Effect of Stiffness of Large Extravascular Hematomas on Their Susceptibility to Boiling Histotripsy Liquefaction in Vitro
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 indwell...
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Published in | Ultrasound in medicine & biology Vol. 46; no. 8; pp. 2007 - 2016 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Inc
01.08.2020
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Abstract | 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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AbstractList | 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. 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. |
Author | Hunter, Christopher Bruce, Matthew Matula, Thomas J. Khokhlova, Vera A. Ponomarchuk, Ekaterina M. Khokhlova, Tatiana D. Kucewicz, John C. Monsky, Wayne |
AuthorAffiliation | Department of Medicine, University of Washington, Seattle, Washington, USA Physics Faculty, Lomonosov Moscow State University, Moscow, Russia Department of Radiology, University of Washington, Seattle, Washington, USA Center for Industrial and Medical Ultrasound, Applied Physics Lab, University of Washington, Seattle, Washington, USA |
AuthorAffiliation_xml | – name: Department of Medicine, University of Washington, Seattle, Washington, USA – name: Physics Faculty, Lomonosov Moscow State University, Moscow, Russia – name: Center for Industrial and Medical Ultrasound, Applied Physics Lab, University of Washington, Seattle, Washington, USA – name: Department of Radiology, University of Washington, Seattle, Washington, USA |
Author_xml | – sequence: 1 givenname: Tatiana D. surname: Khokhlova fullname: Khokhlova, Tatiana D. email: tdk7@uw.edu organization: Department of Medicine, University of Washington, Seattle, Washington, USA – sequence: 2 givenname: John C. surname: Kucewicz fullname: Kucewicz, John C. organization: Center for Industrial and Medical Ultrasound, Applied Physics Lab, University of Washington, Seattle, Washington, USA – sequence: 3 givenname: Ekaterina M. surname: Ponomarchuk fullname: Ponomarchuk, Ekaterina M. organization: Physics Faculty, Lomonosov Moscow State University, Moscow, Russia – sequence: 4 givenname: Christopher surname: Hunter fullname: Hunter, Christopher organization: Center for Industrial and Medical Ultrasound, Applied Physics Lab, University of Washington, Seattle, Washington, USA – sequence: 5 givenname: Matthew surname: Bruce fullname: Bruce, Matthew organization: Center for Industrial and Medical Ultrasound, Applied Physics Lab, University of Washington, Seattle, Washington, USA – sequence: 6 givenname: Vera A. surname: Khokhlova fullname: Khokhlova, Vera A. organization: Center for Industrial and Medical Ultrasound, Applied Physics Lab, University of Washington, Seattle, Washington, USA – sequence: 7 givenname: Thomas J. surname: Matula fullname: Matula, Thomas J. organization: Center for Industrial and Medical Ultrasound, Applied Physics Lab, University of Washington, Seattle, Washington, USA – sequence: 8 givenname: Wayne surname: Monsky fullname: Monsky, Wayne organization: Department of Radiology, University of Washington, Seattle, Washington, USA |
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Keywords | Elastic modulus High-intensity focused ultrasound Hematoma Stiffness Sonothrombolysis Boiling histotripsy Elastography Clot |
Language | English |
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SubjectTerms | Boiling histotripsy Clot Elastic modulus Elastography Hematoma High-intensity focused ultrasound Sonothrombolysis Stiffness |
Title | Effect of Stiffness of Large Extravascular Hematomas on Their Susceptibility to Boiling Histotripsy Liquefaction in Vitro |
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