Integration of semantically annotated data by the KnoFuss architecture

Most of the existing work on information integration in the Semantic Web concentrates on resolving schema-level problems. Specific issues of data-level integration (instance coreferencing, conflict resolution, handling uncertainty) are usually tackled by applying the same techniques as for ontology schema matching or by reusing the solutions produced in the database domain. However, data structured according to OWL ontologies has its specific features: e.g., the classes are organized into a hierarchy, the properties are inherited, data constraints differ from those defined by database schema. This paper describes how these features are exploited in our architecture KnoFuss, designed to support data-level integration of semantic annotations.

The integration of ProxiMAX randomisation with CIS display for the high-throughput production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering. This can allow the analysis of potential new properties thus allowing key residues within a protein to be targeted and randomised. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK) has inherent redundancy and disparities in residue representation. In this we describe the combination of ProxiMAX randomisation and CIS display for the use of generating novel peptides. Unlike other methods ProxiMAX randomisation does not require any intricate chemistry but simply utilises synthetic DNA and molecular biology techniques. Designed ‘MAX’ oligonucleotides were ligated, amplified and digested in an iterative cycle. Results show that randomised ‘MAX’ codons can be added sequentially to the base sequence creating a series of randomised non-degenerate codons that can subsequently be inserted into a gene. CIS display (Isogencia, UK) is an in vitro DNA based screening method that creates a genotype to phenotype link between a peptide and the nucleic acid that encodes it. The use of straight forward in vitro transcription/translation and other molecular biology techniques permits ease of use along with flexibility making it a potent screening technique. Using ProxiMAX randomisation in combination with CIS display, the aim is to produce randomised anti-nerve growth factor (NGF) and calcitonin gene-related (CGRP) peptides to demonstrate the high-throughput nature of this combination.

Mathematical Model and Simulation of a Pneumatic Apparatus for In-Drilling Alignment of an Inertial Navigation Unit during Horizontal Well Drilling

Conventional methods in horizontal drilling processes incorporate magnetic surveying techniques for determining the position and orientation of the bottom-hole assembly (BHA). Such means result in an increased weight of the drilling assembly, higher cost due to the use of non-magnetic collars necessary for the shielding of the magnetometers, and significant errors in the position of the drilling bit. A fiber-optic gyroscope (FOG) based inertial navigation system (INS) has been proposed as an alternative to magnetometer -based downhole surveying. The utilizing of a tactical-grade FOG based surveying system in the harsh downhole environment has been shown to be theoretically feasible, yielding a significant BHA position error reduction (less than 100m over a 2-h experiment). To limit the growing errors of the INS, an in-drilling alignment (IDA) method for the INS has been proposed. This article aims at describing a simple, pneumatics-based design of the IDA apparatus and its implementation downhole. A mathematical model of the setup is developed and tested with Bloodshed Dev-C++. The simulations demonstrate a simple, low cost and feasible IDA apparatus.

Mathematical Optimization for the Train Timetabling Problem

AMS Subj. Classification: 90C57; 90C10;

Fractional Integration of the Product of Bessel Functions of the First Kind

Dedicated to 75th birthday of Prof. A.M. Mathai, Mathematical Subject Classification 2010:26A33, 33C10, 33C20, 33C50, 33C60, 26A09

Theory of hybrid computational and physical measurement-based integration of thermal and dimensional measurement

In dimensional metrology, often the largest source of uncertainty of measurement is thermal variation. Dimensional measurements are currently scaled linearly, using ambient temperature measurements and coefficients of thermal expansion, to ideal metrology conditions at 20˚C. This scaling is particularly difficult to implement with confidence in large volumes as the temperature is unlikely to be uniform, resulting in thermal gradients. A number of well-established computational methods are used in the design phase of product development for the prediction of thermal and gravitational effects, which could be used to a greater extent in metrology. This paper outlines the theory of how physical measurements of dimension and temperature can be combined more comprehensively throughout the product lifecycle, from design through to the manufacturing phase. The Hybrid Metrology concept is also introduced: an approach to metrology, which promises to improve product and equipment integrity in future manufacturing environments. The Hybrid Metrology System combines various state of the art physical dimensional and temperature measurement techniques with established computational methods to better predict thermal and gravitational effects.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

Integration and querying of heterogeneous, autonomous, distributed database systems

Today, databases have become an integral part of information systems. In the past two decades, we have seen different database systems being developed independently and used in different applications domains. Today's interconnected networks and advanced applications, such as data warehousing, data mining & knowledge discovery and intelligent data access to information on the Web, have created a need for integrated access to such heterogeneous, autonomous, distributed database systems. Heterogeneous/multidatabase research has focused on this issue resulting in many different approaches. However, a single, generally accepted methodology in academia or industry has not emerged providing ubiquitous intelligent data access from heterogeneous, autonomous, distributed information sources. ^ This thesis describes a heterogeneous database system being developed at High-performance Database Research Center (HPDRC). A major impediment to ubiquitous deployment of multidatabase technology is the difficulty in resolving semantic heterogeneity. That is, identifying related information sources for integration and querying purposes. Our approach considers the semantics of the meta-data constructs in resolving this issue. The major contributions of the thesis work include: (i) providing a scalable, easy-to-implement architecture for developing a heterogeneous multidatabase system, utilizing Semantic Binary Object-oriented Data Model (Sem-ODM) and Semantic SQL query language to capture the semantics of the data sources being integrated and to provide an easy-to-use query facility; (ii) a methodology for semantic heterogeneity resolution by investigating into the extents of the meta-data constructs of component schemas. This methodology is shown to be correct, complete and unambiguous; (iii) a semi-automated technique for identifying semantic relations, which is the basis of semantic knowledge for integration and querying, using shared ontologies for context-mediation; (iv) resolutions for schematic conflicts and a language for defining global views from a set of component Sem-ODM schemas; (v) design of a knowledge base for storing and manipulating meta-data and knowledge acquired during the integration process. This knowledge base acts as the interface between integration and query processing modules; (vi) techniques for Semantic SQL query processing and optimization based on semantic knowledge in a heterogeneous database environment; and (vii) a framework for intelligent computing and communication on the Internet applying the concepts of our work. ^

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. ^

Segmental body composition determination through a bioelectrical very large scale integration (VLSI) system

The purpose of this investigation was to develop new techniques to generate segmental assessments of body composition based on Segmental Bioelectrical Impedance Analysis (SBIA). An equally important consideration was the design, simulation, development, and the software and hardware integration of the SBIA system. This integration was carried out with a Very Large Scale Integration (VLSI) Field Programmable Gate Array (FPGA) microcontroller that analyzed the measurements obtained from segments of the body, and provided full body and segmental Fat Free Mass (FFM) and Fat Mass (FM) percentages. Also, the issues related to the estimate of the body's composition in persons with spinal cord injury (SCI) were addressed and investigated. This investigation demonstrated that the SBIA methodology provided accurate segmental body composition measurements. Disabled individuals are expected to benefit from these SBIA evaluations, as they are non-invasive methods, suitable for paralyzed individuals. The SBIA VLSI system may replace bulky, non flexible electronic modules attached to human bodies. ^

Exploring the integration of data mining and data visualization

Due to the rapid advances in computing and sensing technologies, enormous amounts of data are being generated everyday in various applications. The integration of data mining and data visualization has been widely used to analyze these massive and complex data sets to discover hidden patterns. For both data mining and visualization to be effective, it is important to include the visualization techniques in the mining process and to generate the discovered patterns for a more comprehensive visual view. In this dissertation, four related problems: dimensionality reduction for visualizing high dimensional datasets, visualization-based clustering evaluation, interactive document mining, and multiple clusterings exploration are studied to explore the integration of data mining and data visualization. In particular, we 1) propose an efficient feature selection method (reliefF + mRMR) for preprocessing high dimensional datasets; 2) present DClusterE to integrate cluster validation with user interaction and provide rich visualization tools for users to examine document clustering results from multiple perspectives; 3) design two interactive document summarization systems to involve users efforts and generate customized summaries from 2D sentence layouts; and 4) propose a new framework which organizes the different input clusterings into a hierarchical tree structure and allows for interactive exploration of multiple clustering solutions.

Development of hardware in the loop real-time control techniques for hybrid power systems involving distributed demands and sustainable energy sources

The future power grid will effectively utilize renewable energy resources and distributed generation to respond to energy demand while incorporating information technology and communication infrastructure for their optimum operation. This dissertation contributes to the development of real-time techniques, for wide-area monitoring and secure real-time control and operation of hybrid power systems. ^ To handle the increased level of real-time data exchange, this dissertation develops a supervisory control and data acquisition (SCADA) system that is equipped with a state estimation scheme from the real-time data. This system is verified on a specially developed laboratory-based test bed facility, as a hardware and software platform, to emulate the actual scenarios of a real hybrid power system with the highest level of similarities and capabilities to practical utility systems. It includes phasor measurements at hundreds of measurement points on the system. These measurements were obtained from especially developed laboratory based Phasor Measurement Unit (PMU) that is utilized in addition to existing commercially based PMU’s. The developed PMU was used in conjunction with the interconnected system along with the commercial PMU’s. The tested studies included a new technique for detecting the partially islanded micro grids in addition to several real-time techniques for synchronization and parameter identifications of hybrid systems. ^ Moreover, due to numerous integration of renewable energy resources through DC microgrids, this dissertation performs several practical cases for improvement of interoperability of such systems. Moreover, increased number of small and dispersed generating stations and their need to connect fast and properly into the AC grids, urged this work to explore the challenges that arise in synchronization of generators to the grid and through introduction of a Dynamic Brake system to improve the process of connecting distributed generators to the power grid.^ Real time operation and control requires data communication security. A research effort in this dissertation was developed based on Trusted Sensing Base (TSB) process for data communication security. The innovative TSB approach improves the security aspect of the power grid as a cyber-physical system. It is based on available GPS synchronization technology and provides protection against confidentiality attacks in critical power system infrastructures. ^

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.

Integration and querying of heterogeneous, autonomous, distributed database systems

Today, databases have become an integral part of information systems. In the past two decades, we have seen different database systems being developed independently and used in different applications domains. Today's interconnected networks and advanced applications, such as data warehousing, data mining & knowledge discovery and intelligent data access to information on the Web, have created a need for integrated access to such heterogeneous, autonomous, distributed database systems. Heterogeneous/multidatabase research has focused on this issue resulting in many different approaches. However, a single, generally accepted methodology in academia or industry has not emerged providing ubiquitous intelligent data access from heterogeneous, autonomous, distributed information sources. This thesis describes a heterogeneous database system being developed at Highperformance Database Research Center (HPDRC). A major impediment to ubiquitous deployment of multidatabase technology is the difficulty in resolving semantic heterogeneity. That is, identifying related information sources for integration and querying purposes. Our approach considers the semantics of the meta-data constructs in resolving this issue. The major contributions of the thesis work include: (i.) providing a scalable, easy-to-implement architecture for developing a heterogeneous multidatabase system, utilizing Semantic Binary Object-oriented Data Model (Sem-ODM) and Semantic SQL query language to capture the semantics of the data sources being integrated and to provide an easy-to-use query facility; (ii.) a methodology for semantic heterogeneity resolution by investigating into the extents of the meta-data constructs of component schemas. This methodology is shown to be correct, complete and unambiguous; (iii.) a semi-automated technique for identifying semantic relations, which is the basis of semantic knowledge for integration and querying, using shared ontologies for context-mediation; (iv.) resolutions for schematic conflicts and a language for defining global views from a set of component Sem-ODM schemas; (v.) design of a knowledge base for storing and manipulating meta-data and knowledge acquired during the integration process. This knowledge base acts as the interface between integration and query processing modules; (vi.) techniques for Semantic SQL query processing and optimization based on semantic knowledge in a heterogeneous database environment; and (vii.) a framework for intelligent computing and communication on the Internet applying the concepts of our work.

Advanced Techniques for Image Quality Assessment of Modern X-ray Computed Tomography Systems

X-ray computed tomography (CT) imaging constitutes one of the most widely used diagnostic tools in radiology today with nearly 85 million CT examinations performed in the U.S in 2011. CT imparts a relatively high amount of radiation dose to the patient compared to other x-ray imaging modalities and as a result of this fact, coupled with its popularity, CT is currently the single largest source of medical radiation exposure to the U.S. population. For this reason, there is a critical need to optimize CT examinations such that the dose is minimized while the quality of the CT images is not degraded. This optimization can be difficult to achieve due to the relationship between dose and image quality. All things being held equal, reducing the dose degrades image quality and can impact the diagnostic value of the CT examination.

A recent push from the medical and scientific community towards using lower doses has spawned new dose reduction technologies such as automatic exposure control (i.e., tube current modulation) and iterative reconstruction algorithms. In theory, these technologies could allow for scanning at reduced doses while maintaining the image quality of the exam at an acceptable level. Therefore, there is a scientific need to establish the dose reduction potential of these new technologies in an objective and rigorous manner. Establishing these dose reduction potentials requires precise and clinically relevant metrics of CT image quality, as well as practical and efficient methodologies to measure such metrics on real CT systems. The currently established methodologies for assessing CT image quality are not appropriate to assess modern CT scanners that have implemented those aforementioned dose reduction technologies.

Thus the purpose of this doctoral project was to develop, assess, and implement new phantoms, image quality metrics, analysis techniques, and modeling tools that are appropriate for image quality assessment of modern clinical CT systems. The project developed image quality assessment methods in the context of three distinct paradigms, (a) uniform phantoms, (b) textured phantoms, and (c) clinical images.

The work in this dissertation used the “task-based” definition of image quality. That is, image quality was broadly defined as the effectiveness by which an image can be used for its intended task. Under this definition, any assessment of image quality requires three components: (1) A well defined imaging task (e.g., detection of subtle lesions), (2) an “observer” to perform the task (e.g., a radiologists or a detection algorithm), and (3) a way to measure the observer’s performance in completing the task at hand (e.g., detection sensitivity/specificity).

First, this task-based image quality paradigm was implemented using a novel multi-sized phantom platform (with uniform background) developed specifically to assess modern CT systems (Mercury Phantom, v3.0, Duke University). A comprehensive evaluation was performed on a state-of-the-art CT system (SOMATOM Definition Force, Siemens Healthcare) in terms of noise, resolution, and detectability as a function of patient size, dose, tube energy (i.e., kVp), automatic exposure control, and reconstruction algorithm (i.e., Filtered Back-Projection– FPB vs Advanced Modeled Iterative Reconstruction– ADMIRE). A mathematical observer model (i.e., computer detection algorithm) was implemented and used as the basis of image quality comparisons. It was found that image quality increased with increasing dose and decreasing phantom size. The CT system exhibited nonlinear noise and resolution properties, especially at very low-doses, large phantom sizes, and for low-contrast objects. Objective image quality metrics generally increased with increasing dose and ADMIRE strength, and with decreasing phantom size. The ADMIRE algorithm could offer comparable image quality at reduced doses or improved image quality at the same dose (increase in detectability index by up to 163% depending on iterative strength). The use of automatic exposure control resulted in more consistent image quality with changing phantom size.

Based on those results, the dose reduction potential of ADMIRE was further assessed specifically for the task of detecting small (<=6 mm) low-contrast (<=20 HU) lesions. A new low-contrast detectability phantom (with uniform background) was designed and fabricated using a multi-material 3D printer. The phantom was imaged at multiple dose levels and images were reconstructed with FBP and ADMIRE. Human perception experiments were performed to measure the detection accuracy from FBP and ADMIRE images. It was found that ADMIRE had equivalent performance to FBP at 56% less dose.

Using the same image data as the previous study, a number of different mathematical observer models were implemented to assess which models would result in image quality metrics that best correlated with human detection performance. The models included naïve simple metrics of image quality such as contrast-to-noise ratio (CNR) and more sophisticated observer models such as the non-prewhitening matched filter observer model family and the channelized Hotelling observer model family. It was found that non-prewhitening matched filter observers and the channelized Hotelling observers both correlated strongly with human performance. Conversely, CNR was found to not correlate strongly with human performance, especially when comparing different reconstruction algorithms.

The uniform background phantoms used in the previous studies provided a good first-order approximation of image quality. However, due to their simplicity and due to the complexity of iterative reconstruction algorithms, it is possible that such phantoms are not fully adequate to assess the clinical impact of iterative algorithms because patient images obviously do not have smooth uniform backgrounds. To test this hypothesis, two textured phantoms (classified as gross texture and fine texture) and a uniform phantom of similar size were built and imaged on a SOMATOM Flash scanner (Siemens Healthcare). Images were reconstructed using FBP and a Sinogram Affirmed Iterative Reconstruction (SAFIRE). Using an image subtraction technique, quantum noise was measured in all images of each phantom. It was found that in FBP, the noise was independent of the background (textured vs uniform). However, for SAFIRE, noise increased by up to 44% in the textured phantoms compared to the uniform phantom. As a result, the noise reduction from SAFIRE was found to be up to 66% in the uniform phantom but as low as 29% in the textured phantoms. Based on this result, it clear that further investigation was needed into to understand the impact that background texture has on image quality when iterative reconstruction algorithms are used.

To further investigate this phenomenon with more realistic textures, two anthropomorphic textured phantoms were designed to mimic lung vasculature and fatty soft tissue texture. The phantoms (along with a corresponding uniform phantom) were fabricated with a multi-material 3D printer and imaged on the SOMATOM Flash scanner. Scans were repeated a total of 50 times in order to get ensemble statistics of the noise. A novel method of estimating the noise power spectrum (NPS) from irregularly shaped ROIs was developed. It was found that SAFIRE images had highly locally non-stationary noise patterns with pixels near edges having higher noise than pixels in more uniform regions. Compared to FBP, SAFIRE images had 60% less noise on average in uniform regions for edge pixels, noise was between 20% higher and 40% lower. The noise texture (i.e., NPS) was also highly dependent on the background texture for SAFIRE. Therefore, it was concluded that quantum noise properties in the uniform phantoms are not representative of those in patients for iterative reconstruction algorithms and texture should be considered when assessing image quality of iterative algorithms.

The move beyond just assessing noise properties in textured phantoms towards assessing detectability, a series of new phantoms were designed specifically to measure low-contrast detectability in the presence of background texture. The textures used were optimized to match the texture in the liver regions actual patient CT images using a genetic algorithm. The so called “Clustured Lumpy Background” texture synthesis framework was used to generate the modeled texture. Three textured phantoms and a corresponding uniform phantom were fabricated with a multi-material 3D printer and imaged on the SOMATOM Flash scanner. Images were reconstructed with FBP and SAFIRE and analyzed using a multi-slice channelized Hotelling observer to measure detectability and the dose reduction potential of SAFIRE based on the uniform and textured phantoms. It was found that at the same dose, the improvement in detectability from SAFIRE (compared to FBP) was higher when measured in a uniform phantom compared to textured phantoms.

The final trajectory of this project aimed at developing methods to mathematically model lesions, as a means to help assess image quality directly from patient images. The mathematical modeling framework is first presented. The models describe a lesion’s morphology in terms of size, shape, contrast, and edge profile as an analytical equation. The models can be voxelized and inserted into patient images to create so-called “hybrid” images. These hybrid images can then be used to assess detectability or estimability with the advantage that the ground truth of the lesion morphology and location is known exactly. Based on this framework, a series of liver lesions, lung nodules, and kidney stones were modeled based on images of real lesions. The lesion models were virtually inserted into patient images to create a database of hybrid images to go along with the original database of real lesion images. ROI images from each database were assessed by radiologists in a blinded fashion to determine the realism of the hybrid images. It was found that the radiologists could not readily distinguish between real and virtual lesion images (area under the ROC curve was 0.55). This study provided evidence that the proposed mathematical lesion modeling framework could produce reasonably realistic lesion images.

Based on that result, two studies were conducted which demonstrated the utility of the lesion models. The first study used the modeling framework as a measurement tool to determine how dose and reconstruction algorithm affected the quantitative analysis of liver lesions, lung nodules, and renal stones in terms of their size, shape, attenuation, edge profile, and texture features. The same database of real lesion images used in the previous study was used for this study. That database contained images of the same patient at 2 dose levels (50% and 100%) along with 3 reconstruction algorithms from a GE 750HD CT system (GE Healthcare). The algorithms in question were FBP, Adaptive Statistical Iterative Reconstruction (ASiR), and Model-Based Iterative Reconstruction (MBIR). A total of 23 quantitative features were extracted from the lesions under each condition. It was found that both dose and reconstruction algorithm had a statistically significant effect on the feature measurements. In particular, radiation dose affected five, three, and four of the 23 features (related to lesion size, conspicuity, and pixel-value distribution) for liver lesions, lung nodules, and renal stones, respectively. MBIR significantly affected 9, 11, and 15 of the 23 features (including size, attenuation, and texture features) for liver lesions, lung nodules, and renal stones, respectively. Lesion texture was not significantly affected by radiation dose.

The second study demonstrating the utility of the lesion modeling framework focused on assessing detectability of very low-contrast liver lesions in abdominal imaging. Specifically, detectability was assessed as a function of dose and reconstruction algorithm. As part of a parallel clinical trial, images from 21 patients were collected at 6 dose levels per patient on a SOMATOM Flash scanner. Subtle liver lesion models (contrast = -15 HU) were inserted into the raw projection data from the patient scans. The projections were then reconstructed with FBP and SAFIRE (strength 5). Also, lesion-less images were reconstructed. Noise, contrast, CNR, and detectability index of an observer model (non-prewhitening matched filter) were assessed. It was found that SAFIRE reduced noise by 52%, reduced contrast by 12%, increased CNR by 87%. and increased detectability index by 65% compared to FBP. Further, a 2AFC human perception experiment was performed to assess the dose reduction potential of SAFIRE, which was found to be 22% compared to the standard of care dose.

In conclusion, this dissertation provides to the scientific community a series of new methodologies, phantoms, analysis techniques, and modeling tools that can be used to rigorously assess image quality from modern CT systems. Specifically, methods to properly evaluate iterative reconstruction have been developed and are expected to aid in the safe clinical implementation of dose reduction technologies.