Dose heterogeneity may not affect the neointimal proliferation after gamma radiation for in-stent restenosis: A volumetric intravascular ultrasound dosimetric study

Objectives The goal of this study was to use serial (postirradiation and follow-up) volumetric intravascular ultrasound (IVUS): 1) to evaluate the actual distribution of gamma radiation in human in-stent restenosis (ISR) lesions, and 2) to analyze the relationship between neointimal regrowth and the delivered radiation dose. Background The relationship between the neointimal regrowth and delivered dose during the treatment of ISR remains unknown. Methods We analyzed 20 actively (gamma emitter) treated, native artery ISR patients from the Washington Radiation for In-Stent restenosis Trial (WRIST) that met the following criteria: on both postirradiation and six-month follow-up IVUS imaging, ≥80% of the external elastic membrane circumference could be identified throughout the treated length including the lesion and proximal and distal reference segments. Intravascular ultrasound images were digitized every 1 mm. Proximal and distal reference and stented segment luminal and adventitial contours were imported and reconstructed. The source was placed circumferentially at the site of the IVUS catheter and longitudinally according to the relationship between the radioactive seeds and stent edges. Using Monte Carlo simulations, dose volume histograms for the adventitia and intima were calculated. The relationship between the neointimal regrowth and calculated doses were evaluated. Results There was large dose heterogeneity at both the intimal and adventitial levels. Most of the sites (93%) received >4 Gy at the adventitia, and all of the sites received >4 Gy at the intima. There was no relationship between neointimal regrowth and radiation dose. Conclusions Although there may be large dose heterogeneity, gamma irradiation (using a fixed dose prescription) appears to deliver a sufficient dose to prevent neointimal regrowth.