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Ultrasound Med Biol. 2020 Feb;46(2):369-376. doi: 10.1016/j.ultrasmedbio.2019.09.019. Epub 2019 Nov 4.

Use of 3-D Contrast-Enhanced Ultrasound to Evaluate Tumor Microvasculature After Nanoparticle-Mediated Modulation.

Author information

1
Department of Radiation Oncology, Hokkaido University, Sapporo, Hokkaido, Japan; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: jihun.k@frontier.hokudai.ac.jp.
2
SonoVol, Inc., Research Triangle Park, North Carolina, USA.
3
Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
4
Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
5
Department of Radiation Oncology, Hokkaido University, Sapporo, Hokkaido, Japan; Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido, Japan.

Abstract

A cost-effective method for serial in vivo imaging of tumor microvasculature has been developed. We evaluated acoustic angiography (AA) for visualizing and assessing non-small cell lung tumor (A549) microvasculature in mice before and after tumor vascular disruption by vascular-targeted gold nanoparticles and radiotherapy. Standard B-mode and microbubble-enhanced AA images were acquired at pre- and post-treatment time points. Using these modes, a new metric, 50% vessel penetration depth, was developed to characterize the 3-D spatial heterogeneity of microvascular networks. We observed an increase in tumor perfusion after radiation-induced vascular disruption, relative to control animals. This was also visualized in vessel morphology mode, which revealed a loss in vessel integrity. We found that tumors with poorly perfused vasculature at day 0 exhibited a reduced growth rate over time. This suggested a new method to reduce in-group treatment response variability using pre-treatment microvessel maps to objectively identify animals for study removal.

KEYWORDS:

Acoustic angiography; Gold nanoparticles; Microvasculature; Radiation therapy; Vascular disruption

PMID:
31694771
PMCID:
PMC6930329
[Available on 2021-02-01]
DOI:
10.1016/j.ultrasmedbio.2019.09.019

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