T1 Mapping MOLLI 5(3)3 Acquisition Scheme Yields High Accuracy in 1.5 T Cardiac Magnetic Resonance.

Objectives: To systematically compare two modified Look-Locker inversion recovery (MOLLI) T1 mapping sequences and their impact on (1) myocardial T1 values native, (2) post-contrast and (3) extracellular volume (ECV). Methods: 200 patients were prospectively included for 1.5 T CMR for work-up of ischemic or non-ischemic cardiomyopathies. To determine native and post-contrast T1 for ECV calculation, two different T1 mapping MOLLI acquisition schemes, 5(3)3 (designed for native scans with long T1) and 4(1)3(1)2 (designed for post-contrast scans with short T1), were acquired in identical mid-ventricular short-axis slices. Both schemes were acquired in native and post-contrast scans. Results: Datasets from 163 patients were evaluated (age 55 ± 17 years; 38% female). Myocardial T1 native for 5(3)3 was 1017 ± 42 ms vs. 956 ± 40 ms for 4(1)3(1)2, with mean intraindividual difference −61 ms (p < 0.0001). Post-contrast myocardial T1 in patients was similar for both acquisition schemes, with 494 ± 48 ms for 5(3)3 and 490 ± 45 ms for 4(1)3(1)2 and mean intraindividual difference −4 ms. Myocardial ECV for 5(3)3 was 27.6 ± 4% vs. 27 ± 4% for 4(1)3(1)2, with mean difference −0.6 percentage points (p < 0.0001). Conclusions: The T1 MOLLI 5(3)3 acquisition scheme provides a reliable estimation of myocardial T1 for the clinically relevant range of long and short T1 values native and post-contrast. In contrast, the T1 MOLLI 4(1)3(1)2 acquisition scheme may only be used for post-contrast scans according to its designed purpose.

Laboratory and Analytical Device Standard (LADS): A Communication Standard Based on OPC UA for Networked Laboratories.

In a similar vein to Industry 4.0 in manufacturing industries, digitisation is making inroads in the laboratory industry in the form of Laboratory 4.0, or networked laboratories. Companies can gain decisive competitive edges by automating their work processes and systems and networking them with each other and primary IT systems. A uniform communication standard such as OPC UA, a well-established global standard in the aforementioned manufacturing industries, is essential to a modular, scalable network of heterogeneous laboratory structures. Can the laboratory industry benefit from this standard and the years of development experience? In SPECTARIS, the German Industry Association for Optics, Photonics, Analytical and Medical Technologies, over 30 global market leaders, hidden champions and drivers of innovation in the laboratory industry put their heads together in the "Networked Laboratory Devices" working group and created the "Laboratory and Analytical Device Standard", or LADS for short. Unlike numerous other attempts to establish communication standards for laboratories, LADS is based on the advanced OPC UA standard and takes an agnostic approach to cover the variety of devices, systems and requirements in laboratories. In this context, "agnostic" refers to the generic design and display of potentially as-yet-unknown aspects of the flow of information or communication structures. For the first time, LADS allows for modular, scalable networking of heterogeneous laboratory structures, efficient data transfers and - currently unused - user, process and device-based data analysis (keywords: big data, predictive analytics, data science) - even taking normative requirements into consideration. This agnostic modelling makes LADS a future-proof communication solution for the laboratory industry, the likes of which the world has never seen.

4D perfusion CT of prostate cancer for image-guided radiotherapy planning: A proof of concept study.

PURPOSE: Advanced forms of prostate cancer (PCa) radiotherapy with either external beam therapy or brachytherapy delivery techniques aim for a focal boost and thus require accurate lesion localization and lesion segmentation for subsequent treatment planning. This study prospectively evaluated dynamic contrast-enhanced computed tomography (DCE-CT) for the detection of prostate cancer lesions in the peripheral zone (PZ) using qualitative and quantitative image analysis compared to multiparametric magnet resonance imaging (mpMRI) of the prostate. METHODS: With local ethics committee approval, 14 patients (mean age, 67 years; range, 57-78 years; PSA, mean 8.1 ng/ml; range, 3.5-26.0) underwent DCE-CT, as well as mpMRI of the prostate, including standard T2, diffusion-weighted imaging (DWI), and DCE-MRI sequences followed by transrectal in-bore MRI-guided prostate biopsy. Maximum intensity projections (MIP) and DCE-CT perfusion parameters (CTP) were compared between healthy and malignant tissue. Two radiologists independently rated image quality and the tumor lesion delineation quality of PCa using a five-point ordinal scale. MIP and CTP were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. RESULTS: The PCa detection rate ranged between 57 to 79% for the two readers for DCE-CT and was 92% for DCE-MRI. DCE-CT perfusion parameters in PCa tissue in the PZ were significantly different compared to regular prostate tissue and benign lesions. Image quality and lesion visibility were comparable between DCE-CT and DCE-MRI (VGC: AUC 0.612 and 0.651, p>0.05). CONCLUSION: Our preliminary results suggest that it is feasible to use DCE-CT for identification and visualization, and subsequent segmentation for focal radiotherapy approaches to PCa.

Downregulation of PMCA2 increases the vulnerability of midbrain neurons to mitochondrial complex I inhibition.

Parkinson's disease is an age-associated disorder characterized by selective degeneration of dopaminergic neurons. The molecular mechanisms underlying the selective vulnerability of this subset of neurons are, however, not fully understood. Employing SH-SY5Y neuroblastoma cells and primary mesencephalic neurons, we here demonstrate a significant increase in cytosolic calcium after inhibition of mitochondrial complex I by means of MPP(+), which is a well-established environmental toxin-based in vitro model of Parkinson's disease. This increase in calcium is correlated with a downregulation of the neuron-specific plasma membrane Ca(2+)-ATPase isoform 2 (PMCA2). Interestingly, two other important mediators of calcium efflux, sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), and Na(+)-Ca(2+)-exchanger (NCX), remained unaltered, indicating a specific role of PMCA2 in maintaining calcium homeostasis in neurons. The observed PMCA2 downregulation was accompanied by reduced levels of phosphorylated CREB protein, an intracellular signaling molecule and transcriptional regulator. In order to investigate the potential influence of PMCA2 on neuronal vulnerability, experimental downregulation of PMCA2 by means of siRNA was performed. The results demonstrate a significant impairment of cell survival under conditions of PMCA2 suppression. Hence, in our cell models increased cytosolic calcium levels as a consequence of insufficient calcium efflux lead to an increased vulnerability of neuronal cells. Moreover, overexpression of PMCA2 rendered the neurons significantly resistant to complex I inhibition. Our findings point toward a dysregulation of calcium homeostasis in Parkinson's disease and suggest a potential molecular mechanism of neurodegeneration via PMCA2.

Differential regulation of apoptosis-associated genes by estrogen receptor alpha in human neuroblastoma cells.

PURPOSE: The neuroendocrinology of female sex hormones is of great interest for a variety of neuropsychiatric disorders. In fact, estrogens and estrogen receptors (ERs) exert neuromodulatory and neuroprotective functions. Here we investigated potential targets of the ER subtype alpha that may mediate neuroprotection and focused on direct modulators and downstream executors of apoptosis. METHODS: We employed subclones of human neuroblastoma cells (SK-N-MC) stably transfected with one of the ER subtypes, ERalpha or ERbeta. Differences between the cell lines regarding the mRNA expression levels were examined by qPCR, changes on protein levels were examined by Western Blot and immunocytochemistry. Differences concerning apoptosis induction were analysed by cell survival assays which included primary rat neurons. RESULTS: In this report we show a potent protection against apoptosis-stimuli in ERalpha expressing cells compared to controls lacking ERalpha. In fact, almost a complete silencing of Caspase 3 expression in SK-ERalpha cells compared to SK-01 control transfected cells was observed. In addition, prosurvival bcl2, bag1 and bag3 expression was highly up-regulated in the presence of ERalpha. CONCLUSION: Taken together, we identified Caspase 3, BAG1 and BAG3 as key targets of ERalpha in neuronal cells that may play a role in ERalpha-mediated neuroprotection.