Evidence map›Paper›PMID 42034785›Full record

ArticleScientific reports2026

Histotripsy dose impacts tumor cellular damage and treatment outcomes in a preclinical model of hepatocellular carcinoma.

Tejaswi Worlikar, Man Zhang, Menggang Yu, Hanna Kim, Jiaqi Shi, Timothy L Hall, Mishal Mendiratta-Lala, Clifford S Cho, Zhen Xu

Abstract read
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In one paragraph

Article in Scientific reports, 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
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

9 authors.

Tejaswi WorlikarDepartment of Radiology, University of Michigan, Ann Arbor, MI, USA. wtejaswi@umich.edu.
Man ZhangDepartment of Radiology, University of Michigan, Ann Arbor, MI, USA.
Menggang YuDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Hanna KimDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Jiaqi ShiDepartment of Pathology, University of Michigan, Ann Arbior, MI, USA.
Timothy L HallDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Mishal Mendiratta-LalaDepartment of Radiology, University of Michigan, Ann Arbor, MI, USA.
Clifford S ChoDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Zhen XuDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.

Funding

Defining epigenetic signaling to reshape pancreatic tumor microenvironmentR37CA262209 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jiaqi Shi · 2022 to 2026
$2.3M
Focused Ultrasound Foundation AWD024539NCI NIH HHS R37 CA262209NIH HHS CA269394NIH HHS R37CA262209
6 · The paper itself

Abstract

Clinically, histotripsy utilizes a fixed, non-optimized dose (defined by the number of histotripsy pulses) to non-invasively ablate liver tumors. This study investigates the impact of histotripsy doses on tumor cellular damage, immune response, and treatment outcomes. Single orthotopic rat HCC liver tumors were established in immunocompetent rats by injecting McA-RH7777 cells into the liver and were classified as intermediate-stage or late-stage. Tumors were treated with doses 20, 50, 100 and 200 pulses per location (ppl) at 20 Hz, 50 Hz, 100 Hz and 200 Hz pulse repetition frequency (PRF) respectively using 1–2 cycle length histotripsy pulses delivered via a 1 MHz custom histotripsy transducer with an estimated peak negative pressure > 30 MPa. Cellular damage and immune response were evaluated in late-stage tumors. Local tumor control, metastasis inhibition, and survival were evaluated and compared across tumor stages. Abscopal response was evaluated by generating multicentric tumors in separate liver lobes but treating only one tumor. As the dose increased from 20 to 200 ppl, histologic cellular disruption increased from sparse-treatment to overtreatment. Dose 100 ppl (intermediate dose resulting in complete treatment) had the greatest infiltration of CD3 + T-cells and NK-cells, highest TUNEL+ area, lowest Ki67 index, and the highest percentage of animals with complete regression in late-stage tumors. Overtreatment dose (200 ppl) did not have the best treatment outcomes for any tumor stage. Dose 100 ppl also demonstrated improved abscopal response in distant untreated tumor. Histotripsy dose impacts histological tumor damage, immune infiltration, local tumor progression, metastasis inhibition, abscopal response, and survival. An intermediate dose had the best outcomes, but overtreatment resulted in worse outcomes, highlighting the need for histotripsy dose optimization.

Indexed as

Carcinoma, HepatocellularHigh-Intensity Focused Ultrasound AblationLiver NeoplasmsAnimalsCell Line, TumorDisease Models, AnimalMaleRatsTreatment OutcomeAbscopal effectsCancerCellular damageDose optimizationHistotripsyImmune effects

Identifiers

PMID42034785
PMCPMC13280371

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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 OpenQuestion graph.