Elastic Properties of Aging Human Hematoma Model In Vitro and Its Susceptibility to Histotripsy Liquefaction.

OBJECTIVE: Tissue susceptibility to histotripsy disintegration has been reported to depend on its elastic properties. This work was aimed at investigation of histotripsy efficiency for liquefaction of human hematomas, depending on their stiffness and degree of retraction over time (0-10 d). METHODS: As an in vitro hematoma model, anticoagulated human blood samples (200 mL) were recalcified at different temperatures. In one set of samples, the shear modulus was measured by shear wave elastography during blood clotting at 10℃, 22℃ and 37℃, and then daily during further aging. The ultrastructure of the samples was analyzed daily with scanning electron microscopy (SEM). Another set of blood samples (50-200 mL) were recalcified at 37℃ for density and retraction measurements over aging and exposed to histotripsy at varying time points. Boiling histotripsy (2.5 ms pulses) and hybrid histotripsy (0.2 ms pulses) exposures (2 MHz, 1% dc, P+/P-/As = 182/-27/207 MPa in situ) were used to produce either individual cigar-shaped or volumetric (0.8-3 mL) lesions in samples incubated for 3 h, 5 d and 10 d. The obtained lesions were sized, then the lysate aspirated under B-mode guidance was analyzed ultrastructurally and diluted in distilled water for sizing of residual fragments. RESULTS: It was found that clotting time decreased from 113 to 25 min with the increase in blood temperature from 10℃ to 37℃. The shear modulus increased to 0.53 ± 0.17 kPa during clotting and remained constant within 8 d of incubation at 2℃. Sample volumes decreased by 57% because of retraction within 10 d. SEM revealed significant echinocytosis but unchanged ultrastructure of the fibrin meshwork. Liquefaction rate and lesion dimensions produced with the same histotripsy protocols correlated with the increase in the degree of retraction and were lower in retracted samples versus freshly clotted samples. More than 80% of residual fibrin fragments after histotripsy treatment were shorter than 150 µm; the maximum length was 208 µm, allowing for unobstructed aspiration of the lysate with most clinically used needles. CONCLUSION: The results indicate that hematoma susceptibility to histotripsy liquefaction is not entirely determined by its stiffness, and correlates with the retraction degree.

Fully nonlinear three-dimensional modeling of parametric interactions in the field of a dual-frequency acoustic array.

An algorithm is developed for fully nonlinear three-dimensional (3D) simulation of a difference-frequency acoustic beam resulting from the interaction of two high-intensity pump waves. Simulations are performed in the frequency domain based on the Khokhlov-Zabolotskaya-Kuznetsov equation. A spectrum filtering method is used to enable accurate solutions for the difference-frequency fields in strongly nonlinear beams and with a high downshift frequency ratio using only dozens of spectral components retained in the algorithm. As an example, the dual-frequency operation of an underwater multi-element ellipsoidal array is considered, and numerical solutions describing parametric interactions in the array field are analyzed. It is shown that difference-frequency beams are more symmetric in transverse directions compared with the pump beams. The most efficient parametric generation of difference-frequency beams corresponded to close and beyond shock-forming conditions. Axial pressure amplitude of the difference frequency was shown to grow first quadratically with the source pressure following the quasi-linear solution and then linearly once shocks start to develop. The percentage of the total power converted to the difference frequency from pump waves increased at high power outputs without saturation. Up to twofold increase in directivity angles of difference-frequency beams under shock-forming conditions was observed compared with quasi-linear conditions.