Image registration is widely used in different areas nowadays. Usually, the efficiency, accuracy, and robustness in the registration process are concerned in applications. This thesis studies these issues by presenting an efficient intensity-based mono-modality rigid 2D-3D image registration method and constructing a novel mathematical model for intensity-based multi-modality rigid image registration. For mono-modality image registration, an algorithm is developed using RapidMind Multi-core Development Platform (RapidMind) to exploit the highly parallel multi-core architecture of graphics processing units (GPUs). A parallel ray casting algorithm is used to generate the digitally reconstructed radiographs (DRRs) to efficiently reduce the complexity of DRR construction. The optimization problem in the registration process is solved by the Gauss-Newton method. To fully exploit the multi-core parallelism, almost the entire registration process is implemented in parallel by RapidMind on GPUs. The implementation of the major computation steps is discussed. Numerical results are presented to demonstrate the efficiency of the new method. For multi-modality image registration, a new model for computing mutual information functions is devised in order to remove the artifacts in the functions and in turn smooth the functions so that optimization methods can converge to the optimal solutions accurately and efficiently. With the motivation originating from the objective to harmonize the discrepancy between the image presentation and the mutual information definition in previous models, the new model computes the mutual information function using both the continuous image function representation and the mutual information definition for continuous random variables. Its implementation and complexity are discussed and compared with other models. The mutual information computed using the new model appears quite smooth compared with the functions computed by others. Numerical experiments demonstrate the accuracy and efficiency of optimization methods in the case that the new model is used. Furthermore, the robustness of the new model is also verified.

<p>Breast cancer screening is currently performed by mammography, which is limited by overlying anatomy and dense breast tissue. Computer aided detection (CADe) systems can serve as a double reader to improve radiologist performance. Tomosynthesis is a limited-angle cone-beam x-ray imaging modality that is currently being investigated to overcome mammography's limitations. CADe systems will play a crucial role to enhance workflow and performance for breast tomosynthesis.</p><p>The purpose of this work was to develop unique CADe algorithms for breast tomosynthesis reconstructed volumes. Unlike traditional CADe algorithms which rely on segmentation followed by feature extraction, selection and merging, this dissertation instead adopts information theory principles which are more robust. Information theory relies entirely on the statistical properties of an image and makes no assumptions about underlying distributions and is thus advantageous for smaller datasets such those currently used for all tomosynthesis CADe studies.</p><p>The proposed algorithm has two 2 stages (1) initial candidate generation of suspicious locations (2) false positive reduction. Images were accrued from 250 human subjects. In the first stage, initial suspicious locations were first isolated in the 25 projection images per subject acquired by the tomosynthesis system. Only these suspicious locations were reconstructed to yield 3D Volumes of Interest (VOI). For the second stage of the algorithm false positive reduction was then done in three ways: (1) using only the central slice of the VOI containing the largest cross-section of the mass, (2) using the entire volume, and (3) making decisions on a per slice basis and then combining those decisions using either a linear discriminant or decision fusion. A 92% sensitivity was achieved by all three approaches with 4.4 FPs / volume for approach 1, 3.9 for the second approach and 2.5 for the slice-by-slice based algorithm using decision fusion.</p><p>We have therefore developed a novel CADe algorithm for breast tomosynthesis. The techniques uses an information theory approach to achieve very high sensitivity for cancer detection while effectively minimizing false positives.</p> / Dissertation

The observability measure based on the mutual information between the last state and the measurement sequence originally proposed by Mohler and Hwang (1988) is analyzed in detail and improved further for linear time invariant discrete-time Gaussian stochastic systems by extending the definition to the observability measure of a state sequence. By using the new observability measure it is shown that the unobservable states of the deterministic system have no effect on this measure and any observable part with no measurement uncertainty makes it infinite. Other distance measures i.e., Bhattacharyya and Hellinger distances are also investigated to be used as observability measures. The relationships between the observability measures and the covariance matrices of Kalman filter and the state sequence conditioned on the measurement sequence are derived. Steady state characteristics of the observability measure based on the last state is examined. The observability measures of a subspace of the state space, an individual state, the modes of the system are investigated. One of the results obtained in this part is that the deterministically unobservable states may have nonzero observability measures. The observability measures based on the mutual information are represented recursively and calculated for nonlinear stochastic systems. Then the measures are applied to a nonlinear stochastic system by using the particle filter methods. The arguments given for the LTI case are also observed for nonlinear stochastic systems. The second moment approximation deviates from the actual values when the nonlinearity in the system increases.

Signal detection plays a critical role in realizing reliable transmission through communication systems. In this dissertation, by applying information theoretic approach, efficient detection schemes and algorithms are designed for three particular communication systems. First, a computation efficient coding and detection algorithm is developed to decode two dimensional inter-symbol interference (ISI) channels. The detection algorithm significantly reduces the computation complexity and makes the proposed equalization algorithm applicable. A new metric, the post-detection mutual information (PMI), is established to quantify the ultimate information rate between the discrete inputs and the hard detected output. This is the first time that the information rate loss caused by the hard mapping of the detectors is considered. Since the hard mapping step in the detector is irreversible, we expect that the PMI is reduced compared to the MI without hard mapping. The conclusion is confirmed by both the simulation and the theoretic results. Random complex field code is designed to achieve the secrecy capacity of wiretap channel with noiseless main channel and binary erasure eavesdroppers' channel. More importantly, in addition to approaching the secrecy capacity, RCFC is the first code design which provides a platform to tradeoff secrecy performance with the erasure rate of the eavesdropper's channel and the secrecy rate.

<p>Recent methods to infer genetic networks are based on identifying gene interactions by similarities in expression profiles. These methods are founded on the assumption that interacting genes share higher similarities in their expression profiles than non-interacting genes. In this dissertation this assumption is validated when using mutual information as a similarity measure. Three algorithms that calculate mutual information between expression data are developed: 1) a basic approach implemented with the histogram technique; 2) an extension of the basic approach that takes into consideration time delay between expression profiles; 3) an extension of the basic approach that takes into consideration that genes are regulated in a complex manner by multiple genes. In our experiments we compare the mutual information distributions for profiles of interacting and non-interacting genes. The results show that interacting genes do not share higher mutual information in their expression profiles than non-interacting genes, thus contradicting the basic assumption that similarity measures need to fulfil. This indicates that mutual information is not appropriate as similarity measure, which contradicts earlier proposals.</p>

Influenza A is a negative stranded RNA virus with a segmented genome. Once the virus infects a cell it must replicate its full length viral genomic RNA (vRNA) through a positive sense complementary intermediate RNA (cRNA) as well as transcribe viral messenger RNA (mRNA) using the vRNA as a template. The regulation of whether the viral polymerase replicates the genome by synthesizing cRNA, or produces mRNA in order to make viral protein involves, the viral nucleoprotein (NP). We tried to find the sequence residues of NP that directly interact with the viral polymerase. We mutated to alanine several residues on NP that are surface exposed on recently solved crystal structures as well as those thought to be oriented toward the viral polymerase complex in cryo-EM studies. As a first screen, we tested these mutants in a mini-genome assay where the NP stimulation of the viral polymerase can be studied in transfected cells. Through this screen we found that the NP mutants that hindered its ability to stimulate polymerase activity the most were located in a loop between two alpha helixes in the head domain of NP located at residues 203 to 209. Specifically, the NP single mutants of R204, W207, and R208 were inactive in the mini-genome assay. Using RT-PCR we found that the cRNA to vRNA step of replication is severely inhibited by these mutations. Immunoprecipitation using transfected cells showed that the NP mutants lost the ability to bind all three polymerase subunits. This indicates that this loss of polymerase binding may be the reason the NP mutant fails to stimulate polymerase activity. To make sure that this loss of polymerase stimulation was not due to altering other functions of NP we made sure that the protein had proper cellular localization, oligomerization, and RNA binding abilities. Using immuniflourescence we found that mutant NP localized to the nucleus just like wild type. In order to test RNA binding and oligomerization we tested NP purified from a baculovirus expressing system. Using fluorescence polarization we found that NP binds single stranded RNA with similar affinity to wild type. Using gel filtration we found that mutant NP forms oligomers just like wild type. Using covariation analysis of how different positions in an amino acid alignment change relative to each other we predicted possible binding sites between NP and the three polymerase subunits PA, PB1 and PB2. Due to more complete crystal structure data we focused on the PA-NP interaction and found that covariation aided in finding binding sequence residues on PA but not NP. Another outcome of developing the covariation method was developing a program to view broad primary structure changes in large sequence alignments. This method has been informative in evaluating how amino acid positions in influenza have changed over time, as well as what defines specific residues as belonging to human or avian viruses. / text

In this work were studied, implemented and evaluated two algorithms of image registration with two similarity metrics of mutual information. These were Viola-Wells Mutual Information [6],[7] and Mattes Mutual Information[11]. Materials and Methods: Two 3D MRI T1 and Τ2 brain images were used. The T1 image was rotated in all three axes , with the 27 possible triples of angles 0.25, 1.5 and 3 degrees and in the T2 image were added 3 Gaussian Noise Levels (1,3,5%). Thus were formed two experiments. The monomodal experiment which was registering the initial T1 image with its 27 rotated instances and the multimodal experiment which was registering the 4 T2 images (0,1,3,5% Gaussian Noise) with the 27 rotated T1 images. The registration framework had also a Regular Step Gradient Descent Optimizer, affine linear transformation and linear interpolator. After the 5 experimental set were registered with both algorithms, then in order for the results to be evaluated, 5 similarity metrics were used. These were: 1) Mean Square Difference 2) Correlation Coefficient 3) Joint Entropy 4) Normalized Mutual Information και 5) Entropy of the Difference Image. Finally t-test was applied, in order to find statistically significant differences. Results: Both algorithms had similar outcome, although the algorithm with Mattes Μutual Information metric, had a slightly improved performance. Statistically important differences were found in the t-test. Conclusions: The two methods should be tested more, using other kinds of transformation, and more data sets. / Σε αυτήν την εργασία μελετήθηκαν, υλοποιήθηκαν και αξιολογήθηκαν δύο αλγόριθμοι αντιστοίχισης ιατρικών εικόνων με δύο μετρικές ομοιότητας με χρήση κοινού πληροφορίας. Συγκεκριμένα η υλοποίηση Viola-Wells [6],[7] και η υλοποίηση Mattes[11]. Υλικά και Μέθοδος: Χρησιμοποιήθηκαν δύο εικόνες 3D MRI T1 και Τ2 που απεικόνιζαν εγκέφαλου. Η εικόνα Τ1 περιστράφηκε με τους 27 δυνατές συνδυασμούς των γωνιών 0.25,1.5,3 μοιρών , σε όλους τους άξονες και στην εικόνα Τ2 προστέθηκαν 3 επίπεδα Gaussian θορύβου (1,3,5%). Έτσι σχηματίστηκαν δύο πειράματα. Το μονο-απεικονιστικό πείραμα (Monomodal) που αντιστοιχούσε την αρχική Τ1 εικόνα με τα 27 περιστρεμμένα στιγμιότυπα της και το πολύ-απεικονιστικό (multimodal) που αντιστοιχούσε τις 4 Τ2 εικόνες (0,1,3,5% Gaussian Noise) με τα 27 περιστρεμμένα στιγμιότυπα της Τ1. Το σχήμα της αντιστοίχισης αποτελούνταν εκτός από τις δύο μετρικές ομοιότητας, από τον Regular Step Gradient Descent βελτιστοποιητή , συσχετισμένο (affine) γραμμικό μετασχηματισμό και γραμμικό interpolator. Αφού τα 5 σύνολα πειραμάτων ταυτίστηκαν και με τους 2 αλγορίθμους στην συνέχεια και προκειμένου να αξιολογηθεί το αποτέλεσμα της αντιστοίχισης, χρησιμοποιήθηκαν 5 μετρικές ομοιότητας. Αυτές ήταν : 1) Mean Square Difference 2) Correlation Coefficient 3) Joint Entropy 4) Normalized Mutual Information και 5) Entropy of the Difference Image. Τέλος εφαρμόστηκε και t-test προκειμένου να επιβεβαιωθούν στατιστικώς σημαντικές διαφορές. Αποτελέσματα: Και οι δύο αλγόριθμοι βρέθηκαν να έχουν παρόμοια συμπεριφορά, ωστόσο ο αλγόριθμος που χρησιμοποιούσε την Mattes Μutual Information μετρική ομοιότητας είχε καλύτερα αποτελέσματα. Στατιστικώς σημαντικές διαφορές επιβεβαιώθηκαν και από το t-test. Συμπέρασμα: Οι δύο μέθοδοι θα πρέπει να αξιολογηθούν χρησιμοποιώντας και άλλους μετασχηματισμούς, καθώς και διαφορετικά data set.

Sub-pixel image alignment estimation is desirable for co-registration of objects in multiple images to a common spatial reference and as alignment input to multi-image processing. Applications include super-resolution, image fusion, change detection, object tracking, object recognition, video motion tracking, and forensics.Information theoretical measures are commonly used for co-registration in medical imaging. The published methods apply Shannon's Entropy to the Joint Measurement Space (JMS) of two images. This work introduces into the same context a new set of statistical divergence measures derived from Fisher Information. The new methods described in this work are applicable to uncorrelated imagery and imagery that becomes statistically least dependent upon co-alignment. Both characteristics occur with multi-modal imagery and cause cross-correlation methods, as well as maximum dependence indicators, to fail. Fisher Information-based estimators, together as a set with an Entropic estimator, provide substantially independent information about alignment. This increases the statistical degrees of freedom, allowing for precision improvement and for reduced estimator failure rates compared to Entropic estimator performance alone.The new Fisher Information methods are tested for performance on real remotely-sensed imagery that includes Landsat TM multispectral imagery and ESR SAR imagery, as well as randomly generated synthetic imagery. On real imagery, the co-registration cost function is qualitatively examined for features that reveal the correct point of alignment. The alignment estimates agree with manual alignment to within manual alignment precision. Alignment truth in synthetic imagery is used to quantitatively evaluate co-registration accuracy. The results from the new Fisher Information-based algorithms are compared to Entropy-based Mutual Information and correlation methods revealing equal or superior precision and lower failure rate at signal-to-noise ratios below one.

Prostate cancer continues to be the most commonly diagnosed cancer among men. Brachytherapy has emerged as one of the definitive treatment options for early stage prostate cancer which entails permanent implantation of radioactive seeds into the prostate to eradicate the cancer with ionizing radiation. Successful brachytherapy requires the ability to perform dosimetry -which requires seed localization- during the procedure but such function is not available today. If dosimetry could be performed intraoperatively, physicians could implant additional seeds into the under-dosed portions of the prostate while the patient is still on the operating table. This thesis addresses the brachytherapy seed localization problem with introducing intensity based registration between transrectal ultrasound (TRUS) that shows only the prostate and a 3D seed model drawn from fluoroscopy that shows only the implanted seeds. The TRUS images are first filtered and compounded, and then registered to the seed model by using mutual information. A training phantom was implanted with 48 seeds and imaged. Various ultrasound filtering techniques were analyzed. The effect of false positives and false negatives in ultrasound was investigated by randomly masking seeds from the fluoroscopy volume or adding seeds to that in random locations. Furthermore, the effect of sparse and dense ultrasound data was analyzed by running the registration for ultrasound data with different spacing. The registration error remained consistently below clinical threshold and capture range was significantly larger than the initial guess guaranteed by the clinical workflow. This fully automated method provided excellent registration accuracy and robustness in phantom studies and promises to demonstrate clinically adequate performance on human data. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2008-09-27 12:35:16.691

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