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CLINICAL STUDY

Dose heterogeneity may not affect the neointimal proliferation after gamma radiation for in-stent restenosis

A volumetric intravascular ultrasound dosimetric study

Akiko Maehara, MD^*, Neil S. Patel, MS, Louis B. Harrison, MD, Neil J. Weissman, MD, FACC^*,*, Anh B. Bui, MD^*, Han-Soo Kim, MD^*, Andrew E. Ajani, MD^*, Marco T. Castagna, MD^*, Taya L. McMillan, MS^*, Nathan Yang, PhD^*, Rosanna Chan, PhD^*, Julliana Pisch, MD, Harry Quan, MD, Sou-Tung Chiu-Tsao, PhD, Ron Waksman, MD, FACC^* and Gary S. Mintz, MD, FACC

^* Cardiovascular Research Institute, Washington Hospital Center, Washington DC, USA
Beth Israel Medical Center and St. Luke’s-Roosevelt Hospital Center, New York, New York, USA
Cardiovascular Research Foundation, New York, New York, USA

Manuscript received September 10, 2001; revised manuscript received February 28, 2002, accepted March 14, 2002.

^* Reprint requests and correspondence: Dr. Neil J. Weissman, Cardiovascular Research Institute, 110 Irving Street, Northwest, Suite 4B-1, Washington, DC 20010, USA.
Neil.J.Weissman{at}medstar.net

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.

Abbreviations and Acronyms   CSA   cross-sectional area   DV   dose volume   DVH   dose volume histogram   EEM   external elastic membrane   ISR   in-stent restenosis   IVUS   intravascular ultrasound   TG-60   Task Group-60 of the American Association of Physicists in Medicine   WRIST   Washington Radiation for In-Stent restenosis Trial

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