Virtual Elastic Sphere Processing Enables Reproducible Quantification of Vessel Stenosis at CT and MR Angiography

Gremse, Felix; Grouls, Christoph; Palmowski, Moritz; Lammers, Twan; Vries, Anke de; Grüll, Holger; Das, Marco; Mühlenbruch, Georg; Akhtar, Shamima; Schober, Andreas; Kießling, Fabian

doi:10.1148/radiol.11110069

Cited by 34 publications

(33 citation statements)

References 25 publications

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“…When combined with high-fat diet (HFD) feeding, this process resulted in advanced stenotic plaques within 6 weeks, as detected by micro-computed tomography (42) and immunostaining (Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI61716DS1). We found that 33 miRs, including miR-155 and miR-147, were increased, and 83 miRs were decreased, in carotid arteries with plaques versus those without ( Figure 1A and Supplemental Tables 1 and 2).…”

Section: Mir Expression Profile In Atherosclerosis and Inflammatory Mmentioning

confidence: 99%

MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages

Nazari-Jahantigh¹,

Wei²,

Noels³

et al. 2012

J. Clin. Invest.

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Macrophages in atherosclerotic plaques drive inflammatory responses, degrade lipoproteins, and phagocytose dead cells. MicroRNAs (miRs) control the differentiation and activity of macrophages by regulating the signaling of key transcription factors. However, the functional role of macrophage-related miRs in the immune response during atherogenesis is unknown. Here, we report that miR-155 is specifically expressed in atherosclerotic plaques and proinflammatory macrophages, where it was induced by treatment with mildly oxidized LDL (moxLDL) and IFN-γ. Leukocyte-specific Mir155 deficiency reduced plaque size and number of lesional macrophages after partial carotid ligation in atherosclerotic (Apoe -/-) mice. In macrophages stimulated with moxLDL/IFN-γ in vitro, and in lesional macrophages, loss of Mir155 reduced the expression of the chemokine CCL2, which promotes the recruitment of monocytes to atherosclerotic plaques. Additionally, we found that miR-155 directly repressed expression of BCL6, a transcription factor that attenuates proinflammatory NF-κB signaling. Silencing of Bcl6 in mice harboring Mir155 -/-macrophages enhanced plaque formation and CCL2 expression. Taken together, these data demonstrated that miR-155 plays a key role in atherogenic programming of macrophages to sustain and enhance vascular inflammation.

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Section: Mir Expression Profile In Atherosclerosis and Inflammatory Mmentioning

confidence: 99%

MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages

Nazari-Jahantigh¹,

Wei²,

Noels³

et al. 2012

J. Clin. Invest.

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456

424

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“…Discrimination of contrast agent and soft tissue was achieved by applying a threshold defined as the mean of contrast agent and soft tissue intensity. The lumen area of the vein was measured with the virtual elastic sphere tool (25) (Fig. 2A).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model

et al. 2016

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f Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cords ex vivo with Bartonella henselae or Acinetobacter baumannii under dynamic flow conditions mimicking the in vivo infection situation of human endothelium. For this purpose, methods for quantifying endotheliumadherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i) A. baumannii binds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models using ex vivo human tissue samples ("organ microbiology") might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially.T he analysis of adhesion to host cells is crucial for the elucidation of bacterial infection mechanisms. Animal infection models or cellular microbiology-based approaches are well established, and many important findings have thereby been gathered. By way of example, the protein injection machineries and the autotransporter adhesins (TAA) of Bartonella henselae and Acinetobacter baumannii have been elucidated in that manner (1-3). Although these methods are well established and widely accepted, they still are hampered by several limitations: animal models might reflect the course of human infections only partially (4) or might not even be available for many pathogens (e.g., B. henselae). Cellular infection models allow very detailed analyses of the interaction of bacteria with host cells under standardized conditions. However, they are usually done statically using cell monolayers, and this mimics the complexity of in vivo infection situation only to some extent. Methods to overcome the species barrier in infection models and to analyze host-pathogen interactions close to the dynamic human situation are urgently needed. Ex vivo infection models, using human organ grafts, might represent an attractive alternative or addition to animal or cellular microbiology experiments.B. henselae causes cat scratch disease and endocarditis, whereas immunosuppressed individuals can suffer from vasculoproliferative disorders such as bacillary angiomatosis. B. henselae is believed to be an endotheliotropic pathogen. Bartonella adhesin A (BadA) has been identified as the key factor involved in the adherence to endothelial cells (ECs) and to extracellular matrix (EC...

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“…Image analysis, segmentation of micro-CT data and quantification of carotid artery lumen area were performed with the Imalytics Preclinical Software (Gremse-IT, Aachen, Germany). Discrimination of contrast-enhanced blood and soft tissue was achieved by applying a threshold defined as the mean of blood and muscle intensity [12]. The lumen areas of the LCCA and RCCA were measured with the virtual elastic sphere tool [12].…”

Section: Methodsmentioning

confidence: 99%

Micro-CT Technique Is Well Suited for Documentation of Remodeling Processes in Murine Carotid Arteries

Schürmann

Gremse

et al. 2015

PLoS ONE

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BackgroundThe pathomechanisms of atherosclerosis and vascular remodelling are under intense research. Only a few in vivo tools to study these processes longitudinally in animal experiments are available. Here, we evaluated the potential of micro-CT technology.MethodsLumen areas of the common carotid arteries (CCA) in the ApoE-/- partial carotid artery ligation mouse model were compared between in vivo and ex vivo micro-CT technique and serial histology in a total of 28 animals. AuroVist-15 nm nanoparticles were used as in vivo blood pool contrast agent in a Skyscan 1176 micro-CT at resolution of 18 μmeter voxel size and a mean x-ray dose of 0.5 Gy. For ex vivo imaging, animals were perfused with MicroFil and imaged at 9 μmeter voxel size. Lumen area was evaluated at postoperative days 7, 14, and 28 first by micro-CT followed by histology.ResultsIn vivo micro-CT and histology revealed lumen loss starting at day 14. The lumen profile highly correlated (r = 0.79, P<0.0001) between this two methods but absolute lumen values obtained by histology were lower than those obtained by micro-CT. Comparison of in vivo and ex vivo micro-CT imaging revealed excellent correlation (r = 0.83, P<0.01). Post mortem micro-CT yielded a higher resolution than in vivo micro-CT but there was no statistical difference of lumen measurements in the partial carotid artery ligation model.ConclusionThese data demonstrate that in vivo micro-CT is a feasible and accurate technique with low animal stress to image remodeling processes in the murine carotid artery.

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Virtual Elastic Sphere Processing Enables Reproducible Quantification of Vessel Stenosis at CT and MR Angiography

Abstract: The virtual elastic sphere tool is applicable to CT, dual-energy CT, and MR angiography, and it improves reproducibility and efficiency over that achieved with manual stenosis measurements.

Cited by 34 publications

References 25 publications

MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages

MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model

Micro-CT Technique Is Well Suited for Documentation of Remodeling Processes in Murine Carotid Arteries

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