Quantitative assessment of damage during MCET: a parametric study in a rodent model

Abstract

BackgroundMyocardial cavitation-enabled therapy (MCET) has been proposed as a means to achieve minimally invasive myocardial reduction using ultrasound to produce scattered microlesions by cavitating contrast agent microbubbles.MethodsRats were treated using burst mode focused ultrasound at 1.5 MHz center frequency and varying envelope and pressure amplitudes. Evans blue staining indicated lethal cardiomyocytic injury. A previously developed quantitative scheme, evaluating the histologic treatment results, provides an insightful analysis for MCET treatment parameters. Such include ultrasound exposure amplitude and pulse modulation, contrast agent dose, and infusion rate.ResultsThe quantitative method overcomes the limitation of visual scoring and works for a large dynamic range of treatment impact. Macrolesions are generated as an accumulation of probability driven microlesion formations. Macrolesions grow radially with radii from 0.1 to 1.6 mm as the ultrasound exposure amplitude (peak negative) increases from 2 to 4 MPa. To shorten treatment time, a swept beam was investigated and found to generate an acceptable macrolesion volume of about 40 μL for a single beam position.ConclusionsUltrasound parameters and administration of microbubbles directly influence lesion characteristics such as microlesion density and macrolesion dimension. For lesion generation planning, control of MCET is crucial, especially when targeting larger pre-clinical models.

Comparison of analytical and numerical approaches for CT-based aberration correction in transcranial passive acoustic imaging

“…7 of that study). A similar finding was subsequently obtained in a simulation study of transcranial sonications with InSightec’s low-frequency (230 kHz) device [53]. …”

Maturation of Lesions Induced by Myocardial Cavitation-Enabled Therapy

“…blue area over 3 mm wide window constrained ventricular wall area. The window width was approximated from average in vivo macrolesion width (Zhu et al, 2015b). As shown in Fig.…”

“…Increased trigger intervals (from 1:4 to 1:8) and pulse durations (from 5 to 10 cycles) seemed to increase bio-effects (Miller et al 2014a). Moreover, square envelope modulation at the highest peak rarefactional pressure amplitude has a larger effective volume in terms of integrated negative pressure over time, compared to Gaussian modulation (Zhu et al, 2015b). Based on these findings, we chose a set of parameters with higher effect (pulse duration of 10 cycles, 4 ms square modulation, 1:8 trigger for 10 min) and another with lower effect (pulse duration of 5 cycles, 15 ms Gaussian modulation, 1:4 trigger for 5 min).…”

Ultrasonic Cavitation-Enabled Treatment for Therapy of Hypertrophic Cardiomyopathy: Proof of Principle

“…When triggered at the end of systole, ECG premature complexes (PCs) indicated microlesion occurrence (although arrhythmia could be avoided by triggering at the R wave without loss of efficacy), and the degree of injury correlated with plasma troponin levels (Miller et al 2014a; Miller et al 2014b; Miller et al 2015). Of note, cardiac function was preserved during therapy and no conduction abnormalities, such as ST segment elevation, persisted beyond a few hours (Miller et al 2014a; Zhu et al 2015a). Additional studies in normal rats evaluated the acute effect and long-term maturation of the myocardium treated with MCET to assess the potential for therapeutic effect (Lu et al 2016).…”