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dc.contributor.advisorNewby, David
dc.contributor.advisorDweck, Marc
dc.contributor.authorSyed, Maaz Bin Junaid
dc.date.accessioned2022-06-29T13:25:50Z
dc.date.available2022-06-29T13:25:50Z
dc.date.issued2022-06-29
dc.identifier.urihttps://hdl.handle.net/1842/39241
dc.identifier.urihttp://dx.doi.org/10.7488/era/2492
dc.description.abstractBACKGROUND: Acute aortic syndrome is an unpredictable and catastrophic condition. It is characterised by medial degeneration which is beyond the resolution of conventional anatomical imaging. Here, we investigate 18F-sodium fluoride positron emission tomography and computed tomography (PET/CT) and circulating biomarkers in patients with acute aortic syndrome. METHODS: We performed 18F-sodium fluoride PET/CT in 56 patients with aortic dissection, intramural haematoma or penetrating aortic ulcers and 20 healthy controls. First, we characterised radiotracer uptake in relation to demographic and clinical factors (Chapter 3). Next, we investigated the role of 18F-sodium fluoride PET/CT and disease progression in patients with aortic dissection or intramural haematomas (Chapter 4). In a sub-study, we measured plasma desmosine concentration in patients with acute aortic syndrome and investigated these in relation to aortic expansion (Chapter 5). Finally, we identified candidate miRNAs and measured their circulating expression in patients with acute aortic syndrome. Again, we related these to disease characteristics and progression (Chapter 6). Patients with acute aortic syndrome had increased 18F-sodium fluoride PET/CT signal compared to healthy controls (tissue-to-background ratio 2.08±0.45 vs 1.36 ±0.39, p<0.001). 18F-Sodium fluoride uptake concentrated at the site of intimal disruption (+32.5%, p<0.001). Radiotracer uptake in the false lumen was associated with aortic expansion independent of aortic diameter (+7.1 mm/yr, p=0.011). Peak 18F-sodium fluoride uptake was independently associated with aortic rupture, repair or aorta-related death (hazard ratio 8.6 [95% CI, 1.1-68.1], p=0.041). Plasma desmosine concentrations were also elevated in patients (0.58±0.26 vs 0.27±0.07 ng/mL, p<0.001) and peaked at presentation (0.82±0.17 ng/mL, p<0.001). Plasma desmosine concentration was associated with aortic expansion, again, independent of aortic diameter (𝛽���������=+2mm/yr, p<0.001). We identified 16 candidate circulating miRNA, several of which were associated with aortic diameter, expansion and 18F-sodium fluoride uptake. miRNA expression was independently associated with major adverse aortic events (hazard ratio 3.32 (1.71-6.46), p<0.001). CONCLUSION: This is the largest PET study in patients with acute aortic syndrome and the first to use 18F-sodium fluoride PET/CT. In this proof-of-concept study, we demonstrate the potential for 18F-sodium fluoride PET/CT to detect acute aortic syndrome and improve risk stratification. Desmosine is a promising circulating biomarker in this condition and may play a role in diagnosis. Finally, we identified a miRNA signature associated with major adverse aortic events following acute aortic syndrome.en
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.subjectacute aortic syndromeen
dc.subject18F-sodium fluorideen
dc.subjectPETen
dc.subjectaortic dissectionen
dc.subjectintramural haematomaen
dc.subjectpenetrating aortic ulceren
dc.subjectmicro-RNAen
dc.subjectdesmosineen
dc.titleNovel imaging and blood biomarkers in acute aortic syndromeen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen
dc.rights.embargodate2023-06-29en
dcterms.accessRightsRestricted Accessen


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