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Multi-modality Imaging to Determine the Role of Calcification and Inflammation on Restenosis Rates Following Lower Limb Angioplasty 10.17863/CAM.53961 Chowdhury, Mohammed Hayes, Paul Rudd, James HF Coughlin, Patrick Peripheral arterial disease (PAD) is a major cause of CVD-related death and disability. Restenosis is common, occurring in 40-60% of cases at 12 months following lower extremity percutaneous transluminal angioplasty (PTA). No such method exists to identify patients who are at risk from restenosis before intervention. Tracers of inflammation (18F-FDG; fluorodeoxyglucose) and calcification (18F-NaF; sodium fluoride) are higher in restenosis following lower limb angioplasty in patients with peripheral arterial disease, and drug-coated balloons (DCB) dampen the inflammatory process, in an atherosclerotic rabbit model. In the prospective clinical study arm (CA), 50 patients with symptomatic PAD underwent 18F-NaF and 18F-FDG PET imaging of the superficial femoral artery (SFA), pre- and 6-weeks post-angioplasty. The primary outcome was restenosis at 12 months. DCB PTA was studied (compared to plain PTA) using near infrared fluorescence-optical coherence tomography hybrid imaging (NIRF-OCT) and plaque burden assessed by intravascular ultrasound (IVUS), in the experimental arm (EA). 40 patients were used for formal analysis. 14 patients (35%) reached the primary outcome of restenosis. Pre-PTA TBRmax in the restenosis group for 18F-FDG (2.43 [IQR 2.29 – 2.61] and 18F-NaF (2.61 [IQR 2.50 – 2.77]) were higher than the no-restenosis equivalent groups (1.63 [IQR 1.52 – 1.78] and 1.69 [IQR 1.54 – 1.77], p< 0.001). Furthermore, in the no-restenosis group there was a drop in both 18F-FDG and 18F-NaF tracer uptake (p=0.034 and 0.047, respectively) between the two timepoints; a finding not observed in the restenosis group. Experimentally, Plaque pathobiology assessment using NIRF after PTA vs. DCB treatment (42.91 nM vs 17.35 nM, p = 0.028) favoured DCB use to reduce inflammatory effects of angioplasty. Furthermore, DCB use demonstrated neointimal area regression (-2.55 % [IQR -5.35 to -0.43]) versus growth with PTA use (+6.29% [IQR 4.20 – 7.79]; p =0.002), as assessed by IVUS. Together our findings suggest that non-invasive and invasive structural-molecular imaging provide unique but complementary insights into the pathophysiology of restenosis, specifically inflammatory and calcific mediators of arterial remodelling following injury. University of Cambridge 2020-06-08 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/306869 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/9b21843b-a9d7-4671-9279-522816bc5384/download fc56a29f29896e591402eda5699b237e https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/3e2913f6-1360-4dfe-948b-a47630dbfde4/download 353adac0d1ebdfd65ab16480263c3c87 http://purl.org/NET/rdflicense/allrightsreserved PAD Molecular imaging PET/CT Restenosis