Assessment of Collaborative Robot (Cobot)-Assisted Histotripsy for Venous Clot Ablation

Bader, Kenneth B.; Hendley, Samuel A.; Bollen, Viktor

doi:10.1109/tbme.2020.3023630

Cited by 16 publications

(9 citation statements)

References 54 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding highlights how the large animal studies can be utilized for testing of clinically relevant devices and treatment methods to optimize experimental protocols prior to clinical use. For instance, recent studies have developed improved robotic guidance systems that can only be properly tested in large animals that replicate human anatomy [116][117][118]. Similarly, studies investigating electronic steering for rapid volumetric ablation require large histotripsy array transducers that will likewise need to be tested in large animal models in order to establish in vivo efficacy prior to clinical translation.…”

Section: Discussionmentioning

confidence: 99%

Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review

Hendricks-Wenger

Arnold

Gannon

et al. 2022

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

View full text Add to dashboard Cite

New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely non-invasive, non-thermal, and non-ionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even near critical structures. Additional benefits include real-time image-guidance, high precision, and the ability to treat tumors of any predetermined size and shape. Unfortunately, the lack of clinically and physiologically relevant pre-clinical cancer models is often a significant limitation with all focal tumor ablation strategies. The majority of studies testing histotripsy for cancer treatment have focused on small animal models, which have been critical in moving this field forward and will continue to be essential for providing mechanistic insight. While these small animal models have notable translational value, there are significant limitations in terms of scale and anatomical relevance. To address these limitations, a diverse range of large animal models and spontaneous tumor studies in veterinary patients have emerged to complement existing rodent models. These models and veterinary patients are excellent at providing realistic avenues for developing and testing histotripsy devices and techniques designed for future use in human patients. Here, we provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports across a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review

Hendricks-Wenger

Arnold

Gannon

et al. 2022

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

View full text Add to dashboard Cite

show abstract

“…Additional flexibility for transducer placement will be required for treatment in vivo . One possible solution to distribute bubble activity throughout the clot burden are collaborative robots, which have six degrees-of-freedom to enable arbitrary angulation of the histotripsy source relative to the target [ 64 ]. Finally, physiological effects due to interaction between the clot and the venous wall were not replicated by this in vitro model.…”

Section: Discussionmentioning

confidence: 99%

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

et al. 2022

Self Cite

View full text Add to dashboard Cite

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 focused ultrasound therapy that generates bubble clouds spontaneously in tissue at depth. The mechanical activity of histotripsy increases the efficacy of thrombolytic therapy at doses consistent with current pharmacomechanical treatments for venous thrombosis. The objective of this study was to determine the influence of lytic dose on histotripsy-enhanced fibrinolysis. Human whole blood clots formed in vitro were exposed to histotripsy and a thrombolytic agent (recombinant tissue plasminogen activator, rt-PA) in a venous flow model perfused with plasma. Lytic was administered into the clot via an infusion catheter at concentrations ranging from 0 (control) to 4.54 μg/mL (a common clinical dose for catheter-directed thrombolysis). Following treatment, perfusate samples were assayed for markers of fibrinolysis, hemolysis, and intact red blood cells and platelets. Fibrinolysis was equivalent between the common clinical dose of rt-PA (4.54 μg/mL) and rt-PA at a reduction to one-twentieth of the common clinical dose (0.23 μg/mL) when combined with histotripsy. Minimal changes were observed in hemolysis for treatment arms with or without histotripsy, potentially due to clot damage from insertion of the infusion catheter. Likewise, histotripsy did not increase the concentration of red blood cells or platelets in the perfusate following treatment compared to rt-PA alone. At the highest lytic dose, a refined histotripsy exposure scheme was implemented to cover larger areas of the clot. The updated exposure scheme improved clot mass loss and fibrinolysis relative to administration of lytic alone. Overall, the data collected in this study indicate the rt-PA dose can be reduced by more than a factor of ten and still promote fibrinolysis when combined with histotripsy.

show abstract

“…Briefly, the location of the transducer focus in the plane of the coaxial imaging array was determined by generating histotripsy pulses in the degassed water outside the lumen. The bubble cloud appeared hyperechoic in the imaging plane as described previously [ 16 ], [ 24 ], [ 38 ]. Once the location of the focus was determined, the transducer was aligned with the distal end of the clot relative to the pump (far right, Fig.…”

Section: Methodsmentioning

confidence: 99%

Clot Degradation Under the Action of Histotripsy Bubble Activity and a Lytic Drug

Hendley

Paul

Maxwell

et al. 2021

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

Self Cite

View full text Add to dashboard Cite

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 procedurerelated complications. Histotripsy is one such adjuvant under development that relies on focused ultrasound for in situ nucleation of bubble clouds. Prior studies have demonstrated synergistic effects for clot dissolution when histotripsy is combined with lytic therapy. The success of this combinational approach is hypothesized to promote thrombolytic efficacy via two mechanisms: erythrocyte fractionation (hemolysis) and increased lytic activity (fibrinolysis). In this study, the contributions of hemolysis and fibrinolysis to clot degradation under histotripsy and a lytic were quantified with measurements of hemoglobin and D-dimer, respectively. Linear regression analysis was used to determine the relationship between hemoglobin, D-dimer, and the overall treatment efficacy (clot mass loss). A similar analysis was conducted to gauge the role of bubble activity, which was assessed with passive cavitation imaging, on hemolysis and fibrinolysis. Tabulation of these data demonstrated hemolysis and fibrinolysis contributed equally to clot mass loss. Furthermore, bubble cloud activity promoted the generation of hemoglobin and D-dimer in equal proportion. These studies indicate a multifactorial process for clot degradation under the action of histotripsy and a lytic therapy.

show abstract

Assessment of Collaborative Robot (Cobot)-Assisted Histotripsy for Venous Clot Ablation

Cited by 16 publications

References 54 publications

Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review

Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

Clot Degradation Under the Action of Histotripsy Bubble Activity and a Lytic Drug

Contact Info

Product

Resources

About