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Signal deconvolution based expression-detection and background adjustment for microarray data.

Background adjustment is an essential stage in analyzing DNA microarrays. Discriminating expressed genes from unexpressed ones (expression detection), and estimating the expression levels of weakly expressed genes, critically depend on accurate treatment of the background intensity. Current methods for background adjustment either do not deal with nonspecific hybridization or strongly depend on the reliability of control probes. Existing model-based methods have limited accuracy. A new platform-independent background adjustment algorithm is presented. The algorithm relies on the deconvoluted experimental signal distribution for evaluating the expression probability and adjusting the background of each probe. Considering expression detection, it is shown, for two-channels cDNA arrays and for the Affymetrix GeneChip platform, that the algorithm performs at least as good or better than control-probes-based algorithms. For the Affymetrix GeneChip arrays, it is further shown that the algorithm outperforms the robust multiarray (RMA) expression measure in estimating genomewide expression levels.

Algorithms↗

Reconstruction of attenuation map using discrete consistency conditions.

Methods of quantitative emission computed tomography require compensation for linear photon attenuation. A current trend in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) is to employ transmission scanning to reconstruct the attenuation map. Such an approach, however, considerably complicates both the scanner design and the data acquisition protocol. A dramatic simplification could be made if the attenuation map could be obtained directly from the emission projections, without the use of a transmission scan. This can be done by applying the consistency conditions that enable us to identify the operator of the problem and, thus, to reconstruct the attenuation map. In this paper, we propose a new approach based on the discrete consistency conditions. One of the main advantages of the suggested method over previously used continuous conditions is that it can easily be applied in various scanning configurations, including fully three-dimensional (3-D) data acquisition protocols. Also, it provides a stable numerical implementation, allowing us to avoid the crosstalk between the attenuation map and the source function. A computationally efficient algorithm is implemented by using the QR and Cholesky decompositions. Application of the algorithm to computer-generated and experimentally measured SPECT data is considered.

Algorithms↗

Precision of QT interval measurement by advanced electrocardiographic equipment.

The costs of clinical investigations of drug-induced QT interval prolongation are mainly related to manual processing of electrocardiographic (ECG) recordings. Potentially, however, these costs can be decreased by automatic ECG measurement. To investigate the improvements in measurement accuracy of the modern ECG equipment, this study investigated QT interval measurement by the "old" and "new" versions of the 12SL ECG algorithm by GE Healthcare (Milwaukee, WI, USA) and compared the results to carefully validated and reconciled manual measurements. The investigation used two sets (A and B) of ECG recordings that originated from large clinical studies. Sets A and B consisted of 15,194, and 29,866 10-second ECG recordings, respectively. All the recordings were obtained with GE Healthcare recorders and were available in digital format compatible with ECG processing software by GE Healthcare. The two sets of recordings differed significantly in ECG quality with set B being substantially more noise polluted. Compared to careful manual QT interval readings in recording set A, the errors of the automatic QT interval measurement were (mean +/- SD) +3.95 +/- 5.50 ms, and +0.51 +/- 12.41 ms for the "new" and "old" 12SL algorithm, respectively. In recording set B, these numbers were +2.41 +/- 9.47 ms, and -0.17 +/- 14.89 ms, respectively (both differences were highly statistically significant, P < 0.000001). In recording set A, 95.9% and 76.6% of ECGs were measured automatically within 10 ms of the manual measurement by the "new" and "old" versions of the 12SL algorithm, In recording set B, these numbers were 83.9% and 59.5%. The errors made by the "new" and "old" version of 12SL algorithm were practically independent each of the other (correlation coefficients of 0.031 and 0.281 in recording sets A and B, respectively). The study shows that (a) compared to the "old" version of the 12SL algorithm, the QT interval measurement by the "new" version implemented in the most recent ECG equipment by GE Healthcare is significantly better, and (b) the precision of automatic measurement by the 12SL algorithm is substantially dependent on the quality of processed ECG recordings. The improved accuracy of the "new" 12SL algorithm makes it feasible to use modern ECG equipment without any manual intervention in selected parts of drug-development program.

Algorithms↗

Elicitation and representation of expert knowledge for computer aided diagnosis in mammography.

OBJECTIVES: To study how professional radiologists describe, interpret and make decisions about micro-calcifications in mammograms. The purpose was to develop a model of the radiologists' decision making for use in CADMIUM II, a computerized aid for mammogram interpretation that combines symbolic reasoning with image processing. METHODS: In Study 1, eleven radiologists were asked to 'think out loud' as they interpreted 20 sets of calcifications. Participants used 159 terms to describe calcifications. We used these data to design a scheme with 50 descriptors. In Study 2, ten radiologists used the scheme to describe 40 sets of calcifications. We assessed the capacity of the terms to discriminate between benign and malignant calcifications, testing them against radiologists' assessments of malignancy and follow-up data. RESULTS: The descriptors that were found to be the most discriminating in Study 2 were included in CADIMUM II's knowledge base. They were represented as arguments for either a benign or a malignant diagnosis. These arguments are the central component of the decision support provided by the system. Other components are: image processing algorithms for the detection and measurement of calcifications and a set of rules that use the measures to decide which of the arguments apply to a given set of calcifications. CONCLUSIONS: Preliminary evaluations of the CADMIUM II prototype reinforce the value of representing explicitly decision making processes in computer aided mammography and of deriving these processes from image processing measurements. Decision support is presented here at a level of description that is both relevant and meaningful to the user.

Algorithms↗

Semiautomated registration using new markers for assessing the accuracy of a navigation system.

OBJECTIVES: New markers are described that can be used for an improved registration procedure and for the exact comparison of navigation systems. The advantages of the markers are demonstrated, together with an automated segmentation algorithm for locating the centroid of the markers in image space. Compared to manual registration, this method shows an improved registration accuracy. MATERIALS AND METHODS: The new markers are detected completely automatically within all scan images. This allows a semiautomatic registration, as a preregistration is performed via the algorithm. Furthermore, the exact coordinates within one scan slice are now determined with the calculation procedure. The calculated data from the preregistration were matched up with a manual preregistration and some reference data, so as to confirm the quality of this new algorithm. The accuracies of several manual and semiautomatic registrations were also compared. RESULTS: The average deviation between the coordinates of the algorithm and the reference data (coordinate measuring machine) was 0.3 mm. The standard deviation amounted to 0.131 mm. Comparing several manual registrations with the reference data showed that the middle fiducial registration error (FRE) was between 0.7 and 2 mm. In comparison, the FRE remained constant at around 0.7 mm for the semiautomatic registration procedure. CONCLUSIONS: The measured results show a significant improvement in the preregistration data using the new markers together with the algorithm. This improvement leads to a reproducible and more accurate registration. The combination of the new marker type with the automated segmentation algorithm minimizes the human error factor, and provides the opportunity to directly compare image-guided and robotic systems.

Algorithms↗

A time domain binaural model based on spatial feature extraction for the head-related transfer function.

A complex-valued head-related transfer function (HRTF) can be represented as a real-valued head-related impulse response (HRIR). The interaural time and level cues of HRIRs are extracted to derive the binaural model and also to normalize each measured HRIR. Using the Karhunen-Loeve expansion, normalized HRIRs are modeled as a weighted combination of a set of basis functions in a low-dimensional subspace. The basis functions and the space samples of the weights are obtained from the measured HRIR. A simple linear interpolation algorithm is employed to obtain the modeled binaural HRIRs. The modeled HRIRs are nearly identical to the measured HRIRs from an anesthetized live cat. Typical mean-square errors and cross-correlation coefficients between the 1816 measured and modeled HRIRs are 1% and 0.99, respectively. The real-valued operations and linear interpolating in the model are very effective for speeding up the model computation in real-time implementation. This approach has made it possible to simulate real free-field signals at the two eardrums of a cat via earphones and to study the neuronal responses to such a virtual acoustic space (VAR).

Acoustic Stimulation↗

GenClust: a genetic algorithm for clustering gene expression data.

BACKGROUND: Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering. RESULTS: GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means. CONCLUSION: Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology.

Algorithms↗

Is diabetes mellitus a risk factor for open-angle glaucoma? The Rotterdam Study.

PURPOSE: To investigate whether diabetes mellitus is a risk factor for open-angle glaucoma (OAG). DESIGN: Prospective population-based cohort study. PARTICIPANTS: Participants ages > or =55 years from the Rotterdam Study, The Netherlands. METHODS: Participants at risk for incident OAG (iOAG) underwent at baseline (1990-1993) and follow-up (1997-1999) the same ophthalmic examination including intraocular pressure (IOP) measurement, visual field testing, and simultaneous stereo optic disc photography. At baseline, diabetes mellitus was defined as the use of antidiabetic medication and/or a random or postload glucose value > or =11.1 mmol/l. The diagnosis of OAG was made with an algorithm based on optic disc measures and visual fields, independent of the IOP. MAIN OUTCOME MEASURE: Incident OAG. RESULTS: In total, 3837 participants without OAG at baseline were reexamined. After a mean follow-up time of 6.5 years, iOAG developed in 87 persons. The relative risk of iOAG associated with baseline diabetes was 0.82 (0.33-2.05). After adjustment for age, gender, follow-up time, IOP, IOP-lowering treatment, body mass index, and systemic hypertension, the relative risk of iOAG was 0.65 (0.25-1.64). CONCLUSIONS: In this prospective population-based study, diabetes mellitus was not a risk factor for OAG.

Aged↗

Assessment of energy expenditure in children and adolescents.

PURPOSE OF THE REVIEW: This is a review on recent studies regarding methodological aspects of assessment of energy expenditure in children and adolescents. RECENT FINDINGS: A variety of methods used for assessment of different components of energy expenditure has been validated and used in children and adolescents. Reference values derived from representative groups of healthy children and adolescents are now available. Variations in the different components of energy expenditure and physical activity have been proposed to be associated with weight gain, and the prevalence of overweight and obesity. However, recent cross-sectional and longitudinal data in children and adolescents do not provide strong evidence for this idea. In contrast, hypermetabolism, which is frequently seen in critically ill children, may contribute to their tissue catabolism. In this case beta blockade seems to be a way to increase 'metabolic economy' and thus to reduce tissue catabolism. In chronically ill children and adolescents (e.g. patients with cystic fibrosis and sickle cell anemia) energy expenditure is also frequently increased and group specific algorithms are needed for predicting energy expenditure when measurement facilities are not available. SUMMARY: Methods for assessment of the different components of energy expenditure have been validated in children and adolescents. The combined use of these methods together with detailed analyses of body composition is recommended for future studies. In patients with acute or chronic illness measurements of energy expenditure are necessary if disease-specific algorithms are not available.

Adolescent↗

Real-time Kalman filter applied to biomechanical data for state estimation and numerical differentiation.

This study focused on the application of real-time Kalman filters to biomechanical data and, in particular, the simulation environment used to compare the performance of modified and standard two-state Kalman filters when estimating displacement and velocity from noisy displacement data. The modification proposed in this paper was the numerical tachometer, augmented by a median smoother. The numerical tachometer integrated the derivative estimates from finite differences of noisy sampled data into the Kalman filter structure; the median smoother acted before differentiation, to protect from grossly erroneous measurements. The numerical tachometer allowed better fits to the simulated data than can be achieved without it: the root mean square errors decreased by 10% in the displacement domain and by 54% in the velocity domain, for sampling frequencies and signal contamination levels that were typical in human movement sciences. The sensitivity to errors in the modelling of the signal and noise characteristics was less than in the standard filter implementation. The use of the median smoother improved the robustness of the filtering algorithm against additive white Gaussian measurement noise and allowed the cancellation of isolated noise spikes.

Algorithms↗

Case-based object recognition for airborne fungi recognition.

OBJECTIVE: Model-based object recognition is a well-known task in Computer Vision. Usually, one object that can be generalized by a model should be detected in an image based on this model. Biomedical applications have the special quality that one object can have a great variation in appearance. Therefore the appearance of this object cannot be generalized by one model. A set of cases of the appearance of this object (sometimes 50 cases or more) is necessary to detect this object in an image. The recognition method is rather case-based object recognition than model-based object recognition. Case-based object recognition is a challenging task. METHODS AND MATERIAL: It puts special requirements to the similarity measure and needs a matching algorithm that can work fast in a large number of cases. It also needs a case acquisition procedure that can capture the great variation in appearance of an object and generalize these data into a case description. In this paper we describe the chosen case representation, the similarity measure and the matching as well as the case acquisition procedure. We evaluate our method based on a large enough set of digital images containing biological objects such as fungi spores. RESULTS: We can show that the similarity measure is superior to detect the objects in the images. The developed method for case acquisition and learning of generalized cases allows us to learn interactively a sufficient number of cases that are further stored into our case base. Finally, we give results on the performance of the system by calculating the recognition rate. CONCLUSION: These result show that we have developed a novel similarity measure for object detection in digital grey-level images and a novel procedure for case acquisition and learning that allows us to learn a sufficiently large enough case base and to generalize over a group of cases.

Algorithms↗

Shape-based nonrigid correspondence with application to heart motion analysis.

A common problem in many biomedical imaging studies is that of finding a correspondence between two plane curves which aligns their shapes. A mathematical formulation and solutions to this problem is proposed in this paper. The formulation exhibits desirable properties. It allows for one-to-one as well as non-one-to-one correspondences, it consistently compares shape, even in nonrigid situations, and it is completely symmetric with respect to the two curves. A numerical implementation of the algorithm for finding the optimal correspondence is also reported. The algorithm is used to estimate nonrigid motion of the endocardium in MRI image sequences of normal and post-infarct dog hearts. The return error (the difference between the starting and ending positions of a point) is used as a performance measure to evaluate the technique. Since heart motion is periodic, the return error is a measure of consistency of the algorithm. Preliminary applications to other data sets are reported as well.

Algorithms↗

Simultaneous absolute measurements of principal angle and phase retardation with a new common-path heterodyne interferometer.

This study demonstrates a new method for simultaneously measuring both the angle of the principal axis and the phase retardation of the linear birefringence in optical materials. We used a circular common-path interferometer (polariscope) as the basic structure modulated by an electro-optic (EO) modulator. An algorithm was developed to simultaneously measure the principal axis and the phase retardation of a lambda/4 or lambda/8 plate as a sample. In the case of a lambda/4 plate, the average absolute error of the principal axis is approximately 3.77 degrees, and that of the phase retardation is approximately 1.03 degrees (1.09%). The retardation error is within the 5% uncertainty range of a commercial wave plate. Fortunately, the nonlinear error caused by the reflection phase retardation of the beam splitter dose not appear in the new system. Therefore the error could be attributed to misalignment and defects in the EO modulator or the other optical components. As for the repeatability of this new common-path heterodyne interferometer, the average deviation for the principal axis is 0.186 degrees and the phase retardation is 0.356 degrees. For the stability, the average deviation for the principal axis is 0.405 degrees and the phase retardation is 0.635 degrees. The resolution of this new system is estimated to be approximately 0.5 degrees, and the principal axis and phase retardation could be measured up to pi and 2pi, respectively, without ambiguity.

Journal Article↗

Assessment of radial aspheres by the Arc-step algorithm as implemented by the Keratron keratoscope.

PURPOSE: To assess the accuracy with which the Keratron (Optikon 2000, Rome, Italy) measured rotationally symmetric, radially aspheric test surfaces according to an arc-step profile reconstruction algorithm and to discriminate between error caused by the algorithm and error from other sources. METHODS: Height, local power, and axial power calculated from radius of curvature centered on the instrument's axis were reported by the Keratron for four surfaces that had radial profiles similar to normal corneas. The Keratron profile reconstruction algorithm was simulated by using ray tracing. Keratron measurements were compared with the surfaces' formulas and the ray-traced simulations. RESULTS: The heights reported by the Keratron were within 0.25 microns from the four surfaces at less than 3 mm from the keratoscope axis and generally within 1 micron of the height calculated from the surfaces' formulas. The Keratron's axial powers were within +/- 0.1 diopter of the simulation of the axial solution between 1 and 4 mm of the axis but were greater central to 1 mm and peripheral to 4 mm. The Keratron's local powers were within -0.25 diopters at less than 4 mm from the axis and peripherally were between +1.75 diopters and -0.75 diopter of power calculated from the surface's instantaneous radii of curvature. Height error because of the arc-step algorithm was less than -0.2 micron. CONCLUSIONS: The Keratron's arc-step profile reconstruction algorithm contributed to its ability to measure height more accurately than keratoscopes that use spherically biased algorithms and provided measurement of local power.

Algorithms↗

Evaluation of a simulation of human performance on random-digit generation: measures of concept and redundancy.

Ginsburg and Karpiuk in 1995 introduced an algorithm that simulates human performance in tasks of generating random digits. We have compared sequences produced by this algorithm with human performance and truly random sequences. It is shown that the algorithm can be used to simulate human performance according to the measures on which it had been constructed. However, other peculiarities of human performance are not captured by the algorithm. The results are discussed with regard to current theories of human random digit generation.

Algorithms↗

Localization Estimation Algorithm (LEA): a supervised prior-based approach for solving the EEG/MEG inverse problem.

Localizing and quantifying the sources of ElectroEncephaloGraphy (EEG) and MagnetoEncephaloGraphy (MEG) measurements is an ill-posed inverse problem, whose solution requires a spatial regularization involving both anatomical and functional priors. The distributed source model enables the introduction of such constraints. However, the resulting solution is unstable since the equation system one has to solve is badly conditioned and under-determined. We propose an original approach for solving the inverse problem, that allows to deal with a better-determined system and to temper the influence of priors according to their consistency with the measured EEG/MEG data. This Localization Estimation Algorithm (LEA) estimates the amplitude of a selected subset of sources, which are localized based on a prior distribution of activation probability. LEA is evaluated through numerical simulations and compared to a classical Weighted Minimum Norm estimation.

Algorithms↗

Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia.

OBJECTIVES: Postprandial symptoms are associated with impaired postprandial gastric accommodation. The aims of this study were to apply a noninvasive method to measure accommodation of the entire stomach in healthy subjects and in patients with idiopathic dyspeptic symptoms, and to assess the frequency of abnormal gastric accommodation and emptying of solids in these patients. METHODS: In 20 healthy volunteers and 32 tertiary referral patients, we used i.v. 99mTc-single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes; we expressed the volume response to feeding ("accommodation") as the change in gastric volume and the ratio of postprandial/fasting volumes. The stomach was identified in transaxial SPECT tomographic images using a semiautomated, intensity-based extraction algorithm. Whole gastric volumes were measured using AnalyzeAVW software. Gastric emptying in patients was measured by scintigraphy. We also assessed dyspeptic symptoms and the association with normal or reduced accommodation. RESULTS: SPECT imaging detects the postprandial change in gastric volume ("accommodation") in health and disease. Among healthy subjects (eight men, 12 women), the postprandial/fasting gastric volume ratio was 4.9+/-1.7 (mean +/- SD; fifth through 95th percentiles 3-8, median 4.6). Thirteen (41%) patients with idiopathic nonulcer dyspepsia had reduced postprandial "accommodation." Gastric emptying was fast in four (13%), normal in 25 (78%), and slow in three (9%) patients. Both tests were normal in 50% of patients. Weight loss of >10 pounds tended to be more frequently observed in those with reduced "accommodation" (62% vs 32%, p = 0.09). CONCLUSIONS: SPECT imaging noninvasively measures fasting and postprandial gastric volumes in humans. Half the patients with idiopathic nonulcer dyspepsia had impaired gastric accommodation or emptying. Reduced gastric "accommodation" was observed in 41% of a group with idiopathic nonulcer dyspepsia. Abnormal gastric emptying is less frequent (22%).

Adult↗

Ultrasonic liver tissues classification by fractal feature vector based on M-band wavelet transform.

This paper describes the feasibility of selecting fractal feature vector based on M-band wavelet transform to classify ultrasonic liver images-normal liver, cirrhosis, and hepatoma. The proposed feature extraction algorithm is based on the spatial-frequency decomposition and fractal geometry. Various classification algorithms based on respective texture measurements and filter banks are presented and tested. Classifications for the three sets of ultrasonic liver images reveal that the fractal feature vector based on M-band wavelet transform is trustworthy. A hierarchical classifier, which is based on the proposed feature extraction algorithm is at least 96.7% accurate in the distinction between normal and abnormal liver images and is at least 93.6% accurate in the distinction between cirrhosis and hepatoma liver images. Additionally, the criterion for feature selection is specified and employed for performance comparisons herein.

Algorithms↗