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1.
Li W  Li Z  Jing F  Deng Y  Wei L  Liao P  Yang X  Li X  Pei F  Wang X  Lei H 《Carbohydrate research》2008,343(4):685-694
Arabinogalactan derivatives conjugated with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) by ethylenediamine (Gd-DTPA-CMAG-A2) or hexylamine (Gd-DTPA-CMAG-A6) have been synthesized and characterized by means of Fourier transform infrared spectra (FTIR), 13C nuclear magnetic resonance (13C NMR), size exclusion chromatography (SEC), and inductively coupled plasma atomic emission spectrometry (ICP-AES). Relaxivity studies showed that arabinogalactan-bound complexes possessed higher relaxation effectiveness compared with the clinically used Gd-DTPA, and the influence of the spacer arm lengths on the T1 relaxivities was studied. Their stability was investigated by competition study with Ca2+, EDTA, and DTPA. MR imaging of Wistar rats showed remarkable enhancement in rat liver and kidney after i.v. injection of Gd-DTPA-CMAG-A2 (0.079+/-0.002 mmol/kg Gd3+): The mean percentage enhancement of the liver parenchyma and kidney was 38.7+/-6.4% and 69.4+/-4.4% at 10-30 min. Our preliminary in vivo and in vitro study indicates that the arabinogalactan-bound complexes are potential liver-specific contrast agents for MRI.  相似文献   

2.
Acute nodularin-induced hepatotoxicity was assessed in vivo, in rats using magnetic resonance (MR) techniques, including MR imaging (MRI), MR spectroscopy (MRS), and electron paramagnetic resonance (EPR) oximetry. Nodularin is a cyclic hepatotoxin isolated from the cyanobacterium Nodularia spumigena. Three hours following the intraperitoneal (i.p.) administration of nodularin (LD50), a region of 'damage', characterized by an increase in signal intensity, was observed proximal to the porta hepatis (PH) region in T2-weighted MR images of rat liver. Image analysis of these regions of apparent 'damage' indicated a statistically significant increase in signal intensity around the PH region following nodularin administration, in comparison with controls and regions peripheral to the PH region. An increase in signal intensity was also observed proximal to the PH region in water chemical shift selective images (CSSI) of nodularin-treated rat livers, indicating that the increased signal observed by MRI is an oedematous response to the toxin. Microscopic assessment (histology and electron microscopy) and serum liver enzyme function tests (aminotransferase (ALT) and aspartate ALT (AST)) confirmed the nodularin-induced tissue injury observed by MRI. In vivo and in vitro MRS was used to detect alterations in metabolites, such as lipids, Glu+Gln, and choline, during the hepatotoxic response (2-3 h post-exposure). Biochemical assessment of perchloric acid extracts of nodularin-treated rat livers were used to confirm the MRS results. In vivo EPR oximetry was used to monitor decreasing hepatic pO2 (approximately 2-fold from controls) 2-3 h following nodularin exposure. In vivo MR techniques (MRI, MRS and EPR oximetry) are able to highlight effects that may not have been evident in single end point studies, and are ideal methods to follow tissue injury progression in longitudinally, increasing the power of a study through repeated measures, and decreasing the number of animals to perform a similar study using histological or biochemical techniques.  相似文献   

3.
 The ligand DOTASA was designed and synthesized in the aim of obtaining a kinetically and thermodynamically stable Gd(III) chelate which, through its uncoordinated carboxylate function, will provide an efficient pathway to couple the complex to bio- or macromolecules without affecting the coordination pattern of DOTA. Furthermore, it allows us to study the influence of an extra carboxylate arm on the parameters determining proton relaxivity in comparison to the commercial agent [Gd(DOTA)(H2O)]. A combined variable-temperature 17O NMR, EPR and nuclear magnetic relaxation dispersion study on the Gd(III) chelate resulted in k 298 ex=(6.3±0.2)×106 s–1 for the water exchange rate and τ298 R=125±2 ps for the rotational correlation time. The slight increase in both k 298 ex and τ298 R, as compared to those for [Gd(DOTA)(H2O)], is attributed to the presence of the extra negative charge. The longer rotational correlation time results in a proton relaxivity of 5.03 mM–1 s–1 for [Gd(DOTASA)(H2O)]2–, which is approximately 30% higher than that for [Gd(DOTA)(H2O)]. The increased water exchange rate of [Gd(DOTASA)(H2O)]2– has no consequence for proton relaxivity since this latter is exclusively limited by fast rotation for both complexes. However, for slowly rotating macromolecular agents, which contain a covalently coupled DOTASA unit instead of a coupled DOTA, this increased exchange rate will have a significant positive effect. Received: 31 December 1998 / Accepted: 4 March 1999  相似文献   

4.
Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C18H37)2NCO(CH2)2CO(AdOO)5-G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C18H37)2NCO(CH2)2COLys(DTPAGlu)CONH2 (DTPAGlu is N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-l-glutamic acid), are characterized for their structural parameters by dynamic light scattering and for their relaxometric properties, in the absence and in the presence of 0.9 wt% NaCl. Two different aggregates (micelles and bilayer structures) are present in the absence of NaCl, while only bilayer structures are observed at physiological ionic strength. The presence of NaCl increases the ionic strength, promoting a decrease in the repulsions between the polar heads and among the aggregates in solution, thus supporting the formation of large-curvature aggregates such as bilayer structures like vesicles. In these conditions the closed, vesicular shape and the large size (hydrodynamic radius of about 300 Å) of the aggregates allow a high number of paramagnetic gadolinium complexes and bioactive peptides to be accommodated on the inner and external surfaces . The presence of the salt causes a variation in the structural arrangement of the molecules and a partial rigidification of the assembled Gd(III) complexes on the surface vesicles, reducing their internal motions and giving an approximately 15% higher relaxivity value (r 1p = 21.0 and 18.6 Mm?1 s?1 in the presence and in the absence of NaCl, respectively). The vesicles obtained, for the high relaxivity of each gadolidium complex and for the presence of a surface-exposed bioactive peptide, are very promising candidates as target-selective MRI contrast agents.  相似文献   

5.
The human skin is an exceedingly complex and multi-layered material. This paper aims to introduce the application of the finite element analysis (FEA) to the in vivo characterization of the non-linear mechanical behaviour of three human skin layers. Indentation tests combined with magnetic resonance imaging (MRI) technique have been performed on the left dorsal forearm of a young man in order to reveal the mechanical behaviour of all skin layers. Using MRI images processing and a pre and post processor allows to make numerically individualized 2D model which consists of three skin layers and the muscles. FEA has been applied to simulate indentation tests. Neo-Hookean slightly compressible material model of two material constants (C10, K) has been used to model the mechanical behaviour of the three skin layers and the muscles. The identification of material model parameters was done by applying Levenberg–Marquardt algorithm (LMA). Our methodology of identification provides a range of values for each constant. Range of values of different material properties of epidermis, dermis, hypodermis are respectively, C10E = 0.12 ± 0.06 MPa, C10D = 1.11 ± 0.09 MPa, C10H = 0.42 ± 0.05 KPa, K E = 5.45 ± 1.7 MPa, K D = 29.6 ± 1,28 MPa, K H = 36.0 ± O.9 KPa.  相似文献   

6.
Two mono-substituted manganese polyoxometalates, K(6)MnSiW(11)O(39) (MnSiW(11)) and K(8)MnP(2)W(17)O(61) (MnP(2)W(17)), have been evaluated by in vivo and in vitro experiments as the candidates of potential tissue-specific contrast agents for magnetic resonance imaging (MRI). T1-relaxivities of 12.1mM(-1)s(-1) for MnSiW(11) and 4.7 mM(-1)s(-1) for MnP(2)W(17) (400 MHz, 25 degrees C) were higher than or similar to that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in BSA and hTf solutions were also reported. After administration of MnSiW(11) and MnP(2)W(17) to Wistar rats, MR imaging showed longer and remarkable enhancement in rat liver and favorable renal excretion capability. The signal intensity increased by 74.0+/-4.9% for the liver during the whole imaging period (90 min) and by 67.2+/-5.3% for kidney within 20-70 min after injection at 40+/-3 micromol kg(-1) dose for MnSiW(11). MnP(2)W(17) induced 71.5+/-15.1% enhancement for the liver in 10-45 min range and 73.1+/-3.2% enhancement for kidney within 5-40 min after injection at 39+/-3 micromol kg(-1) dose. In vitro and in vivo study showed MnSiW(11) and MnP(2)W(17) being favorable candidates as the tissue-specific contrast agents for MRI.  相似文献   

7.

Background

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects with a population prevalence of 0.5% to 1.3%. Identifying patients with BAV is clinically relevant because BAV is associated with aortic stenosis, endocarditis and ascending aorta pathology.

Methods and Results

Patients with severe aortic stenosis necessitating aortic valve replacement surgery were included in this study. All dissected aortic valves were stored in the biobank of the University Medical Centre Utrecht. Additionally to the morphological assessment of the aortic valve by the surgeon and pathologist, echocardiographic and magnetic resonance imaging (MRI) images were evaluated. A total of 80 patients were included of whom 32 (40%) were diagnosed with BAV by the surgeon (gold standard). Patients with BAV were significantly younger (55 vs 71 years) and were more frequently male. Notably, a significant difference was found between the surgeon and pathologist in determining valve morphology. MRI was performed in 33% of patients. MRI could assess valve morphology in 96% vs 73% with echocardiography. The sensitivity of MRI for BAV in a population of patients with severe aortic stenosis was higher than echocardiography (75% vs 55%), whereas specificity was better with the latter (91% vs 79%). Typically, the ascending aorta was larger in patients with BAV.

Conclusion

Among unselected patients with severe aortic valve stenosis, a high percentage of patients with BAV were found. Imaging and assessment of the aortic valve morphology when stenotic is challenging.  相似文献   

8.

Background

In this study, an attempt has been made with the advent of technology to prepare a multifunctional nanobiocomposite (NBC) for targeted drug delivery in cancer therapy.

Methods

Collagen (C) was fabricated as nanofibers with multifunctional moieties viz. CFeAb*D by incorporating iron oxide nanoparticles (Fe), coupling with fluorescein isothiocyanate (FITC) labeled antibody (Ab*) and loading an anticancer gemcitabine drug (D). This NBC was characterized by conventional methods and evaluated for its biological activities.

Results

The UV–vis and FTIR spectroscopic studies revealed the fluorescein to protein ratio and revealed the presence of iron oxide nanoparticles and their interaction with the collagen molecules, respectively. While SDS-PAGE showed the proteinaceous nature of collagen, VSM and TEM studies revealed magnetic saturation as 54.97 emu/g and a magnetic nanoparticle with a diameter in the range of 10–30 nm and the dimension of nanofiber ranging from 97 to 270 nm. A MRI scan has shown a super paramagnetic effect, which reveals that the prepared NBC can be used as a MRI contrast agent. The MTT assay has shown biocompatibility and an apoptotic effect while phase contrast microscopy exhibited receptor mediated uptake of endocytosis.

Conclusion

The novelty in the prepared NBC lies in the collagen nanofibers, which have a higher penetrating property without causing much cell damage, biocompatibility and multifunctional properties and is able to carry multifunctional agents.

General significance

The study has demonstrated the possible use of CFeAb*D as a multifunctional NBC for biomedical applications.  相似文献   

9.
PurposeTo demonstrate the accuracy of an unsupervised (fully automated) software for fat segmentation in magnetic resonance imaging. The proposed software is a freeware solution developed in ImageJ that enables the quantification of metabolically different adipose tissues in large cohort studies.MethodsThe lumbar part of the abdomen (19 cm in craniocaudal direction, centered in L3) of eleven healthy volunteers (age range: 21–46 years, BMI range: 21.7–31.6 kg/m2) was examined in a breath hold on expiration with a GE T1 Dixon sequence. Single-slice and volumetric data were considered for each subject. The results of the visceral and subcutaneous adipose tissue assessments obtained by the unsupervised software were compared to supervised segmentations of reference. The associated statistical analysis included Pearson correlations, Bland-Altman plots and volumetric differences (VD%).ResultsValues calculated by the unsupervised software significantly correlated with corresponding supervised segmentations of reference for both subcutaneous adipose tissue – SAT (R = 0.9996, p < 0.001) and visceral adipose tissue – VAT (R = 0.995, p < 0.001). Bland-Altman plots showed the absence of systematic errors and a limited spread of the differences. In the single-slice analysis, VD% were (1.6 ± 2.9)% for SAT and (4.9 ± 6.9)% for VAT. In the volumetric analysis, VD% were (1.3 ± 0.9)% for SAT and (2.9 ± 2.7)% for VAT.ConclusionsThe developed software is capable of segmenting the metabolically different adipose tissues with a high degree of accuracy. This free add-on software for ImageJ can easily have a widespread and enable large-scale population studies regarding the adipose tissue and its related diseases.  相似文献   

10.
目的:探讨腮腺腺淋巴瘤的MR表现特征。方法:回顾性分析12例经病理证实的腺淋巴瘤患者MR及临床资料,男性10例,女性2例,平均年龄59.1岁。观察病灶的数目、部位、形态、边界、大小以及MR信号特点等。结果:12例中,单发9例,多发3例,共17个病灶。其中12个病灶位于腮腺浅叶后下部,13个病灶为纵向生长椭圆形。T1WI上16个病灶为等或稍高于肌肉信号,1个含有高信号。STIR序列中等稍高信号者7个,10个含有大小不等的明显高信号。增强扫描轻到中度强化者15个,明显强化2个。9个病例颈部可见中等大小淋巴结。结论:50岁以上吸烟男性,发现腮腺浅叶后下方边界清楚、纵向生长椭圆占位,STIR序列信号欠均匀,高度提示腺淋巴瘤。  相似文献   

11.
目的:分析鞍旁海绵状血管瘤MR影像特点及误诊原因,提高对该疾病的诊断及鉴别诊断水平。方法:收集我院经手术病理证实的13例鞍旁海绵状血管瘤,术前均行MRI平扫及增强扫描,5例行3D-ASL检查,分析其影像学资料。结果:9例表现为横向哑铃状,鞍旁大,鞍内小,病灶主体位于颈内动脉外侧,颈内动脉海绵窦段被病灶包绕;1例鞍旁与鞍内病灶大小相似,1例病灶主体位于颈内动脉内侧,2例病灶完全位于颈内动脉外侧;7例垂体显示不清,6例垂体受推移;6例T2W I表现为类似脑脊液的极高信号;仅5例行3D-ASL检查,病灶均呈低灌注。误诊9例,其中4例误诊垂体腺瘤,5例误诊脑膜瘤。结论:横向哑铃状、病灶主体位于颈内动脉外侧及T2W I类似脑脊液的极高信号是鞍旁海绵状血管瘤的典型影像特征。对于不典型病变,借助3D-ASL可以减少误诊,充分掌握MRI影像特征及鉴别诊断的要点,对提高临床术前诊断水平具有重要价值。  相似文献   

12.
目的:总结分析191例腰椎间盘突出症的CT及MRI影像特征。方法:CT组104例,MRI组87例,同时行CT及MR检查44例。结果:CT组中,椎间盘同位于L3-4者12例,L4-5者32例,L5-S1者60例。骨质增生31例,髓核钙化11例,后纵韧带钙化9例。MR组中,椎间盘突出位于L3-4者13例,L4-5者39例,L5-S1者35例,椎间盘突变性41例。  相似文献   

13.
目的:评价MRI多b值DWI序列在孤立性肺结节(SPN)良、恶性鉴别诊断中的价值。方法:选取2015年9月-2016年6月于我院行CT检查发现并未经治疗的78例SPN患者,在穿刺活检或手术前行MRI胸部检查,根据结节直径分为三组:D1≤10mm、10 mmD2≤20 mm、20 mmD3≤30 mm,DWI扫描b值(0 s/mm~2、400 s/mm~2、600 s/mm~2、800 s/mm~2)。分别测量不同b值下结节DWI图的信号评分和拟合ADC图的表观扩散系数(ADCtot值),参照病理结果进行对比分析。结果:在b值为400 s/mm~2时,良恶性结节DWI信号差异在D1组间无统计学意义(P0.05);当b值为600 s/mm~2时,良恶性结节DWI信号差异在(D1、D2、D3)组间均具有统计学意义(P0.05),且结节信号强度越高其恶性可能性越大;在b值为800 s/mm~2时,良恶性结节DWI信号差异在D3组间无统计学意义(P0.05);在良恶性结节ADCtot值对比分析中发现,不同良性结节的ADCtot值均较恶性结节偏高,差异具有统计学意义(P0.05);以3为信号阈值,1.50×10~(-3) mm~2/s为ADCtot阈值,对SPN的特异性、准确性、阳性预测值、阴性预测值均较信号强度评分升高(P0.05)。结论:MRI弥散加权成像评价SPN过程中,多b值拟合ADCtot值对病变良恶性鉴别能力较好。在b值为600 s/mm~2时,其信号强度差异对SPN的良恶性信号评价效能最佳,多b值DWI序列对SPN良恶性的鉴别诊断具有重要价值。  相似文献   

14.
We report the development of functionalized superparamagnetic iron oxide nanoparticles with a PEG-modified, phospholipid micelle coating, and their delivery into living cells. The size of the coated particles, as determined by dynamic light scattering and electron microscopy, was found to be between 12 and 14 nm. The PEG-phospholipid coating resulted in high water solubility and stability, and the functional groups of modified PEG allowed for bioconjugation of various moieties, including a fluorescent dye and the Tat peptide. Efficient delivery of the functionalized nanoparticles into living cells was confirmed by fluorescence microscopy, relaxation time measurements, and magnetic resonance imaging (MRI). This demonstrates the feasibility of using functionalized magnetic nanoparticles with uniform (~10 nm) sizes as an MRI contrast agent for intracellular molecular imaging in deep tissue. These micelle-coated iron oxide nanoparticles offer a versatile platform for conjugation of a variety of moieties, and their small size confers advantages for intracellular molecular imaging with minimal perturbation.Abbreviations CPP cell penetrating peptide - CPMG Carr–Purcell–Meiboom–Gill spin-echo method - CTAB cetyltrimethylammonium bromide - DLS dynamic light scattering - DMEM Dulbeccos modified Eagles medium - DSPE 1,2-distearoyl-sn-glycero-3-phosphoethanolamine - FCS fetal calf serum - FGM-2 fibroblast growth medium 2 - HDF human dermal fibroblast - HS horse serum - MDBK Madin–Darby bovine kidney - MIONs superparamagnetic iron oxide nanoparticles - mMIONs micelle-coated MIONs - MRI magnetic resonance imaging - PBS phosphate-buffered saline - PEG poly(ethylene glycol) - SPDP N-succinimidyl 3-(2-pyridyldithio)propionate - TCEP tris(2-carboxyethyl)phosphine hydrochloride - TEM transmission electron microscopy  相似文献   

15.
目的:探讨局灶性皮质发育不良(FCD)与影像学改变的相关性,并应用日常生活能力量表(ADL)评价FCD患者手术前后的生活质量改善以及癫痫缓解率。方法:回顾性分析60例FCD癫痫患者MRI检查,观察病变部位影像学变化;回顾60例FCD癫痫患者手术前后所填写的生活质量量表,分析患者总体健康水平,总体生命质量,情绪健康,日常精力,认知能力,对药物副作用的担忧,对癫痫发作的担忧,以及社会功能的变化。结果:60例FCD患者有23例(阳性率为38.3%)表现出FCD的病理特征。这23例中表现有四种:灰白质交接模糊,皮层增厚,异常脑沟脑回图案,脑叶萎缩。生活质量量表显示FCD患者(术前)生活质量明显差于正常人群,FCD患者术后的生活质量比术前得到改善。结论:FCD患者的MRI表现呈现多样性,但主要有四种类型。FCD患者术后生活质量得到改善,提示癫痫缓解率提高。  相似文献   

16.
目的:探讨平山病的过屈位颈椎MRI特征性影像学表现及其临床诊断价值。方法:总结分析经临床证实的5例平山病患者的临床及MRI资料,并结合相关文献报道进行回顾性分析。所有患者均行常规生化检查,脑脊液检查,肌电图检查及肌肉活检。结果:5例均为青少年男性,呈单侧上肢远端无力伴萎缩,其中1例患者累及另一侧,尺侧肌萎缩明显,上肢呈斜坡样改变,均无感觉障碍和锥体束征;肌电图检查显示神经源性改变,提示受损节段多在下颈髓前角细胞。屈颈MRI检查均可见下颈髓前移、硬脊膜外间隙增宽,可见迂曲条状血管流空影。结论:平山病的过屈位MRI表现具有一定的特征性,对平山病的诊断具有重要价值。  相似文献   

17.
目的:探讨平山病的过屈位颈椎MRI特征性影像学表现及其临床诊断价值。方法:总结分析经临床证实的5 例平山病患者 的临床及MRI资料,并结合相关文献报道进行回顾性分析。所有患者均行常规生化检查,脑脊液检查,肌电图检查及肌肉活检。结 果:5 例均为青少年男性,呈单侧上肢远端无力伴萎缩,其中1 例患者累及另一侧,尺侧肌萎缩明显,上肢呈斜坡样改变,均无感觉 障碍和锥体束征;肌电图检查显示神经源性改变,提示受损节段多在下颈髓前角细胞。屈颈MRI检查均可见下颈髓前移、硬脊膜 外间隙增宽,可见迂曲条状血管流空影。结论:平山病的过屈位MRI表现具有一定的特征性,对平山病的诊断具有重要价值。  相似文献   

18.
目的:探讨脑弥漫性轴索损伤(DAI)的磁共振成像(MRI)征象及其与格拉斯哥昏迷量表评分(GCS)计分和预后的关系。方 法:回顾性分析2012 年1 月-2014 年7 月我院收集的30 例DAI 患者的临床病历资料,根据病灶累及部位分析其与GCS 计分和 临床预后的关系。结果:30 例患者共53 个病灶,17例多发病灶,13 例单发病灶;42 个病灶T1WI显示出低信号或者是等信号,11 个病灶T1WI显示为高信号;T2WI显示为高信号,FLAIR 序列以及弥散加权像(DWI)上表现出的信号更高,范围更清晰;病灶形 态呈条索状27 例,斑片状11 例,卵圆形8 例,不规则斑点状7 例;病灶未累及脑中线部位的患者临床预后优于病灶累及脑中线 部位的患者,差异有统计学意义(Z=-2.636,P=0.008),病灶累及脑中线部位的患者GCS 计分情况比未累及组严重,计分更低,差 异有统计学意义(Z=-2.519,P=0.012)。结论:DAI病灶累及脑中线部位的患者GCS计分较低、预后差,MRI检查是诊断DAI 首选 的影像学方法,临床有重要的参考价值。  相似文献   

19.
We present a coincidental finding of quadricuspid pulmonary valve and left pulmonary artery aneurysm. As both the pulmonary valve and the pulmonary trunk with its main branches are hard to visualise with cardiac ultrasound, most abnormalities described so far are from autopsy series. With the increasing use of CMR and its excellent potential for visualising both pulmonary valve and pulmonary arteries, we believe more cases will be discovered in the near future. Although pulmonary artery aneurysm are rare, timely detection may prevent lethal bleeding.  相似文献   

20.
Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and a carotid perivascular collar model in apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast administration and at 8 h and 24 h after injection of 30 mg Fe/kg. The results showed MRI signal loss in the carotid atherosclerotic lesions after administration of targeted anti-OxLDL-USPIO at 8 h and 24 h, which is consistent with the presence of the nanoparticles in the lesions. Immunohistochemistry confirmed the colocalization of the OxLDL/macrophages and iron oxide nanoparticles. The nonspecific IgG-USPIO, unconjugated USPIO nanoparticles, and competitive inhibition groups had limited signal changes (p < 0.05). This report shows that anti-OxLDL-USPIO nanoparticles can be used to directly detect OxLDL and image atherosclerotic lesions within 24 h of nanoparticle administration and suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in vivo.  相似文献   

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