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

Yiying I. Zhu, Douglas L. Miller, Chunyan Dou, Xiaofang Lu, Oliver D. Kripfgans

Myocardial 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. Rats 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. The 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. Ultrasound 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.