# Chronic thrombus ablation with histotripsy and thrombolytics

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $692,792

## Abstract

Abstract
 Deep vein thrombosis (DVT) is a major public health problem, affecting 600,000 Americans annually
with a healthcare cost of $10 billion and more than 100,000 deaths. The American Heart Association
recommends catheter-directed thrombolytics or mechanical interventions for critical obstructions to
prevent amputation of the afflicted limb or death. These treatment regimens are not effective for the
chronic thrombus components present in 27 to 43% of DVT cases. Histotripsy is a novel form of
therapeutic ultrasound that employs the mechanical action of bubble clouds to ablate tissue and induce
fluid mixing. The scientific premise of this study is histotripsy, a therapeutic ultrasound modality that
employs the mechanical action of bubble clouds, induces vigorous fluid mixing for improved thrombolytic
delivery and liquefaction of chronic, well organized thrombi. Our preliminary studies demonstrate synergy
between histotripsy and the thrombolytic recombinant tissue plasminogen activator (rt-PA) that enhances
thrombolysis of a retracted venous clot in vitro. We have also shown histotripsy ablation occurs only after
a threshold amount of bubble cloud activity. These preliminary data strongly support our central
hypothesis that the mechanical action of histotripsy-induced bubble clouds enhances a catheter-directed
thrombolytic. In particular, histotripsy causes ablation of chronic thrombus through bubble cloud formation,
and increased rt-PA efficacy via bubble cloud-enhanced fluid mixing. Furthermore, catheter-infusion of
thrombus-targeted echogenic drug delivery vesicles will improve thrombolysis through localized rt-PA
delivery and thrombus ablation. We will examine this hypothesis through the following three specific aims:
In Specific Aim 1, we will develop a prototype DVT histotripsy system to facilitate simultaneous 1-MHz
histotripsy exposure, therapy image guidance, and treatment progress monitoring. In Specific Aim 2, we
will determine the conditions for histotripsy-enhanced thrombolysis. These data will quantify the
synergistic effects observed between the histotripsy excitation and thrombolytic drugs for clot lysis. In
Specific 3, recanalization of DVT with histotripsy and thrombolytic will be assessed in vivo. Successful
completion of the proposed studies will elucidate the efficacy and potential risks of histotripsy for venous
thrombosis, and provide new information to assist the development of targeted ablation methods to
improve thrombolysis in the treatment of currently intractable deep vein thrombosis.

## Key facts

- **NIH application ID:** 9843513
- **Project number:** 5R01HL133334-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Kenneth B. Bader
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $692,792
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843513

## Citation

> US National Institutes of Health, RePORTER application 9843513, Chronic thrombus ablation with histotripsy and thrombolytics (5R01HL133334-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9843513. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*