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4D PC MRI of the aorta has become a routinely available examination, and a multitude of single parameters have been suggested for the quantitative assessment of relevant flow features for clinical studies and diagnosis. However, clinically applicable assessment of complex flow patterns is still challenging. We present a concept for applying radiomics for the quantitative characterization of flow patterns in the aorta. To this end, we derive cross-sectional scalar parameter maps related to parameters suggested in literature such as throughflow, flow direction, vorticity, and normalized helicity. Derived radiomics features are selected with regard to their inter-scanner and inter-observer reproducibility, as well as their performance in the differentiation of sex-, age- and disease-related flow properties. The reproducible features were tested on user-selected examples with respect to their suitability for characterizing flow profile types. In future work, such signatures could be applied for quantitative flow assessment in clinical studies or disease phenotyping.

BACKGROUND: Implementation of four-dimensional flow magnetic resonance (4D Flow MR) in clinical routine requires awareness of confounders. PURPOSE: To investigate inter-vendor comparability of 4D Flow MR derived aortic hemodynamic parameters, assess scan-rescan repeatability, and intra- and interobserver reproducibility. STUDY TYPE: Prospective multicenter study. POPULATION: Fifteen healthy volunteers (age 24.5 ± 5.3 years, 8 females). FIELD STRENGTH/SEQUENCE: 3 T, vendor-provided and clinically used 4D Flow MR sequences of each site. ASSESSMENT: Forward flow volume, peak velocity, average, and maximum wall shear stress (WSS) were assessed via nine planes (P1-P9) throughout the thoracic aorta by a single observer (AD, 2 years of experience). Inter-vendor comparability as well as scan-rescan, intra- and interobserver reproducibility were examined. STATISTICAL TESTS: Equivalence was tested setting the 95% confidence interval of intraobserver and scan-rescan difference as the limit of clinical acceptable disagreement. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used for scan-rescan reproducibility and intra- and interobserver agreement. A P-value 0.9: excellent, 0.75-0.9: good). RESULTS: Ten volunteers finished the complete study successfully. 4D flow derived hemodynamic parameters between scanners of three different vendors are not equivalent exceeding the equivalence range. P3-P9 differed significantly between all three scanners for forward flow (59.1 ± 13.1 mL vs. 68.1 ± 12.0 mL vs. 55.4 ± 13.1 mL), maximum WSS (1842.0 ± 190.5 mPa vs. 1969.5 ± 398.7 mPa vs. 1500.6 ± 247.2 mPa), average WSS (1400.0 ± 149.3 mPa vs. 1322.6 ± 211.8 mPa vs. 1142.0 ± 198.5 mPa), and peak velocity between scanners I vs. III (114.7 ± 12.6 cm/s vs. 101.3 ± 15.6 cm/s). Overall, the plane location at the sinotubular junction (P1) presented most inter-vendor stability (forward: 78.5 ± 15.1 mL vs. 80.3 ± 15.4 mL vs. 79.5 ± 19.9 mL [P = 0.368]; peak: 126.4 ± 16.7 cm/s vs. 119.7 ± 13.6 cm/s vs. 111.2 ± 22.6 cm/s [P = 0.097]). Scan-rescan reproducibility and intra- and interobserver variability were good to excellent (ICC ≥ 0.8) with best agreement for forward flow (ICC ≥ 0.98). DATA CONCLUSION: The clinical protocol used at three different sites led to differences in hemodynamic parameters assessed by 4D flow. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Background: The complex pathophysiological processes that result in fibrotic tissue remodeling in systemic sclerosis involve interplay between multiple cell types (1). Experimental models of fibrosis are essential to provide a conceptual understanding of the pathogenesis of these diseases and to test antifibrotic drugs. Current models of fibrosis have important limitations: the in vivo models rely on species that are phylogenetically distant, whereas the in vitro models are oversimplified cultures of a single cell type in an artificial two-dimensional environment of excessive stiffness, which imposes an unphysiological cell polarization (2). Objectives: Here we evaluated the potential use of vascularized, three-dimensional in vitro human skin equivalents as a novel model of skin fibrosis and a platform for the evaluation of antifibrotic drugs. Methods: Skin equivalents were generated by seeding human endothelial cells, fibroblasts and keratinocytes on a decellularized porcine extracellular matrix with perfusable vascular structure. The skin models were cultured for one month in a system that ensured perfusion of the vascular network at physiological pressure. Fibrotic transformation induced by TGFv and response to nintedanib as an established antifibrotic drug was evaluated by capillary Western immunoassays, qPCR, histology and immunostaining. Results: The vascularized human skin equivalents formed the major skin structures relevant for the pathogenesis of fibrosis: a polarized, fully matured epidermis, a stratified dermis and a perfused vessel system with small capillaries. Exposure to TGFv led to the fibrotic transformation of the skin equivalents, with activated TGFv downstream pathways, increased fibroblast-to-myofibroblast transition and excessive deposition of extracellular matrix. Treatment of models exposed to TGFv with nintedanib (a drug with proven antifibrotic effects) ameliorated the fibrotic transformation of skin equivalents with reduced TGFv signaling, fibroblast-to-myofibroblast transition and decreased extracellular matrix deposition. Conclusion: Here we describe a novel in vitro model of skin fibrosis. Our data show that vascularized skin equivalents can reproduce all skin layers affected by fibrosis, that, upon exposure to TGFv, these models recapitulate key features of fibrotic skin and that these skin models can be used as a platform for evaluation of antifibrotic drugs in a setting with high relevance for human disease.

Objectives: Meniscal injuries often result in the deterioration of meniscal tissue and consequently of articular cartilage. The healing potential of the avascular region of the meniscus is limited and no optimal treatment strategy is available. Replacing torn menisci by a tissue-engineered 3D meniscus[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)