Application of magnetic resonance imaging to radiotherapy treatment planning and neurosurgery / Wayne Allan Beckham.

Bibliography: leaves 148-155.xiv, 210 leaves : ill. (some col.) ; 30 cm.This thesis provides several methods for assessment of total machine dependent distortion which allows the clinical significance of that distortion to be established. A method for removal of machine dependent distortions is also presented and shown to work for a locally produced, large field of view spatial linearity phantom. Finally, a possible method is developed which is suitable for application of the distortion correction method to actual patients.Thesis (Ph.D.)--University of Adelaide, Dept. of Physics and Mathematical Physics, 1997

Improving the Efficacy of Common Cancer Treatments via Targeted Therapeutics towards the Tumour and Its Microenvironment

Cancer is defined as the uncontrolled proliferation of heterogeneous cell cultures in the body that develop abnormalities and mutations, leading to their resistance to many forms of treatment. Left untreated, these abnormal cell growths can lead to detrimental and even fatal complications for patients. Radiation therapy is involved in around 50% of cancer treatment workflows; however, it presents significant recurrence rates and normal tissue toxicity, given the inevitable deposition of the dose to the surrounding healthy tissue. Chemotherapy is another treatment modality with excessive normal tissue toxicity that significantly affects patients’ quality of life. To improve the therapeutic efficacy of radiotherapy and chemotherapy, multiple conjunctive modalities have been proposed, which include the targeting of components of the tumour microenvironment inhibiting tumour spread and anti-therapeutic pathways, increasing the oxygen content within the tumour to revert the hypoxic nature of the malignancy, improving the local dose deposition with metal nanoparticles, and the restriction of the cell cycle within radiosensitive phases. The tumour microenvironment is largely responsible for inhibiting nanoparticle capture within the tumour itself and improving resistance to various forms of cancer therapy. In this review, we discuss the current literature surrounding the administration of molecular and nanoparticle therapeutics, their pharmacokinetics, and contrasting mechanisms of action. The review aims to demonstrate the advancements in the field of conjugated nanomaterials and radiotherapeutics targeting, inhibiting, or bypassing the tumour microenvironment to promote further research that can improve treatment outcomes and toxicity rates

Application of High-Z Nanoparticles to Enhance Current Radiotherapy Treatment

Radiotherapy is an essential component of the treatment regimens for many cancer patients. Despite recent technological advancements to improve dose delivery techniques, the dose escalation required to enhance tumor control is limited due to the inevitable toxicity to the surrounding healthy tissue. Therefore, the local enhancement of dosing in tumor sites can provide the necessary means to improve the treatment modality. In recent years, the emergence of nanotechnology has facilitated a unique opportunity to increase the efficacy of radiotherapy treatment. The application of high-atomic-number (Z) nanoparticles (NPs) can augment the effects of radiotherapy by increasing the sensitivity of cells to radiation. High-Z NPs can inherently act as radiosensitizers as well as serve as targeted delivery vehicles for radiosensitizing agents. In this work, the therapeutic benefits of high-Z NPs as radiosensitizers, such as their tumor-targeting capabilities and their mechanisms of sensitization, are discussed. Preclinical data supporting their application in radiotherapy treatment as well as the status of their clinical translation will be presented

The Implementation of the FAA Industry Training Program in Technically Advanced Aircraft (TAA): Lessons Learned

The proliferation of aircraft with extensive automation, collectively known as Technically Advanced Aircraft (TAA) within the last 10 years in the General Aviation industry has led to a novel approach in flight training. The FAA implemented the FAA-Industry Training Standards (FITS) program that emphasizes the importance of “real world” training exercises in the form of scenario training. The FITS curriculum, which was first empirically tested by Middle Tennessee State University (MTSU), was developed by Embry-Riddle Aeronautical University and the University of North Dakota through the FAA Air Transportation Center of Excellence for General Aviation. Over the last four years, MTSU has evaluated the FITS training approach with students in a FAR 141 accepted, combined Private Certificate/Instrument Rating syllabus in TAA. Our findings indicate the need for inclusion of several maneuver-based lessons that facilitate the physical skills training required for some tasks (e.g. landing), early in the FITS syllabus. The importance of consequences in the flight scenarios, the intensive flight instructor training required prior to FITS implementation, and the incorporation of new elements into the ground school portion of the curriculum are all “lessons learned” over the last several years of FITS implementation at MTSU

A Synergetic Approach Utilizing Nanotechnology, Chemotherapy, and Radiotherapy for Pancreatic Cancer Treatment

The objective of this study was to assess the anticancer effectiveness of gold nanoparticles (GNPs) and lipid-encapsulated docetaxel prodrug (LNPDTX-P) with radiotherapy (RT). The study utilized a co-culture spheroid model comprising MIA PaCa-2 cancer cells and patient-derived cancer-associated fibroblasts (CAF-98) to mimic pancreatic cancer conditions. The spheroids underwent treatment with GNPs (7.5 μg/mL), LNPDTX-P (99 nM of DTX pro-drug), and 2 Gy of RT. Cell viability of the spheroids was evaluated using the CellTiter-Glo 3D assay. At the same time, DNA double-strand breaks (DSBs) were assessed by examining the expression of the DNA damage marker 53BP1 through an immunofluorescence assay. Alt-hough GNPs/RT and RT/LNPDTX-P showed a reduction in spheroid size and an apparent in-crease in DNA DSB damage, the combination of the two nanoparticles, GNPs, and LNPDTX-P, with RT, significantly enhanced the anticancer efficacy, resulting in a 28% decrease in spheroid size and an estimated 39% increase in DNA DSB. The combination of GNPs and LNPDTX-P with RT showed a synergetic effect due to their radiosensitizing properties, improving the ther-apeutic efficacy of each treatment modality alone. This triple modality offers a hopeful strategy to enhance cancer treatment efficacy while reducing adverse effects

Improving the resolution of dynamic intensity modulated radiation therapy delivery by reducing the multileaf collimator sampling distance

The conformality of a dose distribution delivered by a multileaf collimator (MLC) for intensity modulated radiation therapy (IMRT) is limited in the direction perpendicular to leaf motion by the finite leaf width. Two methods of improving the resolution of IMRT intensity maps in this direction were investigated. In the first, the desired fluence distribution is considered to be sampled by the MLC, with the sampling distance being the center-to-center distance between the MLC leaves. The sampling distance is reduced below the leaf width by combining separate irradiations with a couch shift between them. This has been applied to static field therapy [Galvin et al., Int. J. Radiat. Oncol., Biol., Phys. 35, 89–94 (1996)], and was proposed for IMRT by Bortfeld et al. [Med. Phys. 27, 2494–2502 (2000)]. In the second method, two MLC component fluences, with leaf width L = 2Δy and offset by Δy, are combined to reproduce desired intensity bins with Δy width. The effect of MLC leaf sampling distance on dose resolution was quantified for both 1.0 and 0.5 cm MLC leaf widths, utilizing a high resolution bar-pattern fluence, an annular shaped fluence, and an intensity step-edge. Improvement in resolution was found for the 1.0 cm leaf width at a sampling distance of 0.5 cm, with only a small benefit for further reduction. For the 0.5 cm leaf width, a sampling distance of 0.25 cm resulted in a dose resolution that was nearly independent of direction

Repurposing Antimalarial Pyronaridine as a DNA Repair Inhibitor to Exploit the Full Potential of Gold-Nanoparticle-Mediated Radiation Response

Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore, there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel concepts introduced in this study could lay the foundation for the transition of this treatment modality into clinical environments