Non-invasive imaging of ferucarbotran labeled INS-1E cells and rodent islets in vitro and in transplanted diabetic rats.

Transplantation of pancreatic islets is a promising strategy for restoring insulin secretion in diabetes mellitus. To monitor transplanted islets, a method to evaluate the distribution in a non-invasive manner in vivo is needed. INS-1E, a stable differentiated insulin secreting cell line, and rodent islets were used to monitor cell transplantation by MRI. For labeling INS-1E cells in vitro, increasing concentrations of Resovist in culture medium were tested. For MR imaging in a clinical 3T scanner, we placed a layer of labeled INS-1E cells between two layers of 4% gelatin. Viability assay was performed. Cell function was evaluated by static incubation assay to assess insulin secretion. For in vivo imaging, iron labeled rodent islets were transplanted into the liver of streptozotocin induced diabetic rats and visualized by MRI. Blood sugar values were controlled and liver tissue was removed for histological analysis. SPIO labeled INS-1E cells did not show altered viability or reduced glucose stimulated insulin secretion in vitro. Double staining of labeled and unlabeled INS-1E cells showed no difference in the staining pattern. Labeling of rodent islets with SPIOs does not reduce their secretory activity or alter their viability. We visualized SPIO-labeled INS-1E cells and rat islets in vitro using a clinical 3T scanner. Diabetic rats transplanted with SPIO-labeled islets became normoglycemic. MR imaging successfully verified the distribution of labeled transplanted cells in vivo. Labeling INS-1E cells and rat islets with SPIOs does not alter their viability, while enabling MR imaging of labeled cells in vitro and within the living organism.

Early detection of myocardial microcirculatory disturbances after primary PTCA in patients with acute myocardial infarction: coronary blood flow velocity versus sestamibi perfusion imaging.

BACKGROUND: The extent of myocardial salvage after primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) is variable and can not be predicted on the basis of vessel patency. The aim of this study was to evaluate the tissue salvage and the microvascular integrity after successful intervention in AMI by coronary blood flow velocity and sestamibi perfusion imaging. METHODS: Twenty-two patients (17 m, 5f; mean age 57 +/- 14 yrs.) undergoing primary PTCA and stent implantation for AMI were studied. 99mTc Sestamibi was injected intravenously before intervention and single photon emission computed tomography (SPECT) was performed immediately after successful reperfusion to determine the area at risk before PTCA due to the minimal 99mTc Sestamibi redistribution. Sestamibi SPECT was repeated 3 days and 6 months after AMI. Area at risk (%) was determined automatically by myocardial perfusion tomography (PERFIT) with the use of a multistage, 3D iterative inter-subject registration of patient images to normal templates (2SD) and myocardial salvage was calculated. Coronary flow velocity was measured using a Doppler-tipped guidewire in the infarct-related artery after successful completion of primary PTCA and in an angiographically normal reference vessel. Absolute coronary flow reserve (CFR) and relative CFR (rCFR) were calculated using hyperemic to basal average peak velocity. RESULTS: Despite successful reperfusion of the target vessel (TIMI grade III flow) CFR and rCFR remained impaired (1.8 +/- 0.9 and 0.77 +/- 0.21). Area at risk decreased significantly from 21 +/- 9% to 9 +/- 10% (p < 0.05) corresponding to 11 +/- 8% myocardial salvage. Acute CFR and rCFR showed no correlation with the area at risk before and after primary PTCA. The increase of CFR within 6 months correlated with the myocardial salvage (p < 0.05). CONCLUSIONS: Despite successful primary PTCA in AMI, CFR and rCFR often remain impaired because of a significant loss of microvascular integrity. The long-term success of primary PTCA can be assessed by myocardial salvage and the change of CFR which might be a useful parameter for additional reperfusion strategies such as glycoprotein IIb/IIIA receptor inhibition.