[Cardiac magnetic resonance imaging and the myocardium : Differentiation between vital and nonvital tissue]. / Kardiale Magnetresonanztomographie und Myokard : Differenzierung zwischen vitalem und avitalem Gewebe.

Cardiac magnetic resonance (cMR), a well-established imaging tool, is indispensable in the diagnosis and management of cardiovascular disease. Given its high spatial resolution and ability to characterize tissue, cMR represents the gold standard in determining myocardial viability. Gadolinium-based contrast-enhanced cMR can accurately identify myocardial scars and fibrosis in the ventricle and the atria, and differentiate it from normal myocardium. Gadolinium is an extracellular molecule which has been shown to be safe and beneficial in magnetic resonance imaging (MRI). Due to the larger extracellular space in myocardial scars, there is more uptake (wash-in) and slower elimination (wash-out) of gadolinium in those areas as opposed to normal myocardium. When imaged several minutes after intravenous administration of gadolinium, nonviable myocardial areas appear brighter than viable myocardium. The use of late-gadolinium enhancement (LGE) technique in assessing myocardial viability has been shown to highly correlate with histological examinations. Furthermore, this technique is highly reproducible and has very high intra- and interobserver agreement. Extent of LGE after myocardial infarction predicts the occurrence of adverse cardiovascular events. Moreover, LGE is highly accurate in predicting functional recovery of dysfunctional myocardial segments in patients undergoing revascularization and consequently has a key role in guiding revascularization procedures. In addition, use of LGE in the identification of myocardial fibrosis or myocardial damage in inflammatory myocardial disease helps to differentiate the type of cardiomyopathy and to predict sudden cardiac death among patients with heart failure. The role of LGE-MRI in the field of electrophysiology through recognition of different substrate for arrythmias and guiding the ablation therapy is steadily increasing and has fundamentally changed our understanding of atrial myopathy.

Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced Control of Leishmania major, but Not for Spontaneous Cure of Subcutaneous Primary or Secondary L. major Infection.

We previously showed that in mice infected with Leishmania major type I interferons (IFNs) initiate the innate immune response to the parasite at day 1 and 2 of infection. Here, we investigated which type I IFN subtypes are expressed during the first 8 weeks of L. major infection and whether type I IFNs are essential for a protective immune response and clinical cure of the disease. In self-healing C57BL/6 mice infected with a high dose of L. major, IFN-α4, IFN-α5, IFN-α11, IFN-α13, and IFN-ß mRNA were most prominently regulated during the course of infection. In C57BL/6 mice deficient for IFN-ß or the IFN-α/ß-receptor chain 1 (IFNAR1), development of skin lesions and parasite loads in skin, draining lymph node, and spleen was indistinguishable from wild-type (WT) mice. In line with the clinical findings, C57BL/6 IFN-ß-/-, IFNAR1-/-, and WT mice exhibited similar mRNA expression levels of IFN-γ, interleukin (IL)-4, IL-12, IL-13, inducible nitric oxide synthase, and arginase 1 during the acute and late phase of the infection. Also, myeloid dendritic cells from WT and IFNAR1-/- mice produced comparable amounts of IL-12p40/p70 protein upon exposure to L. major in vitro. In non-healing BALB/c WT mice, the mRNAs of IFN-α subtypes (α2, α4, α5, α6, and α9) were rapidly induced after high-dose L. major infection. However, genetic deletion of IFNAR1 or IFN-ß did not alter the progressive course of infection seen in WT BALB/c mice. Finally, we tested whether type I IFNs and/or IL-12 are required for the prophylactic effect of CpG-oligodesoxynucleotides (ODN) in BALB/c mice. Local and systemic administration of CpG-ODN 1668 protected WT and IFN-ß-/- mice equally well from progressive leishmaniasis. By contrast, the protective effect of CpG-ODN 1668 was lost in BALB/c IFNAR1-/- (despite a sustained suppression of IL-4) and in BALB/c IL-12p35-/- mice. From these data, we conclude that IFN-ß and IFNAR1 signaling are dispensable for a curative immune response to L. major in C57BL/6 mice and irrelevant for disease development in BALB/c mice, whereas IL-12 and IFN-α subtypes are essential for the disease prevention by CpG-ODNs in this mouse strain.