Saudi Cultural Missions Theses & Dissertations
Permanent URI for this communityhttps://drepo.sdl.edu.sa/handle/20.500.14154/10
Browse
3 results
Search Results
Item Restricted Using multi-modal PET and MRI to predict the site of tumour recurrence in high-grade glioma(The University of Manchester, 2024) Alfaifi, Bandar Q; Hinz, Rainer; Coope, David; Lewis, Daniel; Jackson, AlanBackground: High-grade gliomas (HGG) are highly aggressive and incurable brain tumours that often recur within 2 cm of the original site, even after complete oncological treatments. Advanced MRI and PET techniques hold promise for better tumour delineation and characterisation. This thesis investigates the spatial characterisation of translocator protein (TSPO) and amino acid PET in initially diagnosed HGG and at the point of post-treatment progression, with a view to identifying future sites of disease progression. Methods: HGG patients underwent prospective imaging with [11C](R)PK11195 and [11C]methionine PET alongside MRI including diffusion tensor imaging (DTI). [11C](R)PK11195 binding potential (BPND) and [11C]methionine tumour-to-background ratio were generated. The PET biomarkers were first used to characterise tumour regions defined on MRI as contrast-enhancing (CE) and peritumoral regions and diffusion connectivity map (N=12 initially diagnosed). Secondly, tumour biological volumes were delineated and compared among [11C](R)PK11195 and [11C]methionine PET and CE-MRI using overlap, Dice and Jaccard similarity coefficients (DSC and JSC), and discrepancy measures at baseline (12- initially diagnosed; 8 post-treatment). Disease progression was assessed using follow-up MRI (N=16) and registered with baseline PET biomarkers to explore overlap and similarity. Results: In newly diagnosed HGG, 67±22% of CE-MRI regions showed positive TSPO/methionine, while 36±15% of peritumoral regions showed positive TSPO but negative methionine. TSPO binding in CE-MRI and peritumoral regions was significantly higher than in the contra-lesional reference. [11C](R)PK11195 PET demonstrated a gradual decrease in TSPO binding along the DTI connectivity map compared to [11C]methionine. [11C](R)PK11195 and [11C]methionine biological volumes showed moderate spatial similarity (DSC=0.65±0.15, JSC=0.50±0.16) at initial diagnosis, which decreased for post-treatment HGG (DSC=0.35±0.15, JSC=0.22±0.11). Both PET volumes exhibited moderate overlap with CE-MRI at initial diagnosis, but post-treatment spatial similarity decreased, with substantial discrepancies. TSPO binding and methionine uptake show signals in areas where future disease progression occurred, with average overlaps of 0.51±0.25 and 0.43±0.26, respectively. Conclusions: This work provides the first detailed spatial characterisation of two PET biomarkers in newly diagnosed HGG and at the point of post-treatment progression. Elevated TSPO binding without increased methionine uptake may indicate inflammatory or discrete neoplastic populations not captured by standard imaging techniques. Both PET radiotracers demonstrated increased uptake beyond initial contrast enhancement, and although the exact site lacked specificity, disease progression almost universally occurred within this area. Notably, the discrepancy between TSPO and methionine binding increases post-treatment, with elevated TSPO expression likely reflecting late-stage inflammation contributing to symptomatic worsening in such patients.19 0Item Restricted The Potential of Radiomic Analysis for Enhancing the Diagnostic Ability of PET and CMR in Cardiac Sarcoidosis(University of Leeds, 2024) Mushari, Nouf; Tsoumpas, CharalamposCardiac sarcoidosis (CS) is a granulomatous inflammatory disease whose aetiology is unknown, which features the existence of non-caseating granulomas. This thesis addresses the challenge of accurately diagnosing CS by enhancing the diagnostic capabilities of [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and late gadolinium-enhanced cardiac magnetic resonance imaging (LGE-CMR). Independently, these modalities face limitations in isolating CS with high specificity and sensitivity. The thesis aimed to improve the diagnostic efficiency by integrating [18F]FDG PET and LGE-CMR through advanced radiomic feature analysis. Radiomic analysis was conducted across various scenarios, encompassing comparisons between positive and negative CS groups, distinguishing between active and inactive disease states, and differentiating CS patients from those experiencing myocardial inflammation due to another cause (post-COVID-19 patients). The thesis concludes that radiomic analysis can enhance the objectivity and complementarity of PET and CMR in identifying cardiac sarcoidosis. While PET- based analyses demonstrate high performance, the project underscores the essential role of CMR-based analysis in mitigating challenges associated with PET image preparation variability.17 0Item Restricted Magnetic Lab-On-A-Bead Fluorescence Assay For Detection Of Proteins In Low Concentration(University of Limerick, 2024-03) Alhassan, Luluh; Soulimane, Tewfik; Silien, ChristopheIn modern world, the fate of toxic proteins in the environment needs a subject of great concern due to their potential detrimental effects on living organisms. These proteins can have significant impacts on ecosystems and human health. Immunoassays, which are diagnostic tests based on antibody-antigen interactions, offer a quantitative method for detecting various diseases. Given the extensive selection of antibodies, these assays have become a cornerstone of modern diagnostics. This technique involves creating a sandwich structure using two antibodies binding to a single specific antigen. This dual-antibody approach enhances the specificity and sensitivity of disease detection in immunoassays. Several technologies have been proposed for protein quantification, including ELISA, PCR, FTIR, SERS and flow cytometry. However, these methods still have limitations such as non-specificity, intricacy, and high expenses. As a result, an optical system has been developed to monitor toxic proteins in real-time, combining the advantages of IMS and fluorescence in a dual-mode assay for accurate protein quantification. We present a novel imaging technique that utilizes commonly used fluorescent complexes and incorporates digital analysis to detect analytes. We investigate a magnetic-recovery lab-on-a- bead protein detection method using 1 um Ser-mag carboxylate modified microparticles as both substrate and sensor. By employing microparticles, we harness the available spatial information to create a ratiometric signal that remains unaffected by variations in microparticle number and volume during the binding process. This eliminates the primary source of uncertainties typically encountered in traditional ensemble assays. The technique involves coating microbeads with capture molecules that specifically bind to the target protein, immersing them in the liquid sample, performing magnetic recovery, and then staining with a fluorescent dye. The bead-protein complexes are subsequently analysed using Laser Confocal Scanning Microscopy at the single bead level. Furthermore, we investigate the influence of various parameters on the measurement process and their impact on the results. This approach offers simple assay protocols, short incubation times, minimal reagent consumption, and eliminates the need for enzymatic signal amplification. To achieve direct counting and imaging of single molecules, we implemented a co-registration process where widefield and fluorescence images are combined. A mask is created, and particle counting is performed by blindly selecting particles in the widefield image to exclude any undesired fluorescence background. By estimating a threshold value, we enhance the fluorescent signal, thereby increasing the measurement sensitivity. Various metrics were employed to develop signal detection. We verified that the fraction of fluorescent beads scales with the concentration of the target protein in the liquid samples, reaching a limit as low as Zeptomolar (100 zM) for model assay systems. The practical benefits of the dual mode IMS/Fluorescence assay are demonstrated through the detection of bacterial proteins in environmental samples and clinical biomarkers in human serum.38 0