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Evaluating Gold Nanoparticle and Radiation Induced Tumor Microvascular Disruption Using Acoustic Angiography

J Kwon*1,3, R Rajamahendiran2, N Virani3, S Kunjachan3, E Snay4, M Harlacher2, M Myronakis3, S Shimizu5,6, H Shirato5,7, T Czernuszewicz2, R Gessner2, R Berbeco3, (1) Department of Radiation Oncology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan, (2) SonoVol, Inc., Durham, NC, (3) Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, (4) Boston Children's Hospital, Harvard Medical School, Boston, MA, (5) Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan, (6) Department of Radiation Oncology, Faculty of Medicine, Hokkaido University, Sapporo, Japan, (7) Department of Radiation Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan


(Sunday, 7/29/2018) 4:00 PM - 4:55 PM

Room: Room 209

Purpose: We evaluated acoustic angiographic (AA) imaging for visualizing and assessing tumor microvasculature in mice prior to and following vascular disruption by vascular-targeted gold nanoparticles and radiotherapy. We developed new metrics to characterize and quantify the 3D spatial heterogeneity of tumor microvascular networks.

Methods: Subcutaneous NSCLC (A549) tumor-bearing mice were used in this study. The three groups were: control, RT (10 Gy), and RT+vascular-targeted gold nanoparticles (RGD-GNP). Standard B-mode and microbubble-enhanced AA ultrasound images (SonoVol, Durham, NC) were acquired at pre-treatment and multiple time points post-treatment up to day 70. Tumors were segmented and vascular metrics were extracted. To characterize the 3D distribution of microvessels, the Danielsson distance filter was applied to define distance from the tumor border. Tumor perfusion was quantified by: 1) 50% Vessel Penetration Depth (normalized depth from the tumor surface at which the vessel density drops to 50% of the total vessel density, VPDâ‚…â‚€) and 2) gradient of the cumulative vessel density (CVD) histogram (linear fit of CVD histogram between 10% and 90%). The pre-treatment VPDâ‚…â‚€ was evaluated to objectively exclude animals.

Results: Both control and RT-only groups did not show significant change in the gradient of CVD histogram and the VPDâ‚…â‚€. However, mice receiving GNP+RT demonstrated an initial decrease of both metrics followed by a slight increase after day 30. This suggests restricted perfusion in the tumor core region caused by vascular disruption. Tumors with poor vascularity at day 0 exhibited a reduced growth rate over time.

Conclusion: We investigated RT-induced changes to 3D microvascular distributions in mice tumors with AA for the first time. We developed new metrics for evaluating tumor perfusion after vascular modulation by RGD-GNPs and RT. Our study also suggests a new method for reducing in-group treatment response variability by using pre-treatment microvessel maps to objectively identify animals for study removal.

Funding Support, Disclosures, and Conflict of Interest: Kwon acknowledges support from a Research Fellowship of the JSPS (KAKENHI Grant Number JP17J03616), and the JSPS Overseas Challenge Program for Young Researchers. Authors Rajamahendiran, Harlacher, Czernuszewicz, and Gessner are employees of SonoVol, Inc., a company which is commercializing ultrasound robotic imaging systems for small animal imaging.


Ultrasonics, Vascular Imaging, Tumor Vasculature


TH- Radiobiology(RBio)/Biology(Bio): Bio- blood flow and vascular

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