<p>In this thesis we consider the need to generate efficient solvers for inverse imaging problems in a way that supports both quality and performance in software, as well as flexibility in the underlying mathematical models. Many problem domains involve large data sizes and rates, and changes in mathematical modelling are limited only by researcher ingenuity and driven by the value of the application. We use a problem in Magnetic Resonance Imaging to illustrate this situation, motivate the need for better software tools and test the tools we develop. The problem is the determination of velocity profiles, think blood-flow patterns, using Phase Contrast Angiography. Despite the name, this method is completely noninvasive, not requiring the injection of contrast agents, but it is too time-consuming with present imaging and computing technology.</p> <p>Our approach is to separate the specification, the mathematical model, from the implementation details required for performance, using a custom language. The Domain Specific Language (DSL) provided to scientists allows for a complete abstraction from the highly optimized generated code. The mathematical DSL is converted to an internal representation we refer to as the Coconut Expression Library. Our expression library uses the directed acyclic graphs as an underlying data structure, which lends itself nicely to our automatic simplifications, differentiation and subexpression elimination. We show how parallelization and other optimizations are encoded as rules which are applied automatically rather than schemes that need to be implemented by the programmer in the low-level implementation. Finally, we present results, both in terms of numerical results and computational performance.</p> / Master of Science (MSc)

<p>MR phase images contain essential information about local magnetic susceptibility sources in the brain, creating a new type of contrast in magnetic resonance imaging (MRI). The goal of this thesis is to demonstrate with a model of the brain how accurately the transformation of phase to susceptibility takes place.</p> <p>A 3D brain model uses the Forward process to calculate magnetic field perturbations caused by susceptibility properties of the tissues in the model. Homodyne High Pass (HP) filter and SHARP algorithm are used to process the simulated phase images. Similarly, MR magnitude data are simulated using tissue properties such as T₁, T₂^* relaxation times and spin density.</p> <p>The halo ring around red nucleus in the real phase data is believed to be an indicator of a capsule around red nucleus. Similar effect is seen in the simulated phase images without including the capsule of red nucleus in the model, this comparison explains that the halo effect may just be entirely or a part of the phase behavior around red nucleus. A negative susceptibility in the internal capsule region, seen in both simulated and real susceptibility maps, is discussed as a possible artifact caused by the processing techniques after comparing the simulated susceptibility maps produced from unprocessed and processed phase data. The brain model is used to determine the optimum echo time of the initial gradient echo sequence in order to produce a high quality susceptibility map with reasonably low error and better time efficiency.</p> / Master of Applied Science (MASc)

<p>This thesis provides new regression methods for the removal of structured noise in datasets. With multivariable data, the variables and the noise can be both temporally correlated (i.e. auto correlated in time) and contemporaneously correlated (i.e. cross-correlated at the same time). In many occasions it is possible to acquire measurements of the noise, or some function of it, during the data collection. Several new constrained latent variable methods (LVM) that are built upon previous LVM regression frameworks are introduced. These methods make use of the additional information available about the noise to decompose a dataset into basis for the noise and signal. The properties of these methods are investigated mathematically, and through both simulation and application to actual biomedical data.</p> <p>In Chapter Two, linear, constrained LVM methods are introduced. The performance of these methods are compared to the other similar LVM methods as well as ordinary PLS throughout several simulation studies. In Chapter Three, a NIPALS type algorithm is developed for the soft constrained PLS method which is also able to account for missing data as well as datasets with large covariance matrices. Chapter Four introduces the nonlinear-kernelized constrained LVM methods. These methods are capable of handling severe nonlinearities in the datasets. The performance of these methods are compared to nonlinear kernel PLS method. In Chapter Five the constrained methods are used to remove ballistocardiographic and muscle artifacts from EEG datasets in combined EEG-fMRI as well as single EEG experiments on patients. The results are shown and compared to the standard noise removal methods used in the field. Finally in Chapter Six, the overall conclusion and scope of the future work is laid out.</p> / Doctor of Philosophy (PhD)

<p>High-content screening (HCS) produces an immense amount of data, often on the scale of Terabytes. This requires considerable processing power resulting in long analysis time. As a result, HCS with a single-core processor system is an inefficient option because it takes a huge amount of time, storage and processing power. The situation is even worse because most of the image processing software is developed in high-level languages which make customization, flexibility and multi-processing features very challenging. Therefore, the goal of the project is to develop a multithreading model in C language. This model will be used to extract subcellular localization features, such as threshold adjacency statistics (TAS) from the HCS data. The first step of the research was to identify an appropriate dye for use in staining the MCF-7 cell line. The cell line has been treated with staurosporin kinase inhibitor, which can provide important physiological and morphological imaging information. The process of identifying a suitable dye involves treating cells with different dye options, capturing the fluorescent images of the treated cells with the Opera microscope, and analyzing the imaging properties of the stained cells. Several dyes were tested, and the most suitable dye to stain the cellular membrane was determined to be Di4-Anepps. The second part of the thesis was to design and develop a parallel program in C that can extract TAS features from the stained cellular images. The program reads the input cell images captured by Opera microscopes, converts it to TIFF format from the proprietary Opera format, identifies the region-of-interest contours of each cell, and computes the TAS features. A significant increase in speed in the order of four fold was obtained using the customized program. Different scalability tests using the developed software were compared against software developed in Acapella scripting language. The result of the test shows that the computational time is proportional to number of cells in the image and is inversely proportional to number of cores in a processor.</p> / Master of Applied Science (MASc)

<p>A microfluidic device capable of drug delivery to multiple wells in a concentration gradient was designed for automated high content and high throughput screening. The design was proposed to utilize a nanoporous polycarbonate membrane to spatially and temporally control drug dosage from the microchannels below to the wells above. Microchannels were to hold to the drugs or reagents, while wells were to culture cells. An array of 16 wells was to fit in the equivalent area of a single well of a 96 well plate. Two simpler devices were created to validate electrokinetic drug delivery to a single well and to characterize cell proliferation and viability in micro-wells. The first device tested drug delivery to a single well with methylene blue dye at applied voltages of 100V, 125V, and 150V. It was validated that the dosage of dye could be controlled by increasing the voltage and by increasing the duration the voltage was applied. The second devices were a series of 9-well arrays, each testing a different diameter (1.2 mm – 0.35 mm). These devices were cultured with MCF-7 breast cancer cells over 5 days. At the end of the 5 day study, all diameters except for 0.5 mm and 0.35 mm measured a cell viability of 99% and exhibited cell growth patterns similar to coverslip glass controls. The proposed integrated cell culture and drug delivery device could have application towards early stage drug discovery and could have compatibility with lab equipment originally designed for well plates.</p> / Master of Applied Science (MASc)

ACL injury has been shown to have long-lasting and severe consequences on the different structures of the knee such as the articular cartilage and meniscus. Cartilage thickness changes in particular are indicative of osteoarthritic changes in the tibiofemoral joint. While there has been significant research focused on cartilage changes of the tibia and femur, there has been little work looking at patellar cartilage. The following goals were set forth for this study. First, to establish a robust coordinate system to accurately determine the location and orientation of the patella. Secondly, to determine the effects of ACL injury on patellar cartilage thickness. Twenty-one individuals (10 males, 11 females) were studied. All individuals had suffered first time ACL injuries to one of their knees. MRI data from both the healthy and injured knees were collected an average of 4 ± 0.9 years. Using MRI data, the bone and cartilage surfaces were manually segmented and imported into MATLAB for study. Differences in cartilage thickness values between the healthy and unhealthy knees within individuals was the primary measure of analysis. Analysis revealed a total of 9 square millimeters of cartilage surface area that were statistically significant. Four square millimeters of significant difference were found in males in the medial superior compartment, (mean thickness difference = -0.381 mm, with SD = 0.084mm, indicating thinning). Five square millimeters of significant difference were found in females in the medial inferior compartment (mean thickness difference = 0.551 mm, SD = 0.015mm, indicating thickening). This suggests regional and sex related cartilage thickness changes occur following ACL injury, surgery, and 4 year follow-up.

One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction. The application of FSLs in medical therapeutics is a recent development, and although they offer many benefits, FSLs also stimulate nonlinear optical effects (NOEs), many of which were insignificant with previously developed lasers. NOEs can change the laser characteristics during propagation through a medium, which can subsequently introduce unique safety concerns for the surrounding tissues. Traditional approaches for characterizing optical effects, laser performance, safety and efficacy do not properly account for NOEs, and there remains a lack of data that describe NOEs in clinically relevant procedures and tissues. As FSL technology continues to expand towards new applications, FSL induced NOEs need to be better understood in order to ensure safety as FSL medical devices and applications continue to evolve at a rapid pace. In order to improve the understanding of FSL-tissue interactions related to NOEs stimulated during laser beam propagation though corneal tissue, research investigations were conducted to evaluate corneal optical properties and determine how corneal tissue properties including corneal layer, collagen orientation and collagen crosslinking, and laser parameters including pulse energy, repetition rate and numerical aperture affect second and third-harmonic generation (HG) intensity, duration and efficiency. The results of these studies revealed that all laser parameters and tissue properties had a substantial influence on HG. The dynamic relationship between optical breakdown and HG was responsible for many observed changes in HG metrics. The results also demonstrated that the new generation of therapeutic FSLs has the potential to generate hazardous effects if not carefully controlled. Finally, recommendations are made to optimize current and guide future FSL applications.

Probiotics are marketed throughout the world to promote the health of the consumer by improving the microorganisms that normally occur in the intestinal tract (Tannock, 1997). It has also been suggested that probiotics can prevent pathogen infections by adhering to the intestinal mucosa (Lee, Lim, Teng, Ouwehand, Tuomola, & Salminen, 2000). While probiotics can be delivered to the infected areas in multiple fashions, microencapsulation is a newer form of delivering probiotics straight to the infected area. A whey protein microcapsule is thought to protect the probiotics from stomach acid and delivers the treatment to the affected area. To ensure this microencapsulation treatment is affective, the microcapsules will be stained and imaged to see if the microcapsules are constructed in a way which is consistent with the theory: a whey protein microcapsule surrounding bacteria and fat droplets. Through these experiments, it was shown that the microcapsule was not constructed as previously thought. Instead of a thin layer of protein surrounding the bacteria, it more closely resembled a solid ball of protein with bacteria and fat trapped inside. The bacteria are able to survive stomach like conditions (0.1M HCl for 8 hours) due to other forms of microencapsulation.

The application of high frequency ultrasound is the key to higher resolution intravascular ultrasound (IVUS) images. The need to further improve the IVUS spatial resolution may drive the transducer center frequency even higher than the current 40 MHz range. However, increasing the center frequency may be challenging as it leads to stronger scattering echoes from blood. The high level of blood scattering echoes may obscure the arterial lumen and make image interpretation difficult. Blood backscatter levels increase with transmission center frequency at a much greater rate compared to arterial tissue. These different frequency dependencies provide a potential method to distinguish blood from tissues by means of multi-frequency processing techniques. To obtain a good blood-tissue contrast with sufficient signal-to-noise ratio, a system with a wider bandwidth is highly desirable. The method described in this paper is based on the ratio of the received signal power between the high (60 MHz) and low (25 MHz) frequency ranges from a novel 40 MHz wideband IVUS catheter. In this paper we will present our in vitro experiment work on porcine blood and a tissue-mimicking arterial wall. Results of multi-frequency processing indicate that blood, at higher frequencies, has a greater backscatter power that is 8X greater than arterial tissue, suggesting this technique will provide a greater contrast between the blood-wall lumen boundary for coronary imaging.

Cervical cancer remains the third most commonly diagnosed gynecological malignancy in the United States and throughout the world despite being potentially preventable. Patients diagnosed with cervical cancer may develop local recurrence in the cervix and surrounding structures (vaginal apex, parametrial, or paracervical), regional recurrence in pelvic lymph nodes, distant metastasis, or a combination of all. The management of such treatment outcomes has not been subject to rigorous investigation. Therefore, there is a need for studies and clinical trials that focus on decision making to support the choice of the best treatment modality that leads to the minimal number of adverse treatment outcomes. Medical imaging plays a vital role in the initial diagnosis, staging, and guiding treatment decisions for cancer patients. Positron Emission Tomography-Computed Tomography (PET/CT) hybrid scanner has proven to be a primary functional imaging modality in the oncology clinic. A typical oncological application of PET/CT aims to examine the whole body for high tracer uptake as a sign of tumorous lesions or metastasis using 18F-Fluoro-2-deoxy-D-glucose (18F-FDG). This radiopharmaceutical has been proven to be useful for the quantitative determination of regional glucose metabolism localized in the brain, heart, bladder, and, fortunately, in tumors. Currently, 18F-FDG measured on PET is the prominent radiotracer in cancer staging and follow-up imaging. In the –omics1 era, mining data to derive inherent information about a system has influenced the medical field, especially oncological imaging. The process of radiomics involves high throughput analysis of medical images to extract a large number of quantified features that are presented as a decision supporting tool for clinicians in terms of various clinical tasks such as staging, prediction, and prognosis. In recent studies, the focus of radiomics has exceeded the whole-tumor analysis to include the quantification of habitats, sub-regions within the tumor volume defined based on specific criteria, with the intent to investigate the diversity extent of the intratumor heterogeneity as robust descriptors and predictors of clinicopathological factors. The presented work is a retrospective analysis of a cohort consisting of pretreatment Positron Emission Tomography and Computed Tomography (PET/CT) hybrid scans of cervical cancer patients consecutively treated with radiochemotherapy. We extracted radiomic features from the primary cervical tumor volumes, and voxel intensity-based features from tumor habitats to analyze the tumors’ heterogeneity based on 18Flourodeoxyglocuse (18F-FDG) uptake of PET, and Hounsfield Units (HU) of CT to obtain useful tumor information, which might be associated with treatment outcomes. To our knowledge, a limited number of studies have focused on investigating the potential role of radiomic features on cervical cancer PET/CT images. Briefly, the workflow of this study consisted of investigating parameters that might affect radiomic features predictive performance by evaluating the reproducibility of radiomic features extracted from 18F-FDG PET images for segmentation methods, gray levels discretization, and PET reconstruction algorithms. Afterward, we used these features to predict cervical treatment outcomes after radiochemotherapy. Due to the use of human data, this research study acquired the approval of the institutional review board (IRB) at the University of South Florida.