Rigid and non-rigid point-based medical image registration

The primary goal of this dissertation is to develop point-based rigid and non-rigid image registration methods that have better accuracy than existing methods. We first present point-based PoIRe, which provides the framework for point-based global rigid registrations. It allows a choice of different search strategies including (a) branch-and-bound, (b) probabilistic hill-climbing, and (c) a novel hybrid method that takes advantage of the best characteristics of the other two methods. We use a robust similarity measure that is insensitive to noise, which is often introduced during feature extraction. We show the robustness of PoIRe using it to register images obtained with an electronic portal imaging device (EPID), which have large amounts of scatter and low contrast. To evaluate PoIRe we used (a) simulated images and (b) images with fiducial markers; PoIRe was extensively tested with 2D EPID images and images generated by 3D Computer Tomography (CT) and Magnetic Resonance (MR) images. PoIRe was also evaluated using benchmark data sets from the blind retrospective evaluation project (RIRE). We show that PoIRe is better than existing methods such as Iterative Closest Point (ICP) and methods based on mutual information. We also present a novel point-based local non-rigid shape registration algorithm. We extend the robust similarity measure used in PoIRe to non-rigid registrations adapting it to a free form deformation (FFD) model and making it robust to local minima, which is a drawback common to existing non-rigid point-based methods. For non-rigid registrations we show that it performs better than existing methods and that is less sensitive to starting conditions. We test our non-rigid registration method using available benchmark data sets for shape registration. Finally, we also explore the extraction of features invariant to changes in perspective and illumination, and explore how they can help improve the accuracy of multi-modal registration. For multimodal registration of EPID-DRR images we present a method based on a local descriptor defined by a vector of complex responses to a circular Gabor filter.

Rigid and Non-rigid Point-based Medical Image Registration

The primary goal of this dissertation is to develop point-based rigid and non-rigid image registration methods that have better accuracy than existing methods. We first present point-based PoIRe, which provides the framework for point-based global rigid registrations. It allows a choice of different search strategies including (a) branch-and-bound, (b) probabilistic hill-climbing, and (c) a novel hybrid method that takes advantage of the best characteristics of the other two methods. We use a robust similarity measure that is insensitive to noise, which is often introduced during feature extraction. We show the robustness of PoIRe using it to register images obtained with an electronic portal imaging device (EPID), which have large amounts of scatter and low contrast. To evaluate PoIRe we used (a) simulated images and (b) images with fiducial markers; PoIRe was extensively tested with 2D EPID images and images generated by 3D Computer Tomography (CT) and Magnetic Resonance (MR) images. PoIRe was also evaluated using benchmark data sets from the blind retrospective evaluation project (RIRE). We show that PoIRe is better than existing methods such as Iterative Closest Point (ICP) and methods based on mutual information. We also present a novel point-based local non-rigid shape registration algorithm. We extend the robust similarity measure used in PoIRe to non-rigid registrations adapting it to a free form deformation (FFD) model and making it robust to local minima, which is a drawback common to existing non-rigid point-based methods. For non-rigid registrations we show that it performs better than existing methods and that is less sensitive to starting conditions. We test our non-rigid registration method using available benchmark data sets for shape registration. Finally, we also explore the extraction of features invariant to changes in perspective and illumination, and explore how they can help improve the accuracy of multi-modal registration. For multimodal registration of EPID-DRR images we present a method based on a local descriptor defined by a vector of complex responses to a circular Gabor filter.

A mathematical resolution to log transformations and the binning effect in applied processing of data in flow cytometry

This dissertation develops a new mathematical approach that overcomes the effect of a data processing phenomenon known as “histogram binning” inherent to flow cytometry data. A real-time procedure is introduced to prove the effectiveness and fast implementation of such an approach on real-world data. The histogram binning effect is a dilemma posed by two seemingly antagonistic developments: (1) flow cytometry data in its histogram form is extended in its dynamic range to improve its analysis and interpretation, and (2) the inevitable dynamic range extension introduces an unwelcome side effect, the binning effect, which skews the statistics of the data, undermining as a consequence the accuracy of the analysis and the eventual interpretation of the data. ^ Researchers in the field contended with such a dilemma for many years, resorting either to hardware approaches that are rather costly with inherent calibration and noise effects; or have developed software techniques based on filtering the binning effect but without successfully preserving the statistical content of the original data. ^ The mathematical approach introduced in this dissertation is so appealing that a patent application has been filed. The contribution of this dissertation is an incremental scientific innovation based on a mathematical framework that will allow researchers in the field of flow cytometry to improve the interpretation of data knowing that its statistical meaning has been faithfully preserved for its optimized analysis. Furthermore, with the same mathematical foundation, proof of the origin of such an inherent artifact is provided. ^ These results are unique in that new mathematical derivations are established to define and solve the critical problem of the binning effect faced at the experimental assessment level, providing a data platform that preserves its statistical content. ^ In addition, a novel method for accumulating the log-transformed data was developed. This new method uses the properties of the transformation of statistical distributions to accumulate the output histogram in a non-integer and multi-channel fashion. Although the mathematics of this new mapping technique seem intricate, the concise nature of the derivations allow for an implementation procedure that lends itself to a real-time implementation using lookup tables, a task that is also introduced in this dissertation. ^

Development, validation and uncertainty analysis of quantitative structure and activity relationship models for Log P of disinfection by -products

Hydrophobicity as measured by Log P is an important molecular property related to toxicity and carcinogenicity. With increasing public health concerns for the effects of Disinfection By-Products (DBPs), there are considerable benefits in developing Quantitative Structure and Activity Relationship (QSAR) models capable of accurately predicting Log P. In this research, Log P values of 173 DBP compounds in 6 functional classes were used to develop QSAR models, by applying 3 molecular descriptors, namely, Energy of the Lowest Unoccupied Molecular Orbital (ELUMO), Number of Chlorine (NCl) and Number of Carbon (NC) by Multiple Linear Regression (MLR) analysis. The QSAR models developed were validated based on the Organization for Economic Co-operation and Development (OECD) principles. The model Applicability Domain (AD) and mechanistic interpretation were explored. Considering the very complex nature of DBPs, the established QSAR models performed very well with respect to goodness-of-fit, robustness and predictability. The predicted values of Log P of DBPs by the QSAR models were found to be significant with a correlation coefficient R2 from 81% to 98%. The Leverage Approach by Williams Plot was applied to detect and remove outliers, consequently increasing R 2 by approximately 2% to 13% for different DBP classes. The developed QSAR models were statistically validated for their predictive power by the Leave-One-Out (LOO) and Leave-Many-Out (LMO) cross validation methods. Finally, Monte Carlo simulation was used to assess the variations and inherent uncertainties in the QSAR models of Log P and determine the most influential parameters in connection with Log P prediction. The developed QSAR models in this dissertation will have a broad applicability domain because the research data set covered six out of eight common DBP classes, including halogenated alkane, halogenated alkene, halogenated aromatic, halogenated aldehyde, halogenated ketone, and halogenated carboxylic acid, which have been brought to the attention of regulatory agencies in recent years. Furthermore, the QSAR models are suitable to be used for prediction of similar DBP compounds within the same applicability domain. The selection and integration of various methodologies developed in this research may also benefit future research in similar fields.

A generalized adaptive mathematical morphological filter for LIDAR data

Airborne Light Detection and Ranging (LIDAR) technology has become the primary method to derive high-resolution Digital Terrain Models (DTMs), which are essential for studying Earth's surface processes, such as flooding and landslides. The critical step in generating a DTM is to separate ground and non-ground measurements in a voluminous point LIDAR dataset, using a filter, because the DTM is created by interpolating ground points. As one of widely used filtering methods, the progressive morphological (PM) filter has the advantages of classifying the LIDAR data at the point level, a linear computational complexity, and preserving the geometric shapes of terrain features. The filter works well in an urban setting with a gentle slope and a mixture of vegetation and buildings. However, the PM filter often removes ground measurements incorrectly at the topographic high area, along with large sizes of non-ground objects, because it uses a constant threshold slope, resulting in "cut-off" errors. A novel cluster analysis method was developed in this study and incorporated into the PM filter to prevent the removal of the ground measurements at topographic highs. Furthermore, to obtain the optimal filtering results for an area with undulating terrain, a trend analysis method was developed to adaptively estimate the slope-related thresholds of the PM filter based on changes of topographic slopes and the characteristics of non-terrain objects. The comparison of the PM and generalized adaptive PM (GAPM) filters for selected study areas indicates that the GAPM filter preserves the most "cut-off" points removed incorrectly by the PM filter. The application of the GAPM filter to seven ISPRS benchmark datasets shows that the GAPM filter reduces the filtering error by 20% on average, compared with the method used by the popular commercial software TerraScan. The combination of the cluster method, adaptive trend analysis, and the PM filter allows users without much experience in processing LIDAR data to effectively and efficiently identify ground measurements for the complex terrains in a large LIDAR data set. The GAPM filter is highly automatic and requires little human input. Therefore, it can significantly reduce the effort of manually processing voluminous LIDAR measurements.

A mathematical resolution to log transformations and the binning effect in applied processing of data in flow cytometry

This dissertation develops a new mathematical approach that overcomes the effect of a data processing phenomenon known as "histogram binning" inherent to flow cytometry data. A real-time procedure is introduced to prove the effectiveness and fast implementation of such an approach on real-world data. The histogram binning effect is a dilemma posed by two seemingly antagonistic developments: (1) flow cytometry data in its histogram form is extended in its dynamic range to improve its analysis and interpretation, and (2) the inevitable dynamic range extension introduces an unwelcome side effect, the binning effect, which skews the statistics of the data, undermining as a consequence the accuracy of the analysis and the eventual interpretation of the data. Researchers in the field contended with such a dilemma for many years, resorting either to hardware approaches that are rather costly with inherent calibration and noise effects; or have developed software techniques based on filtering the binning effect but without successfully preserving the statistical content of the original data. The mathematical approach introduced in this dissertation is so appealing that a patent application has been filed. The contribution of this dissertation is an incremental scientific innovation based on a mathematical framework that will allow researchers in the field of flow cytometry to improve the interpretation of data knowing that its statistical meaning has been faithfully preserved for its optimized analysis. Furthermore, with the same mathematical foundation, proof of the origin of such an inherent artifact is provided. These results are unique in that new mathematical derivations are established to define and solve the critical problem of the binning effect faced at the experimental assessment level, providing a data platform that preserves its statistical content. In addition, a novel method for accumulating the log-transformed data was developed. This new method uses the properties of the transformation of statistical distributions to accumulate the output histogram in a non-integer and multi-channel fashion. Although the mathematics of this new mapping technique seem intricate, the concise nature of the derivations allow for an implementation procedure that lends itself to a real-time implementation using lookup tables, a task that is also introduced in this dissertation.