18F-fluoride PET/MR in cardiac amyloid: A comparison study with aortic stenosis and age- and sex-matched controls

Objectives: Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls. Methods: In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBR_MEAN) after correction for blood pool activity in the right atrium. Results: 53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBR_MEAN values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P =.0006), aortic stenosis (0.73 ± 0.12, P <.0001), and those with AL amyloid (0.96 ± 0.08, P =.01). TBR_MEAN values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P =.003]). A TBR_MEAN threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P =.0004). Conclusion: Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition.