Evidence map›Paper›PMID 39253521›Full record

ArticlebioRxiv : the preprint server for biology2025

Focused Ultrasound Augments the Delivery and Penetration of Model Therapeutics into Cerebral Cavernous Malformations.

Delaney G Fisher, Matthew R Hoch, Catherine M Gorick, Claire Huchthausen, Victoria R Breza, Khadijeh A Sharifi, Petr Tvrdik, G Wilson Miller, Richard J Price

Abstract readPreprint
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In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

9 authors.

Delaney G FisherDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA.
Matthew R HochDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA.
Catherine M GorickDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA.
Claire HuchthausenDepartment of Physics, University of Virginia, Charlottesville, VA.
Victoria R BrezaDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA.
Khadijeh A SharifiDepartment of Neuroscience, University of Virginia, Charlottesville, VA.
Petr TvrdikDepartment of Neuroscience, University of Virginia, Charlottesville, VA.
G Wilson MillerDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA.
Richard J PriceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA.ORCID 0000-0002-0237-2102

Funding

Genome Editing the Blood-Brain Barrier with Sonoselective Focused UltrasoundR01EB030744 · NIBIB · UNIVERSITY OF VIRGINIA · PI PRICE, RICHARD J. · 2021 to 2024
$2.4M
Focused ultrasound pre-conditioning for augmented nanoparticle penetration in infiltrative gliomasR01EB030409 · NIBIB · UNIVERSITY OF VIRGINIA · PI HANES, JUSTIN S., PRICE, RICHARD J. · 2021 to 2024
$2.3M
Toward precision radiotherapy: Physiological modeling of respiratory motion based on ultra-quality 4D-MRIR01CA226899 · NCI · UNIVERSITY OF VIRGINIA · PI CAI, JING, MILLER, G. WILSON · 2019 to 2023
$2.2M
Small-Animal 9.4T MRI for Biomedical ResearchS10OD025024 · OD · UNIVERSITY OF VIRGINIA · PI BERR, STUART S. · 2019 to 2019
$2.0M
MR Image-Guided Drug Delivery to Cerebral Cavernous Malformations with Focused UltrasoundR01CA279134 · NCI · UNIVERSITY OF VIRGINIA · PI Richard J. Price · 2024 to 2026
$1.8M
Role of Microglial Calcium Waves in Ischemic StrokeR21NS116431 · NINDS · UNIVERSITY OF VIRGINIA · PI TVRDIK, PETR · 2021 to 2022
$444k
ImmunoPET Assessment of anti-CD47 Immunotherapy Delivery to Glioblastoma with Focused UltrasoundR21NS118278 · NINDS · UNIVERSITY OF VIRGINIA · PI PRICE, RICHARD J. · 2020 to 2020
$420k
NCI NIH HHS R01 CA226899NCI NIH HHS R01 CA279134NIBIB NIH HHS R01 EB030409NIBIB NIH HHS R01 EB030744NIH HHS S10 OD025024NINDS NIH HHS R21 NS116431NINDS NIH HHS R21 NS118278
6 · The paper itself

Abstract

backgroundCerebral cavernous malformations (CCMs) are vascular neoplasms in the brain that can cause debilitating symptoms. Current treatments pose significant risks to some patients, motivating the development of new nonsurgical options. We recently discovered that focused ultrasound-microbubble treatment (FUS) arrests CCM formation and growth. Here, we build on this discovery and assess the ability of FUS to deliver model therapeutics into CCMs.

methodsQuantitative T1 mapping MRI sequences were used with 1 kDa (MultiHance; MH) and 17 kDa (GadoSpin D; GDS) contrast agents to assess the FUS-mediated delivery and penetration of model small molecule drugs and biologics, respectively, into CCMs of Krit1 mutant mice.

resultsFUS elevated the rate of MH delivery to both the lesion core (4.6-fold) and perilesional space (6.7-fold). Total MH delivery more than doubled in the lesion core and tripled in the perilesional space when FUS was applied immediately prior to MH injection. For the model biologic drug (i.e. GDS), FUS was of greater relative benefit, resulting in 21.7-fold and 3.8-fold delivery increases to the intralesional and perilesional spaces, respectively.

conclusionsFUS augments the delivery and penetration of therapeutics into the complex and disorganized CCM microenvironment. Benefits to small molecule drug delivery are more evident in the perilesional space, while benefits to biologic delivery are more evident in CCM cores. These findings, when combined with ability of FUS alone to control CCMs, highlight the potential of FUS to serve as a powerful non-invasive therapeutic platform for CCM.

Identifiers

PMID39253521
PMCPMC11383029

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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.