Quantitative Magnetic Resonance Imaging of the Liver and Heart In Iron Overload

Systemic iron overload (IO) is considered a principal determinant in the clinical outcome of different forms of IO and in allogeneic hematopoietic stem cell transplantation (alloSCT). However, indirect markers for iron do not provide exact quantification of iron burden, and the evidence of iron-induced adverse effects in hematological diseases has not been established. Hepatic iron concentration (HIC) has been found to represent systemic IO, which can be quantified safely with magnetic resonance imaging (MRI), based on enhanced transverse relaxation. The iron measurement methods by MRI are evolving. The aims of this study were to implement and optimise the methodology of non-invasive iron measurement with MRI to assess the degree and the role of IO in the patients. An MRI-based HIC method (M-HIC) and a transverse relaxation rate (R2*) from M-HIC images were validated. Thereafter, a transverse relaxation rate (R2) from spin-echo imaging was calibrated for IO assessment. Two analysis methods, visual grading and rSI, for a rapid IO grading from in-phase and out-of-phase images were introduced. Additionally, clinical iron indicators were evaluated. The degree of hepatic and cardiac iron in our study patients and IO as a prognostic factor in patients undergoing alloSCT were explored. In vivo and in vitro validations indicated that M-HIC and R2* are both accurate in the quantification of liver iron. R2 was a reliable method for HIC quantification and covered a wider HIC range than M-HIC and R2*. The grading of IO was able to be performed rapidly with the visual grading and rSI methods. Transfusion load was more accurate than plasma ferritin in predicting transfusional IO. In patients with hematological disorders, the prevalence of hepatic IO was frequent, opposite to cardiac IO. Patients with myelodysplastic syndrome were found to be the most susceptible to IO. Pre-transplant IO predicted severe infections during the early post-transplant period, in contrast to the reduced risk of graft-versus-host disease. Iron-induced, poor transplantation results are most likely to be mediated by severe infections.

Effects of Weight Loss on Adipose Tissue, Liver and Heart Metabolism in Humans

Obesity has become the leading cause of many chronic diseases, such as type 2 diabetes and cardiovascular diseases. The prevalence of obesity is high in developed countries and it is also a major cause of the use of health services. Ectopic fat accumulation in organs may lead to metabolic disturbances, such as insulin resistance.Weight loss with very-low-energy diet is known to be safe and efficient. Weight loss improves whole body insulin sensitivity, but its effects on tissue and organ level in vivo are not well known. The aims of the studies were to investigate possible changes of weight loss in glucose and fatty acid uptake and perfusion and fat distribution at tissue and organ level using positron emission tomography and magnetic resonance imaging and spectroscopy in 34 healthy obese subjects. The results showed that whole-body insulin sensitivity increased after weight loss with very-low-energy diet and this is associated with improved skeletal muscle insulin-stimulated glucose uptake, but not with adipose tissue, liver or heart glucose uptake. Liver insulin resistance decreased after weight loss. Liver and heart free fatty acid uptakes decreased concomitantly with liver and heart triglyceride content. Adipose tissue and myocardial perfusion decreased. In conclusion, enhanced skeletal muscle glucose uptake leads to increase in whole-body insulin sensitivity when glucose uptake is preserved in other organs studied. These findings suggest that lipid accumulation found in the liver and the heart in obese subjects without co-morbidies is in part reversible by reduced free fatty acid uptake after weight loss. Reduced lipid accumulation in organs may improve metabolic disturbances, e.g. decrease liver insulin resistance. Keywords: Obesity, weight loss, very-low-energy diet, adipose tissue metabolism, liver metabolism, heart metabolism, positron emission tomography