The development of optimized high performance liquid chromatography systems for the analysis of improvised explosives

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.

Field programmable gate array based target detection and gesture recognition

The move from Standard Definition (SD) to High Definition (HD) represents a six times increases in data, which needs to be processed. With expanding resolutions and evolving compression, there is a need for high performance with flexible architectures to allow for quick upgrade ability. The technology advances in image display resolutions, advanced compression techniques, and video intelligence. Software implementation of these systems can attain accuracy with tradeoffs among processing performance (to achieve specified frame rates, working on large image data sets), power and cost constraints. There is a need for new architectures to be in pace with the fast innovations in video and imaging. It contains dedicated hardware implementation of the pixel and frame rate processes on Field Programmable Gate Array (FPGA) to achieve the real-time performance. ^ The following outlines the contributions of the dissertation. (1) We develop a target detection system by applying a novel running average mean threshold (RAMT) approach to globalize the threshold required for background subtraction. This approach adapts the threshold automatically to different environments (indoor and outdoor) and different targets (humans and vehicles). For low power consumption and better performance, we design the complete system on FPGA. (2) We introduce a safe distance factor and develop an algorithm for occlusion occurrence detection during target tracking. A novel mean-threshold is calculated by motion-position analysis. (3) A new strategy for gesture recognition is developed using Combinational Neural Networks (CNN) based on a tree structure. Analysis of the method is done on American Sign Language (ASL) gestures. We introduce novel point of interests approach to reduce the feature vector size and gradient threshold approach for accurate classification. (4) We design a gesture recognition system using a hardware/ software co-simulation neural network for high speed and low memory storage requirements provided by the FPGA. We develop an innovative maximum distant algorithm which uses only 0.39% of the image as the feature vector to train and test the system design. Database set gestures involved in different applications may vary. Therefore, it is highly essential to keep the feature vector as low as possible while maintaining the same accuracy and performance^

Functionalized carbon micro/nanostructures for biomolecular detection

Advancements in the micro-and nano-scale fabrication techniques have opened up new avenues for the development of portable, scalable and easier-to-use biosensors. Over the last few years, electrodes made of carbon have been widely used as sensing units in biosensors due to their attractive physiochemical properties. The aim of this research is to investigate different strategies to develop functionalized high surface carbon micro/nano-structures for electrochemical and biosensing devices. High aspect ratio three-dimensional carbon microarrays were fabricated via carbon microelectromechanical systems (C-MEMS) technique, which is based on pyrolyzing pre-patterned organic photoresist polymers. To further increase the surface area of the carbon microstructures, surface porosity was introduced by two strategies, i.e. (i) using F127 as porogen and (ii) oxygen reactive ion etch (RIE) treatment. Electrochemical characterization showed that porous carbon thin film electrodes prepared by using F127 as porogen had an effective surface area (Aeff 185%) compared to the conventional carbon electrode. To achieve enhanced electrochemical sensitivity for C-MEMS based functional devices, graphene was conformally coated onto high aspect ratio three-dimensional (3D) carbon micropillar arrays using electrostatic spray deposition (ESD) technique. The amperometric response of graphene/carbon micropillar electrode arrays exhibited higher electrochemical activity, improved charge transfer and a linear response towards H2O2 detection between 250&mgr;M to 5.5mM. Furthermore, carbon structures with dimensions from 50 nano-to micrometer level have been fabricated by pyrolyzing photo-nanoimprint lithography patterned organic resist polymer. Microstructure, elemental composition and resistivity characterization of the carbon nanostructures produced by this process were very similar to conventional photoresist derived carbon. Surface functionalization of the carbon nanostructures was performed using direct amination technique. Considering the need for requisite functional groups to covalently attach bioreceptors on the carbon surface for biomolecule detection, different oxidation techniques were compared to study the types of carbon-oxygen groups formed on the surface and their percentages with respect to different oxidation pretreatment times. Finally, a label-free detection strategy using signaling aptamer/protein binding complex for platelet-derived growth factor oncoprotein detection on functionalized three-dimensional carbon microarrays platform was demonstrated. The sensor showed near linear relationship between the relative fluorescence difference and protein concentration even in the sub-nanomolar range with an excellent detection limit of 5 pmol.

Automating Hospitality Information: Network Technology and Systems Management

The local area network (LAN) interconnecting computer systems and soft- ware can make a significant contribution to the hospitality industry. The author discusses the advantages and disadvantages of such systems.

Temporal Mining for Distributed Systems

Many systems and applications are continuously producing events. These events are used to record the status of the system and trace the behaviors of the systems. By examining these events, system administrators can check the potential problems of these systems. If the temporal dynamics of the systems are further investigated, the underlying patterns can be discovered. The uncovered knowledge can be leveraged to predict the future system behaviors or to mitigate the potential risks of the systems. Moreover, the system administrators can utilize the temporal patterns to set up event management rules to make the system more intelligent. With the popularity of data mining techniques in recent years, these events grad- ually become more and more useful. Despite the recent advances of the data mining techniques, the application to system event mining is still in a rudimentary stage. Most of works are still focusing on episodes mining or frequent pattern discovering. These methods are unable to provide a brief yet comprehensible summary to reveal the valuable information from the high level perspective. Moreover, these methods provide little actionable knowledge to help the system administrators to better man- age the systems. To better make use of the recorded events, more practical techniques are required. From the perspective of data mining, three correlated directions are considered to be helpful for system management: (1) Provide concise yet comprehensive summaries about the running status of the systems; (2) Make the systems more intelligence and autonomous; (3) Effectively detect the abnormal behaviors of the systems. Due to the richness of the event logs, all these directions can be solved in the data-driven manner. And in this way, the robustness of the systems can be enhanced and the goal of autonomous management can be approached. This dissertation mainly focuses on the foregoing directions that leverage tem- poral mining techniques to facilitate system management. More specifically, three concrete topics will be discussed, including event, resource demand prediction, and streaming anomaly detection. Besides the theoretic contributions, the experimental evaluation will also be presented to demonstrate the effectiveness and efficacy of the corresponding solutions.

A Behavior Based Approach to Virus Detection

Fast spreading unknown viruses have caused major damage on computer systems upon their initial release. Current detection methods have lacked capabilities to detect unknown virus quickly enough to avoid mass spreading and damage. This dissertation has presented a behavior based approach to detecting known and unknown viruses based on their attempt to replicate. Replication is the qualifying fundamental characteristic of a virus and is consistently present in all viruses making this approach applicable to viruses belonging to many classes and executing under several conditions. A form of replication called self-reference replication, (SR-replication), has been formalized as one main type of replication which specifically replicates by modifying or creating other files on a system to include the virus itself. This replication type was used to detect viruses attempting replication by referencing themselves which is a necessary step to successfully replicate files. The approach does not require a priori knowledge about known viruses. Detection was accomplished at runtime by monitoring currently executing processes attempting to replicate. Two implementation prototypes of the detection approach called SRRAT were created and tested on the Microsoft Windows operating systems focusing on the tracking of user mode Win32 API system calls and Kernel mode system services. The research results showed SR-replication capable of distinguishing between file infecting viruses and benign processes with little or no false positives and false negatives.

Ensemble Fuzzy Belief Intrusion Detection Design

With the rapid growth of the Internet, computer attacks are increasing at a fast pace and can easily cause millions of dollar in damage to an organization. Detecting these attacks is an important issue of computer security. There are many types of attacks and they fall into four main categories, Denial of Service (DoS) attacks, Probe, User to Root (U2R) attacks, and Remote to Local (R2L) attacks. Within these categories, DoS and Probe attacks continuously show up with greater frequency in a short period of time when they attack systems. They are different from the normal traffic data and can be easily separated from normal activities. On the contrary, U2R and R2L attacks are embedded in the data portions of the packets and normally involve only a single connection. It becomes difficult to achieve satisfactory detection accuracy for detecting these two attacks. Therefore, we focus on studying the ambiguity problem between normal activities and U2R/R2L attacks. The goal is to build a detection system that can accurately and quickly detect these two attacks. In this dissertation, we design a two-phase intrusion detection approach. In the first phase, a correlation-based feature selection algorithm is proposed to advance the speed of detection. Features with poor prediction ability for the signatures of attacks and features inter-correlated with one or more other features are considered redundant. Such features are removed and only indispensable information about the original feature space remains. In the second phase, we develop an ensemble intrusion detection system to achieve accurate detection performance. The proposed method includes multiple feature selecting intrusion detectors and a data mining intrusion detector. The former ones consist of a set of detectors, and each of them uses a fuzzy clustering technique and belief theory to solve the ambiguity problem. The latter one applies data mining technique to automatically extract computer users’ normal behavior from training network traffic data. The final decision is a combination of the outputs of feature selecting and data mining detectors. The experimental results indicate that our ensemble approach not only significantly reduces the detection time but also effectively detect U2R and R2L attacks that contain degrees of ambiguous information.

Design Strategies for an Artificial Neural Network Based Algorithm for Automatic Incident Detection on Major Arterial Streets

Traffic incidents are non-recurring events that can cause a temporary reduction in roadway capacity. They have been recognized as a major contributor to traffic congestion on our national highway systems. To alleviate their impacts on capacity, automatic incident detection (AID) has been applied as an incident management strategy to reduce the total incident duration. AID relies on an algorithm to identify the occurrence of incidents by analyzing real-time traffic data collected from surveillance detectors. Significant research has been performed to develop AID algorithms for incident detection on freeways; however, similar research on major arterial streets remains largely at the initial stage of development and testing. This dissertation research aims to identify design strategies for the deployment of an Artificial Neural Network (ANN) based AID algorithm for major arterial streets. A section of the US-1 corridor in Miami-Dade County, Florida was coded in the CORSIM microscopic simulation model to generate data for both model calibration and validation. To better capture the relationship between the traffic data and the corresponding incident status, Discrete Wavelet Transform (DWT) and data normalization were applied to the simulated data. Multiple ANN models were then developed for different detector configurations, historical data usage, and the selection of traffic flow parameters. To assess the performance of different design alternatives, the model outputs were compared based on both detection rate (DR) and false alarm rate (FAR). The results show that the best models were able to achieve a high DR of between 90% and 95%, a mean time to detect (MTTD) of 55-85 seconds, and a FAR below 4%. The results also show that a detector configuration including only the mid-block and upstream detectors performs almost as well as one that also includes a downstream detector. In addition, DWT was found to be able to improve model performance, and the use of historical data from previous time cycles improved the detection rate. Speed was found to have the most significant impact on the detection rate, while volume was found to contribute the least. The results from this research provide useful insights on the design of AID for arterial street applications.

Integrity-based kernel malware detection

Kernel-level malware is one of the most dangerous threats to the security of users on the Internet, so there is an urgent need for its detection. The most popular detection approach is misuse-based detection. However, it cannot catch up with today's advanced malware that increasingly apply polymorphism and obfuscation. In this thesis, we present our integrity-based detection for kernel-level malware, which does not rely on the specific features of malware. ^ We have developed an integrity analysis system that can derive and monitor integrity properties for commodity operating systems kernels. In our system, we focus on two classes of integrity properties: data invariants and integrity of Kernel Queue (KQ) requests. ^ We adopt static analysis for data invariant detection and overcome several technical challenges: field-sensitivity, array-sensitivity, and pointer analysis. We identify data invariants that are critical to system runtime integrity from Linux kernel 2.4.32 and Windows Research Kernel (WRK) with very low false positive rate and very low false negative rate. We then develop an Invariant Monitor to guard these data invariants against real-world malware. In our experiment, we are able to use Invariant Monitor to detect ten real-world Linux rootkits and nine real-world Windows malware and one synthetic Windows malware. ^ We leverage static and dynamic analysis of kernel and device drivers to learn the legitimate KQ requests. Based on the learned KQ requests, we build KQguard to protect KQs. At runtime, KQguard rejects all the unknown KQ requests that cannot be validated. We apply KQguard on WRK and Linux kernel, and extensive experimental evaluation shows that KQguard is efficient (up to 5.6% overhead) and effective (capable of achieving zero false positives against representative benign workloads after appropriate training and very low false negatives against 125 real-world malware and nine synthetic attacks). ^ In our system, Invariant Monitor and KQguard cooperate together to protect data invariants and KQs in the target kernel. By monitoring these integrity properties, we can detect malware by its violation of these integrity properties during execution.^

The Development of High Performance Liquid Chromatography Systems for the Analysis of Improvised Explosives

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.

Text Analytics of Social Media: Sentiment Analysis, Event Detection and Summarization

In the last decade, large numbers of social media services have emerged and been widely used in people's daily life as important information sharing and acquisition tools. With a substantial amount of user-contributed text data on social media, it becomes a necessity to develop methods and tools for text analysis for this emerging data, in order to better utilize it to deliver meaningful information to users. Previous work on text analytics in last several decades is mainly focused on traditional types of text like emails, news and academic literatures, and several critical issues to text data on social media have not been well explored: 1) how to detect sentiment from text on social media; 2) how to make use of social media's real-time nature; 3) how to address information overload for flexible information needs. In this dissertation, we focus on these three problems. First, to detect sentiment of text on social media, we propose a non-negative matrix tri-factorization (tri-NMF) based dual active supervision method to minimize human labeling efforts for the new type of data. Second, to make use of social media's real-time nature, we propose approaches to detect events from text streams on social media. Third, to address information overload for flexible information needs, we propose two summarization framework, dominating set based summarization framework and learning-to-rank based summarization framework. The dominating set based summarization framework can be applied for different types of summarization problems, while the learning-to-rank based summarization framework helps utilize the existing training data to guild the new summarization tasks. In addition, we integrate these techneques in an application study of event summarization for sports games as an example of how to better utilize social media data.

Availability estimation and management for complex processing systems

“Availability” is the terminology used in asset intensive industries such as petrochemical and hydrocarbons processing to describe the readiness of equipment, systems or plants to perform their designed functions. It is a measure to suggest a facility’s capability of meeting targeted production in a safe working environment. Availability is also vital as it encompasses reliability and maintainability, allowing engineers to manage and operate facilities by focusing on one performance indicator. These benefits make availability a very demanding and highly desired area of interest and research for both industry and academia. In this dissertation, new models, approaches and algorithms have been explored to estimate and manage the availability of complex hydrocarbon processing systems. The risk of equipment failure and its effect on availability is vital in the hydrocarbon industry, and is also explored in this research. The importance of availability encouraged companies to invest in this domain by putting efforts and resources to develop novel techniques for system availability enhancement. Most of the work in this area is focused on individual equipment compared to facility or system level availability assessment and management. This research is focused on developing an new systematic methods to estimate system availability. The main focus areas in this research are to address availability estimation and management through physical asset management, risk-based availability estimation strategies, availability and safety using a failure assessment framework, and availability enhancement using early equipment fault detection and maintenance scheduling optimization.

Industrial fault detection and diagnosis using Bayesian belief network

Rapid development in industry have contributed to more complex systems that are prone to failure. In applications where the presence of faults may lead to premature failure, fault detection and diagnostics tools are often implemented. The goal of this research is to improve the diagnostic ability of existing FDD methods. Kernel Principal Component Analysis has good fault detection capability, however it can only detect the fault and identify few variables that have contribution on occurrence of fault and thus not precise in diagnosing. Hence, KPCA was used to detect abnormal events and the most contributed variables were taken out for more analysis in diagnosis phase. The diagnosis phase was done in both qualitative and quantitative manner. In qualitative mode, a networked-base causality analysis method was developed to show the causal effect between the most contributing variables in occurrence of the fault. In order to have more quantitative diagnosis, a Bayesian network was constructed to analyze the problem in probabilistic perspective.

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.

Numerical detection of the Gardner transition in a mean-field glass former.

Recent theoretical advances predict the existence, deep into the glass phase, of a novel phase transition, the so-called Gardner transition. This transition is associated with the emergence of a complex free energy landscape composed of many marginally stable sub-basins within a glass metabasin. In this study, we explore several methods to detect numerically the Gardner transition in a simple structural glass former, the infinite-range Mari-Kurchan model. The transition point is robustly located from three independent approaches: (i) the divergence of the characteristic relaxation time, (ii) the divergence of the caging susceptibility, and (iii) the abnormal tail in the probability distribution function of cage order parameters. We show that the numerical results are fully consistent with the theoretical expectation. The methods we propose may also be generalized to more realistic numerical models as well as to experimental systems.