Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography

Transplantation of primary human hepatocytes is a promising approach in certain liver diseases. For the visualization of the hepatocytes during and following cell application and the ability of a timely response to potential complications, a non-invasive modality for imaging the transplanted cells has to be established. The aim of this study was to label primary human hepatocytes with micron-sized iron oxide particles (MPIOs), enabling the detection of cells by clinical magnetic resonance imaging (MRI). Primary human hepatocytes isolated from 13 different donors were used for the labelling experiments. Following the dose-finding studies, hepatocytes were incubated with 30 particles/cell for 4 hrs in an adhesion culture. Particle incorporation was investigated via light, fluorescence and electron microscopy, and labelled cells were fixed and analysed in an agarose suspension by a 3.0 Tesla MR scanner. The hepatocytes were enzymatically resuspended and analysed during a 5-day reculture period for viability, total protein, enzyme leakage (aspartate aminotransferase [AST], lactate dehydrogenase [LDH]) and metabolic activity (urea, albumin). A mean uptake of 18 particles/cell could be observed, and the primary human hepatocytes were clearly detectable by MR instrumentation. The particle load was not affected by resuspension and showed no alternations during the culture period. Compared to control groups, labelling and resuspension had no adverse effects on the viability, enzyme leakage and metabolic activity of the human hepatocytes. The feasibility of preparing MPIO-labelled primary human hepatocytes detectable by clinical MR equipment was shown in vitro. MPIO-labelled cells could serve for basic research and quality control in the clinical setting of human hepatocyte transplantation

The ability of computed tomography angiography to predict 5-year mortality in the SYNTAX III REVOLUTION trial

Background The feasibility of using coronary computed tomography angiography (CCTA) for long-term prediction of vital prognosis post-revascularization remains unknown. Objectives To compare the prognostic value of the SYNTAX score II 2020 (SS-2020) derived from invasive coronary angiography (ICA) or CCTA in patients with three-vessel disease and/or left main coronary artery disease undergoing percutaneous or surgical revascularization. Methods In the SYNTAX III REVOLUTION trial, the probability of death at five years was retrospectively assessed by calculating the SS-2020 using ICA and CCTA. High- and low-risk patients for mortality were categorized according to the median percentages of predicted mortality based on both modalities. The discriminative abilities of the SS-2020 were assessed using Harrell's C statistic. Results The vital status at five years of the 215 patients revascularized percutaneously (64 patients, 29.8%) or surgically (151 patients, 70.2%) was established through national registries. In patients undergoing revascularization, the SS-2020 was possibly helpful in discriminating vital prognosis at 5 years, with similar results seen with ICA and CCTA (C-index with ICA ​= ​0.75, intercept ​= ​−0.19, slope ​= ​0.92 and C-index with CCTA ​= ​0.75, intercept ​= ​−0.22, slope ​= ​0.99). In high- and low-risk patients, Kaplan-Meier estimates showed significant, and almost identical relative differences in observed mortality, irrespective of imaging modality (ICA: 93.8% vs 78.7%, log-lank P ​< ​0.001; CCTA: 93.7% vs 78.5%, log-lank P ​< ​0.001). Conclusions The predictive ability of the SS-2020 for five-year all-cause mortality derived from ICA and CCTA was comparable, and could helpfully discriminate vital prognosis in high- and low-risk patients