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Non-rigid image registration using a median-filtered coarse-to-fine displacement field and a symmetric correlation ratio.

Conventional approaches to image registration are generally limited to image-wide rigid transformations. However, the body and its internal organs are non-rigid structures that change shape due to changes in the body's posture during image acquisition, and due to normal, pathological and treatment-related variations. Inter-subject matching also constitutes a non-rigid registration problem. In this paper, we present a fully automated non-rigid image registration method that maximizes a local voxel-based similarity metric. Overlapping image blocks are defined on a 3D grid. The transformation vector field representing image deformation is found by translating each block so as to maximize the local similarity measure. The resulting sparsely sampled vector field is median filtered and interpolated by a Gaussian function to ensure a locally smooth transformation. A hierarchical strategy is adopted to progressively establish local registration associated with image structures at diminishing scale. Simulation studies were carried out to evaluate the proposed algorithm and to determine the robustness of various voxel-based cost functions. Mutual information, normalized mutual information, correlation ratio (CR) and a new symmetric version of CR were evaluated and compared. A T1-weighted magnetic resonance (MR) image was used to test intra-modality registration. Proton density and T2-weighted MR images of the same subject were used to evaluate inter-modality registration. The proposed algorithm was tested on the 2D MR images distorted by known deformations and 3D images simulating inter-subject distortions. We studied the robustness of cost functions with respect to image sampling. Results indicate that the symmetric CR gives comparable registration to mutual information in intra- and inter-modality tasks at full sampling and is superior to mutual information in registering sparsely sampled images.

Algorithms↗

A comparative study on feature selection methods for drug discovery.

Feature selection is frequently used as a preprocessing step to machine learning. The removal of irrelevant and redundant information often improves the performance of learning algorithms. This paper is a comparative study of feature selection in drug discovery. The focus is on aggressive dimensionality reduction. Five methods were evaluated, including information gain, mutual information, a chi2-test, odds ratio, and GSS coefficient. Two well-known classification algorithms, Naïve Bayesian and Support Vector Machine (SVM), were used to classify the chemical compounds. The results showed that Naïve Bayesian benefited significantly from the feature selection, while SVM performed better when all features were used. In this experiment, information gain and chi2-test were most effective feature selection methods. Using information gain with a Naïve Bayesian classifier, removal of up to 96% of the features yielded an improved classification accuracy measured by sensitivity. When information gain was used to select the features, SVM was much less sensitive to the reduction of feature space. The feature set size was reduced by 99%, while losing only a few percent in terms of sensitivity (from 58.7% to 52.5%) and specificity (from 98.4% to 97.2%). In contrast to information gain and chi2-test, mutual information had relatively poor performance due to its bias toward favoring rare features and its sensitivity to probability estimation errors.

Algorithms↗

Evaluating similarity metrics in an image matching tool for image guided spine surgery.

This paper presents a comparison study of the effect of three similarity measures (mutual information, normalized mutual information, and mean squared error on the edges of the input image) in an image matching tool that can be used in image guided spine surgery. Using 3D rotational x-rays and magnetic resonance images of a spine phantom, it was found that the similarity measures had similar effect. Therefore, experiments with other datasets are needed before making conclusions about the suitability of these similarity metrics for image guided surgery.

Humans↗

Mutual Information-based Prognostic Biomarker Discovery in Cancer Genomics: Conceptual Framework and Representative Applications of MI-POG.

Mutual information (MI)-based approaches have increasingly been applied to cancer genomics; however, their use for genome-wide prognostic biomarker discovery remains relatively underexplored. The present article summarizes the conceptual workflow of Mutual Information-based Prognostic Omics Gene (MI-POG) based on previously published applications in breast cancer, lower-grade glioma, and other cancer datasets. The framework consists of clinical endpoint discretization, genome-wide MI-based screening, candidate ranking, and downstream validation using conventional survival-analysis approaches. Previous MI-POG applications identified solute carrier family 20 member 1 (SLC20A1) as a prognostic biomarker in hormone receptor-positive breast cancer. Elevated SLC20A1 expression was associated with unfavorable survival outcomes and was independently validated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. Methodological analyses demonstrated how survival endpoints can be integrated into an information-theoretic framework through fixed-time outcome discretization, enabling model-independent assessment of molecular-clinical dependencies. Applications across multiple cancer datasets suggested the potential applicability of the framework across biologically distinct tumor types, although further validation will be required to establish its robustness and generalizability. In conclusion, MI-POG can be formalized as an information-theoretic framework for genome-wide identification of prognostic biomarkers by quantifying molecular-clinical dependencies using mutual information. Representative applications from previously published studies suggest that MI-POG may complement conventional survival-analysis approaches and provide a useful strategy for biomarker discovery, although additional benchmarking and prospective validation will be required.

Humans↗

Mutual information-based analysis of JPEG2000 contexts.

Context-based arithmetic coding has been widely adopted in image and video compression and is a key component of the new JPEG2000 image compression standard. In this paper, the contexts used in JPEG2000 are analyzed using the mutual information, which is closely related to the compression performance. We first show that, when combining the contexts, the mutual information between the contexts and the encoded data will decrease unless the conditional probability distributions of the combined contexts are the same. Given I, the initial number of contexts, and F, the final desired number of contexts, there are S(I, F) possible context classification schemes where S(I, F) is called the Stirling number of the second kind. The optimal classification scheme is the one that gives the maximum mutual information. Instead of using an exhaustive search, the optimal classification scheme can be obtained through a modified generalized Lloyd algorithm with the relative entropy as the distortion metric. For binary arithmetic coding, the search complexity can be reduced by using dynamic programming. Our experimental results show that the JPEG2000 contexts capture the correlations among the wavelet coefficients very well. At the same time, the number of contexts used as part of the standard can be reduced without loss in the coding performance.

Algorithms↗

Mutual information-based rigid and nonrigid registration of ultrasound volumes.

We investigated the registration of ultrasound volumes based on the mutual information measure, a technique originally applied to multimodality registration of brain images. A prerequisite for successful registration is a smooth, quasi-convex mutual information surface with an unambiguous maximum. We discuss the necessary preprocessing to create such a surface for ultrasound volumes. Abdominal and thoracic organs imaged with ultrasound typically move relative to the exterior of the body and are deformable. Consequently, four specific instances of image registration involving progressively generalized transformations were studied: rigid-body, rigid-body + uniform scaling, rigid-body + nonuniform scaling, and affine. Registration was applied to clinically acquired volumetric images. The accuracy was comparable with the voxel dimension for all transformation modes, although it degraded as the transformation grew more complex. Likewise, the capture range became narrower with the complexity of transformation. As the use of real-time three-dimensional ultrasound becomes more prevalent, the method we present should work well for a variety of applications examining serial anatomic and physiologic changes. Developers of these clinical applications would match the deformation model of their problem to one of the four transformation models presented here.

Algorithms↗

Covariation of mutations in the V3 loop of human immunodeficiency virus type 1 envelope protein: an information theoretic analysis.

The V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein is a highly variable region that is both functionally and immunologically important. Using available amino acid sequences from the V3 region, we have used an information theoretic quantity called mutual information, a measure of covariation, to quantify dependence between mutations in the loop. Certain pairs of sites, including non-contiguous sites along the sequence, do not have independent mutations but display considerable, statistically significant, covarying mutations as measured by mutual information. For the pairs of sites with the highest mutual information, specific amino acids were identified that were highly predictive of amino acids in the linked site. The observed interdependence between variable sites may have implications for structural or functional relationships; separate experimental evidence indicates functional linkage between some of the pairs of sites with high mutual information. Further specific mutational studies of the V3 loop's role in determining viral phenotype are suggested by our analyses. Also, the implications of our results may be important to consider for V3 peptide vaccine design. The methods used here are generally applicable to the study of variable proteins.

Amino Acid Sequence↗

Validation and functional annotation of expression-based clusters based on gene ontology.

BACKGROUND: The biological interpretation of large-scale gene expression data is one of the paramount challenges in current bioinformatics. In particular, placing the results in the context of other available functional genomics data, such as existing bio-ontologies, has already provided substantial improvement for detecting and categorizing genes of interest. One common approach is to look for functional annotations that are significantly enriched within a group or cluster of genes, as compared to a reference group. RESULTS: In this work, we suggest the information-theoretic concept of mutual information to investigate the relationship between groups of genes, as given by data-driven clustering, and their respective functional categories. Drawing upon related approaches (Gibbons and Roth, Genome Research 12:1574-1581, 2002), we seek to quantify to what extent individual attributes are sufficient to characterize a given group or cluster of genes. CONCLUSION: We show that the mutual information provides a systematic framework to assess the relationship between groups or clusters of genes and their functional annotations in a quantitative way. Within this framework, the mutual information allows us to address and incorporate several important issues, such as the interdependence of functional annotations and combinatorial combinations of attributes. It thus supplements and extends the conventional search for overrepresented attributes within a group or cluster of genes. In particular taking combinations of attributes into account, the mutual information opens the way to uncover specific functional descriptions of a group of genes or clustering result. All datasets and functional annotations used in this study are publicly available. All scripts used in the analysis are provided as additional files.

Algorithms↗

Inferring consensus structure from nucleic acid sequences.

This paper presents an unsupervised inference method for determining the higher-order structure from sequence data. The method is general, but in this paper it is applied to nucleic acid sequences in determining the secondary (2-D) and tertiary (3-D) structure of the macromolecule. The method evaluates position - position interdependence of the sequence using an information measure known as expected mutual information. The expected mutual information is calculated for each pair of positions and the chi-square test is used to screen statistically significant position pairs. In the calculation of expected mutual information, an unbiased probability estimator is used to overcome the problem associated with zero observation in conserved sites. A selection criterion based on known structural constraints of the strongest interdependent position pairs is applied yielding position pairs most indicative of secondary and tertiary interactions. The method has been tested using tRNA and 5S rRNA sequences with very good results.

Algorithms↗

Further analysis of interpolation effects in mutual information-based image registration.

This paper presents an analysis of the mutual information (MI) metric in rigid-body registration of two digital images, in particular, local fluctuations of the MI value due to interpolation. In contrast to existing work in this area, this paper starts with two hypothetical continuous images, based on which both sampling and interpolation effects are analyzed. This analysis indicates that an "ideal" interpolator may not be able to completely suppress the undesirable local minima of the MI metric if the sampling effect is not negligible. Several preprocessing methods are discussed for reducing the interpolation effects.

Algorithms↗

Mutual information-based CT-MR brain image registration using generalized partial volume joint histogram estimation.

Mutual information (MI)-based image registration has been found to be quite effective in many medical imaging applications. To determine the MI between two images, the joint histogram of the two images is required. In the literature, linear interpolation and partial volume interpolation (PVI) are often used while estimating the joint histogram for registration purposes. It has been shown that joint histogram estimation through these two interpolation methods may introduce artifacts in the MI registration function that hamper the optimization process and influence the registration accuracy. In this paper, we present a new joint histogram estimation scheme called generalized partial volume estimation (GPVE). It turns out that the PVI method is a special case of the GPVE procedure. We have implemented our algorithm on the clinically obtained brain computed tomography and magnetic resonance image data furnished by Vanderbilt University. Our experimental results show that, by properly choosing the kernel functions, the GPVE algorithm significantly reduces the interpolation-induced artifacts and, in cases that the artifacts clearly affect registration accuracy, the registration accuracy is improved.

Algorithms↗

Information entropy analysis of discrete aiming movements.

Information entropy and mutual information were investigated in discrete movement aiming tasks over a wide range of spatial (20-160 mm) and temporal (250-1250 ms) constraints. Information entropy was calculated using two distinct analyses: (1) with no assumption on the nature of the data distribution; and (2) assuming the data have a normal distribution. The two analyses showed different results in the estimate of entropy that also changed as a function of task goals, indicating that the movement trajectory data were not from a normal distribution. It was also found that the information entropy of the discrete aiming movements was lower than the task defined indices of difficulty (ID) that were selected for the congruence with Fitts' law. Mutual information between time points of the trajectory was strongly influenced by the average movement velocity and the acceleration/deceleration segments of the movement. The entropy analysis revealed structure to the variability of the movement trajectory and outcome that has been masked by the traditional distributional analyses of discrete aiming movements.

Adult↗

Mutual information-based feature selection in studying perturbation of dendritic structure caused by TSC2 inactivation.

In this study, the effect of protein Tuberous sclerosis 2 (TSC2) on the dendritic spine density and length was demonstrated by using TSC2-RNAinactivation. In addition, the role of rapamycin, an antagonist of the molecular target of rapamycin, in the morphological changes of spine caused by TSC2 silencing was investigated. The features were extracted from highresolution three-dimensional image stacks collected by two-photon laser scanning microscopy of green fluorescing pyramidal cells expressing TSC2-RNA interference (RNAi), or TSC2-RNAi and rapamycin treatment in rat hippocampal slice cultures. We proposed to apply the lognormal distribution method for feature extraction. The extracted features of three cases under investigation, namely, (1) green-fluorescent protein GFP vs TSC2-RNAi, (2) GFP vs TSC2-RNAi and rapamycin, and (3) TSC2-RNAi vs TSC2-RNAi and rapamycin, were analyzed by mutual information-based feature selection and evaluated by three classifiers, K-nearest neighbor, Perceptron, and two-layer neural networks. The results showed that both the spine density and length have significant morphological changes after TSC2-RNAi treatment. However, rapamycin treatment could reverse the effect of TSC2-RNAi on spine length but not on spine density. These results are consistent with the results reported in the scientific literature. Finally, we explored the application of pattern recognition method in a small sample with richer feature properties, namely bootstrap mutual information estimation and a mutual information- based feature selection method.

Algorithms↗

Information transmission and recovery in neural communications channels.

Biological neural communications channels transport environmental information from sensors through chains of active dynamical neurons to neural centers for decisions and actions to achieve required functions. These kinds of communications channels are able to create information and to transfer information from one time scale to the other because of the intrinsic nonlinear dynamics of the component neurons. We discuss a very simple neural information channel composed of sensory input in the form of a spike train that arrives at a model neuron, then moves through a realistic synapse to a second neuron where the information in the initial sensory signal is read. Our model neurons are four-dimensional generalizations of the Hindmarsh-Rose neuron, and we use a model of chemical synapse derived from first-order kinetics. The four-dimensional model neuron has a rich variety of dynamical behaviors, including periodic bursting, chaotic bursting, continuous spiking, and multistability. We show that, for many of these regimes, the parameters of the chemical synapse can be tuned so that information about the stimulus that is unreadable at the first neuron in the channel can be recovered by the dynamical activity of the synapse and the second neuron. Information creation by nonlinear dynamical systems that allow chaotic oscillations is familiar in their autonomous oscillations. It is associated with the instabilities that lead to positive Lyapunov exponents in their dynamical behavior. Our results indicate how nonlinear neurons acting as input/output systems along a communications channel can recover information apparently "lost" in earlier junctions on the channel. Our measure of information transmission is the average mutual information between elements, and because the channel is active and nonlinear, the average mutual information between the sensory source and the final neuron may be greater than the average mutual information at an earlier neuron in the channel. This behavior is strikingly different than the passive role communications channels usually play, and the "data processing theorem" of conventional communications theory is violated by these neural channels. Our calculations indicate that neurons can reinforce reliable transmission along a chain even when the synapses and the neurons are not completely reliable components. This phenomenon is generic in parameter space, robust in the presence of noise, and independent of the discretization process. Our results suggest a framework in which one might understand the apparent design complexity of neural information transduction networks. If networks with many dynamical neurons can recover information not apparent at various waystations in the communications channel, such networks may be more robust to noisy signals, may be more capable of communicating many types of encoded sensory neural information, and may be the appropriate design for components, neurons and synapses, which can be individually imprecise, inaccurate "devices."

Action Potentials↗

Cooperative information maximization with Gaussian activation functions for self-organizing maps.

In this paper, we propose a new information-theoretic method to produce explicit self-organizing maps (SOMs). Competition is realized by maximizing mutual information between input patterns and competitive units. Competitive unit outputs are computed by the Gaussian function of distance between input patterns and competitive units. A property of this Gaussian function is that, as distance becomes smaller, a neuron tends to fire strongly. Cooperation processes are realized by taking into account the firing rates of neighboring neurons. We applied our method to uniform distribution learning, chemical compound classification and road classification. Experimental results confirmed that cooperation processes could significantly increase information content in input patterns. When cooperative operations are not effective in increasing information, mutual information as well as entropy maximization is used to increase information. Experimental results showed that entropy maximization could be used to increase information and to obtain clearer SOMs, because competitive units are forced to be equally used on average.

Cluster Analysis↗

Mutual information-based degrees of coherence of partially polarized light with Gaussian fluctuations.

The spatiotemporal coherence properties of partially polarized light with Gaussian probability distributions are analyzed using the mutual information that is a standard measure of statistical dependence. This approach leads to intrinsic degrees of coherence that have powerful invariance properties and that provide new information in comparison with other recently introduced degrees of coherence.

Journal Article↗

Comparison of mutual information-based warping accuracy for fusing body CT and PET by 2 methods: CT mapped onto PET emission scan versus CT mapped onto PET transmission scan.

UNLABELLED: This article assesses the resulting accuracies of 2 registration methods using the same multimodal mutual information registration algorithm. In the indirect, fusion method, the CT dataset is warped onto the PET transmission scan, and then the patient's attenuation-corrected emission dataset is substituted for the transmission dataset. In the direct, fusion method, the CT is warped directly onto the attenuation-corrected emission dataset. METHODS: CT and (18)F-FDG PET image datasets from 14 subjects with malignant lesions in the thorax were registered. In both CT and PET imaging acquisitions, the patient's arms were at the patient's side, resting on the scanning couch in a manner similar to that of routine PET acquisition procedures. The accuracy of the 2 warping registrations was assessed by measuring the distance between lesion centroids on CT and PET emission after fusion. RESULTS: The indirect method has a statistically smaller mean error, 6.2 mm, than the direct method, 10.6 mm. CONCLUSION: The indirect method appears to be the more accurate/reliable choice for fusing body CT and FDG PET.

Algorithms↗