Experimental and Theoretical Model of Microvascular Network Remodeling and Blood Flow Redistribution Following Minimally Invasive Microvessel Laser Ablation

Introduction: 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.

Materials and

Methods: In this study, we developed a double transgenic mouse line, αSMA DsRed/Tie2 and GFP/FVB, and conducted a series of experiments using a dorsal skin fold chamber (DSFC) model to investigate microvascular remodeling in response to precise laser ablation. Our experimental protocols received approval from the Institutional Animal Care and Use Committee of the Massachusetts General Hospital and were carried out in strict adherence to the ARRIVE guidelines. This research involved multi-photon laser imaging and optical coherence tomography (OCT) to monitor and quantify dynamic vascular responses and remodeling patterns at multiple time intervals after ablation.
A computational model of the microvascular network was also employed to analyze fluid dynamics and assess the sensitivity of blood flow to alterations in network topology due to targeted vessel disruptions. This approach allowed us to observe and document the adaptive responses of the vascular system to localized trauma and provided a mathematical framework to explore the implications of these changes on overall vascular function. Through these detailed methodological applications, we were able to gather significant insights into the mechanisms of vascular injury and repair, enhancing our understanding of the underlying processes involved in microvascular resilience and regeneration.

Results, Conclusions, and Discussions: 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 2.5x and 3.3x, 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.

Acknowledgements (Optional): Research reported in this publication was supported in part by the Norwegian Financial Mechanism 2014-2021 under the project RO-NO-2019-0138, 19/2020 “Improving Cancer Diagnostics in Flexible Endoscopy using Artificial Intelligence and Medical Robotics” IDEAR, Contract No. 19/2020.