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Abstract
Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. Many patients are not eligible for curative therapies, such as surgical resection of the tumor or a liver transplant. Transarterial embolization is one therapy clinically used in these cases; however, this requires a long procedure and careful placement of an intraarterial catheter. Gas embolization has been proposed as a fast, easily administered, more spatially selective, and less invasive alternative. Here, we demonstrate the feasibility and efficacy of using acoustic droplet vaporization to noninvasively generate gas emboli within vasculature. Intravital microscopy experiments were performed using the rat cremaster muscle to visually observe the formation of occlusions. Large gas emboli were produced within the vasculature in the rat cremaster, effectively occluding blood flow. Following these experiments, the therapeutic efficacy of gas embolization was investigated in an ectopic xenograft model of hepatocellular carcinoma in mice. The treatment group exhibited a significantly lower final tumor volume (ANOVA, p = 0.008) and growth rate than control groups – tumor growth was completely halted. Additionally, treated tumors exhibited significant necrosis as determined by histological analysis. To our knowledge, this study is the first to demonstrate the therapeutic efficacy of gas embolotherapy in a tumor model.
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Details
1 Tulane University, Department of Biomedical Engineering, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588)
2 University of Michigan, Data Office for Clinical and Translational Research, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
3 University of Michigan, Department of Radiology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
4 Stanford University, Department of Oncology, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
5 Tulane University, Department of Neuroscience, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588)
6 University of Michigan, Department of Biomedical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)