Regional quantitative analysis of small animal myocardial sympathetic innervation and initial application in streptozotocin induced diabetes

Abstract

In several disease models it is known that heterogeneous dysinnervation occurs in the sympathetic nervous system. We therefore adapted the (123)I-MIBG imaging procedure in small animals to allow quantification of both global and regional uptake and wash-out rate using high specific activity (123)I-MIBG in the myocardium of rats. After evaluation of the image procedure in normal animals, we then applied our imaging protocol to visualize the regional dysinnervation in cardiac autonomic neuropathy occurring in streptozotocin-induced diabetes. Seven normal Lewis rats underwent (123)I-MIBG pinhole SPECT with low specific activity (123)I-MIBG (lsa MIBG) and high specific activity (123)I-MIBG (hsa MIBG) with a 2 week interval. Twelve normal rats and 12 rats 8 weeks after streptozotocin injection underwent the same hsa MIBG imaging protocol. The imaging protocol consisted of two SPECT acquisitions for every animal. The imaging sequence started at 20 min after tracer injection. The percentage of injected activity (%IA) and the wash-out rate in the global myocardium were measured. Left ventricular regional MIBG kinetics were analyzed in the six midventricular segments of the 17 segment model. Compared with lsa MIBG, the wash-out rate of hsa MIBG was significantly slower, in association with a higher cardiac uptake. Regional analysis showed a maximal uptake in the anterolateral segment, without significant differences between segments. We noted a significantly higher global wash-out rate in the streptozotocin group compared to controls (p < 0.05). Regional analysis confirmed the increased wash-out rate, reaching statistical significance in the inferior and the inferoseptal walls. High-quality (123)I-MIBG images and accurate measurements can be obtained using hsa (123)I-MIBG with image acquisitions performed at relatively early time points. Small animal MIBG SPECT imaging allows for regional analysis of the myocardium. In the streptozotocin group, wash-out of MIBG is globally increased, compatible with a higher sympathetic tonus or decreased reuptake of MIBG. The highest increase is located in the inferior, inferoseptal and anteroseptal walls. These findings further suggest the occurrence of diabetic cardiomyopthy after streptozotocin injection.