Evidence map›Paper›PMID 27401956›Full record

ArticleUltrasound in medicine & biology2016

Visualizing the Histotripsy Process: Bubble Cloud-Cancer Cell Interactions in a Tissue-Mimicking Environment.

Eli Vlaisavljevich, Adam Maxwell, Lauren Mancia, Eric Johnsen, Charles Cain, Zhen Xu

Open access · greenAbstract read
In one paragraph

Article in Ultrasound in medicine & biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 13% of its field
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

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.

  1. Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound.International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2021
    Pooled it
  2. Injectable radiopaque targets for cone-beam CT guided histotripsy.International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2026
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  16. MR-Cavitation Dynamics Encoded (MR-CaDE) imaging.Magnetic resonance in medicine · 2025
    Article
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  18. Article
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  20. Thyroid-Targeted Nano-Bombs Empower HIFU for Graves' Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article

14 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Eli VlaisavljevichDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: evlaisav@umich.edu.
Adam MaxwellDepartment of Urology, University of Washington, Seattle, Washington, USA.
Lauren ManciaDepartment of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Eric JohnsenDepartment of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Charles CainDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Zhen XuDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, University of Michigan, Ann Arbor, Michigan, USA.
University of Michigan–Ann Arbor · USUniversity of Washington · US

Funding

Image-Guided Non-Invasive Ultrasonic Thrombolysis Using HistotripsyR01EB008998 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI XU, ZHEN · 2008 to 2017
$4.5M
Novel Ultrasonic Technology to Treat Hemorrhagic StrokeR21NS093121 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI XU, ZHEN · 2015 to 2016
$426k
NIBIB NIH HHS R01 EB008998NINDS NIH HHS R21 NS093121
6 · The paper itself

Abstract

Histotripsy is a non-invasive ultrasonic ablation method that uses cavitation to mechanically fractionate tissue into acellular debris. With a sufficient number of pulses, histotripsy can completely fractionate tissue into a liquid-appearing homogenate with no cellular structures. The location, shape and size of lesion formation closely match those of the cavitation cloud. Previous work has led to the hypothesis that the rapid expansion and collapse of histotripsy bubbles fractionate tissue by inducing large stress and strain on the tissue structures immediately adjacent to the bubbles. In the work described here, the histotripsy bulk tissue fractionation process is visualized at the cellular level for the first time using a custom-built 2-MHz transducer incorporated into a microscope stage. A layer of breast cancer cells were cultured within an optically transparent fibrin-based gel phantom to mimic cells inside a 3-D extracellular matrix. To test the hypothesis, the cellular response to single and multiple histotripsy pulses was investigated using high-speed optical imaging. Bubbles were always generated in the extracellular space, and significant cell displacement/deformation was observed for cells directly adjacent to the bubble during both bubble expansion and collapse. The largest displacements were observed during collapse for cells immediately adjacent to the bubble, with cells moving more than 150-300 μm in less than 100 μs. Cells often underwent multiple large deformations (>150% strain) over multiple pulses, resulting in the bisection of cells multiple times before complete removal. To provide theoretical support to the experimental observations, a numerical simulation was conducted using a single-bubble model, which indicated that histotripsy exerts the largest strains and cell displacements in the regions immediately adjacent to the bubble. The experimental and simulation results support our hypothesis, which helps to explain the formation of the sharp lesions formed in histotripsy therapy localized to the regions directly exposed to the bubbles.

Indexed as

Cell CommunicationComputer SimulationPhantoms, ImagingLithotripsyMammary Neoplasms, ExperimentalCancerCavitationCell–bubble interactionsHistotripsyTissue fractionation

Identifiers

PMID27401956
PMCPMC5010997
OpenAlexW2468159549

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.