the k-TSP method to be a useful tool for cancer classification from microarray gene expression data. AVAILABILITY: The software and datasets are available at http://www.ccbm.jhu.edu CONTACT: actan@jhu.edu.

Algorithms↗

Towards a robust BCI: error potentials and online learning.

Recent advances in the field of brain-computer interfaces (BCIs) have shown that BCIs have the potential to provide a powerful new channel of communication, completely independent of muscular and nervous systems. However, while there have been successful laboratory demonstrations, there are still issues that need to be addressed before BCIs can be used by nonexperts outside the laboratory. At IDIAP Research Institute, we have been investigating several areas that we believe will allow us to improve the robustness, flexibility, and reliability of BCIs. One area is recognition of cognitive error states, that is, identifying errors through the brain's reaction to mistakes. The production of these error potentials (ErrP) in reaction to an error made by the user is well established. We have extended this work by identifying a similar but distinct ErrP that is generated in response to an error made by the interface, (a misinterpretation of a command that the user has given). This ErrP can be satisfactorily identified in single trials and can be demonstrated to improve the theoretical performance of a BCI. A second area of research is online adaptation of the classifier. BCI signals change over time, both between sessions and within a single session, due to a number of factors. This means that a classifier trained on data from a previous session will probably not be optimal for a new session. In this paper, we present preliminary results from our investigations into supervised online learning that can be applied in the initial training phase. We also discuss the future direction of this research, including the combination of these two currently separate issues to create a potentially very powerful BCI.

Algorithms↗

Data driven image models through continuous joint alignment.

This paper presents a family of techniques that we call congealing for modeling image classes from data. The idea is to start with a set of images and make them appear as similar as possible by removing variability along the known axes of variation. This technique can be used to eliminate "nuisance" variables such as affine deformations from handwritten digits or unwanted bias fields from magnetic resonance images. In addition to separating and modeling the latent images-i.e., the images without the nuisance variables-we can model the nuisance variables themselves, leading to factorized generative image models. When nuisance variable distributions are shared between classes, one can share the knowledge learned in one task with another task, leading to efficient learning. We demonstrate this process by building a handwritten digit classifier from just a single example of each class. In addition to applications in handwritten character recognition, we describe in detail the application of bias removal from magnetic resonance images. Unlike previous methods, we use a separate, nonparametric model for the intensity values at each pixel. This allows us to leverage the data from the MR images of different patients to remove bias from each other. Only very weak assumptions are made about the distributions of intensity values in the images. In addition to the digit and MR applications, we discuss a number of other uses of congealing and describe experiments about the robustness and consistency of the method.

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