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1.
The objective of this work was to examine differences in DNA double‐strand break induction in peripheral blood lymphocytes after in vitro X‐ray irradiation between iodinated contrast agents. Four different iodinated X‐ray contrast agents – three of them with two different iodine concentrations – and mannitol (negative control; concentration of 150 mg mannitol per ml blood) were pipetted into blood samples so that there was a concentration of 0, 7.5 or 15 mg of iodine per ml blood in the samples. Negative controls without contrast medium (0 mg of iodine per ml blood) were also processed for every irradiation dose. The tubes were exposed to 0, 20 or 500 mGy in vitro X‐ray irradiation. After that, the lymphocytes were separated by using density‐gradient centrifugation. Fluorescence microscopy was applied to determine the average number of γH2AX‐foci per lymphocyte in the presence or absence of different contrast media or mannitol. Differences in the number of γH2AX‐foci were statistically analysed by one‐way ANOVA and post‐hoc Tukey's honestly significant difference test. Iodinated contrast agents led to a statistically significant increase in DNA double‐strand breaks after in vitro irradiation. This effect increased statistically significant with rising radiation dose and appeared independent of the contrast agent used (iopromid, iodixanol, iomeprol, iopamidol). A statistically significant difference in DNA damage between the different tested contrast agents was not found. Therefore, the increase in DNA double‐strand breaks depends solely on the amount of iodine applied. For evaluation of clinical consequences, our findings could be tested in further animal studies. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

2.
Paediatric cardiac catheterizations may result in the administration of substantial amounts of iodinated contrast media and ionizing radiation. The aim of this work was to investigate the effect of iodinated contrast media in combination with in vitro and in vivo X‐ray radiation on lymphocyte DNA. Six concentrations of iodine (15, 17.5, 30, 35, 45, and 52.5 mg of iodine per mL blood) represented volumes of iodinated contrast media used in the clinical setting. Blood obtained from healthy volunteers was mixed with iodinated contrast media and exposed to radiation doses commonly used in paediatric cardiac catheterizations (0 mGy, 70 mGy, 140 mGy, 250 mGy and 450 mGy). Control samples contained no iodine. For in vivo experimentation, pre and post blood samples were collected from children undergoing cardiac catheterization, receiving iodine concentrations of up to 51 mg of iodine per mL blood and radiation doses of up to 400 mGy. Fluorescence microscopy was performed to assess γH2AX‐foci induction, which corresponded to the number of DNA double‐strand breaks. The presence of iodine in vitro resulted in significant increases of DNA double‐strand breaks beyond that induced by radiation for ≥17.5 mg/mL iodine to blood. The in vivo effects of contrast media on children undergoing cardiac catheterization resulted in a 19% increase in DNA double‐strand breaks in children receiving an average concentration of 19 mg/mL iodine to blood. A larger investigation is required to provide further information of the potential benefit of lowering the amount of iodinated contrast media received during X‐ray radiation investigations. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

3.
To assess the ability of dual‐energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double‐contrast enhanced scans using iodinated intravenous contrast and experimental enteric non‐iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (?100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30–44% and 36–45%, both p < 0.001) higher for double‐contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double‐contrast DECT was scored 29 and 35 percentage points (95% CI 20–35% and 33–39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double‐contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15–31% and 28–33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double‐contrast DECT with iodinated intravenous and either tantalum‐ or tungsten‐based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

4.
目的 探讨第三代双源CT早期鉴别诊断急性缺血性脑卒中(AIS)血管内治疗后颅内出血灶与碘对比剂的价值。方法 纳入78例接受血管内治疗的AIS患者,治疗后采用第三代双源CT行脑部CT双能量(80 kV/Sn150 kV)扫描,经后处理得到碘分布图和虚拟平扫图像。以发病24~48 h后常规脑部CT图像为参考,计算双能量CT(DECT)诊断颅内出血的准确率、敏感度、特异度、阳性预测值(PPV)和阴性预测值(NPV)。结果 共31例患者(53个颅内高密度灶)纳入分析,其中DECT正确诊断26个高密度灶为存在出血,23个高密度灶为碘对比剂;1个钙化灶误诊为出血合并对比剂,3个DECT诊断为对比剂的病灶出现延迟性出血转化。DECT鉴别诊断颅内出血灶与碘对比的敏感度、特异度和准确率分别为89.66%(26/29)、95.83%(23/24)和92.45%(49/53),PPV为96.30%(26/27),NPV为88.46%(23/26)。结论 第三代双源CT能早期准确诊断AIS血管内治疗后的出血转化,有助于临床及时调整治疗方案。  相似文献   

5.
The feasibility of using Gd dendrimer‐based macromolecules (Gd‐G8 dendrimer) as a dual CT and MR contrast agent for monitoring convection‐enhanced delivery of therapy in the brain is evaluated both in vitro and in vivo with optimal dosing established. In vitro CT attenuation values of the Gd‐based agents (~6.0 HU mM ?1) were ~1.6 times greater than iodine‐based agents and the attenuation of the Gd‐DTPA was comparable to Gd‐G8 dendrimer. Visible enhancement was observed on both CT and MR using Gd‐G8 dendrimer over a range of 23–78 mM ; however, a concentration of at least 47 mM in Gd was required for adequate delineation of the injection site on both CT and MR. MR offers greater sensitivity than CT in estimating the volume of distribution (Vd) and effectively quantified the agent's concentration and diffusion using T1 mapping at much lower concentrations of Gd (<10 mM in [Gd]). Copyright © 2008 John Wiley & Sons, Ltd.  相似文献   

6.
Among all the diagnostic imaging modalities, X‐ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X‐ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X‐ray imaging. To date, clinically used X‐ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X‐ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X‐rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X‐ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X‐ray contrast agents are discussed and the parameters that influence the efficacy of X‐ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine‐free NP‐based X‐ray contrast agents are then provided, emphasizing the studies performed to evaluate their X‐ray attenuation capabilities and their toxicity in vitro and in vivo. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

7.
Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of the two agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH–CEST ratio correlation for each agent. These results showed that the two agents had similar performance characteristics, although iopromide produced a pH measurement with a higher dynamic range while iopamidol produced a more precise pH measurement. We then compared the performance of the two agents to measure in vivo extracellular pH (pHe) within xenograft tumor models of Raji lymphoma and MCF‐7 breast cancer. Our results showed that the pHe values measured with each agent were not significantly different. Also, iopromide consistently measured a greater region of the tumor relative to iopamidol in both tumor models. Therefore, an iodinated contrast agent for acidoCEST MRI should be selected based on the measurement properties needed for a specific biomedical study and the pharmacokinetic properties of a specific tumor model. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

8.
Noninvasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro‐CT cardiac imaging. eXIA 160 creates strong contrast between blood and tissue immediately after its injection and is subsequently taken up by the myocardium and other metabolically active tissues over time. We focus on these properties of eXIA and show its use in imaging myocardial infarction in mice. Five C57BL/6 mice were imaged ~2 weeks after left anterior descending coronary artery ligation. Six C57BL/6 mice were used as controls. Immediately after injection of eXIA 160, an enhancement difference between blood and myocardium of ~340 HU enabled cardiac function estimation via 4D micro‐CT scanning with retrospective gating. Four hours post‐injection, the healthy perfused myocardium had a contrast difference of ~140 HU relative to blood while the infarcted myocardium showed no enhancement. These differences allowed quantification of infarct size via dual‐energy micro‐CT. In vivo micro‐SPECT imaging and ex vivo triphenyl tetrazolium chloride (TTC) staining provided validation for the micro‐CT findings. Root mean squared error of infarct measurements was 2.7% between micro‐CT and SPECT, and 4.7% between micro‐CT and TTC. Thus, micro‐CT with eXIA 160 can be used to provide both morphological and functional data for preclinical studies evaluating myocardial infarction and potential therapies. Further studies are warranted to study the potential use of eXIA 160 as a CT molecular imaging tool for other metabolically active tissues in the mouse. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

9.
Background: To determine the optimal phases of dynamic computed tomography (CT) for detecting hepatocellular carcinoma (HCC). Methods: Fifty-two patients with 85 HCC nodules were examined by means of unenhanced and triple-phase CT images of the whole liver. The time for obtaining the arterial-phase images was 25–55 s after intravenous bolus injection of contrast material, the time for obtaining the portal venous-phase images was 65–100 s, and the time for obtaining late-phase images was 145 s to 4 min. Detectability of the HCC nodules for all phases was statistically compared. Results: The detection rates for the arterial- and late-phase images were significantly higher than for the unenhanced and portal venous-phase images (p < 0.01). The combination of arterial- and late-phase images showed the same number of HCC nodules in the same number of patients as did the combination of unenhanced and triple-phase images. Conclusion: The combination of the arterial- and late-phase imagings was best for detecting HCC nodules. Received: 8 July 1998/Revision accepted: 18 November 1998  相似文献   

10.
IntroductionComputed tomography (CT) measurements of hepatic steatosis can be performed using unenhanced CT images. The purpose of this study was to assess the occurrence of hepatic steatosis using unenhanced CT images for patients undergoing cholecystectomy or having cholelithiasis.MethodsA total of 143 unenhanced CT cases from a single centre were retrospectively examined. The CT number of liver, ratio of CT number of liver to spleen, and CT number of liver minus CT number of spleen were measured in three groups: (1) patients undergoing cholecystectomy, (2) patients having cholelithiasis, and (3) control group. Abdominal circumference, anterior subcutaneous fat tissue thickness, and body mass index were obtained.ResultsMean CT number of liver was significantly different between the group of patients with cholecystectomy and cholelithiasis and the control group (P < .001) and also between cases of cholecystectomy and cholelithiasis (P = .041), with the lowest CT number of liver in the cholecystectomy group. The mean CT number of liver minus CT number of spleen and mean CT number (liver/spleen) ratios, evaluated separately for both lobes, were not different comparing the cholelithiasis and cholecystectomy groups. The mean CT number of liver minus CT number of spleen and mean CT number (liver/spleen) ratios differed significantly between the control group and both patient groups (P < .001). Positive correlations were identified between abdominal circumference, subcutaneous fat depth, body mass index, and liver size and hepatic steatosis.ConclusionThere was an increased occurrence of hepatic steatosis in patients who have undergone a cholecystectomy compared with patients treated for cholelithiasis and the control group.  相似文献   

11.
Gadolinium‐based contrast agents (primarily those with linear chelates) are associated with a dose‐dependent signal hyperintensity in the dentate nucleus and the globus pallidus on unenhanced T1‐weighted MRI following administration to selected patients with normal renal function. The accumulation of gadolinium has also been reported in the skin, heart, liver, lung, and kidney of patients with impaired renal function suffering from nephrogenic systemic fibrosis (NSF). Here we report on three patients with impaired renal function and vascular calcification (two with confirmed NSF) whose unenhanced T1‐weighted MRIs showed conspicuous high signal intensity in the dentate nucleus and the globus pallidus after they had been exposed to relatively low doses of linear gadolinium‐based contrast agents (0.27, 0.45, and 0.68 mmol/kg). Signal ratios between dentate nucleus and pons and between globus pallidus and thalamus were comparable with previously reported measurements in subjects without renal impairment. Of note, all three analysed patients suffered from transient signs of neurological disorders of undetermined cause. In conclusion, the exposure to 0.27‐0.68 mmol/kg of linear gadolinium‐based contrast agent was associated with probable gadolinium accumulation in the brain of three patients suffering from impaired renal function and vascular calcification. © 2016 The Authors. Contrast Media & Molecular Imaging published by John Wiley & Sons Ltd.  相似文献   

12.
Background: Prior to attempting placement of one or more electrodes to revise existing rhythm control devices, patency of the central veins should be documented, in view of a high incidence of significant chronic occlusions. Since iodinated contrast venography may be contraindicated in select situations, imaging of the axillo‐subclavian venous system with gaseous carbon dioxide (CO2) was evaluated prospectively in 23 consecutive individuals who were considered for revision of previously implanted pacemaker or automatic cardioverter defibrillator lead systems. Methods: Approximately 20 mL of CO2 were manually infused via CO2 primed injection tubing into a vein at or above the level of the antecubital fossa ipsilateral to the side of prior lead placements. Digital subtraction imaging over the axillo‐subclavian region, lower neck, and mediastinum was performed. Formal interpretation was obtained from one of three interventional radiologists and at least one electrophysiologist. Results: Significant venous occlusions were identified in five (22%) patients. Vascular access utilized for the subsequent 18 revisions performed included the imaged patent ipsilateral vein in 14 patients and the contralateral, right‐sided subclavian venous system in three patients. One patient required epicardial left ventricular lead placement. There were no complications from venography. Conclusions: Axillo‐subclavian venography with gaseous CO2 in patients undergoing pacemaker or implantable cardioverter defibrillator lead revisions is feasible and safe when use of iodinated dye is contraindicated. This technique should be employed in patients with azotemia, dye contrast allergies, or significant inflammation in the vicinity of the intravenous line insertion. (PACE 2010; 790–794)  相似文献   

13.
To explore the feasibility of coronary artery calcium (CAC) measurement from low-dose contrast enhanced coronary CT angiography (CCTA) as this may obviate the need for an unenhanced CT scan. 52 patients underwent unenhanced cardiac CT and prospectively ECG triggered contrast enhanced CCTA (Discovery HD 750, GE Healthcare, Milwaukee, WI, USA). The latter was acquired in single-source dual-energy mode [gemstone spectral imaging (GSI)]. Virtual unenhanced images were generated from GSI CCTA by monochromatic image reconstruction of 70 keV allowing selective iodine material suppression. CAC scores from virtual unenhanced CT were compared to standard unenhanced CT including a linear regression model. After iodine subtraction from the contrast enhanced CCTA the attenuation in the ascending aorta decreased significantly from 359 ± 61 to 54 ± 8 HU (P < 0.001), the latter comparing well to the value of 64 ± 55 HU found in the standard unenhanced CT (P = ns) confirming successful iodine subtraction. After introducing linear regression formula the mean values for Agatston, Volume and Mass scores of virtual unenhanced CT were 187 ± 321, 72 ± 114 mm3, and 27 ± 46 mg/cm3, comparing well to the values from standard unenhanced CT (187 ± 309, 72 ± 110 mm3, and 27 ± 45 mg/cm3) yielding an excellent correlation (r = 0.96, r = 0.96, r = 0.92; P < 0.001). Mean estimated radiation dose revealed 0.83 ± 0.02 mSv from the unenhanced CT and 1.70 ± 0.53 mSv from the contrast enhanced CCTA. Single-source dual-energy scanning with GSI allows CAC quantification from low dose contrast enhanced CCTA by virtual iodine contrast subtraction.  相似文献   

14.
Background We designed and evaluated a low-attenuation oral contrast agent for abdominal-pelvic computed tomography (CT). Methods In vitro studies, were performed initially to evaluate the imaging characteristics of multiple solutions. These studies resulted in two solutions being compared with the presently accepted oral CT agents of dilute iodinated contrast and water. Ninety-eight consecutive subjects already scheduled for routine outpatient abdominal-pelvic CT were enrolled. Subjects were randomized to water (n = 30), fiber solution (n = 32), polyethylene glycol (PEG; n = 11), or dilute iodinated solution (DI; n = 25). Examinations were then evaluated for gastric distention, small bowel distention, small bowel wall visualization, and colonic transit. A questionnaire was given to the study subjects for feedback concerning taste and potential side effects from these agents. Results PEG tended to provide better bowel distention, wall visualization, and colonic transit compared with water, fiber solution, and DI. Areas of statistical significance included: (1) average bowel diameter in the left upper quadrant for water was 17.50 mm, whereas that for PEG was 21.88 mm (p < 0.05); (2) average bowel diameter in the pelvis for water was 14.79 mm, that for fiber was 15.67 mm, and that for PEG was 18.48 mm (p < 0.05); (3) wall visualization was better with PEG than with fiber (p < 0.05); (4) successful transit of contrast to the colon occurred in every subject who received PEG compared with only 20% of those received water and 39% of those who received fiber (p < 0.05). Similar trends for the superiority of PEG over DI were noted, although many of these did not reach statistical significance. Conclusion PEG solution has imaging characteristics related to bowel wall visualization, luminal distention, and colonic transit that make it an effective oral agent for abdominal pelvic CT examination.  相似文献   

15.
Human gastric mucin MUC5AC is secreted in the colonic mucus of cancer patients and is a specific marker of precancerous lesions called aberrant crypt foci. Using MUC5AC as a specific marker can improve sensitivity in the detection of early colorectal cancer. Here we demonstrated that the accumulation of MUC5AC in xenograft and mouse stomach can be detected by magnetic resonance imaging (MRI). We used ultrasmall particles of iron oxide (USPIOs) conjugated with disulfide constrained heptapeptide that were identified using a screening phage display. To accomplish this, we employed positive selection of the phage display library on MUC5AC purified from fresh human colonic adenomas in combination with negative selection of the phage library on purified human MUC2, which is predominantly found in normal colorectal tissues. This conjugate was tested on human colorectal cancer cell lines that were either able or unable to secrete MUC5AC, both in vitro and in vivo. MUC5AC–USPIO contrast agent and USPIOs alone were not detected in cell lines unable to secrete MUC5AC. A combination of MRI and microscopy studies was performed to detect a specific accumulation of the contrast agent in vivo. Thus, the MUC5AC contrast agent enabled non‐invasive detection of precancerous lesions and colorectal cancer, highlighting its potential use in diagnostics, in the early detection of colorectal cancer recurrences after treatment and in mechanistic studies implicating MUC5AC. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

16.
Background To date, no study has compared unenhanced and contrast-enhanced (Levovist) power Doppler ultrasound with three-phase helical computed tomography (CT) for the analysis of the vascularization of hepatic lesions in patients who have alveolar echinococcosis.Methods Fifteen patients (11 female and four male; average age, 45.8 years) with confirmed Echinococcus multilocularis infection underwent unenhanced and contrast-enhanced (Levovist) power Doppler ultrasound (2- to 5-MHz transducer head) and three-phase helical CT. The largest identified lesion in each patient was studied.Results CT visualized vascularization peripheral or central to the largest echinococcal lesions in 11 of 15 patients. Vascularization in the area of the echinococcal lesions was not visualized by unenhanced or contrast-enhanced power Doppler ultrasound in any of the 15 patients studied.Conclusion Three-phase helical CT visualizes the vascularization associated with Echinococcus multilocularis lesions in the liver. Neither unenhanced nor contrast-enhanced ultrasound in power mode is suitable for this application.  相似文献   

17.
Background: In a prospective study, we compared power Doppler with and without contrast medium in the depiction of vascularity for the characterization of hyperechoic renal lesions. Methods: Forty-one hyperechoic renal expansive lesions (29 benign, 12 malignant) in 32 patients were studied with power-Doppler ultrasonography before and after administration of an echo-enhancing agent (Levovist Schering AG, Berlin, Germany). Vascular architecture of the lesions was categorized into five different patterns. Results: Power Doppler ultrasonography showed vascular structures in 25 lesions. The study enhanced with Levovist showed vascularity in eight of 16 lesions not seen on the unenhanced study. The characterization of vascular patterns with unenhanced power Doppler ultrasonography improved diagnostic accuracy compared with gray-scale ultrasonography (59% vs. 32%). The combination of B mode and power Doppler produced even greater diagnostic accuracy (78%), independent of the administration of echo-enhancing agent. Levovist administration was useful in the differential diagnosis between pseudotumor and neoplasm. Conclusion: The use of songraphic contrast agent did not increase the diagnostic accuracy of power Doppler in the differential diagnosis of hyperechoic renal lesions but was advantageous for the characterization of suspected pseudomasses. Received: 6 September 2000/Accepted: 13 December 2000  相似文献   

18.
目的 比较虚拟平扫图像(VUE)和抑碘图像(MSI)与常规CT平扫图像(TUE)质量,观察能谱CT虚拟平扫技术在胸部CT成像中的应用价值。方法 前瞻性收集40例患者行胸部平扫联合增强检查,采用常规扫描模式获得胸部TUE,以GSI Assist模式行双期增强扫描。采用VUE技术基于原始数据重建动脉期、静脉期虚拟平扫图像(AP-VUE、VP-VUE),通过后处理抑碘技术获得双期抑碘图(AP-MSI、VP-MSI)。测量胸主动脉、肺动脉、竖脊肌及胸壁皮下脂肪CT值及其标准差(SD值),并计算CNR,采用5分法对图像进行主观评分,以单因素方差分析及Kruskal-Wallis H法、Mann-Whitney U法进行统计学分析。结果 AP-MSI肺动脉及胸主动脉CT值与TUE比较差异有统计学意义(P均<0.005),VP-MSI及双期VUE各部位CT值、CNR值及SD值与TUE间差异无统计学意义(P均>0.005)。双期MSI及AP-VUE图像各项主观评分均低于TUE(P均<0.005),VP-VUE图像各项主观评分与TUE比较差异均无统计学意义(P均>0.005)。虚拟平扫较常规平扫辐射剂量降低19.29%。结论 VUE技术可在降低辐射剂量的同时获得较MSI更好的图像质量,尤其VP-VUE与TUE图像质量相当,有代替常规胸部平扫的潜能。  相似文献   

19.
目的:初步评价乳化碘油增强CT对大鼠肝脏炎性假瘤的诊断作用。材料与方法:将甘油、卵磷脂及超液化碘油乳化成油包水乳剂;按0.422g碘/kg剂量,静脉注入10只大鼠肝炎性假瘤模型,CT观察瘤灶的显示情况。结果:正常肝脏均匀一致高度强化,清楚显示出低密度瘤灶。结论:乳化碘油是一种有潜在价值的肝脾高度特异性造影剂,对肝脏小病灶显示有重要作用。  相似文献   

20.
Targeting of the endothelial inflammatory adhesion molecule E‐selectin by magnetic resonance imaging (MRI) was performed with a superparamagnetic contrast agent in the context of in vitro and in vivo models of inflammation. The specific contrast agent was obtained by grafting a synthetic mimetic of sialyl Lewisx (sLex), a natural ligand of E‐selectin expressed on leukocytes, on the dextran coating of ultrasmall particles of iron oxide (USPIO). This new contrast agent, called USPIO‐g‐sLex, was tested, in vitro, on cultured human umbilical vein endothelial cells (HUVECs) stimulated to express inflammatory adhesion molecules, and in vivo, on a mouse model of hepatitis. In vitro, HUVECs were stimulated with the pro‐inflammatory cytokine tumor necrosis factor alpha (TNF‐α) and were then incubated with USPIO‐g‐sLex or ungrafted USPIO. In vivo, hepatitis was induced on NMRI mice by injection of concanavalin A (Con A). USPIO‐g‐sLex and ungrafted USPIO were injected intravenously. In vitro results showed an extensive retention of USPIO‐g‐sLex on TNF‐α stimulated HUVECs. Image intensity and R2 measurements performed on T2‐weighted MR images demonstrated a significantly higher binding of USPIO‐g‐sLex on stimulated HUVECs. In vivo, USPIO are known to pass through the fenestrae of the liver and to be captured by Kupffer cells, inducing a loss of signal intensity on T2‐weighted MR images. Unexpectedly, when injected to Con A‐treated mice, USPIO‐g‐sLex induced a significantly lower attenuation of liver signal intensity than USPIO or USPIO‐g‐sLex injected to healthy mice, or USPIO injected to Con A‐treated mice, suggesting that the specific contrast media is retained extracellularly by an interaction with E‐selectin overexpressed on the vascular endothelium. Both in vitro and in vivo results therefore indicate that USPIO‐g‐sLex is recognizing endothelial E‐selectin. USPIO‐g‐sLex is thus well suited for the MRI diagnosis of inflammation and for the in vitro evaluation of endothelial cells activation. Copyright © 2006 John Wiley & Sons, Ltd.  相似文献   

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