Cardiac Multifrequency Time-harmonic Elastography: In Silico Validation and In Vivo Application

To introduce and validate optimized multifrequency cardiac time-harmonic elastography (THE) with portable drivers and multiple-heartbeat acquisitions for detecting abnormal diastolic stiffness using in silico testing and investigating participants with confirmed cardiac wild-type transthyretin amyloidosis (ATTRwt), a model disease for myocardial stiffness, compared to healthy controls.

Cardiac THE was performed using continuous vibrations of 60, 70, and 80 Hz induced by a portable driver. Shear wave speed (SWS) maps, as a proxy for myocardial stiffness, were acquired over 4 seconds in a parasternal long axis view. Cardiac ultrasound simulations with CT-data-based anatomies were used for in silico validation and parameter optimization. Diagnostic performance was assessed using the area under the ROC curve (AUC) with 95% confidence interval (95%-CI).

Healthy controls (N=10; median age: 32 years [range: 27-56]; five men) and participants with ATTRwt (N=11; median age: 83 years [range: 64-86]; ten men) were investigated, resulting in accurate amyloidosis detection (AUC: 1.00; 95%-CI: 0.94-1.00). In-silico-estimated SWS agreed with ground-truth values (r²=0.94; median error: 5.6% [range: -26.2-19.7]) across various stiffnesses [range: 1.3-4.0 m s^-1] and thicknesses [range: 10-20 mm]. A trend towards underestimation was only observed in the unlikely scenario of thin and very stiff septa.

For the first time, the accuracy of cardiac THE was quantified both in silico and in vivo, specifically in a cohort including patients with ATTRwt. Multifrequency shear waves induced by portable drivers and encoded in standard ultrasound provide a rapid, low-cost echocardiographic contrast that aids the detection of cardiomyopathies such as amyloidosis.