<p> One pathway for a new device to gain access to the marketplace requires demonstration that it is equivalent to, or substantially better than, a legally marketed device. To evaluate the equivalence of a medical imaging device, we propose measuring the intra- or inter-reader agreement in a reader study, where the clinicians (readers) make diagnoses on the medical images (cases) using both the new and old imaging devices. Such an endpoint, as well as its variance estimate, enable us to make a statistical inference on the equivalence of two devices. A method for multiple-reader multiple-case agreement analysis was presented in Gallas et al. (2016) for fully-crossed study designs, where every reader reads every case. In practice, having every reader read every case may be impossible when readers have a limited amount of time to participate in the study. One alternative study design is the split-plot study design, where both the readers and the cases are partitioned into a fixed number of groups, and each group of readers reads its own group of cases. In this thesis, we adapt the multiple-reader multiple-case agreement analysis method in Gallas et al. (2016) to analyze split-plot study designs, and propose a new variance estimator based on splitting the analysis across the groups. In each split sub-study, we compute an estimate, and then combine these estimates to obtain the final estimate for the full study. Our numerical studies show that the "split-analysis" variance estimator provides more accurate estimation of the variance of concordance measurements than the full-study-based method for unbalanced split-plot study designs.</p><p>

No description available.

No description available.

No description available.

Quantitative magnetic resonance imaging (MRI) measurements of the pediatric spinal cord is important for both diagnostic and treatment planning. In recent years several quantitative MRI (qMRI) techniques that have been developed and tested to measure functional and structural information of the spinal cord tissue and microstructure. Several of the existing structural and functional imaging biomarkers (i.e., diffusion tensor imaging (DTI)) have demonstrated potential for providing microstructural information about the spinal cord. However, due to the lack of a standard anatomical template of the pediatric spinal cord, quantification of the spinal cord tissue has been challenging. Therefore, one of the goals of this work is to develop and test tools for quantification as well as the creation of a standard structural template of the typically developing (TD) pediatric spinal cord. This will allow automated measurement of normative values of the spinal cord cross-sectional area (SCCSA) at various levels of the spinal cord. Furthermore, to examine the white matter (WM) microstructure of the pediatric cord we developed a processing pipeline for the atlas-based generation of TD pediatric spinal cord WM tracts. This will facilitate the measurements of normative diffusion values for various WM tracts.A group of 30 TD subjects (age range of 6-17 years old (12.38 ±2.81)), who had no evidence of spinal cord injury or pathology were recruited. We utilized a multiparametric MRI protocol, including high-resolution T2-w structural and diffusion-weighted MRI images to scan the subjects on a 3T MRI scanner. The diffusion data were acquired using a novel iFOV DTI sequence. For quantification, a post-processing pipeline was utilized to generate the structural pediatric template. Next, WM tracts were generated using an atlas-based approach, and diffusion metrics (FA, MD, RD and AD) were quantified in 34 tracts identified in the processing pipeline. Normative SCCSA and DTI diffusion indices were generated for the TD population. Lastly, we demonstrated that DTI indices (i.e. FA) can be a predictive measure of components of the clinical test for spinal cord injury, as well as an indicator of the white matter tracts integrity. Therefore, in the final step of this work, we expanded our quantitative analysis to look at the microstructural and macrostructural changes in 15 children with chronic spinal cord injury (SCI) (AIS A-D, mean age of 12.8 ± 3.1 years). This included measurements of SCCSA, diffusion metrics and T2* WM/GM ratio of various white matter tracts in the patient population. We also examined the relationships between all the metrics and the ISNCSCI clinical scores in SCI subjects. We then compared these measurements between the TD and SCI patients to evaluate the diagnostic utility of these techniques and biomarkers. Statistically significant difference was observed between the two populations in the studied metrics. The results show that the proposed techniques may have the potential to be used as surrogate biomarkers for the quantification of the injured spinal cord. Keywords: diffusion tensor imaging, typically developing, spinal cord injury, spinal cord cross-sectional area, fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity / Bioengineering

No description available.

No description available.

No description available.

Magnetic resonance based diffusion imaging has been gaining more utility and clinical relevance over the past decade. Using conventional echo planar techniques it is possible to acquire and characterize water diffusion within the central nervous system (CNS); namely in the form of Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI). While each modality provides valuable clinical information in terms of the presence of diffusion, DWI, and its directionality, DTI, the techniques used for analysis are limited to assuming an ideal Gaussian distribution for water displacement with no intermolecular interactions. This assumption reduces the amount of relevant information that can be interpreted in a clinical setting. By measuring the excess kurtosis, or peakedness, of the Gaussian distribution it is possible to get a better understanding of the underlying cellular structure. The objective of this work is to provide mathematical and experimental evidence that Diffusion Kurtosis Imaging (DKI) can provide additional information about the micromolecular environment of the pediatric spinal cord by more completely characterizing the probabilistic nature of random water displacement. A novel DKI imaging sequence based on a 2D spatially selective radio frequency pulse providing reduced FOV imaging with view angle tilting (VAT) was implemented, optimized on a 3Tesla MRI scanner, and tested on pediatric subjects (normal:15; patients with spinal cord injury:5). Software was developed and validated in-house for post processing of the DKI images and estimation of the tensor parameters. The results show statistically significant differences in kurtosis parameters (mean kurtosis, axial kurtosis) between normal and patients. DKI provides incremental and new information over conventional diffusion acquisitions that can be integrated into clinical protocols when coupled with higher order estimation algorithms. / Electrical and Computer Engineering

The wide band gap semiconductor Cadmium Zinc Telluride (CZT) is of recent interest for medical imaging at room temperature. A number of properties, including superior energy resolution, 3D photon position sensitivity, compact size, direct photon conversion and energy-resolving capability, make CZT a promising candidate for positron emission tomography (PET) and photon-counting X-ray imaging systems. Despite these advantages, drawbacks, such as low mobility of holes, hole trapping, charge sharing effect and characteristic X-ray escape degrade the performance of large volume CZT detectors. In this research, characterization and evaluation of single-crystal CZT photon detector using simulation and experimental studies were done. First, a comprehensive analytical model was developed and implemented by using Monte Carlo simulation and finite element analyses. This model includes the generation and transportation of charge carries within CZT detectors, and it provides useful guidance in optimizing the electrode design and associated readout circuits. Second, the performance of a 20×20×5mm3 CZT crystal with 8×8 pixel anodes and a planar cathode was integrated with readout electronics that can be used to build a PET system was studied. The experiments demonstrate an energy resolution of ~2.26±0.84% full width half maximum (FWHM) at 662 keV and 19±3 ns coincidence time resolution with planar parallel field configuration. A novel algorithm based on charge sharing effect and transient signal analysis targeting the improvement of spatial resolution, was proposed. The sub-pitch spatial resolution is found to be ~30 µm and ~250 µm under signal-to-noise ratio of ~17, for inside and outside the valid range of charge sharing, respectively. Finally, the feasibility of CZT in photon-counting Computed Tomography (CT) was studied by using monoenergetic sources, with a special attention paid to energy degradation due to characteristic X-ray escape and the charge sharing effect. The effects of detector configuration and incident beam location were also investigated. The results show that the pixel size can be reduced to 500 µm without significant count loss (~5%) and charge loss (~15%) for the photo-counting X-ray applications. / Thesis / Doctor of Philosophy (PhD)