Browsing by Author "Edsall, Connor"

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    Bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic or artificial cavitation nuclei
    Edsall, Connor; Khan, Zerin Mahzabin; Mancia, Lauren; Hall, Sarah; Mustafa, Waleed; Johnsen, Eric; Klibanov, Alexander L.; Durmaz, Yasemin Yuksel; Vlaisavljevich, Eli (2021-03)
    The study described here examined the effects of cavitation nuclei characteristics on histotripsy. High-speed optical imaging was used to compare bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic and artificial cavitation nuclei (gas-filled microbubbles, fluid-filled nanocones). Results showed a significant decrease in the cavitation threshold for microbubbles and nanocones compared with intrinsic-nuclei controls, with predictable and well-defined bubble clouds generated in all cases. Red blood cell experiments showed complete ablations for intrinsic and nanocone phantoms, but only partial ablation in microbubble phantoms. Results also revealed a lower rate of ablation in artificial-nuclei phantoms because of reduced bubble expansion (and corresponding decreases in stress and strain). Overall, this study demonstrates the potential of using artificial nuclei to reduce the histotripsy cavitation threshold while highlighting differences in the bubble cloud behavior and ablation capacity that need to be considered in the future development of these approaches. (E-mail: cwedsall@vt.edu) (C) 2020 The Author(s). Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.
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    Focused Ultrasound Biofilm Ablation: Investigation of Histotripsy for the Treatment of Catheter-Associated Urinary Tract Infections (CAUTIs)
    Childers, Christopher; Edsall, Connor; Gannon, Jessica; Whittington, Abby R.; Muelenaer, Andre A.; Rao, Jayasimha; Vlaisavljevich, Eli (IEEE, 2021-09-01)
    Urinary catheters often become contaminated with biofilms, resulting in catheter-associated urinary tract infections (CAUTIs) that adversely affect patient outcomes. Histotripsy is a non-invasive focused ultrasound therapy previously developed for the non-invasive ablation of cancerous tumors and soft tissues. Histotripsy has also previously shown the ability to treat biofilms on glass slides and surgical meshes. Here, we investigate the potential of histotripsy for the treatment of CAUTIs for the first time in vitro. Clinically relevant catheter materials (Tygon, Silicone, and latex catheter mimics) and commonly used clinical catheters were tested to determine the feasibility of producing luminal histotripsy bubble clouds. A Pseudomonas aeruginosa (strain PA14) biofilm model was developed and tested to produce luminal biofilms in an in vitro Tygon catheter mimic. This model was treated with histotripsy to determine the ability to remove a luminal biofilm. Finally, the bactericidal effects of histotripsy were tested by treating PA14 suspended inside the Tygon catheter mimic. Results showed that histotripsy produced precise luminal cavitation within all tested catheter mimics and clinical catheters. Histotripsy treatment of a PA14 biofilm with histotripsy reduced luminal biofilm OD590 signal down to background levels. Further, the treatment of suspended PA14 in LB showed a 3.45±0.11 log10 reduction in CFU/mL after 6 histotripsy scans across the catheter mimics. Overall, the results of this study demonstrate the potential of histotripsy to provide a new modality for removing bacterial biofilms from catheter-based medical devices and suggest that additional work is warranted to investigate histotripsy for the treatment of CAUTIs and other biomaterial-associated infections.
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    Focused ultrasound extraction (FUSE) for the rapid extraction of DNA from tissue matrices
    Holmes, Hal R.; Haywood, Morgan; Hutchison, Ruby; Zhang, Qian; Edsall, Connor; Hall, Timothy L.; Baisch, David; Holliday, Jason A.; Vlaisavljevich, Eli (2020-10-09)
    Rapid DNA extraction is a critical barrier for routine and fieldable genetics tests for applications in conservation, such as illegal trafficking and fraudulent mislabelling. Here, we develop a non-thermal focused ultrasound extraction (FUSE) technique that creates a dense cloud of high-pressure acoustic cavitation bubbles to disintegrate targeted tissues into an acellular debris, resulting in the rapid release of entrapped DNA. In this work, we demonstrate the proof-of-concept of the FUSE technique by obtaining species identifiable sequences and shotgun sequencing reads from DNA extracted from Atlantic salmon Salmo salar tissues. Having mitigated the key risks for this technique, we hypothesize future developments with this technology can be applied to accelerate and simplify DNA extraction from exceedingly difficult samples with complex tissue matrices (i.e. fibrous tissue and timber samples) in both laboratory and field settings.
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    Particle-mediated Histotripsy for the Targeted Treatment of Intraluminal Biofilms in Catheter-based Medical Devices
    Childers, Christopher; Edsall, Connor; Mehochko, Isabelle; Mustafa, Waleed; Yuksel Durmaz, Yasemin; Klibanov, Alexander L.; Rao, Jayasimha; Vlaisavljevich, Eli (American Association for the Advancement of Science (AAAS), 2022-08-09)
    Objective: This paper is an initial work towards developing particle-mediated histotripsy (PMH) as a novel method of treating catheter-based medical device (CBMD) intraluminal biofilms. Impact Statement: CBMDs commonly become infected with bacterial biofilms leading to medical device failure, infection, and adverse patient outcomes. Introduction: Histotripsy is a noninvasive focused ultrasound ablation method that was recently proposed as a novel method to remove intraluminal biofilms. Here, we explore the potential of combining histotripsy with acoustically active particles to develop a PMH approach that can noninvasively remove biofilms without the need for high acoustic pressures or real-time image guidance for targeting. Methods: Histotripsy cavitation thresholds in catheters containing either gas-filled microbubbles (MBs) or fluid-filled nanocones (NCs) were determined. The ability of these particles to sustain cavitation over multiple ultrasound pulses was tested after a series of histotripsy exposures. Next, the ability of PMH to generate selective intraluminal cavitation without generating extraluminal cavitation was tested. Finally, the biofilm ablation and bactericidal capabilities of PMH were tested using both MBs and NCs. Results: PMH significantly reduced the histotripsy cavitation threshold, allowing for selective luminal cavitation for both MBs and NCs. Results further showed PMH successfully removed intraluminal biofilms in Tygon catheters. Finally, results from bactericidal experiments showed minimal reduction in bacteria viability. Conclusion: The results of this study demonstrate the potential for PMH to provide a new modality for removing bacterial biofilms from CBMDs and suggest that additional work is warranted to develop histotripsy and PMH for treatment of CBMD intraluminal biofilms.