Kenneth B Bader

• Ph.D.
• Professor (Assistant) at University of Chicago

italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Objective: Passive cavitation imaging (PCI) derived metrics can serve as surrogates for the outcome of bubble-mediated therapies. Passive cavitation imaging is limited by poor axial resolution and side lobe artifacts, particularly when algorithms such a...

A 2012 review of therapeutic ultrasound was published to educate researchers and physicians on potential applications and concerns for unintended bioeffects (doi: 10.7863/jum.2012.31.4.623 ). This review serves as an update to the parent article, highlighting advances in therapeutic ultrasound over the past 12 years. In addition to general mechanis...

Renal cell carcinoma cancer (RCC) is the sixth most common cancer in the United States. Although surgery remains the primary choice for the initial treatment, the number of patients who qualify decreases annually due to an aging population with multiple comorbidities. Histotripsy, a non-thermal focused ultrasound technique that ablates tissue throu...

Real-time monitoring is necessary for histotripsy to ensure accurate targeting of tumors. Delineating the bubble cloud can be challenging when the tumors are deep-seated. In this talk, I will discuss collaborative work on harnessing nonlinear signal processing to visualize the histotripsy-induced bubble cloud. Specifically, we employed chirp-coded...

Volterra filtering combined with subharmonic imaging was previously reported to enhance the visualization of the histotripsy bubble cloud. In this study, we compared the bubble cloud size obtained by imaging to the histotripsy ablation region using receiver operating characteristic (ROC) analysis. Histotripsy was performed in a red blood cell (RBC)...

italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Objective: Histotripsy is a focused ultrasound therapy that ablates tissue via the action of bubble clouds. It is under investigation to treat a number of ailments, including renal tumors. Ultrasound imaging is used to monitor histotripsy, though there...

Histotripsy is a focused ultrasound therapy that ablates tissue via bubble cloud activity. Real-time ultrasound image guidance is used to ensure safe and effective treatment. Plane-wave imaging enables tracking of histotripsy bubble clouds at a high frame rate but lacks adequate contrast. Further, bubble cloud hyperechogenicity is reduced in abdomi...

Introduction: For venous thrombosis patients, catheter-directed thrombolytic therapy is the standard-of-care to recanalize the occluded vessel. Limitations with thrombolytic drugs make the development of adjuvant treatments an active area of research. One potential adjuvant is histotripsy, a focused ultrasound therapy that lyses red blood cells wit...

Background Neuroblastoma (NB) is the most common extracranial solid tumor of childhood, and high-risk disease is resistant to intensive treatment. Histotripsy is a focused ultrasound therapy under development for tissue ablation via bubble activity. The goal of this study was to assess outcomes of histotripsy ablation in a xenograft model of high-r...

Histotripsy is a non-thermal focused ultrasound therapy under development to ablate tissue mechanically via bubble cloud activity. Real-time ultrasound imaging is used for treatment guidance. Bubble cloud hyperechogenicity is reduced in deep abdominal targets, making contrast-specific imaging an active area of research. Subharmonic imaging with chi...

Liver cancer is a major burden on the American public, with an estimated 30k new diagnoses in 2022. The limitations of current treatment options motivate alternative approaches to improve patient outcomes. Histotripsy is a focused ultrasound therapy that ablates tissue with bubble cloud activity. The capacity of this technology to address liver les...

Objective: Histotripsy is a form of focused ultrasound therapy that uses the mechanical activity of bubbles to ablate tissue. While histotripsy alone degrades the cellular content of tissue, recent studies have demonstrated it effectively disrupts the extracellular structure of pathologic conditions such as venous thrombosis when combined with a t...

No PDF available ABSTRACT Histotripsy is a bubble-based focused ultrasound therapy under development for tissue ablation, including the treatment of venous thrombosis. Histotripsy is effective for lysing erythrocytes within the clot, but not its fibrin structures. Our prior work has demonstrated when combined with a standard-of-care thrombolytic dr...

No PDF available ABSTRACT Deep vein thrombosis (DVT) is a substantial burden to the American public. Thrombolytics drugs are the front-line approach to treat the most egregious forms of DVT. Histotripsy is a bubble-based focused ultrasound therapy that enhances thrombolytic activity while simultaneously breaking down erythrocytes within the thrombu...

No PDF available ABSTRACT Children diagnosed with high-stage neuroblastoma (NB) have a <50% 5-year survival rate, resisting intensive treatment. Histotripsy, a focused ultrasound method, can ablate subcutaneous tumors. Here, we characterize histotripsy in an abdominal NB-xenograft model.Intrarenal injection of NGP-Luciferase cells in female NCr Nud...

Deep vein thrombosis is a major source of morbidity and mortality worldwide. Catheter-directed thrombolytics are the frontline approach for vessel recanalization, though fibrinolytic efficacy is limited for stiff, chronic thrombi. Although thrombin has been used in preclinical models to induce thrombosis, the effect on lytic susceptibility and clot...

No PDF available ABSTRACT Deep vein thrombosis is a major global burden. For critical obstructions, administration of a thrombolytic drug via catheter infusion is the frontline therapy for restoration of flow. Histotripsy is a focused ultrasound therapy utilized for soft tissue ablation via the generation and action of bubble clouds. Thrombolytics...

Deep vein thrombosis is a major source of morbidity and mortality worldwide. For acute proximal deep vein thrombosis, catheter-directed thrombolytic therapy is an accepted method for vessel recanalization. Thrombolytic therapy is not without risk, including the potential for hemorrhagic bleeding that increases with lytic dose. Histotripsy is a focu...

Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ , which prohibits mechanistic investigation of...

Histotripsy is a focused ultrasound therapy for tissue ablation via the generation of bubble clouds. These effects can be achieved noninvasively, making sensitive and specific bubble imaging essential for histotripsy guidance. Plane wave ultrasound imaging can track bubble clouds with excellent temporal resolution, but there is a significant reduct...

Aesthetic ultrasound is used for fat reduction and to improve skin appearance. In this review, the fundamental mechanisms by which ultrasound can alter tissue are outlined. The technologies that are commercially available or under development are discussed. Finally, recommendations are made for safe and effective use of aesthetic ultrasound.

No PDF available ABSTRACT Deep vein thrombosis is a serious health concern worldwide. Administration of catheter-directed thrombolytics is the primary approach to achieve vessel patency for critical obstructions. Adjuvant techniques that localize thrombolytic delivery will improve treatment outcomes and reduce the potential caustic bleeding associa...

No PDF available ABSTRACT For most folks, ultrasound in medicine is associated with fetal imaging, and it remains among the most widely available and frequently used imaging modalities in the clinic. Recent advances have expanded the capacity of ultrasound imaging to include the ability to quantify mechanical properties of tissue (elastography), mi...

Chronic thrombi of the deep veins of the leg are resistant to dissolution or removal by current interventions and can act as thrombogenic sources. Histotripsy, a focused ultrasound therapy, uses the mechanical activity of bubble clouds to liquefy target tissues. In vitro experiments have shown that histotripsy enhances thrombolytic agent recombin...

Mechanical ablation with the focused ultrasound therapy histotripsy relies on the generation and action of bubble clouds. Despite its critical role for ablation, quantitative metrics of bubble activity to gauge treatment outcomes are still lacking. Here, plane wave imaging was used to track the dissolution of bubble clouds following initiation with...

Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ, which prohibits mechanistic investigation of...

No PDF available ABSTRACT Histotripsy is a focused ultrasound therapy under development as an adjuvant to lytic therapy for the treatment of deep vein thrombosis. In this study, we investigate the mechanisms of clot disintegration (e.g., hemolysis and thrombolysis) under the action of histotripsy and catheter-directed thrombolytics, and demonstrate...

No PDF available ABSTRACT Histotripsy is a focused ultrasound therapy under development for thrombus ablation through bubble cloud nucleation, and combining it with a thrombolytic-loaded theragnostic agent will expand its treatment capacity. In this study, echogenic liposomes encapsulating a lytic were exposed to histotripsy pulses, and the resulti...

No PDF available ABSTRACT In vitro porcine blood clots mimicking deep vein thrombosis were formed in glass pipettes using 2.5 U/ml or 15 U/ml bovine thrombin and incubated at 37°C for 15, 30, 60, or 120 min. Clot stiffness, measured by shear wave elastography, increased and rt-PA susceptibility decreased with incubation time until 3-day old highly...

Deep vein thrombosis is a major source of morbidity worldwide. For critical obstructions, catheter-directed thrombolytics are the frontline therapy to achieve vessel recanalization. Techniques that aid lytic therapy are under development to improve treatment efficacy and reduce procedure-related complications. Histotripsy is one such adjuvant under...

No PDF available ABSTRACT Deep vein thrombosis is a major source of morbidity worldwide, affecting 5% of the population. For critical obstructions, catheter-directed thrombolytics are the frontline therapy for vessel recanalization. Adjuvant therapies to lytics are under development to improve treatment efficacy and reduce procedure-related complic...

Objective: The application of bubble-based ablation with the focus ultrasound therapy histotripsy is gaining traction for the treatment of venous thrombosis, among other pathologies. For extensive clot burden, the histotripsy source must be translated to ensure uniform bubble activity throughout the vascular obstruction. The purpose of this study...

Although primarily known as an ablative modality, histotripsy can increase the efficacy of lytic therapy in a retracted venous clot model. Bubble cloud oscillations are the primary mechanism of action for histotripsy, and the type of bubble activity is dependent on the pulse duration. A retracted human venous clot model was perfused with and withou...

No PDF available ABSTRACT Histotripsy is an emerging therapeutic ultrasound modality for mechanical tissue liquefaction via bubble cloud activity. Image guidance schemes for histotripsy necessitate both quantification of the bubble cloud activity and accurate delineation of the treatment zone. In this study, magnetic resonance (MR) and passive cavi...

As a bubble-based ablative therapy, the efficacy of histotripsy has been demonstrated in healthy or acutely diseased models. Chronic conditions associated with stiff tissues may require additional bubble activity prior to histotripsy liquefaction. In this study, histotripsy pulses were generated in agarose phantoms of Young's moduli ranging from 12...

Focused ultrasound therapies are a noninvasive means to ablate tissue. Histotripsy utilizes short ultrasound pulses with sufficient tension to nucleate bubble clouds that impart lethal strain to the surrounding tissues. Tracking bubble cloud dissolution between the application of histotripsy pulses is critical to ensure treatment efficacy. In this...

Histotripsy is a therapeutic ultrasound modality under development to liquefy tissue mechanically via bubble clouds. Image guidance of histotripsy requires both quantification of the bubble cloud activity and accurate delineation of the treatment zone. In this study, magnetic resonance (MR) and diagnostic ultrasound imaging were combined to assess...

The concentration of Definity utilized in this study, 2 μL/mL, resulted in a final concentration of 2 × 10⁷ particles/mL, not 1 × 10⁴ particles/mL as originally reported. This number density of bubbles is higher than the recommended dose for left ventricular opacification. The authors regret any inconvenience to the readers.

Histotripsy is a focused ultrasound therapy for non-invasive tissue ablation. Unlike thermally ablative forms of therapeutic ultrasound, histotripsy relies on the mechanical action of bubble clouds for tissue destruction. Although acoustic bubble activity is often characterized as chaotic, the short-duration histotripsy pulses produce a unique and...

Histotripsy is a focused ultrasound therapy that ablates tissue via the mechanical activity of bubble clouds. While effective for healthy tissues, histotripsy-induced bubble expansion will be mitigated in stiff chronic pathologies. In this study, the bubble cloud activity necessary for liquefaction of agarose phantoms with elastic moduli ranging fr...

Catheter-directed thrombolytics are the frontline therapy for iliofemoral deep vein thrombosis. We have demonstrated that histotripsy can enhance the efficacy of the thrombolytic recombinant tissue plasminogen activator (rt-PA) through the mechanical activity of bubble clouds. Depending on the histotripsy pulse duration, bubble activity can be init...

Chronic thrombus components are resistant to removal by current interventional techniques and can act as thrombogenic sources. Histotripsy is a focused ultrasound therapy that utilizes the mechanical activity of bubble clouds to liquefy target tissues. In vitro experiments have demonstrated histotripsy provides enhancement of the thrombolytic agent...

Deep vein thrombosis (DVT) is a major public health problem, affecting 600,000 Americans annually with a healthcare cost of $10 billion. Standard interventional techniques are not effective for the chronic thrombus components present in 27% to 43% of DVT cases. Histotripsy is a focused ultrasound therapy that employs the mechanical action of bubble...

Histotripsy is a focused ultrasound therapy under development for tissue ablation via the mechanical action of bubble clouds. While strong bubble activity is a hallmark of histotripsy, persistent bubble clouds shield the focal zone from subsequent pulses and prevent complete liquefaction of the target tissues. The diffusion of gas into the bubble d...

Bubble cloud persistence reduces the efficacy of mechanical liquefaction with shock-scattering histotripsy. In this study, the contribution of gas transfer to bubble longevity was investigated in silico by solving the equations for bubble oscillations and diffusion in parallel. The bubble gas content increased more than 5 orders of magnitude during...

Histotripsy is a form of therapeutic ultrasound that liquefies tissue mechanically via acoustic cavitation. Bubble expansion is paramount in the efficacy of histotripsy therapy, and the cavitation dynamics are strongly influenced by the medium elasticity. In this study, an analytic model to predict histotripsy-induced bubble expansion in a fluid wa...

Histotripsy is a form of therapeutic ultrasound that liquefies tissue mechanically via acoustic cavitation. Bubble growth due to histotripsy excitation has been calculated analytically with high accuracy in a fluid medium. Tissue elasticity is a determining factor in the therapeutic efficacy of histotripsy, and has not been considered in analytic b...

Histotripsy utilizes focused ultrasound to generate bubble clouds for transcutaneous tissue liquefaction. Image guidance of histotripsy pulses is required to provide spatially resolved monitoring of treatment progress. The aim of this study was to investigate the feasibility of plane wave B-mode and passive cavitation images to be used as binary cl...

Apfel’s three golden rules (know thy sound field, know thy liquid, and know when something happens) should be considered when monitoring acoustic cavitation-based ultrasound therapies. The third rule is often followed using passive cavitation detection with a single-element transducer. However, therapy guidance demands monitoring cavitation activit...

Echogenic liposomes loaded with the thrombolytic recombinant tissue-type plasminogen activator (rt-PA) are under development for the treatment of ischemic stroke. These agents are designed to co-encapsulate cavitation nuclei to promote bubble activity in response to ultrasound exposure, and to enable localized delivery of thrombolytic. Stable cavit...

http://www.fusfoundation.org/symposium/2016/docs/FUSF_Symposium_2016_Abstracts_web.pdf

Passive cavitation detection has been an instrumental technique for measuring cavitation dynamics, elucidating concomitant bioeffects, and guiding ultrasound therapies. Recently, techniques have been developed to create images of cavitation activity to provide investigators with a more complete set of information. These techniques use arrays to rec...

Histotripsy utilizes the oscillations of bubbles within a cloud for transcutaneous mechanical ablation of tissue and is currently under development to treat benign prostatic hyperplasia. The bubble clouds are hyperechoic, enabling standard B-mode imaging to be used for image guidance. The volumetric oscillations of the bubbles also generate acousti...

Histotripsy, a form of therapeutic ultrasound that uses the mechanical action of microbubble clouds for tissue ablation, is under development to treat chronic deep vein thrombosis (DVT). We hypothesize that combining thrombolytic agents with histotripsy will enhance clot lysis. Recombinant tissue plasminogen activator (rt-PA) and rt-PA-loaded echog...

Tissue-mimicking phantoms are employed for the assessment of shocked histotripsy pulses in vitro. These broadband shock waves are critical for tissue ablation and are influenced by the frequency-dependent attenuation of the medium. The density, sound speed and attenuation spectra (2-25 MHz) were measured for phantoms that mimic key histotripsy targ...

Histotripsy is a focused ultrasound therapy that ablates tissue through the mechanical action of cavitation. Histotripsy-initiated cavitation activity is generated from shocked ultrasound pulses that scatter from incidental nuclei (shock scattering histotripsy), or purely tensile ultrasound pulses (microtripsy). The Yang/Church model was numericall...

Thrombo-occlusive disease is a leading cause of morbidity and mortality. In this chapter, the use of ultrasound to accelerate clot breakdown alone or in combination with thrombolytic drugs will be reported. Primary thrombus formation during cardiovascular disease and standard treatment methods will be discussed. Mechanisms for ultrasound enhancemen...

Theoretical models of therapeutic ultrasound expand the understanding of the mechanisms of treatment, and expedite the development of regulatory standards. For focused ultrasound therapies that rely on thermal mechanisms to generate lesions, only modeling of the incident sound field needs is sufficient. Modeling of microbubble clouds formed through...

Deep vein thrombosis is a debilitating condition that can result in pulmonary embolism, or post-thrombotic syndrome. Clot lysis can be initiated with histotripsy, a novel form of therapeutic ultrasound that uses the mechanical action of microbubble clouds to ablate tissue. Thrombolytic-loaded echogenic liposomes (t-ELIP) have fibrin targeting capab...

Cardiovascular disease is the number one cause of death worldwide, and thrombo-occlusive disease is a leading cause of morbidity and mortality. Ultrasound has been developed as a tool to induce the release, delivery, and enhanced efficacy of a thrombolytic drug (rt-PA) and bioactive gases from echogenic liposomes. By encapsulating drugs into micron...

Echogenic liposomes (ELIP), that can encapsulate both recombinant tissue-type plasminogen activator (rt-PA) and microbubbles, are under development to improve the treatment of thrombo-occlusive disease. However, the enzymatic activity, thrombolytic efficacy, and stable cavitation activity generated by this agent has yet to be evaluated and compared...

Tissue-mimicking phantoms have previously been developed for assessing the efficacy of therapeutic ultrasound. A new modality of focused ultrasound, histotripsy, relies on the formation of shockwave-induced cavitation to ablate tissue mechanically. The objective of this study was to use a broadband ultrasound method to determine the frequency-depen...

The use of ultrasound and microbubbles as an effective adjuvant to thrombolytics has been reported in vitro, ex vivo and in vivo. However, the specific mechanisms underlying ultrasound-enhanced thrombolysis have yet to be elucidated. We present visual observations illustrating two mechanisms of ultrasound-enhanced thrombolysis: acoustic cavitation...

The Image-guided Ultrasound Therapeutic Laboratories (IgUTL) are located at the University of Cincinnati in the Heart, Lung, and Vascular Institute, a key component of efforts to align the UC College of Medicine and UC Health research, education, and clinical programs. These extramurally funded laboratories, directed by Prof. Christy K. Holland, ar...

Echogenic liposomes can be used as a vector for co-encapsulation of the thrombolytic drug rt-PA and microbubbles. These agents can be acoustically activated for localized cavitation-enhanced drug delivery. The objective of our study was to characterize thrombolytic efficacy and sustained cavitation nucleation and activity from rt-PA-loaded echogeni...

Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine c...

The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of transducers. Viscoelastic shell parameters of...

Acoustically induced loss of echogenicity (LOE) from ultrasound contrast agents (UCAs) has been exploited in imaging techniques to improve delineation of pathology. Determination of the type of cavitation that accompanies LOE can be experimentally difficult to determine due to the complex microbubble activity elicited. A theoretical model has been...

Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration-dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was...

The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of trans- ducers. Viscoelastic shell parameters...

The mechanical index (MI) was formulated to gauge the likelihood of adverse bioeffects from inertial cavitation. However, the MI formulation did not consider bubble activity from stable cavitation. This type of bubble activity can be readily nucleated from ultrasound contrast agents (UCAs) and has the potential to promote beneficial bioeffects. Her...

The prevalence of stroke worldwide and the paucity of effective therapies have triggered interest in the use of transcranial ultrasound as an adjuvant to thrombolytic therapy. Previous studies have shown that 120 kHz ultrasound enhanced thrombolysis and allowed efficient penetration through the temporal bone. The objective of our study was to devel...

Recent investigations of cavitation in fluids pressurized up to 30 MPa found that the intensity of light emissions increased by 1000-fold over that measured for single bubble sonoluminescence. A series of measurements is reported here to extend this original work by resolving the static pressure dependence of the shock wave and light emissions from...

Clinical ultrasound scanners use the Mechanical Index (MI) to gauge the potential for bioeffects due to inertial cavitation. However, the advent of ultrasound contrast agents (UCA) introduces nucleation mechanisms for bubble activity far different than that assumed in the development of the MI. Such exogenous agents promote bubble activity at subst...

Adjuvant ultrasound exposure improves rtPA thrombolysis in stroke patients. Transmission of 120-kHz ultrasound through the temporal bone is efficient but exhibits skull-dependent distortion and reflection. Numerical models of acoustic propagation through human skull based on computed tomography (CT) data have been developed. The objective of our st...

The amplitude of the acoustic pressure required to nucleate a gas or vapor bubble in a fluid, and to have that bubble undergo an inertial collapse, is termed the inertial cavitation threshold. The magnitude of the inertial cavitation threshold is typically limited by mechanisms other than homogeneous nucleation such that the theoretical maximum is...

The conditions within an inertially collapsing bubble are known to produce high temperatures and pressures. Previous investigators have proposed various mechanisms for driving the collapse in order to maximize the energy density of the bubble’s contents. Working in fluids at high static pressures (up to 30 MPa) has shown some promising results. Pre...

The amplitude of the acoustic pressure required to nucleate a gas and/or vapor bubble in a fluid, and to have that bubble undergo an inertial collapse, is termed the inertial cavitation threshold. The hydrostatic dependence of the inertial cavitation threshold was measured up to 30 MPa in ultrapure water using a high quality factor spherical resona...

It is well known from observations in the ocean, as well as limited experimental measurements and theoretical predictions for spherical bubbles, that the threshold acoustic pressure for generation of inertial cavitation increases with hydrostatic pressure. However, the precise nature of the relationship between hydrostatic and acoustic pressures at...

The creation of a bubble in a liquid is energetically favorable when the liquid is subject to a netan overall tension less than of its saturated vapor pressure. This gain is offset by the creation of a liquid-vaporgas interface, and only bubbles larger than some critical size will spontaneously grow. The magnitude of the acoustic pressure required...

This paper describes a spherical acoustical resonator system used to study acoustic cavitation phenomena in liquids as part of an effort to scale up the energy density of collapse of transient cavitation. The resonator is formed by a stainless steel spherical shell 24.1 cm in diameter (OD) and either 1.27 cm or 1.90 cm thick designed for generating...

This paper describes the vibrational dynamics of a spherical acoustical resonator system used in the study of acoustic cavitation phenomena in liquids as part of an effort to scale up the energy density of collapse of transient cavitation. The system consists of a stainless steel shell (10" OD and 0.5" thick) filled with degassed water that exhibit...

In order to model possible effects of cavitation on bone structure, the formation of cavitation along an acoustically reflective PVC surface was studied. The bubbles were generated by a commerical therapeutic transducer (1 MHz), for both water and agar gel mediums. Bubble formation and activity were monitored using light scattering techniques: a He...