Monitoring Large Vessel Vasculitis With PET/MR Imaging

Large vessel vasculitis (LVV) is a multi-system, autoimmune disease characterised by non-specific symptoms, pain and high glucocorticoid requirements. The lack of a robust biomarker that tracks disease activity makes disease monitoring difficult. This leads to both disease over-treatment, resulting in adverse effects of glucocorticoids, and under-treatment, with the potential for significant vascular complications. Additionally, the link between LVV and cardiovascular disease (CVD), which is the main cause of death in these patients, remains poorly characterised. An imaging tool which is capable of accurately monitoring disease activity over time is urgently required. Positron emission tomography with magnetic resonance imaging (PET/MR) and retinal optical coherence tomography (OCT) have the potential to meet this need. PET/MR is uniquely useful for imaging CVD and utilises \~50% of the radiation dose of PET with computerised tomography. OCT is a novel potential biomarker of microvascular dysfunction, systemic inflammation and CVD risk in small vessel vasculitis. Participants with a new diagnosis or recent flare of LVV will undergo serial PET/MR and OCT scanning alongside established measures of CVD risk. Results will be compared with current clinical measures of disease activity and with banked control data.

Primary outcomes

• Maximum standardised uptake values (SUVmax) [0 and 6 months]: Maximum standardised uptake values (SUVmax) will be assessed using PETMR. This information will be used to quantify disease activity and atheroma at pre-specified vascular segments.

Secondary outcomes

• Choroidal thickness in microns [0 and 6 months]: Assessment of choroidal thickness as measured using optical coherence tomography will be made at baseline and 6 months
• Choroidal volume in mm3 [0 and 6 months]: Assessment of choroidal volume using optical coherence tomography will be made at baseline and 6 months
• Retinal vasculature morphology [0 and 6 months]: Visual assessment of arteriolar thickness, branching coefficient and branching angle, fractal dimension, and venular tortuosity will be made using OPTOS imaging at baseline and 6 months
• 24-hour ambulatory blood pressure in mmHg [0 and 6 months]: Assessment of 24-hour ambulatory systolic and diastolic blood pressure will be made at baseline and 6 months
• Pulse wave velocity [0 and 6 months]: Assessment of arterial stiffness will be made using pulse wave velocity as measured using SphygmoCor technology. Percentage change in pulse wave velocity will be compared between baseline and 6 months

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* A new diagnosis of LVV or a known diagnosis of LVV presenting with disease relapse

Exclusion Criteria:

* Predominantly cranial symptoms
* LVV secondary to other conditions
* Treatment with high dose glucocorticoids for >2 weeks at time of recruitment
* Contraindication to MR or PET
* Unable to travel to Edinburgh
* Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2
* Unable to provide informed consent
* Pregnant or breastfeeding

• Results publication: Pugh D, Patel D, Macnaught G, Czopek A, Bruce L, Donachie J, Gallacher PJ, Tan S, Ahlman M, Grayson PC, Basu N, Dhaun N. 18F-FDG-PET/MR imaging to monitor disease activity in large vessel vasculitis. Nat Commun. 2024 Aug 25;15(1):7314. doi: 10.1038/s41467-024-51613-1. PMID 39183340

• Neeraj Dhaun, MBChB PhD, Principal investigator, University of Edinburgh