Publications by authors named "Ekaterina M Ponomarchuk"

2 Publications

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Ultrastructural Analysis of Volumetric Histotripsy Bio-effects in Large Human Hematomas.

Ultrasound Med Biol 2021 Sep 9;47(9):2608-2621. Epub 2021 Jun 9.

Laboratory for Industrial and Medical Ultrasound, Physics Faculty, M. V. Lomonosov Moscow State University, Moscow, Russian Federation; Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA.

Large-volume soft tissue hematomas are a serious clinical problem, which, if untreated, can have severe consequences. Current treatments are associated with significant pain and discomfort. It has been reported that in an in vitro bovine hematoma model, pulsed high-intensity focused ultrasound (HIFU) ablation, termed histotripsy, can be used to rapidly and non-invasively liquefy the hematoma through localized bubble activity, enabling fine-needle aspiration. The goals of this study were to evaluate the efficiency and speed of volumetric histotripsy liquefaction using a large in vitro human hematoma model. Large human hematoma phantoms (85 cc) were formed by recalcifying blood anticoagulated with citrate phosphate dextrose/saline-adenine-glucose-mannitol solution. Typical boiling histotripsy pulses (10 or 2 ms) or hybrid histotripsy pulses using higher-amplitude and shorter pulses (0.4 ms) were delivered at 1% duty cycle while continuously translating the HIFU focus location. Histotripsy exposures were performed under ultrasound guidance with a 1.5-MHz transducer (8-cm aperture, F# = 0.75). The volume of liquefied lesions was determined by ultrasound imaging and gross inspection. Untreated hematoma samples and samples of the liquefied lesions aspirated using a fine needle were analyzed cytologically and ultrastructurally with scanning electron microscopy. All exposures resulted in uniform liquid-filled voids with sharp edges; liquefaction speed was higher for exposures with shorter pulses and higher shock amplitudes at the focus (up to 0.32, 0.68 and 2.62 mL/min for 10-, 2- and 0.4-ms pulses, respectively). Cytological and ultrastructural observations revealed completely homogenized blood cells and fibrin fragments in the lysate. Most of the fibrin fragments were less than 20 μm in length, but a number of fragments were up to 150 μm. The lysate with residual debris of that size would potentially be amenable to fine-needle aspiration without risk for needle clogging in clinical implementation.
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September 2021

Effect of Stiffness of Large Extravascular Hematomas on Their Susceptibility to Boiling Histotripsy Liquefaction in Vitro.

Ultrasound Med Biol 2020 08 20;46(8):2007-2016. Epub 2020 May 20.

Department of Radiology, University of Washington, Seattle, Washington, USA.

Large intra-abdominal, retroperitoneal and intramuscular hematomas are common consequences of sharp and blunt trauma and post-surgical bleeds, and often threaten organ failure, compartment syndrome or spontaneous infection. Current therapy options include surgical evacuation and placement of indwelling drains that are not effective because of the viscosity of the organized hematoma. We have previously reported the feasibility of using boiling histotripsy (BH)-a pulsed high-intensity focused ultrasound method-for liquefaction of large volumes of freshly coagulated blood and subsequent fine-needle aspiration. The goal of this work was to evaluate the changes in stiffness of large coagulated blood volumes with aging and retraction in vitro, and to correlate these changes with the size of the BH void and, therefore, the susceptibility of the material to BH liquefaction. Large-volume (55-200 mL) whole-blood clots were fabricated in plastic molds from human and bovine blood, either by natural clotting or by recalcification of anticoagulated blood, with or without addition of thrombin. Retraction of the clots was achieved by incubation for 3 h, 3 d or 8 d. The shear modulus of the samples was measured with a custom-built indentometer and shear wave elasticity (SWE) imaging. Sizes of single liquefied lesions produced with a 1.5-MHz high-intensity focused ultrasound transducer within a 30-s standard BH exposure served as the metric for susceptibility of clot material to this treatment. Neither the shear moduli of naturally clotted human samples (0.52 ± 0.08 kPa), nor their degree of retraction (ratio of expelled fluid to original volume 50%-58%) depended on the length of incubation within 0-8 d, and were significantly lower than those of bovine samples (2.85 ± 0.17 kPa, retraction 5%-38%). In clots made from anticoagulated bovine blood, the variation of calcium chloride concentration within 5-40 mmol/L did not change the stiffness, whereas lower concentrations and the addition of thrombin resulted in significantly softer clots, similar to naturally clotted human samples. Within the achievable shear modulus range (0.4-1.6 kPa), the width of the BH-liquefied lesion was more affected by the changes in stiffness than the length of the lesion. In all cases, however, the lesions were larger compared with any soft tissue liquefied with the same BH parameters, indicating higher susceptibility of hematomas to BH damage. These results suggest that clotted bovine blood with added thrombin is an acceptable in vitro model of both acute and chronic human hematomas for assessing the efficiency of BH liquefaction strategies.
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August 2020