An imaging-based approach to investigate the pathophysiology of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Long COVID and Postural Orthostatic Tachycardia Syndrome

Online questionnaires: All participants(ME/CFS, Long COVID, POTS patient group and healthy control group) will be sent a web link to a series of online questionnaires to be completed prior to clinic visits. REDCap is a secure web platform for building and managing online databases and surveys. There are seven questionnaires which will take about three hours in total.. Clinic visits: All participants(ME/CFS, Long COVID, POTS patient group and healthy control group) will be asked to visit the Melbourne Brain Centre Imaging Unit (MBCIU) twice. The first visit will take approx. 2 hours, the second approx. 4 hours. The two visits should be separated more than 2 days. An investigator will accompany participants through these two visits. In addition, an registered nurse will assess participants' status by direct observation and equipment inspection. The medical procedures for these two visits are summarised as follows. Blood collection(both visit1 and visit2):10 mL of fasting whole blood will be collected by trained staff at visit1. 10 mL of whole blood will be collected prior and after to the MRI by trained staff at visit2. Random Blood Glucose Test(visit1): Participants will be asked to prick their finger to provide a small sample of blood, which will then be analysed using a blood glucose meter. Urine collection and pregnancy test(both visit1 and visit2):At each clinic visit, a 20ml sample of midstream urine will be collected by participants themselves. After collecting the urine, it is applied by the clinic nurse to a test strip or cassette, which will indicate the result of pregnancy within a few minutes. 10 minutes standing test:(visit1) At visit1, participants will be asked to remove their shoes and lie on their back. After lying quietly for 5-10 minutes, their blood pressure and pulse will be recorded. Next, participants will be asked to rise and stand straight while leaning against the wall for 10 minutes. Their blood pressure and pulse measurements will be recorded every minute from the Caretaker Vital Stream which is a wireless, wearable continuous cardiac output, and blood pressure monitor. 18F-Fluorodeoxyglucose(FDG) PET Scan(visit1): At visit1, participants will get a small amount of 18F-FDG, injected into a vein in their arm. After the injection, they will stand for 10 minutes and then rest in a quiet, dark room for 20 minutes. Next, they will have a 30-minute brain scan, followed by a 15-minute scan of their lower legs. After the scan, they will be checked if they feel okay before they go home. Brain MRI and MRS scan(visit2): Prior to the MRI session, participants will receive an email to familiarise themselves with the scanning procedure and be asked to fill out an safety screening form. At visit2, both MRI and MRS scan will be undertaken lying down in an scanner for about 60 minutes in total. Whilst lying in the scanner, they will be able to watch a video of their choosing. For brief periods they will be asked to respond to some prompts on the screen by squeezing a force measuring device. 18F-SMBT-1 PET Scan(visit2): At visit2, participants will receive an injection of the tracer 18F-SMBT-1 into a vein in their arm. After allowing one hour for the tracer to circulate around the body, they will have a 30-minute brain scan. This will be followed by a 15-minute scan of lower legs. After the scan, they will be checked to ensure they’re feeling well before they go home.