Saudi Cultural Missions Theses & Dissertations
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Item Restricted Advanced Ultrasound Applications for Assessing Arteriovenous Fistula Surgery Outcomes in End Stage Renal Failure(Imperial College London, 2024-03-01) Faqihi, Wael; Aslam, MohammedArteriovenous fistulas are critical for facilitating hemodialysis, yet a considerable proportion fail to mature, presenting challenges in predicting their outcomes. This study explores the impact of arterial stiffness and endothelial dysfunction on AVF maturation utilising advanced measurement techniques. A prospective cohort observational study was conducted involving 76 end-stage renal failure patients undergoing AVF surgery. Various assessments, including 2DSWE, 2DSST, LDF, and FMD, were performed to evaluate arterial properties and endothelial function preoperatively. Additionally, intraoperative BVF measurements were taken using Transonic vascular flow probes. Results revealed a 22% AVF failure rate, with hypertension, diabetes, and cardiovascular disease prevalent among the cohort. Higher arterial stiffness was observed in the failure group, while the mature group exhibited better endothelial function. Intraoperative BVF emerged as a significant predictor of immediate maturation outcomes, with defined cutoff values. The developed AVF prediction model demonstrated good performance. These findings underscore the potential of advanced measurement techniques in understanding AVF maturation dynamics and highlight the importance of intraoperative BVF assessment in guiding clinical decisions. Further validation in larger clinical trials is warranted to consolidate these findings.18 0Item Restricted Role of Tissue Doppler Ultrasonography for Emergency Assessment of Stroke(Saudi Digital Library, 2023-12-01) Almudayni, Alanoud; Chung, Emma; Lecchini-Visintini, AndreaBackground: The primary aims of my PhD project were to explore the feasibility of acquiring high quality brain tissue pulsation (BTP) measurements from stroke patients. The impact of artefacts on BTP estimates, and potential differences in BTP amplitude between patients and healthy controls are explored. My secondary aim was to better understand the impact of middle cerebral artery blood flow velocity (MCAv) changes on BTP amplitude. Methods: A systematic review was conducted to explore existing methods of investigating BTPs using MR techniques. A reduction in MCAv, induced in healthy volunteers through ingestion of caffeine, was used to explore the impact of lowering MCAv on BTP amplitude (measured using a transcranial tissue Doppler [TCTD] system) under controlled conditions. TCTD and physiological measurement data were obtained from stroke patients to investigate the quality of recordings, impact of artefacts on BTP estimates, and impact of stroke on BTP amplitude. Results: The systematic review confirmed that brain motion varies regionally within the brain, and that BTPs may be altered in the presence of pathology (e.g. Chiari I malformation). The physiological measurement study showed that BTP amplitude increases in response to caffeine. Analysis of healthy volunteer and patient data showed that artefacts tended to increase estimates of BTP amplitude. Analysis of the first 20 gates (which show limited penetration) from 18 ischaemic stroke patients and control subjects suggested a median (IQR) BTP amplitude in ischaemic stroke patients measured through the forehead of 8 μm (5.7, 13.6) compared to 16.2 μm (10.6, 24) in 24 age-matched control subjects. Waveform shapes appeared qualitatively similar to control subjects. Conclusions: BTP amplitude appears to be lower in stroke patients compared to healthy controls but increases in response to caffeine, which lowers MCAv. Further work is required to better understand the relationship between BTPs and cerebrovascular physiology.20 0Item Restricted Ultrasound Nano-Scale Phase Change Contrast Agent for Hepatocellular Carcinoma Radiosensitization(Saudi Digital Library, 2023-08-05) Falatah, Hebah; Eisenbrey, John; Wheatley, MargaretThe purpose of this study was to develop and characterize nano-scale phase change droplets less than 200 nm from commercially available ultrasound contrast agents and demonstrate their ability to enhance hepatocellular carcinoma (HCC) radiosensitization, which is critically needed to enhance the poor outcomes (two years survival < 50%) of current HCC radiotherapy treatments. Primary liver cancer is the third cause of cancer death worldwide with 906,000 new cases and 830,000 deaths annually. Of these, 75-85% of patients present with hepatocellular carcinoma (HCC), while the remaining 15-25% are intrahepatic cholangiocarcinoma and other types. Due to the late clinical presentation of the disease and treatment limitations of chemotherapy and immunotherapies, HCC has a poor prognosis. Localized radiotherapy in the early and mid-stages of HCC has shown some success in treatment response 25-50%. In such therapy, the hepatic artery supplying blood to the cancer is injected with radioisotope yttrium-90 (Y90), a beta particle emitter that provides localized radiation therapy. Another therapeutic option is external beam radiation (XRT) with MRI or CT guidance. XRT has been used cautiously in HCC treatment due to the radiosensitivity of liver tissue and technological limitations. Fractionated approaches are used to overcome the toxicity to the liver or radiation-induced liver diseases caused by high doses of radiation. The result of these limitations is that the overall five years survival for HCC patients in the United States is 20%, and the two years survival is less than 50%.Therefore, developing more effective HCC treatments is essential to improve patient outcomes. In recent years, researchers have been exploring a variety of radiosensitizers as a means of overcoming radiotherapy resistance. One promising radiotherapy enhancement mechanism is ultrasound-mediated microbubble destruction, which has been shown to sensitize solid tumors to radiotherapy through endothelial cell disruption in tumors. Ultrasound microbubbles have a diameter between 1 to 8 (micrometers) μm and consist of a high molecular weight gas encapsulated by a lipid, protein, or polymer shell. However, the relatively large size of the bubbles prevents them from passing into extravascular spaces, and as a result researchers have developed phase-change contrast agents (PCCAs). PCCAs contain a low boiling point such as -37oC liquid in place of the usual gas and can transition from the liquid to the gaseous state under external stimuli. This technology has been widely used in ultrasound medical imaging, vascular occlusion, and cavitation activity enhancement. The small diameters < 400 nm of these PCCAs allow them to diffuse and accumulate in solid tumors via the enhanced permeability and retention effect before the phase transition. Using ultrasound as an acoustic stimulus can provide local vaporization as well as cavitation of the resultant microbubble, thereby generating local force in tumor tissues. The development and characterization of sub-micrometer (< 200 nm diameter) phase change droplets from commercial ultrasound contrast agents, including their ability to decrease tumor vascularity and enhance cell apoptosis are described in addition to their ability to enhance HCC tumor radiosensitization.18 0Item Open Access Application and Development of Contrast-Enhanced Ultrasound for Perfusion Quantification in Kidney Disease(2023-02-18) Almushayt, Shatha Jamal Abdullah; Selby, NicholasChanges in microvascular perfusion play a critical role in the pathophysiology of kidney disease and its sequelae. This thesis describes research work that aimed to optimise and use an ultrasound imaging method to quantify tissue perfusion in patients with kidney disease, specifically Contrast Enhanced Ultrasound (CEUS) applied in the kidneys and in skeletal muscle. This work systematically reviewed prior evidence about the acute changes that haemodialysis exerts on skeletal muscle perfusion, metabolism and function. In a clinical study, changes in skeletal muscle microvascular perfusion during haemodialysis are then explored, as a potential factor that could contribute to skeletal muscle wasting in this population. Findings are then corroborated by an analysis of pre-existing data looking at the associations between hand-grip strength, dialysis related parameters (e.g. blood pressure and ultrafiltration volume) and nutritional measures. In the second half of the thesis, CEUS is used to assess renal perfusion, optimising the protocol for CEUS in healthy volunteers. Then, intra-subject repeatability of the different CEUS perfusion parameters was determined in healthy volunteers studied twice, as well as inter-operator repeatability of image analysis. Finally, a pilot study was undertaken in patients with AKI applying CEUS in this setting and generating preliminary clinical data.11 0Item Restricted Evaluation of Tomographic 3D Ultrasound for the Assessment of Vascular Pathology(2023-05-31) ALZAHRANI, Adel; Aslam, MTomographic 3D ultrasound (t3DUS) is a promising imaging technique for quantifying vascular diseases by measuring the degree of stenosis and plaque volume. However, its accuracy and reliability for the assessment of vascular diseases need to be investigated. Therefore, this thesis aims to assess the accuracy and reproducibility of t3DUS for quantifying vascular diseases, including grading stenosis and measuring plaque volume in-vitro and in-vivo. A literature review was performed to evaluate the use of three-dimensional ultrasound (3DUS) for assessing carotid stenosis in patients with carotid diseases showing that 3DUS is more accurate in quantifying carotid diseases and has a low level of inter and intra-observer variability when compared to 2DUS. However, it requires prolonged time for images to be reconstructed into 3DUS, which may currently limit its use in clinical practice. The analysis from the in-vitro study on the vascular phantom, including channels with different grades of stenosis, demonstrated that t3DUS has an excellent inter-operator agreement with low variability and is more accurate than 2DUS for grading stenosis when compared to the reference values with an Intra-Class Correlation (ICC) value of 0.96 (95% confidence interval (CI) 0.90 – 0.98, p <0.001. Based on these findings, two clinical studies were conducted investigating the reproducibility and accuracy of t3DUS for measuring carotid plaque volume (CPV) within the internal carotid artery (ICA) in patients undergoing carotid endarterectomy (CEA) (n=25), and the potential benefits of t3DUS in providing more precise measurement of stenosis in the superficial femoral artery (SFA) in patients with the peripheral arterial disease (PAD) (n=50). The results showed an excellent agreement level between t3DUS and reference test (i.e., Ex-vivo carotid plaque volume from carotid endarterectomy specimen) and intra-observer agreement in measuring carotid plaque volume. This result demonstrates that t3DUS can measure the disease severity of SFA in patients with lower limb arterial disease with a correlation value (r) = 0.99, p<0.001. The findings of this thesis indicated that t3DUS is a reliable and reproducible method for quantifying vascular diseases, including grading stenosis and measurements of CPV. Further research investigating the potential of the added value of t3DUS in assessing the different ranges of vascular diseases, including aneurysms, arteriovenous fistula (AVF) for haemodialysis access, and venous mapping, should be considered.25 0