<p> Oral cavity cancer (OCC) is a type of cancer of the lip, tongue, salivary glands and other sites in the mouth <i>(buccal or oral cavity)</i> and is the sixth leading cause of cancer worldwide. Patients with OCC are treated based on a staging system: low-stage patients typically receive less aggressive therapy compared to high-stage patients. Unfortunately, low-stage patients are sometimes at risk for locoregional recurrence. Recently, a semi-quantitative risk scoring system has been developed to assess the locoregional recurrence risk for low-stage patients. This risk scoring system is based on tissue characteristics determined on 2D histopathology images under a microscope. This modality limits the appreciation of the 3D architecture of the tumor and its associated morphological features. This thesis aims to visualize 3D models of the tumor-host interface reconstructed from serially-sectioned histopathology slides and quantify their clinically validated morphological features to predict locoregional recurrence after treatment. The 3D models are developed and quantified for 6 patient cases using readily available tools. This pilot study provides a framework for an automated diagnostic technique for 3D visualization and morphological analysis of tumor biology which is traditionally done using 2D analysis.</p>

<p> Central nervous system (CNS) related conditions and diseases like mild traumatic brain injury (mTBI) and multiple sclerosis (MS) affect people&rsquo;s life quality, yet there is no single test for the diagnosis of these diseases or conditions. Patients may need to wait for years until they are diagnosed correctly to get the correct treatment, which is often too late. Thus, there is a strong need to develop some techniques to aid the diagnosis of CNS-related conditions and diseases. The conventional MRI can reveal the structure of the brain but cannot detect the difference between the healthy tissue and the anomalies. Diffusion tensor imaging (DTI) has been used for detecting white matter integrity and demyelination for the past decade in experiments and has been proven to have the ability to depict the problem effectively. In the past decade, many techniques were found based on DTI data, and these techniques improved pre-processing, processing, and post-processing. </p><p> Though there are many software and APIs that can provide functions for DTI file input/output (IO), visualization and other DTI related topics, there is no general software or API that is dedicated to covering the whole processing procedure of DTI that at the same time can be extended easily by the user. This thesis is dedicated to developing a software that can be used to aid in the diagnosis of CNS-related conditions and diseases while at the same time trying to cover as many topics as possible. Another purpose is to make the software highly extensible. </p><p> This thesis work first introduces the background of CNS-related disease and uses MS as an example to introduce the process of demyelination and the white matter integrity problem, which are involved in these CNS-related diseases and conditions. Then the diffusion process and the technique that can detect the diffusion signal (DTI) is presented. After this, concepts and meaning of the secondary metrics are discussed. Then, current existing software and APIs and their advantages and disadvantages are outlined. After these points, the techniques that are discussed in this thesis as well as their advantages are outlined. This part is followed by the charts and code samples which can illustrate the process and structure of this software. Then different modules and their results are explained. </p><p> In this software, the results are represented by images and 3D models. There are color images, pseudo color images with different schemes and gray scale images. Images are mainly included to represent the FA and MD data. In this software, streamlines are generated from the eigenvalue and eigenvector. Then a bundled result for the streamline is also realized in this software. The streamline and bundled results are 3D models. For 3D models, there are mainly two ways to display the real 3D model. One is the naked eye 3D which doesn&rsquo;t require the user to wear glasses but has less stereoscopic characteristics. As the stereoscopic monitors and glasses are more and more popular and easily accessible, this software also provides stereoscopic views for 3D models, and the user can choose red &amp; blue, interlaced techniques with proper glasses. </p><p> This thesis work ends with the discussion of the results and limitations of DTI. Finally, there is a discussion about the future work that can improve the performance of this software and topics that need to be covered.</p>

<p> Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in the world and the liver is a common site of metastases from other primary neoplasms. Many patients are not surgical candidates. Radioembolization is an intra-arterial therapy delivering high doses of radiation emitted from microspheres infused selectively into the tumor feeding arteries. These microspheres land in the tumor microcirculation and deposit radiation to the tumor tissues. Over the past ten years, radioembolization has become part of the treatment guidelines for unresectable HCC, liver-dominant metastatic colorectal cancer, and neuroendocrine liver metastases, and it is often used in the salvage setting for patients with hepatic malignancy progressing on other therapies. The overarching goal of the thesis work was to advance the basic science of ⁹⁰Y radioembolization based on existing clinical needs to ultimately improve patient outcomes. This included 1) setup of pre-clinical laboratory to study radioembolization, 2) optimization of radioembolization protocols in research animals, 3) validation of ⁹⁰Y PET/CT imaging techniques to monitor microsphere delivery and dosing, 4) blood oxygen-level dependent (BOLD) imaging and evaluation of tumor biology and physiology after radioembolization in the VX2 rabbit model at a fixed dose of 50 Gy, 5) evaluation of normal tissue pathology (fibrosis, atrophy) and biology (hepatocyte proliferation, microvessel density, stellate cell activation) in rats after ⁹⁰Y radiation lobectomy at clinically relevant dosing from 150 to >4,000 Gy, and 6) development of new yttrium microsphere compositions for combination therapy with electromagnetic hyperthermia.</p>

<p> Although 1.5 and 3 Tesla (T) magnetic resonance (MR) systems remain the clinical standard, the number of 7 T MR systems has increased over the past decade because of the promise of higher signal-to-noise ratio (SNR), which can translate to images with higher resolution, improved image quality and faster acquisition times. However, there are a number of technical challenges that have prevented exploiting the full potential of ultra-high field (&ge; 7 T) MR imaging (MRI), such as the inhomogeneous distribution of the radiofrequency (RF) electromagnetic field and specific energy absorption rate (SAR), which can compromise image quality and patient safety. </p><p> To better understand the origin of these issues, we first investigated the dependence of the spatial distribution of the magnetic field associated with a surface RF coil on the operating frequency and electrical properties of the sample. Our results demonstrated that the asymmetries between the transmit (<i>B</i>₁⁺) and receive (<i>B</i>₁^&ndash;) circularly polarized components of the magnetic field, which are in part responsible for RF inhomogeneity, depend on the electric conductivity of the sample. On the other hand, when sample conductivity is low, a high relative permittivity can result in an inhomogeneous RF field distribution, due to significant constructive and destructive interference patterns between forward and reflected propagating magnetic field within the sample. </p><p> We then investigated the use of high permittivity materials (HPMs) as a method to alter the field distribution and improve transmit and receive coil performance in MRI. We showed that HPM placed at a distance from an RF loop coil can passively shape the field within the sample. Our results showed improvement in transmit and receive sensitivity overlap, extension of coil field-of-view, and enhancement in transmit/receive efficiency. We demonstrated the utility of this concept by employing HPM to improve performance of an existing commercial head coil for the inferior regions of the brain, where the specific coil&rsquo;s imaging efficiency was inherently poor. Results showed a gain in SNR, while the maximum local and head SAR values remained below the prescribed limits. We showed that increasing coil performance with HPM could improve detection of functional MR activation during a motor-based task for whole brain fMRI. </p><p> Finally, to gain an intuitive understanding of how HPM improves coil performance, we investigated how HPM separately affects signal and noise sensitivity to improve SNR. For this purpose, we employed a theoretical model based on dyadic Green&rsquo;s functions to compare the characteristics of current patterns, i.e. the optimal spatial distribution of coil conductors, that would either maximize SNR (ideal current patterns), maximize signal reception (signal-only optimal current patterns), or minimize sample noise (dark mode current patterns). Our results demonstrated that the presence of a lossless HPM changed the relative balance of signal-only optimal and dark mode current patterns. For a given relative permittivity, increasing the thickness of the HPM altered the magnitude of the currents required to optimize signal sensitivity at the voxel of interest as well as decreased the net electric field in the sample, which is associated, via reciprocity, to the noise received from the sample. Our results also suggested that signal-only current patterns could be used to identify HPM configurations that lead to high SNR gain for RF coil arrays. We anticipate that physical insights from this work could be utilized to build the next generation of high performing RF coils integrated with HPM.</p><p>

<p>MRI can benefit from an increase in the sensitivity of contrast agents. The CEST MRI technique in particular suffers from very poor sensitivity when using diamagnetic contrast agents. Polymerized CEST MRI contrast agents could increase the sensitivity per macromolecule over monomer contrast agents. The increase in sensitivity is related to the increase in number of contrast agents per polymer. A contrast agent with increased sensitivity can be used to image on the molecular level in vivo, where the concentration of targets is very low. A polymerized diaCEST contrast agent was synthesized by coupling a salicylic acid analogue to a poly (acrylic acid) backbone. The CEST effect of the coupled analogue was compared to its uncoupled form for different concentrations and pH values. A RL-QUEST method was used to calculate the exchange rate of the analogue for different pH values before and after coupling. The polymerized diaCEST agent was attempted to be loaded into DOPC and bis-SorbPC liposomes, and was also attempted to be targeted to folate receptors in a KB cell culture. These studies establish the foundation for translation of polymerized diaCEST contrast agents to additional in vitro and in vivo investigations. </p>

<p> In traumatic brain injury (TBI), the skull-brain interface, composed of three meningeal layers: the dura mater, arachnoid mater, and pia mater, along with cerebrospinal fluid (CSF) between the layers, plays a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is a noninvasive imaging modality capable of providing <i> in vivo</i> estimates of tissue motion and material properties. The objective of this work is to augment human and phantom MRE studies to better characterize the mechanical contributions of the skull-brain interface to improve the parameterization and validation of computational models of TBI. Three specific aims were to: 1) relate 3D skull kinematics estimated from tri-axial accelerometers to brain tissue motion (rigid-body motion and deformation) estimated from MRE, 2) modify existing MRE data collection methods to capture simultaneous scalp and brain displacements, and 3) create cylindrical and cranial phantoms capable of simulating a CSF interface and dural membranes. Achievement of these aims has provided new quantitative understanding of the transmission of skull motion to the brain.</p><p>