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Canadian Journal of Cardiology

B-MODE ULTRASOUND-GUIDED LOW-LEVEL FOCUSED-ULTRASOUND SONODYNAMIC THERAPY OF NEOINTIMAL HYPERPLASIA USING PHOTOFRIN-LOADED MICROBUBBLES

      Background

      In vascular surgery, neointimal hyperplasia is a significant clinical phenomenon because it reduces the long-term effectiveness of surgical and endovascular procedures. We devised an experimental sonodynamic therapy protocol and tested its efficacy on neointimal hyperplasia reduction in this study, in which diagnostic B-mode ultrasound is paired with focused-ultrasound with the goal of greater safety.

      Methods and Results

      Golden Syrian hamsters were subjected to endothelial denaturation damage by abdominal aorta ballooning (approximately 0.5 cm superior to the iliac bifurcation). Histopathology results after eight weeks revealed increased smooth muscle cell proliferation in the intimal layer, culminating in vessel wall thickening. The treatment group, then received sonodynamic therapy with pulsed-low-level focused-ultrasound (F= 1.1 MHz, P= 15 W, PD= 250 ms) and sonosensitizer photofrin-loaded PESDA (Perflurocarbon Exposed Sonicated Dextrose Albumin) microbubbles (100ml/kg, 2-5 105 bubbles/ml). The development of inertial cavitation in the abdominal aorta was revealed by B-mode ultrasound imaging combined with ultrasound sonodynamic therapy. In addition, when comparing the treatment group to the other groups, histopathological results revealed a substantial reduction in the mean value for smooth muscle cell density, lumen wall mean thickness, and percentage of luminal cross-sectional area of stenosis (p < 0.05).

      Conclusion

      Enhanced cytoxic effect of photofrin, induced by low-level focused-ultrasound sonodynamic therapy combined with enhanced sonoporation effect of focused ultrasound, induced by collapsed bubbles, can cause intimal layer thickness to be reduced and the luminal cross-sectional area of stenosis to be significantly dilated.