Evidence map›Paper›PMID 42554561›Full record

ArticleJACC. Cardiovascular imaging2026

Ultrasound Cavitation of Microbubbles Augments Limb Perfusion and Promotes Ulcer Healing in Chronic Limb-Threatening Ischemia.

Bethany A Gholson, Matteo Morello, Sofia Capdeville, J Todd Belcik, James Hodovan, Yujin Choi, Ruei-Jen Abraham-Fan, Khanh P Nguyen, Brian P Davidson, Jeffry Powers and 1 more

Abstract read
In one paragraph

Article in JACC. Cardiovascular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Bethany A GholsonCardiovascular Division, University of Virginia, Charlottesville, Virginia, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Matteo MorelloCardiovascular Division, University of Virginia, Charlottesville, Virginia, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Sofia CapdevilleRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
J Todd BelcikKnight Cardiovascular Institute, Portland, Oregon, USA.
James HodovanKnight Cardiovascular Institute, Portland, Oregon, USA.
Yujin ChoiCardiovascular Division, University of Virginia, Charlottesville, Virginia, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Ruei-Jen Abraham-FanCardiovascular Division, University of Virginia, Charlottesville, Virginia, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Khanh P NguyenKnight Cardiovascular Institute, Portland, Oregon, USA; Division of Vascular Surgery, Oregon Health & Science University, Portland, Oregon, USA; Portland Veterans Administration Health Care System, Portland, Oregon, USA.
Brian P DavidsonKnight Cardiovascular Institute, Portland, Oregon, USA; Portland Veterans Administration Health Care System, Portland, Oregon, USA.
Jeffry PowersPhilips Ultrasound, Bothell, Washington, USA.
Jonathan R LindnerCardiovascular Division, University of Virginia, Charlottesville, Virginia, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA. Electronic address: jlindner@virginia.edu.

Funding

Targeted CEU Imaging of Atherosclerosis and AngiogenesisR01HL078610 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LINDNER, JONATHAN R · 2004 to 2022
$6.8M
Augmentation of Tissue Perfusion with Ultrasound-mediated CavitationR01HL130046 · NHLBI · UNIVERSITY OF VIRGINIA · PI LINDNER, JONATHAN R · 2016 to 2023
$5.5M
Advanced Non-invasive Imaging in the Investigation of Aortic Stenosis PathobiologyR01HL165422 · NHLBI · UNIVERSITY OF VIRGINIA · PI Jonathan R Lindner · 2022 to 2026
$3.5M
Ultrasound Cavitation for Facilitated Cardiac Transduction of AAVR01HL171377 · NHLBI · UNIVERSITY OF VIRGINIA · PI Brent A French, Jonathan R Lindner · 2024 to 2026
$2.1M
NHLBI NIH HHS R01 HL078610NHLBI NIH HHS R01 HL130046NHLBI NIH HHS R01 HL165422NHLBI NIH HHS R01 HL171377
6 · The paper itself

Abstract

backgroundIn patients with peripheral artery disease and chronic limb-threatening ischemia (CLTI), there is a lack of effective treatment options when arterial revascularization is not feasible. In preclinical models, ultrasound (US) cavitation of microbubble contrast agents can augment limb perfusion through multiple shear-mediated vasoactive pathways.

objectivesThis study aims to evaluate whether US cavitation increases limb tissue perfusion and accelerates healing of ischemic ulcers in patients with CLTI.

methodsPatients (n = 24) with CLTI and chronic nonhealing ulcers were randomized to standard care or cavitation therapy, which was performed every 3 days × 6. Definity was infused, and US (1.3 MHz, mechanical index: 1.3) was performed for 15 minutes at the wound site and simultaneously over the ipsilateral femoral artery to leverage conducted vasodilation. The primary endpoints at day 18 were change in ulcer area and ulcer microvascular perfusion.

resultsComplete or partial ulcer healing occurred in almost all cavitation-treated patients, with a significant reduction in ulcer size only in the cavitation group and not the control group (median: -36.6% [Q1-Q3: -15.4% to -65.0%] vs +3.4% [Q1-Q3: -14.7% to +20.0%]; P = 0.039). In cavitation-treated patients, there was a 2.5-fold increase in ulcer margin perfusion, a 1.6-fold increase in functional microvascular density on super-resolution US microangiography, and a 1.8-fold increase in femoral artery flow (P < 0.05 for all parameters). These flow parameters did not increase in control patients.

conclusionsIn patients with CLTI and nonhealing ulcers, periodic therapy with cavitation of microbubbles using US parameters approved for diagnostic imaging promotes healing of ischemic ulcers, likely through improvement in tissue perfusion and microvascular vascularity.

Indexed as

cavitationchronic limb threatening ischemiamicrobubblesmicrocirculationperipheral artery diseasetherapeutic ultrasound

Identifiers

PMID42554561
PMCPMC13449238

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.