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101.

Purpose

Fat accumulation and iron overload are important cofactors in chronic liver disease. Clinical quantifications of fat fraction and iron are currently assessed using MRI protocols. The purpose is to improve these measurements to simultaneously provide iron and fat maps from a single acquisition.

Methods

Ten healthy volunteers and ten patients with steatosis underwent MRI for fat fraction (FF: IDEAL-IQ®), iron overload concentration (IOC: Gandon, Starmap®) and viscoelastic characterization (MR-Touch®). IDEAL-IQ® data, the clinical FF reference, were compared to the advanced Gandon protocol, post-treated with a 3pt Dixon method. The originality was to use IDEAL-IQ® fat sequence to quantify iron volumetrically using the Wood equation. To validate the iron data, the reference Gandon protocol was applied and improved to provide map of IOC. Then, IOC data were also compared to another clinical sequence (Starmap®) which was also improved (scale, number of ROI). The estimated error associated with each method was evaluated with the coefficient of variation.

Results

IDEAL-IQ® and Gandon protocols were modified to provide simultaneously FF and IOC maps (2D, volume). Healthy FF were in the same range with all protocols (≈3%). For patients with steatosis, Gandon protocols underestimated the FF value (≈7%) compared to IDEAL-IQ®. Healthy and fibrosis patients were correctly diagnosed (no hemochromatosis) with all the protocols and viscoelastic properties were in the same range.

Conclusion

Manufacturer's tools were improved to simultaneously quantify liver markers saving time for the patient and the clinical setting. These parameters are of great value for clinical diagnostics and novel therapeutics to treat liver diseases.  相似文献   
102.

Background and aims

Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated.

Methods

FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro.

Results

FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism.

Conclusion

Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.  相似文献   
103.
Despite substantial evidence for the central role of hemodynamic shear stress in the functional integrity of vascular endothelial cells, hemodynamic and molecular regulation of the endocardial endothelium lining the heart chambers remains understudied. We propose that regional differences in intracardiac hemodynamics influence differential endocardial gene expression leading to phenotypic heterogeneity of this cell layer. Measurement of intracardiac hemodynamics was performed using 4-dimensional flow MRI in healthy humans (n=8) and pigs (n=5). Local wall shear stress (WSS) and oscillatory shear indices (OSI) were calculated in three distinct regions of the LV – base, mid-ventricle (midV), and apex. In both the humans and pigs, WSS values were significantly lower in the apex and midV relative to the base. Additionally, both the apex and midV had greater oscillatory shear indices (OSI) than the base. To investigate regional phenotype, endocardial endothelial cells (EEC) were isolated from an additional 8 pigs and RNA sequencing was performed. A false discovery rate of 0.10 identified 1051 differentially expressed genes between the base and apex, and 321 between base and midV. Pathway analyses revealed apical upregulation of genes associated with translation initiation. Furthermore, tissue factor pathway inhibitor (TFPI; mean 50-fold) and prostacyclin synthase (PTGIS; 5-fold), genes prominently associated with antithrombotic protection, were consistently upregulated in LV apex. These spatio-temporal WSS values in defined regions of the left ventricle link local hemodynamics to regional heterogeneity in endocardial gene expression.  相似文献   
104.
目的:分析比较CT与MR对肝硬化背景下小肝癌检出情况,探究CT与MR在肝硬化背景下小肝癌的诊断价值。方法:选择2010年6月~2015年6月期间,我院收治确诊为肝硬化背景下小肝癌患者91例为研究对象,病理及临床相关方法确诊102个病灶,其中小肝癌69个和微小肝癌33个,患者均在不同时期或序列下行多排螺旋CT与MRI检查,分析比较两者对小肝癌和微小肝癌的检出率。结果:多排螺旋CT检查发现肝癌小病灶91个,其中66个小肝癌,25个微小肝癌;MRI检查发现95个病灶,小肝癌67个,微小肝癌28个;69个小肝癌病灶,检出率最高的为CT动脉期(92.75%)与LAVA动脉期(92.75%),检出率最低的为CT平扫(76.81%);33个微小肝癌病灶,检出率最高为LAVA动脉期(75.76%),检出率最低的为LAVA平衡期(36.36%);CT平扫、门静脉期、动脉期、平衡期、MRI-IN-PHASE、LAVA平衡期、LAVA平扫对小肝癌的检出率显著高于对微小肝癌的检出率(P0.05);CT对小肝癌的检出率显著高于微小肝癌的检出率(P0.05),MRI对小肝癌与微小肝癌的检出率无显著差异(P0.05);MRI与CT对小肝癌的检出率不存在差异(P0.05),但MRI对微小肝癌的检出率显著高于CT(P0.05)。结论:MRI-LAVA的动脉期序列对小肝癌病灶与微小肝癌病灶的检出率最高;CT与MRI在对小肝癌的检出率不存在差异,但MRI对微小肝癌的检出具有更明显的优势。  相似文献   
105.
Recent evidence suggests that loss of ovarian function following ovariectomy is a risk factor for Alzheimer's disease (AD); however, the biological basis of this risk remains poorly understood. We carried out an fMRI study into the interaction between loss of ovarian function (after Gonadotropin Hormone Releasing Hormone agonist (GnRHa) treatment) and scopolamine (a cholinergic antagonist used to model the memory decline associated with aging and AD). Behaviorally, cholinergic depletion produced a deficit in verbal recognition performance in both GnRHa-treated women and wait list controls, but only GnRHa-treated women made more false positive errors with cholinergic depletion. Similarly, cholinergic depletion produced a decrease in activation in the left inferior frontal gyrus (LIFG; Brodmann area 45) - a brain region implicated in retrieving word meaning - in both groups, and activation in this area was further reduced following GnRHa treatment. These findings suggest biological mechanisms through which ovarian hormone suppression may interact with the cholinergic system and the LIFG. Furthermore, this interaction may provide a useful model to help explain reports of increased risk for cognitive decline and AD in women following ovariectomy.  相似文献   
106.
The biological response after exposure to a high‐strength static magnetic field (SMF) has recently been widely discussed from the perspective of possible health benefits as well as potential adverse effects. To clarify this issue, CD34+ cells from human placental and umbilical cord blood were exposed under conditions of high‐strength SMF in vitro. The high‐strength SMF exposure system was comprised of a magnetic field generator with a helium‐free superconducting magnet with built‐in CO2 incubator. Freshly prepared CD34+ cells were exposed to a 5 tesla (T) SMF with the strongest magnetic field gradient (41.7 T/m) or a 10 T SMF without magnetic field gradient for 4 or 16 h. In the harvested cells after exposure to 10 T SMF for 16 h, a significant increase of hematopoietic progenitors in the total burst‐forming unit erythroid‐ and megakaryocytic progenitor cells‐derived colony formation was observed, thus producing 1.72‐ and 1.77‐fold higher than the control, respectively. Furthermore, early hematopoiesis‐related and cell cycle‐related genes were found to be significantly up‐regulated by exposure to SMF. These results suggest that the 10 T SMF exposure may change gene expressions and result in the specific enhancement of megakaryocytic/erythroid progenitor (MEP) differentiation from pluripotent hematopoietic stem cells and/or the proliferation of bipotent MEP. Bioelectromagnetics 30:280–285, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   
107.
Japanese monkeys walked spontaneously on their hind limbs, when their vision was impaired either by narrowing the visual field or by reducing the incoming light. These variables were manipulated via goggles with translucent pipes and neutral density filters. The bipedal locomotion was observed more frequently as the impairment of the incoming visual information increased. It is very likely that facultative bipeds walk on their hind limbs when they feel the need to “free” their forelimbs to grope their way.  相似文献   
108.
Unravelling the factors determining the allocation of carbon to various plant organs is one of the great challenges of modern plant biology. Studying allocation under close to natural conditions requires non-invasive methods, which are now becoming available for measuring plants on a par with those developed for humans. By combining magnetic resonance imaging (MRI) and positron emission tomography (PET), we investigated three contrasting root/shoot systems growing in sand or soil, with respect to their structures, transport routes and the translocation dynamics of recently fixed photoassimilates labelled with the short-lived radioactive carbon isotope 11C. Storage organs of sugar beet ( Beta vulgaris ) and radish plants ( Raphanus sativus ) were assessed using MRI, providing images of the internal structures of the organs with high spatial resolution, and while species-specific transport sectoralities, properties of assimilate allocation and unloading characteristics were measured using PET. Growth and carbon allocation within complex root systems were monitored in maize plants ( Zea mays ), and the results may be used to identify factors affecting root growth in natural substrates or in competition with roots of other plants. MRI–PET co-registration opens the door for non-invasive analysis of plant structures and transport processes that may change in response to genomic, developmental or environmental challenges. It is our aim to make the methods applicable for quantitative analyses of plant traits in phenotyping as well as in understanding the dynamics of key processes that are essential to plant performance.  相似文献   
109.
近期的脑成像研究在盲人等感官缺陷被试者身上发现了感觉替换现象,即传统上认为仅对单一感觉通道刺激反应的皮层区域也参与其他感觉通道的信息加工.类似的效应在感觉剥夺(蒙住眼睛)的明视人被试中也被观察到,提示脑内可能预存着多感觉交互作用的神经通路.通常认为,上述神经通路在常态的人脑中是以潜伏形式存在的,只有当感觉剥夺时才显露出来或得到加强.但是,感觉剥夺是否是该类神经通路发挥作用的必要条件,已有的研究尚缺乏确切的证据.采用统计力度较强的实验设计,给未蒙眼明视人被试听觉呈现一组名词,要求其对听到的每一个词语做出是人工物体还是自然物体的语义判断.对同步采集的功能磁共振信号进行统计分析,观察到视皮层脑区有显著激活.这些结果表明,跨感觉通道的神经通路在未实施感觉剥夺的条件下依然能够显示出来,因而在常态人脑中也不是完全以潜伏形式存在的.上述研究为建立多感觉交互作用神经机制的具体理论模型提供了一个约束条件.  相似文献   
110.
To study the regulation of cardiac muscle contraction by the myosin essential light chain (ELC) and the physiological significance of its N-terminal extension, we generated transgenic (Tg) mice by partially replacing the endogenous mouse ventricular ELC with either the human ventricular ELC wild type (Tg-WT) or its 43-amino-acid N-terminal truncation mutant (Tg-Δ43) in the murine hearts. The mutant protein is similar in sequence to the short ELC variant present in skeletal muscle, and the ELC protein distribution in Tg-Δ43 ventricles resembles that of fast skeletal muscle. Cardiac muscle preparations from Tg-Δ43 mice demonstrate reduced force per cross-sectional area of muscle, which is likely caused by a reduced number of force-generating myosin cross-bridges and/or by decreased force per cross-bridge. As the mice grow older, the contractile force per cross-sectional area further decreases in Tg-Δ43 mice and the mutant hearts develop a phenotype of nonpathologic hypertrophy while still maintaining normal cardiac performance. The myocardium of older Tg-Δ43 mice also exhibits reduced myosin content. Our results suggest that the role of the N-terminal ELC extension is to maintain the integrity of myosin and to modulate force generation by decreasing myosin neck region compliance and promoting strong cross-bridge formation and/or by enhancing myosin attachment to actin.  相似文献   
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