Molecular Imaging of Cardiac Amyloidosis

Abstract

Transthyretin and light-chain amyloidosis are the 2 main causes of cardiac amyloidosis. Recent developments in molecular imaging have transformed our ability to diagnose transthyretin cardiac amyloidosis noninvasively and unmasked a hitherto unrecognized prevalence of the disease. This review summarizes the current and evolving imaging approaches, their molecular structural basis, and the gaps in imaging capabilities that have arisen as a result of parallel developments in pharmacotherapy delivering the first effective treatment options for this condition.

Keywords: ATTR; SPECT; bone-seeking tracers; cardiac amyloidosis; molecular imaging.

FIGURE 1.

Molecular mechanism of amyloidosis and imaging characteristics illustrated for ATTR amyloidosis and AL amyloidosis. Echocardiography, CMR, and thioflavin-analog PET tracers detect both types, whereas ^99mTc-labeled bone tracers (BST) are avidly taken up only by ATTR amyloidosis. Notably, hereditary amyloidosis resulting from some mutations result in type B amyloid fibrils, which are less avid for BST. On the other hand, prior reports suggest that some patients with AL may show BST uptake. Differentiation of ATTR from AL amyloidosis is a critical step in evaluation of patients with suspected CA. Wt = wild-type.

FIGURE 2.

(Left) ^99mTc-pyrophosphate planar scan showing avid myocardial tracer uptake (Perugini grade 3, myocardial uptake greater than rib). (Right) Cardiac SPECT showing diffuse myocardial tracer uptake in short-axis images (top row), vertical-long axis images (middle row), and horizontal long-axis (bottom row). This scan is diagnostic of ATTR cardiomyopathy if serum and urine studies for AL amyloidosis are negative.

FIGURE 3.

(Left) ^99mTc-pyrophosphate planar scan showing mild myocardial tracer uptake (Perugini grade 1, myocardial uptake of tracer less than rib). (Right) Chest SPECT images showing tracer in left ventricular cavity as seen best in coronal views (top 2 rows and magnified image) compared with sagittal view (third row from top) or transaxial view (bottom row), illustrating value of SPECT for differentiating blood pool from myocardial activity. In cases without myocardial tracer uptake, it is easier to perform chest reconstruction than cardiac reconstruction.

FIGURE 4.

Congo red, thioflavin T, and its analogs ¹¹C-PIB, ¹⁸F-florbetapir, and ¹⁸F-florbetapen bind to both ATTR and AL amyloid fibrils. ^99mTc bone-seeking tracers show avid uptake in ATTR, possibly related to microcalcification. Increased uptake of ¹⁸F-FDG in AL is attributed to inflammation and macrophage infiltration. Serum amyloid P component (SAP) in ¹²³I-SAP binds to both ATTR and AL fibrils. 11-1F4 is monoclonal antibody against immunoglobulin ALs.