<p> While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation. Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow. </p><p> To determine candidate materials for phantom and software development, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature. Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries, compared against previously published 1.0 T results, and integrated into the 3DSlicer application platform. </p><p> To evaluate the performance of synthetic CTs in an image guided workflow, magnetic resonance simulation and CT simulation images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism. </p><p> Over the sampled FOV, non-negligible residual gradient distortions existed as close as 9.5 cm from isocenter, with a maximum distortion of 7.4mm as close as 23 cm from isocenter. Over 6 months, average gradient distortions were -0.07&plusmn;1.10 mm and 0.10&plusmn;1.10 mm in the x and y-directions for the transverse plane, 0.03&plusmn;0.64 and -0.09&plusmn;0.70 mm in the sagittal plane, and 0.4&plusmn;1.16 and 0.04&plusmn;0.40 mm in the coronal plane. After implementing 3D correction maps, distortions were reduced to &lt; 1 pixel width (1mm) for all voxels up to 25 cm from magnet isocenter. </p><p> Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4&plusmn;0.5 mm, 0.0&plusmn;0.5 mm, and 0.1&plusmn;0.3 mm for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6&plusmn;0.4 mm (range, 0.2 to 1.6 mm), 0.2&plusmn;0.4 mm, and 0.2&plusmn;0.3 mm for the S-I, L-R, and A-P axes, respectively. The CT-SIM and synCT derived margins were &lt;0.3mm different. </p><p> This work has characterized the inaccuracies related to GNL distortion for a previously uncharacterized MR-SIM system at large FOVs, and established that while distortions are still non-negligible after current vendor corrections are applied, simple post-processing methods can be used to further reduce these distortions to less than 1mm for the entire field of view. Additionally, it was important to not only establish effective corrections, but to establish the previously uncharacterized temporal stability of these corrections. This work also developed methods to improve the accessibility of these distortion characterizations and corrections. We first tested the application of a more readily available 2D phantom as a surrogate for 3D distortion characterization by stepping the table with an integrated batch script file. Later we developed and constructed a large modular distortion phantom using easily obtainable materials, and showed and constructed a large modular distortion phantom using easily obtainable materials, and used it to characterize the distortion on several widely available MR systems. To accompany this phantom, open source software was also developed for easy characterization of system-dependent distortions. Finally, while the dosimetric equivalence of synCT with CT has been well established, it was necessary to characterize any differences that may exist between synCT and CT in an IGRT setting. This work has helped to establish the geometric equivalence of these two modalities, with some caveats that have been discussed at length. (Abstract shortened by ProQuest.) </p>

<p> Prostate cancer is among the most prevalent and deadly of malignancies in both the United States and worldwide. Ongoing diagnostic challenges in prostate cancer include differentiating low-risk and high-risk tumors, and monitoring responses to therapy in patients with aggressive disease. Prostate cancer metabolism is characterized by a shift to aerobic glycolysis with lactate production and efflux, as well as increased tricarboxylic acid cycle activity, which has led to the investigation and development of metabolic imaging strategies such as hyperpolarized 13C MRI. However, it is nontrivial to study human prostate cancer metabolism in vivo, and the capability to better characterize tumor metabolism from a variety of disease states would be valuable for metabolic imaging biomarker development. This dissertation focuses on developing ex vivo strategies to measure metabolism in benign and malignant living human prostate tissue. First, because prostate tissue heterogeneity can impact metabolic measurements, we present the engineering of a 600 MHz radiofrequency (RF) microcoil to assess the heterogeneity of freshly acquired human prostate biopsies using microscale diffusion-weighted imaging (DWI). Next, we demonstrate the capability of micro-DWI to determine the biopsy percentage of glandular tissue, setting the stage for establishing the percentage and grade of cancer using this approach. After this, we develop a protocol for nuclear magnetic resonance (NMR) quantification of lactate production and efflux and glutamate fractional enrichment in freshly acquired living human prostate biopsies cultured with [1,6-13C2]glucose. In this study we demonstrate a significantly higher lactate efflux rate coming from low-grade prostate cancer versus benign biopsies in an early-stage patient population. This sets the stage for studies of metabolic fluxes and steady-state metabolite levels in biopsies from patients with aggressive disease before and after non-surgical therapy. Finally, due to recent interest in the potential role of Myc amplification and glutaminolysis upregulation in treatment insensitive castrate-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC), we present metabolic labeling results from a study of primary human prostate tissue slice cultures (TSCs) obtained at surgery and cultured with either [1,6-13C2]glucose or [3-13C]glutamine. Our results are consistent with prior thinking on the role of glucose and glutamine metabolism in treatment-na&iuml;ve prostate cancer.</p><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> The purpose of this pilot protocol was to examine the process of instillation of a bladder cancer optical imaging agent for blue light cystoscopy (BLC) procedures in a preoperative area in Bronx, NY with registered nurses (RNs). The RNs followed a process flowchart and completed a checklist. </p><p> A retrospective review was completed by the Assistant Director of Research for Urology and the Study Principal Investigator on 20 charts with four time stamps. The time stamps included the &ldquo;Scheduled Time of Surgery&rdquo;, &ldquo;In Pre Procedure&rdquo;, &ldquo;Medication Administration Record (MAR)&rdquo;, and &ldquo;In Room&rdquo;. The prospective review was completed on 10 BLC procedures by the preoperative RNs. In addition to the time stamps, there were three other questions descriptively examined on consent completion, an instill catheter order, and catheter placement at the bedside. </p><p> The Wilcoxon Test Statistic was utilized to determine whether there was a significant difference between prospective and retrospective timeframes upon implementation of a standardized protocol for a preoperative procedure. The Chi-square test was performed to determine whether there was a significant difference between retrospective and prospective information on &ldquo;MAR&rdquo; documentation. </p><p> There is no standard protocol for the BLC procedure at this hospital. Inconsistent processes with instillation of the optical imaging agent can result in negative outcomes, delays, and unsafe environments. This pilot protocol for the BLC procedure is important to develop a standard protocol for all preoperative areas that utilize this technology across the United States. </p><p>