Saudi Cultural Missions Theses & Dissertations
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Item Restricted Development of a Patient-Specific Streamlined Workflow for a Predictive Tool for Coronary Artery Bypass Graft Outcomes(University College London, 2024-12-01) Alsaleh, Abdullah; Torii, RyoCoronary artery disease is one of the leading causes of mortality worldwide and is treatable by only a few procedures, such as coronary artery bypass grafting (CABG). However, predicting the long-term success of CABG, particularly in terms of graft patency and disease progression, remains a challenge. This thesis aims to develop a patient-specific streamlined workflow for a predictive tool that integrates peri-operative Coronary Computed Tomography Angiography (CCTA) with Computational Fluid Dynamics (CFD) simulations to predict post-CABG outcomes. The patient-specific streamlined workflow for a predictive tool for CABG outcomes is designed to simulate hemodynamic conditions within grafts, providing personalized predictions to guide surgical decisions and improve patient outcomes. The methodology includes creating anatomically accurate 3D models, simulating hemodynamic conditions, and validating the results against clinical data. While the patient-specific streamlined workflow for the predictive tool shows promise, significant challenges remain in terms of boundary condition setup, data integration, and discrepancies between simulation results and hospital data. The overestimation of flow rates and high wall shear stress observed in the simulations indicate the need for refinements in model assumptions, including incorporating non-Newtonian blood properties, vessel wall compliance, and pulsatile blood flow. Despite these limitations, this study demonstrates the potential of a patient-specific streamlined workflow for a predictive tool for CABG outcomes and offers a path forward for personalized cardiovascular treatment. Future work will focus on refining the model to enhance its accuracy, and clinical applicability, and commercializing the method.29 0Item Restricted Exploring Muscle Structure, Function, and Gait Patterns in People with Distal Hereditary Motor Neuropathy: Natural History and the Effect of Rehabilitation Interventions(University College London (UCL), 2024-09) Alangary, Aljwhara; Ramdharry, Gita; Morrow, Jasper; Laura, MatildeBackground: Distal Hereditary Motor Neuropathy (DHMN) is a rare heterogenous inherited neuromuscular disorder. It is characterised by distal progressive weakness. Objectives: This thesis provides preliminary longitudinal data to describe the natural history of DHMN in terms of muscle structure, muscle strength, and gait parameters, also to investigate the effect of commonly used rehabilitation interventions. Methods: DHMN adult participants underwent the following measures: MRI scans of the foot, calf, and thigh muscles, isokinetic and isometric strength measures of the lower limb using dynamometer, 3D motion analysis to capture kinetic and kinematic data of walking gait. For direct comparison, matched health controls underwent the same measures. Measures were repeated after 6 and 12 months to explore the natural history of the disease. DHMN participants underwent additional gait analysis wearing bilateral carbon fibre ankle foot orthoses to explore the effect on gait. Eligible DHMN participants were prescribed a home based resistance training program, and the response to training was analysed by the same measures after 6 months of training. Results: The study identified significant progressive muscle atrophy and increased intramuscular fat accumulation at the calf in DHMN participants, with a notable decline in muscle strength over time and altered gait mechanics. The use of ankle-foot orthoses showed improvements in gait stability, while the resistance training program indicated potential benefits in maintaining muscle function, but adherence was a key challenge. Conclusion: The preliminary data from this study provide valuable insights into the natural history of DHMN, highlighting the progressive nature of muscle degeneration and functional decline. These findings offer useful guidance for health practitioners in managing DHMN and emphasize the need for targeted rehabilitation interventions to improve patient outcomes. Future research should focus on longer-term studies with larger cohorts to validate these findings and further explore effective management strategies.15 0Item Restricted Regulation of Food Intake in Adults with and without Obesity: The Role of the Gastrointestinal Tract and Gut- Brain Axis(The University of Nottingham, 2023-11-03) Althubeati, Sarah; Salter, Andrew; Eldeghaidy, Sally; Lobo, Dileep.N; Avery, AmandaObesity is a complex global health issue affecting a significant portion of the population. In the UK, it is estimated that approximately 1 in 4 adults and 1 in 5 children aged 10 to 11 years are living with obesity. Impairment in food intake regulation, including hunger and satiety sensations, are key factors contributing to overeating and weight gain, particularly in individuals with obesity. While various mechanisms may explain these alterations, such as altered appetite and satiety regulators, accelerated gastric emptying (GE), and heightened brain responses to food cues and reward, it remains inconclusive whether these mechanisms are altered in people living with obesity compared to normal-weight (NW) adults. There are various approaches to studying food regulation, each offering unique insights into the complex mechanisms that control appetite, satiety, and food intake. Non-invasive imaging, particularly magnetic resonance imaging (MRI), provides a powerful tool for investigating the physiological mechanisms underlaying the regulation of food intake. The work in this PhD thesis aims to combine physiological measurements obtained by using MRI with behavioural assessments (i.e., subjective satiety rating), to provide a more comprehensive understanding of appetite control in NW adults and alterations associated with obesity. The work in this thesis included a functional neuroimaging meta-analysis, and three eating behaviour intervention studies, two of which used MRI techniques. A functional neuroimaging meta-analysis was performed to identify brain areas associated with changes in appetite and satiety regulators in NW and Obese adults. The caudate nucleus and hypothalamus were identified as key areas associated with satiety regulators in NW participants. However, conclusive findings for Obese participants were limited due to the small number of studies conducted in this area. An MRI study was conducted to investigate the effect of a standard meal on gastrointestinal (GI) responses. The study found that GI responses including gastric content volume (GCV), GE rate, small bowel water content (SBWC), and superior mesenteric artery (SMA) blood flow, and appetite and satiety regulators were not significantly altered by obesity following the meal. However, Obese participants showed lower satiety subjective rating, and higher insulin and triglyceride levels compared to NW participants. Different macronutrients play distinct roles in influencing feelings of fullness and satiety, and their impact on the satiety sensation can be a valuable strategy for weight loss. In a pilot MRI study combining gut and brain imaging, responses to a high-fat (HF) emulsion drink and a carbohydrate drink that is matched in caloric content, volume, and viscosity were assessed in NW and Obese participants. Data collection in this study was significantly impacted by the COVID pandemic; therefore, findings from this work are focused on GI responses. The results suggest that the HF drink might induce higher GCV, SBWC, SMA blood flow, and subjective satiety ratings when compared to an iso-caloric, and iso-viscous high carbohydrate drink (HC) in both NW and Obese. The final study investigated the satiating effect of acute high protein consumption compared to high carbohydrate in NW and Obese participants using ad libitum meal intake and subjective satiety ratings. This study found no significant differences in ad libitum energy intake, subjective satiety, or energy intake between the drinks in either NW or Obese participants. This research integrated different approaches to measuring the regulation of food intake and alterations in obesity. This holistic approach facilitates a comprehension understanding of the mechanisms governing food regulation, including the impact of macronutrient composition, hormonal influences, gastrointestinal responses, neural signalling, and eating behaviours. While the studies in the thesis did not reveal significant differences in certain aspects of appetite regulation between NW and Obese, including macronutrient compositions, they did highlight several areas requiring further investigations. The complicated nature of obesity and appetite regulation necessitates continued research to better understand these complex mechanisms and inform strategies for obesity management and prevention.12 0Item Restricted Non-Invasive Colonic Imaging Studies in Inflammatory Bowel Disease(University of Nottingham, 2024) Alshammari, Meshari Turki; Moran, Gordon; Marciani, LucaThe global incidence of Inflammatory Bowel Disease (IBD) is rising, with current prevalence of 0.3%. Objective assessment of colonic inflammation is paramount for diagnosis, monitoring, and clinical management. Endoscopy is the gold standard for objective assessment of colonic disease activity in IBD. However, it has limitations; it requires bowel preparation, can be uncomfortable, is invasive and associated with rare but potentially serious risks such as perforation. Non-invasive colonic imaging may have a role in quantifying colonic disease activity. Non-invasive colonic imaging modalities are widely available, well tolerated, require less intensive bowel preparation, and are routinely used to assess small bowel inflammation. However, the utility of these modalities in assessing colonic inflammation is less clear. This thesis work aimed to investigate their utility. Firstly, a systematic literature review was undertaken to appraise the diagnostic accuracy of non-invasive colonic imaging in both Crohn’s disease (CD) and ulcerative colitis (UC). A meta-analysis of the data was also performed using a bivariate model approach separately for each non-invasive colonic imaging modality. The mean sensitivity and specificity for magnetic resonance imaging (MRI) studies was 0.75 and 0.91, respectively, while for bowel ultrasound (US) studies it was 0.82 and 0.90, respectively. The area under the ROC curves (AUC) was 0.88 (95% CI, 0.82 to 0.93) for MRI, and 0.90 (95% CI, 0.75 to 1.00) for US. Both MRI and US showed high diagnostic accuracy in the assessment of colonic disease activity in IBD patients. Secondly, an evaluation of the dependence of a tagging measurement was performed (for assessing chyme mixing) on inter-observer variability in both the ascending colon (AC) and descending colon (DC). The temporal variation and hence reliability of the colonic tagging technique was also investigated by acquiring multiple measurements over time on healthy participants. The MRI tagging technique can provide an assessment of colonic chyme mixing. The inter-observer study data showed high inter-rater agreement. The temporal variation study showed some individual variations with time suggesting multiple measurements may be needed to increase accuracy. A prospective study was then conducted to determine the feasibility of an MRI protocol to visualise and assess diffusion-weighted imaging (DWI) and motility of the colon wall and content in UC patients. The preliminary findings show that this MR protocol, including quantitative DWI, motility scans, and tagging in the colonic segments, is feasible for use in UC patients. Further data is needed to determine whether any of the parameters measured provide sensitivity to disease activity and inflammation.28 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 Supplemental breast cancer-screening by magnetic resonance imaging (MRI) in women with dense breasts: A systematic review(Saudi Digital Library, 2023-11-23) Almutairi, Jamilah; Polycarpou, Irene; Buckley, David; Bacon, Sarah- Objectives: In the context of women with dense breasts, the purpose of this systematic review is to evaluate the diagnostic performance and the cost-effectiveness of MRI as an additional screening method for breast cancer. - Methods: The study utilizes the Medline, Embase, and Scopus databases to conduct a comprehensive search from 2005 to July 2023 in order to identify relevant research articles. - Results: 8 of the 14 studies included in this review assessed the diagnostic performance of MRI in the screening of women with dense breasts. The remaining 6 research investigated the cost-effectiveness of utilizing MRI as an additional screening method. The combined results showed that MRI has a sensitivity of 75% – 100% and, a specificity of 87% – 97% whereas positive predictive values (PPV) showed a spectrum from 7.7% – 56%, the negative predictive values (NPV) varying between 99.7% – 100%. The cost-effectiveness of MRI in the context of screening women with dense breasts is noteworthy, confirming its potential benefit in this particular setting. - Conclusions: An increased sensitivity in cancer detection has been shown by the utilization of additional MRI in breast cancer screening among women with dense breast tissue. However, it produced variable positive predictive values (PPV) for the identification of breast cancer and slightly decreased diagnostic specificity. The inclusion of additional MRI in the detection of breast cancer in women with dense breasts remains economically advantageous, according to the cost-effectiveness studies.12 0Item Restricted The Effects of Iron and Inflammation on Alzheimer’s Disease in 5xFAD Mice(Saudi Digital Library, 2023-09-01) Aljuhani, Manal; So, Po-WahBoth neuroinflammation and iron dyshomeostasis feature in, and contribute to, Alzheimer’s disease (AD), and have been shown to interact synergistically. This thesis aims to investigate: 1) the short-term effect of peripheral iron administration on the progression of AD in 5xFAD and wildtype in both male and female mice and 2) the short/long term effects of peripheral iron administration, with and without inflammatory priming, on the progression of AD in 5xFAD and wildtype mice. A multimodality approach was used to assess the progression of AD: behavioural assessments to evaluate cognitive performance; in-vivo magnetic resonance imaging studies, relaxation rates R1 and R2, as putative indices of inflammation and iron accumulation, respectively; quantitative iron assessments and immunohistochemical assessments of both neuroinflammation and plaque deposition. Iron treatment led to increased numbers of plaques and microglia in the hippocampus accompanying cognitive impairment and higher levels of hippocampal iron in 5xFAD female mice. Conversely, 5xFAD male mice treated with iron demonstrated increased levels of plaque deposition, but cognitive impairment was not observed. Male and female mice had a differential response to iron treatment. In the short-term effect, hippocampal and cortical R1 were increased by lipopolysaccharide (LPS) treatment alone, and combined with iron, in wildtype mice. Moreover, microglial branch length and number of end points were higher in LPS and LPS + iron. Conversely, in 5xFAD mice, plaque deposition was increased post-iron and -LPS treatments in the hippocampus and cortex but reduced when the two treatments were combined (LPS+iron). In the long-term, hippocampal and cortical R2 were increased by LPS treatment in 5xFAD mice. Additionally, plaque deposition was higher by LPS, alone or combined with iron, along with an increase of iron concentration in the hippocampus. In the long term, R2 correlated with Aβ plaque deposition, and with iron content consistent with previous reports. I demonstrate sex- and region-dependent effects of peripheral inflammation and/or iron in 5xFAD mice and wildtype littermates. The data provides evidence for further study of iron dyshomeostasis and inflammation as potential therapeutic targets in AD.12 0Item Restricted MRI assessment of Subclinical Cardiac Dysfunction and its association with Ectopic fat in adults with Type 2 Diabetes(Saudi Digital Library, 2023-09-15) Althagafi, Loai; Maccann, Gerry; Brady, EmerBackground Visceral adipose tissue (VAT) is metabolically active and has been implicated in the development of Heart Failure with Preserved Ejection Fraction (HFpEF) through dysregulation of circulating adipokines in people with type 2 diabetes (T2D). Objective The purpose of this research was to determine whether VAT is independently related to subclinical cardiac dysfunction in a multi-ethnic cohort of obese people with T2D using magnetic resonance imaging (MRI). Methods Data was derived from two randomised controlled trials: the LYDIA study (NCT02043054) and the DIASTOLIC study (NCT02590822). Participants had T2D and obesity with no history or symptoms of cardiovascular disease. They underwent one of five interventions in open-label, blinded endpoint designs: 1) standard care, 2) supervised exercise training, 3) a meal replacement program, and 4) liraglutide or sitagliptin. Multiparametric cardiovascular MRI strain rate analysis using feature tracking and 2-point Dixon (fat-water) imaging for VAT quantification were performed at baseline and follow-up. Multivariable regression was used to identify the associations between VAT and liver fat with LV systolic strain/diastolic strain rates and LV mass:volume in subjects with T2D. Multivariable models were adjusted for age, sex, ethnicity, systolic BP, BMI, and WHR at baseline and for change in SBP and weight at follow-up, with leptin and adiponectin added to the final model. Results At baseline, 132 working-age adults, respectively, with T2D (mean age: 47.5±7.3, 54.5% male and 59.8% White European, VAT: 100/mL) showed a significant association with circumferential PEDSR (P = 0.046) independent of age, sex, ethnicity, systolic BP, BMI, and WHR. This association shows that for every 100 mL or VAT mL/cm increase in VAT volume is associated with a decrease in circumferential PEDSR (s-1) that is equivalent to the coefficient ( = -3.225). A total of 103 working-age adults with T2D (mean age of 47.5±7.3 years, 54.5% male and 60% WE) completed the trials. A significant reduction in weight was reported (mean change 4.3 kg, (3.3, 5.4), p < 0.001), systolic BP (3.5(1.5,5.4), p < 0.001) and strain and strain rates were reported. A reduction in VAT volume was associated with an improvement in circumferential PEDSR (p = 0.019) independent of independent of age, sex, ethnicity, systolic BP, and weight. This equated to reduction in circumferential PEDSR, s-1 of 0.022 (, (0.004, 0.040)) for every 100 mL reduction in VAT volume. The association continued to do show significance when leptin and adiponectin were added to the model separately (p = 0.004, p = 0.007) respectively. Conclusion VAT (100/mL) and a reduction in VAT (100/mL) are independently associated with diastolic strain rates. These findings support the putative role of VAT in the development and possible management of HFpEF in people living with obesity and T2D18 0Item Restricted Characterisation of physiological and blood biomarker changes in paediatric congenital cardiac interventions(2022-11-01) Alablani, Fatmah Jamal; Chung, EmmaBackground: Physiological and blood biomarker changes could give new insights into brain injury mechanisms associated with paediatric congenital heart disease (CHD) surgery. Objectives: This thesis aimed to characterise physiological and blood biomarker changes associated with paediatric CHD interventions. Methods: A systematic review was performed to investigate the incidence of perioperative brain MRI findings from studies that had conducted both pre- and post-surgery brain MRI. As preparation for our clinical study, a neonatal TCD probe holder was developed, and the accuracy of our TCD equipment was verified through development of a Doppler phantom mimicking the middle cerebral artery. Finally, a prospective observational study was conducted involving measurement of pre-, intra- and post-operative cerebral blood flow velocity (CBFV), physiological monitoring, analysis of blood-based brain injury and inflammatory biomarkers, and brain MRI in infants undergoing CHD interventions (on-pump, off-pump, and catheterisation). Results: Our systematic review demonstrated that new brain MRI findings are typically present in 51% of infants following CHD surgery. Our in vitro study provided a better understand of TCD CBFV measurements and revealed differences between manufacturers at high velocities. CBFV monitoring using TCD at various perioperative time-points in 38 CHD infants revealed differences in cerebral haemodynamics between CHD repair groups. Analysis of 12 blood-based brain injury and inflammatory biomarkers in 20 infants revealed high levels of biomarkers, especially in infants undergoing on-pump surgery. Finally, a case-study is reported, which includes brain MRI findings in a 3-month-old infant who underwent trans-catheter CHD repair. Conclusion: TCD monitoring, blood biomarkers, and MRI, could be valuable in addressing knowledge gaps around perioperative brain injury and have the potential to support the evaluation of methods for improving outcome. Further work should also assess neurodevelopmental outcome for comparison with TCD, blood biomarkers, and brain MRI outcomes around the time of surgery in a larger group of patients.12 0Item Restricted Brain Imaging Biomarkers in Multiple Sclerosis(2023-05-10) Altokhis, Amjad; Evangelou , Nikos; Constantinescu, CrisBackground: Iron rim lesions (IRLs), white matter lesions (WMLs) accumulation and linear brain atrophy measurements have been suggested to be important imaging biomarkers in multiple sclerosis (MS). The extent to which these markers are related to MS diagnosis and predict disease prognosis remains unclear. Furthermore, research Magnetic Resonance Imaging (MRI) findings need validation in clinical settings before they can be incorporated into clinical practice. Methods: I conducted two reviews one was a mapping review on IRLs and the other was a meta-analysis on WMLs in MS. I then tested the diagnostic and prognostic usefulness of the IRL in two studies: (1) a large, cross-sectional, multi-centre study of patients with MS and mimicking disorders using 3T MRI, (2) a retrospective single-centre study of patients with first presentation of a clinically isolated syndrome (CIS) or at the early stage of the disease using 7T MRI. I also explored the utility of routine, non-standardised MRI scans measuring WMLs number, volume and linear measures of atrophy at the early stage of the disease and examined their role in predicting long-term disability. Results: The IRLs achieved high specificity (up to 99%) in diagnosing MS compared to MS-mimics but low sensitivity of 24%. All patients with IRLs showing a central vein sign (CVS) had MS or CIS, giving a diagnostic specificity of 100% but equally low sensitivity of 21%. Moreover, the presence of IRLs was also a predictor of long-term disability, especially in patients with ≥4 IRLs. IRLs had a greater impact on disability compared to the WMLs number and volume. Linear brain atrophy of Inter-Caudate Distance (ICD) and Third Ventricle Width (TVW) had a significant impact in predicting disability after 10 years. Conclusions: The perilesional IRLs may reduce diagnostic uncertainty in MS by being a highly specific imaging diagnostic biomarker, especially when used in conjunction with the CVS. Also, the presence and number of IRLs hold prognostic value for long-term physical disability in MS. Simple and reliable assessment of brain atrophy remains challenging in clinical practice.18 0