家兔动脉粥样硬化模型微量元素谱的计算机多元分析

为了查明微量元素谱与动脉粥样硬化症的关连，用多元分析研究了白兔动脉粥样硬化模型中的生物样品微量元素谱。ＩＣＰ－ＡＥＳ测定动脉粥样硬化模型和对照组的兔器官和 组织中１９种元素。因子分析法处理数据，得到一系列因子得分分布图，各图象表明动脉粥样硬化组与对照组的样品点分布在图上不同区域，且两组样品点可分辨。     

A method for the making and utility of gadolinium-labeled albumin microbubbles

Objective

Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) binds scavenger receptors and can be noninvasively imaged. To enhance imaging, gadolinium (Gd)-labeled PESDA was developed and tested in a model of vascular inflammation by magnetic resonance imaging (MRI).

Methods and Results

Purified human serum albumin (HSA) (5%) was labeled with Gd via the covalent binding of diethylenetriaminepentacetic acid. Abdominal aortic tissues in Sprague-Dawley rats (n=5 per group) were analyzed by 7-T MRI and scanning electron microscopy to evaluate PESDA binding. Labeling-purified 5% human albumin resulted in an average of 16.1 Gd atoms per albumin molecule as determined by atomic absorption. Forty-eight hours after balloon angioplasty, aortic tissue was enhanced with Gd-PESDA as compared to control tissue. 7-T MRI of explanted tissues was sensitive to the detection of retained PESDA. Enhancement of aortic tissue in vivo was present albeit to a lesser extent than explanted tissue from the same animals.

Conclusions

HSA was successfully labeled, and an albumin-based microbubble with Gd was synthesized. This contrast agent, Gd-PESDA, may serve as an additional agent for the MRI evaluation of innate inflammation and used to noninvasively image early vascular pathophysiologic processes.

Condensed Abstract

In this study, Gd-PESDA microbubbles and were synthesized and shown to detect the binding of these microbubbles using MRI in injured aortic tissue. The method for synthesizing Gd-PESDA is detailed, and the proposed utility of this new contrast agent is discussed.     

Noninvasive detection of intimal xanthoma using combined ultrasound, strain rate and photoacoustic imaging

Background and motivation

The structure, composition and mechanics of carotid artery are good indicators of early progressive atherosclerotic lesions. The combination of three imaging modalities (ultrasound, strain rate and photoacoustic imaging) which could provide corroborative information about the named arterial properties could enhance the characterization of intimal xanthoma.

Methods

The experiments were performed using a New Zealand white rabbit model of atherosclerosis. The aorta excised from an atherosclerotic rabbit was scanned ex vivo using the three imaging techniques: (1) ultrasound imaging of the longitudinal section: standard ultrasound B-mode (74 Hz frame rate); (2) strain rate imaging: the artery was flushed with blood and a 1.5 Hz physiologic pulsation was induced, while the ultrasound data were recorded at higher frame rate (296 Hz); (3) photoacoustic imaging: the artery was irradiated with nanosecond pulsed laser light of low fluence in the 1210-1230 nm wavelength range and the photoacoustic data was recorded at 10 Hz frame rate. Post processing algorithms based on cross-correlation and optical absorption variation were implemented to derive strain rate and spectroscopic photoacoustic images, respectively.

Results

Based on the spatio-temporal variation in displacement of different regions within the arterial wall, strain rate imaging reveals differences in tissue mechanical properties. Additionally, spectroscopic photoacoustic imaging can spatially resolve the optical absorption properties of arterial tissue and identify the location of lipid pools.

Conclusions

The study demonstrates that ultrasound, strain rate and photoacoustic imaging can be used to simultaneously evaluate the structure, the mechanics and the composition of atherosclerotic lesions to improve the assessment of plaque vulnerability.     

血流动力学数值模拟与动脉粥样硬化研究进展

血流动力学因素被认为与动脉粥样硬化等病理改变密切相关。目前血流动力学数值模拟的对象,主要集中于分支动脉、弯曲动脉以及因血管内膜增生而导致的局部狭窄动脉,这些都是动脉粥样硬化多发的病灶部位。精确的血流动力学数值模拟,必须依赖于解剖精确的血管几何模型和生理真实的血流与管壁有限变形的非线性瞬态流－固耦合。只有在“虚拟血液流动”的基础上,综合考虑血管内的壁面剪应力、粒子滞留时间和氧气的跨血管壁传输等多种因素,血流动力学的数值模拟才能真正有助于人们理解动脉粥样硬化的血流动力学机理,才有可能应用于有关动脉疾病的外科手术规划中。      

Co-registration of the distribution of wall shear stress and 140 complex plaques of the aorta

Previous studies provide evidence that atherosclerosis develops in vascular regions exposed to low wall shear stress (WSS) and high oscillatory shear index (OSI). 4D flow MRI was analyzed in 70 stroke patients with complex plaques (≥ 4 mm thickness, ulcerated or superimposed thrombi) and in 12 young healthy volunteers. The segmental distribution of peak systolic WSS_systole and OSI was quantified in analysis planes positioned directly at the location of 140 complex plaques found in the 70 patients. In addition, WSS_systole and OSI were evaluated in 8 standard analysis planes distributed along the aorta. Complex plaques were predominantly found at the inner curvature of the aortic arch and of the descending aorta. High OSI was co-located with the segments mostly affected by complex plaque while WSS_systole demonstrated a homogenous distribution. In standard analysis planes, patients demonstrated significantly (p < 0.01) altered distribution of wall parameters compared to volunteers (reduced WSS_systole in 91% of aortic wall segments, increased OSI in 48% of segments). OSI distribution was asymmetric with higher values at the inner curvature of the aorta. While WSS and OSI showed expected changes in patients compared to healthy controls, their distribution pattern at complex plaques indicated a more complex and heterogeneous relationship than previously anticipated.     

Magnetic characterization of human blood in the atherosclerotic process in coronary arteries

In the last decades there has been an increasing interest in biomagnetism—a field of biophysics concerned with the magnetic properties of living organisms. Biomagnetism focuses on the measurement of magnetic properties of biological samples in the clinical environment. Progress in this field can provide new data for the understanding of the pathomechanism of atherosclerosis and support the diagnostic options for the evaluation and treatment of atherothrombotic complications. Lyophilized human blood samples from patients with atherosclerotic lesions (calcium scoring (CS) CS>0) and without atherosclerotic lesions (CS=0) were magnetically investigated. Magnetic measurements (performed in room and low temperature) indicated significant magnetic differences between these two groups of patients. Atherosclerotic blood samples are characterized by higher concentration of ferrimagnetic particles (magnetite and/or maghemite) and significant changes in the superparamagnetic behaviour. This research presents that magnetometry, in combination with medical research can lead to a better understanding of iron physiology in the atherosclerotic process.     

Improved in vivo human carotid artery wall T2 estimation

T₂^? quantification has been shown to noninvasively and accurately estimate tissue iron content in the liver and heart; applying this to thin-walled carotid arteries introduces a new challenge to the estimation process. With most imaging voxels in a vessel being along its boundaries, errors in parameter estimation may result from partial volume mixing and misregistration due to motion in addition to noise and other common error sources. To minimize these errors, we propose a novel technique to reliably estimate T₂^? in thin regions of vessel wall. The technique weights data points to reduce the influence of expected error sources. It uses neighborhoods of data to increase the number of points for fitting and to assess lack of fit for automated outlier detection and deletion. The performance of this method was observed in simulations, phantom and in vivo patient studies and compared to results obtained using a pixelwise linear least squares estimation of T₂^?. The new proposed method showed a closer match to the expected results, and a 4.2-fold decrease in interobserver variability for in vivo studies. This increased confidence in estimation should improve the ability to reliably quantify iron noninvasively in the arterial wall.     

脂质响应型探针用于动脉粥样硬化成像及治疗的研究进展

动脉粥样硬化是心血管疾病的主要威胁之一, 可能导致如急性心肌梗死在内的急性冠状动脉综合征、 卒中, 甚至猝死等一系列严重的不良后果. 脂质的异常积累是动脉粥样硬化的标志之一, 有必要观察它们在体内的数量、 定位和分布. 荧光探针具有可操作性强、 高时空分辨率和与活体生物相容性佳的优点, 有望成为了解动脉粥样硬化中的脂质功能的有利工具. 本文综合评述了基于罗丹明、 香豆素、 氟化硼二吡咯(BODIPY)、 1,8-萘酰亚胺等有机框架结构以及金属配合物的脂滴特异性光学成像探针的研究进展, 并重点介绍了其在动脉粥样硬化斑块成像、 手术导航及治疗等领域的应用. 最后, 对该研究领域进行了总结和展望, 希望可为相关研究提供有益参考.     

Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy

Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe₁, is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe₁ nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe₁ nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE^−/−) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.