In vivo evaluation of angiogenic activity and its correlation with efficacy of indirect revascularization surgery in pediatric moyamoya disease.

Abstract

Indirect revascularization is the most widely used treatment to induce angiogenesis in pediatric moyamoya disease (MMD). Molecular imaging methods targeted for angiogenesis have recently been developed. We performed angiogenesis imaging in indirect revascularization surgery for MMD to evaluate angiogenic activity and its correlation with treatment efficacy. Twelve patients with pediatric MMD were prospectively enrolled. Encephaloduroarteriosynangiosis surgery was conducted, and (68)Ga-Arg-Gly-Asp (RGD) PET was performed 3.7 ± 1.0 mo after surgery. Basal perfusion and stress perfusion (PStr) in the middle cerebral artery territory were evaluated by acetazolamide-stress brain perfusion SPECT using statistical probabilistic anatomic mapping, at preoperative, early postoperative, and long-term follow-up states. Angiogenic activity was assessed on the images in terms of maximal uptake ratio, volume of increased uptake, and uptake-volume product. Basal perfusion and PStr were significantly improved after surgery. Increased angiogenic activity was observed in the revascularized area, mainly around the bony flap. Angiogenic activity gradually decreased with time and significantly correlated with the postoperative time interval (P = 0.0015 for maximal uptake ratio and 0.0069 for volume of increased uptake). It was estimated to normalize at 6.3 mo after surgery. Uptake-volume product was inversely correlated with PStr improvement at the early postoperative state (r = -0.5960, P = 0.0409) and also weakly correlated with PStr improvement at long-term follow-up (r = -0.5010, P = 0.1165). Angiogenesis PET imaging with (68)Ga-RGD was successfully used for the assessment of angiogenic activity in indirect revascularization surgery for MMD, and angiogenic activation measured at approximately 3.7 mo after surgery was inversely correlated with perfusion improvement. The assessment of angiogenic activity using (68)Ga-RGD PET is expected to be effective for evaluating the mechanism or efficacy of revascularization treatment.