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High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation.

ABSTRACT: Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm² and 6 mJ/cm² laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm² laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.

SUBMITTER: Hu Z

PROVIDER: S-EPMC5225605 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation.

Hu Zizhong Z Zhang Haonan H Mordovanakis Aghapi A Paulus Yannis M YM Liu Qinghuai Q Wang Xueding X Yang Xinmai X

Scientific reports 20170111

Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ul ...[more]

PMID: 28074839

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Project description:BackgroundWe studied the microvascular structure and function of in situ glioblastoma using ultrasound localization microscopy (ULM).MethodsThe in vivo study was conducted via craniotomy in six Sprague-Dawley rats. Capillary pattern, capillary hemodynamics, and functional quantitative parameters were compared among tumor core, invasive zone, and normal brain tissue with ex vivo micro-computed tomography (micro-CT) and scanning electron microscopy. Correlations between quantitative parameters and histopathological vascular density (VD-H), proliferation index, and histopathological vascular maturity index (VMI-H) were evaluated. Kruskal-Wallis H, ANOVA, Mann-Whitney U, Pearson, and Spearman correlation statistics were used.ResultsCompared to the tumor core, the invasive zone exhibited higher microvascularity structural disorder and complexity, increased hemodynamic heterogeneity, higher local blood flow perfusion (p ≤ 0.033), and slightly lower average flow velocity (p = 0.873). Significant differences were observed between the invasive zone and normal brain tissue across all parameters (p ≤ 0.001). ULM demonstrated higher microstructural resolution compared to micro-CT and a nonsignificant difference compared to scanning electron microscopy. The invasive zone vascular density correlated with VD-H (r = 0.781, p < 0.001). Vessel diameter (r = 0.960, p < 0.001), curvature (r = 0.438, p = 0.047), blood flow velocity (r = 0.487, p = 0.025), and blood flow volume (r = 0.858, p < 0.001) correlated with proliferation index. Vascular density (r = -0.444, p = 0.044) and fractal dimension (r = -0.933, p < 0.001) correlated with VMI-H.ConclusionULM provided high-resolution, noninvasive imaging of glioblastoma microvascularity, offering insights into structural/functional abnormalities.Relevance statementULM technology based on ultrafast ultrasound can accurately quantify the microvessels of glioblastoma, providing a new method for evaluating the effectiveness of antiangiogenic therapy and visualizing disease progression. This method may facilitate early therapeutic assessment.Key pointsULM reliably captures the vascular structures and hemodynamic features of glioblastoma in rats. Micro-CT and scanning electron microscopy validated its effectiveness in microvascular non-invasion characterization. ULM is expected to effectively evaluate glioblastoma anti-vascular therapy response.

Project description:Overly dense microvascular networks are treated by selective reduction of vascular elements. Inappropriate manipulation of microvessels could result in loss of host tissue function or a worsening of the clinical problem. Here, experimental, and computational models were developed to induce blood flow changes via selective artery and vein laser ablation and study the compensatory collateral flow redistribution and vessel diameter remodeling. The microvasculature was imaged non-invasively by bright-field and multi-photon laser microscopy, and optical coherence tomography pre-ablation and up to 30 days post-ablation. A theoretical model of network remodeling was developed to compute blood flow and intravascular pressure and identify vessels most susceptible to changes in flow direction. The skin microvascular remodeling patterns were consistent among the five specimens studied. Significant remodeling occurred at various time points, beginning as early as days 1-3 and continuing beyond day 20. The remodeling patterns included collateral development, venous and arterial reopening, and both outward and inward remodeling, with variations in the time frames for each mouse. In a representative specimen, immediately post-ablation, the average artery and vein diameters increased by 14% and 23%, respectively. At day 20 post-ablation, the maximum increases in arterial and venous diameters were 2.5× and 3.3×, respectively. By day 30, the average artery diameter remained 11% increased whereas the vein diameters returned to near pre-ablation values. Some arteries regenerated across the ablation sites via endothelial cell migration, while veins either reconnected or rerouted flow around the ablation site, likely depending on local pressure driving forces. In the intact network, the theoretical model predicts that the vessels that act as collaterals after flow disruption are those most sensitive to distant changes in pressure. The model results correlate with the post-ablation microvascular remodeling patterns.

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High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation.

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High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation.

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