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

doi:10.1109/tuffc.2021.3077704

Cited by 13 publications

(22 citation statements)

References 53 publications

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“…Histotripsy can therefore ablate three-dimensional volumes of any required size and shape by translating the focal zone, as determined by the diffraction pattern of the array, through a predetermined volume. Due to these features, histotripsy is currently being developed for many clinical applications including the treatment of kidney stones (Duryea et al 2011), benign prostatic hyperplasia (Hempel et al 2011, Roberts et al 2014, Schuster et al 2018, deep vein thrombosis (Maxwell et al 2011a, Zhang et al 2015, Goudot et al 2019, Bader et al 2021, congenital heart disease (Xu et al 2010, Owens et al 2011, Miller et al 2013, biofilm ablation (Xu et al 2012, Bigelow et al 2018, Childers et al 2021, and cancer (Vlaisavljevich et al 2013b, 2016b, Brisbane et al 2017, Smolock et al 2018, Longo et al 2019, Schade et al 2019.…”

Section: Introductionmentioning

confidence: 99%

Effects of frequency on bubble-cloud behavior and ablation efficiency in intrinsic threshold histotripsy

Edsall¹,

Ham²,

Holmes³

et al. 2021

Phys. Med. Biol.

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Objective. Histotripsy is a non-thermal focused ultrasound ablation method that destroys tissue through the generation of a cavitation bubble cloud. Previous work studying intrinsic threshold histotripsy has shown that dense bubble clouds can be formed by a single-cycle pulse when the negative pressure exceeds an intrinsic threshold of ∼25–30 MPa, with the ablation efficiency dependent upon the size and density of bubbles within the cloud. This work investigates the effects of frequency on bubble-cloud behavior and ablation efficiency in intrinsic threshold histotripsy. Approach. A modular transducer was used to expose agarose tissue phantoms to 500 kHz, 1 MHz, or 3 MHz, histotripsy pulses. Optical imaging was used to measure the bubble-cloud dimensions, bubble density, and bubble size. The effects of frequency on ablation efficiency were also investigated by applying histotripsy to red blood cell (RBC) phantoms. Main results. Results revealed that the bubble-cloud size closely matched theoretical predictions for all frequencies. The bubble density, which is a measure of the number of bubbles per unit area, was shown to increase with increasing frequency while the size of individual bubbles within the cloud decreased at higher frequencies. Finally, RBC phantom experiments showed decreasing ablation efficiency with increasing frequency. Significance. Overall, results demonstrate the effects of frequency on histotripsy bubble-cloud behavior and show that lower frequency generates more efficient tissue ablation, primarily due to enhanced bubble expansion.

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Section: Introductionmentioning

confidence: 99%

Effects of frequency on bubble-cloud behavior and ablation efficiency in intrinsic threshold histotripsy

Edsall¹,

Ham²,

Holmes³

et al. 2021

Phys. Med. Biol.

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“…As a result, tissue can be homogenized into components at a subcellular level. Such an effect can be employed to liquefy blood clots from cardiovascular events (Maxwell et al 2009, Burgess et al 2012, destroy tumors (Vlaisavljevich et al 2013a, Vidal-Jove et al 2022, kill bacteria (Bigelow et al 2009, Childers et al 2021, Matula et al 2021, and structurally modify tissue to address congenital anomalies (Owens et al 2009, Maxwell et al 2014.…”

Section: Introductionmentioning

confidence: 99%

Cavitation-induced pressure saturation: a mechanism governing bubble nucleation density in histotripsy

Maxwell,

Vlaisavljevich

2024

Phys. Med. Biol.

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Objective: Histotripsy is a noninvasive focused ultrasound therapy that mechanically disintegrates tissue by acoustic cavitation clouds. In this study, we investigate a mechanism limiting the density of bubbles that can nucleate during a histotripsy pulse. In this mechanism, the pressure generated by the initial bubble expansion effectively negates the incident pressure in the vicinity of the bubble. From this effect, the immediately adjacent tissue is prevented from experiencing the transient tension to nucleate bubbles. Approach: A Keller-Miksis-type single-bubble model was employed to evaluate the dependency of this effect on ultrasound pressure amplitude and frequency, viscoelastic medium properties, bubble nucleus size, and transducer geometric focusing. This model was further combined with a spatial propagation model to predict the peak negative pressure field as a function of position from a cavitating bubble.Main results: The single-bubble model showed the peak negative pressure near the bubble surface is limited to the inertial cavitation threshold. The predicted bubble density increased with increasing frequency, tissue viscosity, and transducer focusing angle. The simulated results were consistent with the trends observed experimentally in prior studies, including changes in density with ultrasound frequency and transducer f-number. Significance: The efficacy of the therapy is dependent on several factors, including the density of bubbles nucleated within the cavitation cloud formed at the focus. These results provide insight into controlling the density of nucleated bubbles during histotripsy and the therapeutic efficacy. 

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“…In addition to eukaryotic tissues such as tumors, studies have shown that histotripsy will disrupt bacterial biofilms on surgical meshes, microscope slides, and graphic discs [22][23][24][25][26]. More recently, our lab showed that conventional histotripsy methods could be used to precisely target the lumen of urinary catheters, remove luminal biofilms, and kill suspended bacteria [15].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, our team conducted a study investigating histotripsy for the treatment of luminal biofilms [ 15 ]. Histotripsy is an image-guided and nonthermal focused ultrasound ablation method that uses high-pressure acoustic pulses to noninvasively ablate biofilms and tissues through acoustic cavitation [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…This work builds upon our previous study that established the feasibility of utilizing conventional histotripsy methods for the treatment of luminal biofilms [ 15 ]. Although the results of that study were promising, conventional histotripsy requires high peak negative pressures (

) often greater than 25 MPa to create cavitation bubble clouds.…”

Section: Introductionmentioning

confidence: 99%

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Particle-Mediated Histotripsy for the Targeted Treatment of Intraluminal Biofilms in Catheter-Based Medical Devices

et al. 2022

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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.

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Focused Ultrasound Biofilm Ablation: Investigation of Histotripsy for the Treatment of Catheter-Associated Urinary Tract Infections (CAUTIs)

Cited by 13 publications

References 53 publications

Effects of frequency on bubble-cloud behavior and ablation efficiency in intrinsic threshold histotripsy

Effects of frequency on bubble-cloud behavior and ablation efficiency in intrinsic threshold histotripsy

Cavitation-induced pressure saturation: a mechanism governing bubble nucleation density in histotripsy

Particle-Mediated Histotripsy for the Targeted Treatment of Intraluminal Biofilms in Catheter-Based Medical Devices

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