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

Abstract

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.

Keywords: 18F-fluoride; Amyloid; Aortic stenosis; CMR; PET; PET/MR.

Figure 1

Derivation of myocardial and LGE volumes of interest. Panel A is a 4-chamber view with LGE showing typical myocardial nulling difficulties in a patient with TTR cardiac amyloidosis. The standardized 3 × 15 mm green cylindrical VOI is placed in the septum at the mid-ventricular level. Panel B shows the fused PET/MR with high uptake in the septal and lateral wall of the left ventricle and free wall of the right ventricle (VOI TBR_MEAN inset). Panel C shows the LGE image in the short axis with extensive diffuse LGE affecting most of the myocardium with the corresponding short axis view of the septal VOI. Panel D shows the fused PET/MR image of the same slice with diffuse uptake within the left and right ventricular myocardium. Note the intensely high uptake within the most diseased myocardial segment (within the septal VOI) and the difference in TBR_MEAN compared to panel B

Figure 2

Patterns of 18F-fluoride uptake between cohorts. Columns represent each cohort and rows imaging modality in the short axis view. Panel A shows a delayed enhanced image of a control subject with normal myocardial mass and no LGE. The corresponding fused PET/MR image (E) shows uptake only in the blood pool. Panel B is a patient with aortic stenosis and elevated LV mass. Note the absence of myocardial 18F-fluoride uptake on panel F and similar to the healthy control, uptake is greater in the blood pool than myocardium. Panel C shows a patient with AL amyloid displaying the characteristic myocardial nulling difficulties with LGE found in cardiac amyloidosis. Panel G shows patchy lateral wall uptake greater than the blood pool. Panel D shows similar LGE findings, but this time in TTR amyloid. Note the striking and extensive biventricular uptake in panel H, much greater than the blood pool and what was seen in AL

Figure 3

Comparison of myocardial TBR_MEAN across all cohorts and both subtypes of cardiac amyloid. TBR_MEAN in graph A allows differentiation between ATTR and all cohorts. Further differentiation between amyloid subtypes can be appreciated in graph B with TTR displaying greater uptake than AL. Moreover, within areas of LGE, a cut-off value of > 1.14 gives 100% sensitivity and 100% specificity to detect ATTR over AL. Ordinary one-way ANOVA and unpaired t test. *< 0.05, **< 0.01, ***< 0.001, ****< 0.0001