Vein wall shrinkage induced by thermal coagulation with high-intensity-focused ultrasound: numerical modeling and in vivo experiments in sheep.

BACKGROUND: Varicose veins are a common disease that may significantly affect quality of life. Different approaches are currently used in clinical practice to treat this pathology. MATERIALS AND METHODS: In thermal therapy (radiofrequency or laser therapy), the vein is directly heated to a high temperature to induce vein wall coagulation, and the heat induces denaturation of the intramural collagen, which results macroscopically in vein shrinkage. Thermal vein shrinkage is a physical indicator of the efficiency of endovenous treatment. High-intensity focused ultrasound (HIFU) is a noninvasive technique that can thermally coagulate vein walls and induce vein shrinkage. In this study, we evaluated the vein shrinkage induced in vivo by extracorporeal HIFU ablation of sheep veins: six lateral saphenous veins (3.4mm mean diameter) were sonicated for 8 s with 3MHz continuous waves. Ultrasound imaging was performed before and immediately post-HIFU to quantify the HIFU-induced shrinkage. RESULTS: Luminal constriction was observed in 100% (6/6) of the treated veins. The immediate findings showed a mean diameter constriction of 53%. The experimental HIFU-induced shrinkage data were used to validate a numerical model developed to predict the thermally induced vein contraction during HIFU treatment. CONCLUSIONS: This model is based on the use of the k-wave library and published contraction rates of vessels immersed in hot water baths. The simulation results agreed well with those of in vivo experiments, showing a mean percent difference of 5%. The numerical model could thus be a valuable tool for optimizing ultrasound parameters as functions of the vein diameter, and future clinical trials are anticipated.

Efficacy and safety assessment of an ultrasound-based thermal treatment of varicose veins in a sheep model.

Purpose: Varicose veins are a common pathology that can be treated by endovenous thermal procedures like radiofrequency ablation (RFA). Such catheter-based techniques consist in raising the temperature of the vein wall to 70 to 120 °C to induce vein wall coagulation. Although effective, this treatment option is not suited for all types of veins and can be technically challenging.Materials and methods: In this study, we used High-Intensity Focused Ultrasound (HIFU) as a non-invasive thermal ablation procedure to treat varicose veins and we assessed the long-term efficacy and safety of the procedure in a sheep model. In vivo experiments were first conducted on two saphenous veins to measure the temperature rise induced at the vein wall during HIFU ablation and were compared with reported RFA-induced thermal rise. Thermocouples were inserted in situ to perform 20 measurements during 8-s ultrasound pulses at 3 MHz. Eighteen saphenous veins of nine anesthetized sheep (2-2.5 % Isoflurane) were then exposed to similar pulses (85 W acoustic, 8 s). After treatments, animals recovered from anesthesia and were followed up 30, 60 and 90 days post-treatment (n = 3 animals per group). At the end of the follow-up, vein segments and perivenous tissues were harvested and histologically examined.Results: Temperatures induced by HIFU pulses were found to be comparable to reported RFA treatments. Likewise, histological findings were similar to the ones reported after RFA and laser-based coagulation necrosis of the vein wall, thrombotic occlusions and vein wall fibrosis.Conclusion: These results support strongly the effectiveness and safety of HIFU for ablating non-invasively veins.

Influence of Skin and Subcutaneous Tissue on High-Intensity Focused Ultrasound Beam: Experimental Quantification and Numerical Modeling.

High-intensity focused ultrasound (HIFU) enables the non-invasive thermal ablation of tumors. However, numerical simulations of the treatment remain complex and difficult to validate in clinically relevant situations. In this context, needle hydrophone measurements of the acoustic field downstream of seven rabbit tissue layers comprising skin, subcutaneous fat and muscle were performed in different geometrical configurations. Increasing curvature and thickness of the sample were found to decrease the focusing of the beam: typically, a curvature of 0.05 mm(-1) decreased the maximum pressure by 45% and doubled the focal area. A numerical model based on k-Wave Toolbox was found to be in very good agreement with the reported measurements. It was used to extrapolate the effect of the superficial tissues on peak positive and peak negative pressure at focus, which affects both cavitation and target heating. The shape of the interface was found to have a strong influence on the values, and it is therefore an important parameter to monitor or to control in the clinical practice. This also highlights the importance of modeling realistic configurations when designing treatment procedures.

Simulation of high-intensity focused ultrasound lesions in presence of boiling.

BACKGROUND: The lesions induced by high-intensity focused ultrasound (HIFU) thermal ablations are particularly difficult to simulate due to the complexity of the involved phenomena. In particular, boiling has a strong influence on the lesion shape. Thus, it must be accounted for if it happens during the pulses to be modeled. However, no acoustic model enables the simulation of the resulting wave scattering. Therefore, we propose an equivalent model for the heat deposition pattern in the presence of boiling. METHODS: Firstly, the acoustic field is simulated with k-Wave and the heat source term is calculated. Then, a thermal model is designed, including the equivalent model for boiling. It is rigorously calibrated and validated through the use of diversified ex vivo and in vivo data, including usually unexploited data types related to the bubble clouds. RESULTS: The proposed model enabled to efficiently simulate unitary pulses properties, including the sizes of the lesions, their morphology, the boiling onset time, and the influence of the boiling onset time on the lesions sizes. CONCLUSIONS: In this article, the whole procedure of model design, calibration, and validation is discussed. In addition to depicting the creative use of data, our modeling approach focuses on the understanding of the mechanisms influencing the shape of the lesion. Further work is required to study the influence of the remaining bubble clouds in the context of pulse groups.