<p> Amyloid-&beta; (A&beta;) peptide is generated after sequential cleavage of the constitutively expressed amyloid precursor protein (APP) by &gamma; and &beta; secretases, and is recognized as the primary causative agent underlying the neuropathogenesis of Alzheimer&rsquo;sDisease (AD). Once generated, monomeric A&beta; demonstrates a high propensity to aggregate into toxic A&beta; oligomers (A&beta;O) of various sizes, which eventually accumulate in the brain in the form of amyloid plaques. Mutations in either the gene for APP or one or both of its processing genes, presenilin-1 (PS1) and presenilin-2 (PS2) of the secretases complex leading to accumulation of A&beta; and early-onset familial AD. Late onset AD is modulated by mutations in the gene for apolipoprotein E (apo-E), with the isoform apo-E4 leading to an approximate eight-fold increase in risk for AD, and by environmental and life style factors. The Alzheimer&rsquo;s disease process develops over decades, with substantial neurological loss occurring before a clinical diagnosis of dementia can be rendered. A major roadblock to the management of AD is the inability to definitively diagnose AD until post-mortem examination. It is therefore imperative to develop methods that permit safe, early detection and monitoring of disease progression. Magnetic resonance imaging (MRI) is a non-invasive way to detect and monitor AD progression and therapy, but so far MRI contrast has been obtained only using Gd(III) based contrast agents. Fluorene compounds have garnered attention as amyloid imaging agents. Our lab has developed a spin labeled fluorene (SLF) compound that contains a fluorene moiety with known affinity for A&beta; and a pyrroline nitroxyl spin-label moiety. We hypothesized that the SLF compound will specifically coat assemblies of amyloid beta in the brain and, by establishing a boundary of magnetic field inhomogeneity, produce MRI contrast in tissues with elevated levels of the A&beta; peptide. I found that labeling of brain specimens with the SLF compound produces negative contrast in samples from AD model mice whereas no negative contrast is seen in specimens harvested from wild-type mice. Injection of SLF into live mice resulted in good brain penetration, with the compound able to generate contrast 24-hr post injection. (Abstract shortened by ProQuest.)</p>

<p> The proposed project presents a methodology to detect how susceptible or resistant certain bacteria are to an applied antibiotic. This detection is achieved by calculating the area of Zone of Inhibition (ZOI) regions present in the petri dish and comparing the results to the prescribed standards. The ZOI regions are empty areas formed around an antibiotic disc when placed on a petri dish containing a sample of the bacterial culture. Digital image processing techniques are employed to automate the process of ZOI detection. Experimental results show that the proposed project is successful in detecting ZOI regions of various shapes, such as perfectly circular, irregular, and overlapping. The experimental results also show that the accuracy of detection is typically over 95%, and it remains above 90%, even when the image is degraded by additive Gaussian noise.</p><p>

The aim of this project was to compare and evaluate other, non-EPI, diffusion-weighted MRI (DWI) sequences, through imaging experiments, on a phantom and in vivo, (using a 0.95 T system) and computer simulations, and to develop improved DWI methodology which could be implemented on standard hardware. Pulsed gradient spin echo (PGSE) and diffusion-weighted STEAM are slow multiple shot sequences, with measurement times of several minutes. Both sequences are highly sensitive to patient motion, but motion artifact was virtually eliminated using navigator echo phase correction and EGG triggering when diffusion-sensitisation was in the phase-encoding direction. It was demonstrated that both sequences can provide high quality images and allow accurate and straightforward diffusion-coefficient measurement when an imaging time period in the region of 20-30 minutes is available and when diffusion-sensitisation is required in one or two directions. A third direction of diffusion-sensitisation may be feasible if more sophisticated immobilisation or phase correction techniques are employed. A choice between PGSE or STEAM for a given application should take account of the Ti and T2 values of the imaged tissues, since a higher SNR might be provided by STEAM when the T1T2 ratio is high. A diffusion-weighted CE-FAST sequence was implemented with the novel modification of acquisition of a navigator gradient-echo, which was shown to reduce motion artifact when diffusion-sensitisation was in the phase-encoding direction. However, it has been demonstrated by other workers that unknown signal losses due to motion-induced phase incoherence between signal components may remain. The SNR (normalised with respect to the square root of the imaging time) in the phantom and in white matter was similar to that obtained using PGSE, but an advantage of CE- FAST is that it can be performed in a fraction of the measurement time of PGSE. Diffusion-sensitivity was much higher than in other sequences and the diffusion- attenuation was found to agree with an analysis presented in the literature. However, a major disadvantage of the technique, which precludes its use for many DWI applications, is the requirement of accurate knowledge of Ti, T2 and flip angle in order to calculate the diffusion coefficient or tensor. Prior to a study of diffusion-weighted snapshot FLASH, the effects of magnetisation evolution during snapshot FLASH acquisition on image quality and parameter measurement accuracy were first investigated, through phantom experiments and computer simulations, in the context of a r2-weighted snapshot FLASH sequence. It was demonstrated that magnetisation evolution effects can lead to significant error in parameter measurement, but that this error can be eliminated by using crusher gradients to prevent evolved magnetisation from contributing to the acquired signal. However, qualitative effects are not entirely eliminated, since a significant degree of edge blurring may remain, and there is a 50% loss of SNR inherent to the crusher gradient technique. It was then shown, theoretically and experimentally, that in diffusion-weighted snapshot FLASH, the crusher gradient technique not only addresses the problem of magnetisation evolution, but also eliminates the effect of phase shifts arising during the diffusion-preparation sequence.

<p>On-board image guidance, such as cone-beam CT (CBCT) and kV/MV 2D imaging, is essential in many radiation therapy procedures, such as intensity modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). These imaging techniques provide predominantly anatomical information for treatment planning and target localization. Recently, studies have shown that treatment planning based on functional and molecular information about the tumor and surrounding tissue could potentially improve the effectiveness of radiation therapy. However, current on-board imaging systems are limited in their functional and molecular imaging capability. Single Photon Emission Computed Tomography (SPECT) is a candidate to achieve on-board functional and molecular imaging. Traditional SPECT systems typically take 20 minutes or more for a scan, which is too long for on-board imaging. A robotic multi-pinhole SPECT system was proposed in this dissertation to provide shorter imaging time by using a robotic arm to maneuver the multi-pinhole SPECT system around the patient in position for radiation therapy. </p><p>A 49-pinhole collimated SPECT detector and its shielding were designed and simulated in this work using the computer-aided design (CAD) software. The trajectories of robotic arm about the patient, treatment table and gantry in the radiation therapy room and several detector assemblies such as parallel holes, single pinhole and 49 pinholes collimated detector were investigated. The rail mounted system was designed to enable a full range of detector positions and orientations to various crucial treatment sites including head and torso, while avoiding collision with linear accelerator (LINAC), patient table and patient.</p><p>An alignment method was developed in this work to calibrate the on-board robotic SPECT to the LINAC coordinate frame and to the coordinate frames of other on-board imaging systems such as CBCT. This alignment method utilizes line sources and one pinhole projection of these line sources. The model consists of multiple alignment parameters which maps line sources in 3-dimensional (3D) space to their 2-dimensional (2D) projections on the SPECT detector. Computer-simulation studies and experimental evaluations were performed as a function of number of line sources, Radon transform accuracy, finite line-source width, intrinsic camera resolution, Poisson noise and acquisition geometry. In computer-simulation studies, when there was no error in determining angles (&alpha;) and offsets (&rho;) of the measured projections, the six alignment parameters (3 translational and 3 rotational) were estimated perfectly using three line sources. When angles (&alpha;) and offsets (&rho;) were provided by Radon transform, the estimation accuracy was reduced. The estimation error was associated with rounding errors of Radon transform, finite line-source width, Poisson noise, number of line sources, intrinsic camera resolution and detector acquisition geometry. The estimation accuracy was significantly improved by using 4 line sources rather than 3 and also by using thinner line-source projections (obtained by better intrinsic detector resolution). With 5 line sources, median errors were 0.2 mm for the detector translations, 0.7 mm for the detector radius of rotation, and less than 0.5° for detector rotation, tilt and twist. In experimental evaluations, average errors relative to a different, independent registration technique were about 1.8 mm for detector translations, 1.1 mm for the detector radius of rotation (ROR), 0.5° and 0.4° for detector rotation and tilt, respectively, and 1.2° for detector twist. </p><p>Simulation studies were performed to investigate the improvement of imaging sensitivity and accuracy of hot sphere localization for breast imaging of patients in prone position. A 3D XCAT phantom was simulated in the prone position with nine hot spheres of 10 mm diameter added in the left breast. A no-treatment-table case and two commercial prone breast boards, 7 and 24 cm thick, were simulated. Different pinhole focal lengths were assessed for root-mean-square-error (RMSE). The pinhole focal lengths resulting in the lowest RMSE values were 12 cm, 18 cm and 21 cm for no table, thin board, and thick board, respectively. In both no table and thin board cases, all 9 hot spheres were easily visualized above background with 4-minute scans utilizing the 49-pinhole SPECT system while seven of nine hot spheres were visible with the thick board. In comparison with parallel-hole system, our 49-pinhole system shows reduction in noise and bias under these simulation cases. These results correspond to smaller radii of rotation for no-table case and thinner prone board. Similarly, localization accuracy with the 49-pinhole system was significantly better than with the parallel-hole system for both the thin and thick prone boards. Median localization errors for the 49-pinhole system with the thin board were less than 3 mm for 5 of 9 hot spheres, and less than 6 mm for the other 4 hot spheres. Median localization errors of 49-pinhole system with the thick board were less than 4 mm for 5 of 9 hot spheres, and less than 8 mm for the other 4 hot spheres. </p><p>Besides prone breast imaging, respiratory-gated region-of-interest (ROI) imaging of lung tumor was also investigated. A simulation study was conducted on the potential of multi-pinhole, region-of-interest (ROI) SPECT to alleviate noise effects associated with respiratory-gated SPECT imaging of the thorax. Two 4D XCAT digital phantoms were constructed, with either a 10 mm or 20 mm diameter tumor added in the right lung. The maximum diaphragm motion was 2 cm (for 10 mm tumor) or 4 cm (for 20 mm tumor) in superior-inferior direction and 1.2 cm in anterior-posterior direction. Projections were simulated with a 4-minute acquisition time (40 seconds per each of 6 gates) using either the ROI SPECT system (49-pinhole) or reference single and dual conventional broad cross-section, parallel-hole collimated SPECT. The SPECT images were reconstructed using OSEM with up to 6 iterations. Images were evaluated as a function of gate by profiles, noise versus bias curves, and a numerical observer performing a forced-choice localization task. Even for the 20 mm tumor, the 49-pinhole imaging ROI was found sufficient to encompass fully usual clinical ranges of diaphragm motion. Averaged over the 6 gates, noise at iteration 6 of 49-pinhole ROI imaging (10.9 µCi/ml) was approximately comparable to noise at iteration 2 of the two dual and single parallel-hole, broad cross-section systems (12.4 µCi/ml and 13.8 µCi/ml, respectively). Corresponding biases were much lower for the 49-pinhole ROI system (3.8 µCi/ml), versus 6.2 µCi/ml and 6.5 µCi/ml for the dual and single parallel-hole systems, respectively. Median localization errors averaged over 6 gates, for the 10 mm and 20 mm tumors respectively, were 1.6 mm and 0.5 mm using the ROI imaging system and 6.6 mm and 2.3 mm using the dual parallel-hole, broad cross-section system. The results demonstrate substantially improved imaging via ROI methods. One important application may be gated imaging of patients in position for radiation therapy.</p><p>A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150-L110 robot). An imaging study was performed with a phantom (PET CT Phantom<super>TM</super>), which includes 5 spheres of 10, 13, 17, 22 and 28 mm in diameter. The phantom was placed on a flat-top couch. SPECT projections were acquired with a parallel-hole collimator and a single-pinhole collimator both without background in the phantom, and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180 degrees and 228 degrees respectively. The pinhole detector viewed a 14.7 cm-diameter common volume which encompassed the 28 mm and 22 mm spheres. The common volume for parallel-hole was a 20.8-cm-diameter cylinder which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the flat-top table while avoiding collision with the table and maintaining the closest possible proximity to the common volume. For image reconstruction, detector trajectories were described by radius-of-rotation and detector rotation angle &#952;. These reconstruction parameters were obtained from the robot base and tool coordinates. The robotic SPECT system was able to maneuver the parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector to center-of-rotation (COR) distance. In no background case, all five spheres were visible in the reconstructed parallel-hole and pinhole images. In with background case, three spheres of 17, 22 and 28 mm diameter were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameter) were readily observed in the pinhole ROI imaging.</p><p>In conclusion, the proposed on-board robotic SPECT can be aligned to LINAC/CBCT with a single pinhole projection of the line-source phantom. Alignment parameters can be estimated using one pinhole projection of line sources. This alignment method may be important for multi-pinhole SPECT, where relative pinhole alignment may vary during rotation. For single pinhole and multi-pinhole SPECT imaging onboard radiation therapy machines, the method could provide alignment of SPECT coordinates with those of CBCT and the LINAC. In simulation studies of prone breast imaging and respiratory-gated lung imaging, the 49-pinhole detector showed better tumor contrast recovery and localization in a 4-minute scan compared to parallel-hole detector. On-board SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frames could be an effective means to estimate detector pose for use in SPECT image reconstruction.</p> / Dissertation

<p> <b>Introduction:</b> Endovascular chemotherapy treatment allows localized delivery adjacent to the target tumor; allowing an increased dosage and decreased leakage to other areas. It also allows for the opportunity to filter chemotherapy escaping the target tumor and entering the bloodstream. The ChemoFilter - a temporarily deployable, endovascular device will do just that; reducing systemic toxicity thus reducing adverse side effects from chemotherapy treatment. This will allow further increased dosage, increased tumor suppression, and increased tolerance to treatment. ChemoFilter has successfully filtered the chemotherapeutic Doxorubicin, but had yet to be tested in other chemotherapeutics. This study evaluates binding with new chemotherapeutics: Cisplatin, Carboplatin, and a cocktail comprised of Cisplatin and Doxorubicin.</p><p> <b>Materials and Methods:</b> ChemoFilter prototypes based on: 1.) Genomic DNA and 2.) Dowex (ion-exchange) resin, were evaluated for their ability to bind chemotherapy in vitro in phosphate-buffered saline (PBS). ChemoFilter was tested free in solution and encapsulated in nylon or polyester mesh packets of various dimensions. Concentrations were quantified using inductively coupled plasma mass spectrometry (IPC-MS), ultraviolet-visible spectrophotometry (UV-Vis), or fluorospectrometry. ¹¹C, ¹³C, and/or ¹⁴C radiolabeling Carboplatin began for in vitro and in vivo ChemoFilter quantification. In vitro quantification can include scintillation and/or gamma counting. In vivo may include Positron Emission Tomography (PET) imaging, Hyperpolarized ¹³C Magnetic Resonance Imaging (MRI), and/or Magnetic Resonance Spectroscopy (MRS) for real-time visualization. Reactions were verified using High Performance Liquid Chromatography (HPLC) for chemical species identification.</p><p> <b>Results and Discussion:</b> Results indicate significant and nearly complete, ~99% (p&lt;0.01) clearance of Cisplatin using the DNA ChemoFilter sequestered in Nylon mesh, quantified with gold standard ICP-MS (evidenced at 214 and 265 nm). The Ion-exchange ChemoFilter has significant clearance, within seconds, of both Doxorubicin and Cisplatin mixed in a cocktail solution. However, it appears some Cisplatin is binding to the Nylon Mesh itself. Size, shape, and material of the mesh have been optimized. A potential mechanism for ¹¹C, ¹³C, or ¹⁴C radiolabeling of Carboplatin has been developed and early results have been successful. ChemoFilter works much more efficiently when sequestered in nylon packets of specific geometries. Significant improvements have been made to ChemoFilter, moving the device closer to clinical trials.</p>

<p> <b>INTRODUCTION:</b> Accurate body composition assessment is crucial for determining health consequences due to excess body fat (BF). While several techniques exist there are few that are accurate, non-invasive, fast, and comfortable for subjects. The Three Dimensional (3D) body scanner is a new body composition assessment method that might serve as another option for investigators and practitioners. The purpose of this study was to determine the accuracy of the 3D body scanner at measuring body composition using dual energy x-ray absorptiometry (DXA) and Air displacement plethysmography (Bod Pod) as criterion measures. The 3D body scanner was evaluated on its ability to work with differences in normal versus overweight subjects as determined by BMI. Also, a new prediction equation was created and compared to that of an existing equation used by the 3D body scanner developed by the Department of Defense (DoD).</p><p> <b>METHODS:</b> Eighty-Five male subjects (21.70 &plusmn; 2.28 yr old; 81.00 &plusmn; 12.21 kg; 25.37 &plusmn; 3.40 kg/m²) completed all body composition assessment techniques on the same day. Tests preformed included: DXA, Bod Pod, and 3D body scanning. Subjects did not eat or drink 2 hr previous to testing and did not exercise 4 hr previous to testing. Data was analyzed using SPSS version 17.0. Bland-Altmand plots, Pearson correlations, and a oneway ANOVA comparing means were performed. A prediction equation (3D MU) was created using a stepwise regression based on correlation to DXA.</p><p> <b>RESULTS:</b> Mean comparison of body composition techniques were as follows: DXA BF 16.30 &plusmn; 4.67; Bod Pod 12.17&plusmn; 7.19; DoD 13.53 &plusmn; 6.43; 3D MU 16.49 &plusmn; 4.16. 3D MU had a SEE=3.09 over the entire sample compared to DoD SEE=3.67 and Bod Pod SEE=2.45. Although body volumes of Bod Pod and 3D Scanner were highly correlated (r = 0.984; p =0.001), the 3D Scanner underestimated body volume. Improvement in making consistent estimations of head, hand, and feet are necessary for the 3D body scanner to be used for body composition assessment.</p><p> <b>CONCLUSION:</b> Although the 3D body scanner shows promise as a method of evaluating BF, more work is needed before it can be considered an acceptable laboratory method of assessment. A 3D MU prediction equation was created that appears to be more accurate for young men than the current DoD equation. 3D body scanning shows potential as a method for determining body composition in overweight subjects.</p><p>

<p> Duchenne&rsquo;s Muscular Dystrophy is a debilitating disease that affects skeletal and cardiac muscle of 1 in 5000 male births. In the last thirty years, the gene responsible for the encoding of Dystrophin has been identified, sequenced and the variations of mutations described. There remains a void in the successful treatment of the disease although corticosteroid use has proven useful in delaying progression. Novel therapies are produced in the categories of virus-mediated gene delivery and stem cells, but evaluating their efficacy is hindered by an inability to contemporaneously assess the changes in muscle. The purpose of this pilot study was to characterize the changes in skeletal and cardiac muscle in a clinically advanced population of dogs affected with Duchenne Muscular Dystrophy. Using traditional sequences, delayed gadolinium enhancement, novel sequences and spectroscopy, changes in the investigated muscle were characterized. By establishing the differences between affected and unaffected dogs, the long-term goal of this body of work is to characterize these changes longitudinally and design a non-invasive method for tissue assessment as novel treatments are trialed.</p><p>

<p> Visual knowledge plays an important role in many highly skilled applications, such as medical diagnosis, geospatial image analysis and pathology diagnosis. Medical practitioners are able to interpret and reason about diagnostic images based on not only primitive-level image features such as color, texture, and spatial distribution but also their experience and tacit knowledge which are seldom articulated explicitly. This reasoning process is dynamic and closely related to real-time human cognition. Due to a lack of visual knowledge management and sharing tools, it is difficult to capture and transfer such tacit and hard-won expertise to novices. Moreover, many mission-critical applications require the ability to process such tacit visual knowledge in real time. Precisely how to index this visual knowledge computationally and systematically still poses a challenge to the computing community.</p><p> My dissertation research results in novel computational approaches for highthroughput visual knowledge analysis and retrieval from large-scale databases using latest technologies in big data ecosystems. To provide a better understanding of visual reasoning, human gaze patterns are qualitatively measured spatially and temporally to model observers&rsquo; cognitive process. These gaze patterns are then indexed in a NoSQL distributed database as a visual knowledge repository, which is accessed using various unique retrieval methods developed through this dissertation work. To provide meaningful retrievals in real time, deep-learning methods for automatic annotation of visual activities and streaming similarity comparisons are developed under a gaze-streaming framework using Apache Spark. </p><p> This research has several potential applications that offer a broader impact among the scientific community and in the practical world. First, the proposed framework can be adapted for different domains, such as fine arts, life sciences, etc. with minimal effort to capture human reasoning processes. Second, with its real-time visual knowledge search function, this framework can be used for training novices in the interpretation of domain images, by helping them learn experts&rsquo; reasoning processes. Third, by helping researchers to understand human visual reasoning, it may shed light on human semantics modeling. Finally, integrating reasoning process with multimedia data, future retrieval of media could embed human perceptual reasoning for database search beyond traditional content-based media retrievals.</p><p>

<p> Spherical Mean technique (SMT) is a novel method of quantifying the diffusion properties of the nerve fibers bundles in the central nervous system. It does this by calculating the spherical mean of the diffusion signal and fitting it to a parametric equation to obtain per voxel diffusion coefficients. We used Expectation&ndash;Maximization to obtain Gaussian Mixture Models (GMM) to find distinct clusters in per voxel coefficient space. We found that the diffusion properties of all the white matter fibers were clustered into a single Gaussian distribution in 867 brain volume samples. This implies that the diffusion properties of the white matter fibers are relatively homogeneous. Then, we checked this result by comparing the clusters obtained using GMM with tissue classification outputs obtained by clustering Fractional Anisotropy (obtained using Diffusion Tensor modeling), T1 weighted image intensity and B0 image intensity for 867 brain volume samples; we observed that the specific clusters of per voxel diffusion coefficients obtained using GMM represent specific tissue types (grey matter fibers, white matter fibers, cerebrospinal fluid). Since the parameters derived from SMT represent the physical diffusion properties that are independent of microscopic fiber orientation and the distribution of diffusion coefficients of white matter can be modeled by a single Gaussian distribution, we can conclude that the diffusion properties of all white matter fiber are homogeneous.</p><p>

Most EIT machine operates at high frequencies above 10 kHz. Biological systems demonstrate dispersions of electrical impedance characteristics at very low frequencies below 2 kHz due to the presence of membrane surrounding the cells and diffusion polarisation effects. A study was made on the feasibility of the use of low frequencies in a range of 1.12 Hz to 4.55 kHz in EIT. One high frequency of 77.712 kHz similar to that normally used in common EIT was also used as a comparison. The impedance measurements employed a four-terminal method using the BULFIS, an ultra low frequency impedance spectrometer and used conducting and insulating material as the objects/phantoms. The results show that the conductance and capacitance of a metal object disperses at frequency range of 0.1 -10 kHz, which is consistent to the electrical properties of a double layer forming at the metal-electrolyte interface similar to the electrical properties of a membrane. The reconstructed images reveal that at low frequencies the conducting and the insulating bodies were indistinguishable. They appear differently at high frequencies above 4.55 kHz indicating that the use of multi frequency instrumentation in EIT covering the very low frequency range provides information that instrumentation restricted to frequencies above 10 kHz does not supply. While the internal structure of the double layers could not be delineated, the presence of the double layers could be readily detected by the behaviour of the images as the frequency was varied. This has potential for EIT because it might allow the detection of structures from the variation of the images with frequency. This variation with frequency does not occur at the higher frequencies more usually used for EIT.