MRI增强扫描评价兔VX2肿瘤血管生成:Gd-DTPA与USPIO的比照研究

目的 通过对比钆喷替酸葡钾胺(Gd-DTPA)和自制超小超顺磁性氧化铁颗粒(USPIO)的MRI增强扫描,研究两者在评价兔VX2肿瘤血管生成方面的能力.材料与方法 6只兔两侧大腿接种VX2肿瘤,2周后行Gd-DTPA和USPIO-T1WI增强扫描.计算不同扫描序列的最大强化比例(ERmax)、曲线斜率值(Slope)和达峰时间(Tmax),比较不同扫描序列之间的增强参数,并计算其与病理学指标间的Spearman秩相关系数.结果 VX2肿瘤模型成瘤率为100%.行USPIO-T1WI增强扫描后肿瘤组织早期未见明显强化,而后表现为渐进强化.各增强参数在不同扫描序列间的差异有显著统计学意义(P值均＜0.01).增强参数与病理学指标之间具有统计学意义的秩相关系数基本只出现在肿瘤周围;Gd-DTPA的增强参数与病理学指标之间的秩相关系数低于USPIO-T1WI增强扫描的秩相关系数. 结论 USPIO-T1WI增强扫描较Gd-DTPA动态增强扫描,能更好的替代病理学指标定量动态监测肿瘤血管的生成.     

Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro

To evaluate the capacity of human monocytes to phagocytose various approved iron oxide based magnetic resonance (MR) contrast agents and to optimize in vitro labeling of these cells. Human monocytes were incubated with two superparamagnetic iron oxide particles (SPIO) as well as two ultrasmall SPIO (USPIO) at varying iron oxide concentrations and incubation times. Iron uptake in monocytes was proven by histology, quantified by atomic emission absorption spectrometry and depicted with T2* weighted fast field echo (FFE) MR images at 1.5 T. Additionally, induction of apoptosis in iron oxide labeled monocytes was determined by YO-PRO-1 staining. Cellular iron uptake was significantly (P<0.01) higher after incubation with SPIO compared with USPIO. For SPIO, the iron oxide uptake was significantly (P<0.01) higher after incubation with the ionic Ferucarbotran as compared with the non-ionic Ferumoxides. Efficient cell labeling was achieved after incubation with Ferucarbotran at concentrations 500 g Fe/ml and incubation times 1 h, resulting in a maximal iron oxide uptake of up to 50 pg Fe/cell without impairment of cell viability. In vitro labeling of human monocytes for MR imaging is most effectively obtained with the approved SPIO Ferucarbotran. Potential subsequent in vivo cell tracking applications comprise, e.g. specific targeting of inflammatory processes.     

In vitro function of radiocolloid-labelled monocytes

Human monocytes in a mononuclear cell suspension were labelled specifically using ¹¹¹In-Fe-colloid, with the ultimate goal of using them for monocyte kinetic studies in haematological malignancies. In order to examine the function of the labelled monocytes, in vitro function tests were performed on cell suspensions containing labelled or non-labelled monocytes. These tests were: phagocytosis of opsonized zymosan particles and ability of monocytes to mature into macrophages when cultured in glass tissue chambers. There were no significant differences in in vitro function between labelled and non-labelled monocytes. Cell viability was always greater than 90%. During culture, a rapid loss of monocyte-bound radioactivity took place. We conclude that the labelling procedures do not interfere with subsequent in vitro cell function. However, because of the rapid loss of cell bound radioactivity in vitro, monocytes labelled by this method do not seem suited for long-term studies in vivo.     

脐血间充质干细胞磁探针标记和MR成像研究

目的　应用磁性氧化铁纳米粒子和多聚赖氨酸 (Poly L Lysine ,PLL)的偶联物Fe2 O3 PLL ,体外标记人脐血间充质干细胞 (mesenchymalstemcells,MSCS) ,磁共振进行标记细胞成像。方法　制备Fe2 O3 PLL ,分离人脐血MSCS 进行纯化并传代培养 ,标记Fe2 O3 PLL ,普鲁士蓝染色显示细胞内铁 ,四氮噻唑蓝 (MTT)比色试验评价不同浓度Fe2 O3 PLL标记MSCS 后对细胞生长状况的影响 ,Annexin/碘化吡啶 (PI)双染色法检测细胞凋亡 ,应用MR的T1WI、T2 WI、T2 WI3个序列进行细胞群成像。结果　普鲁士蓝染色清晰显示蓝色铁颗粒位于MSCS 胞质内 ,MTT比色试验示 5～ 2 0 0 μg/ml等7个铁浓度组 ,Fe2 O3 PLL标记后细胞的光吸收值与未标记MSCS 者比较 ,各组间总体比较差异无统计学意义(Kruskal Wallis秩和检验 ,χ2 =10 35 ,P =0 17)。标记MSCS 时 ,铁浓度采用 2 0 μg/ml较合适。标记MSCS、未标记MSCS 者晚期凋亡及坏死细胞分别为 5 4 3%、2 95 % ,早期凋亡细胞分别为 9 93%、10 14 %。在MR的T1WI、T2 WI、T2 WI中 ,标记 1× 10 6个MSCS 者、标记 5× 10 5个MSCS 者较未标记MSCS 者均有信号降低改变 ,且前者的降低率大于后者 ,3个序列中以T2 WI的信号强度变化率最大 ;标记 1× 10 6个MSCS 者 ,标记后培养 8d的信号     

大鼠骨髓间充质干细胞磁标记及MR成像研究

目的应用菲立磁．多聚左旋赖氨酸复合物标记大鼠骨髓间充质干细胞，探讨MR成像显示磁标记干细胞的可行性。方法制备菲立磁-多聚左旋赖氨酸复合物。分离培养Wistar大鼠骨髓间充质干细胞，以菲立磁-多聚左旋赖氨酸复合物标记干细胞。分别于标记后24h及1、2、3周行普鲁士蓝染色观察细胞内铁，台盼蓝排除试验检测细胞活力。应用1．5TMR仪，以SE序列T1WI、T2WI和梯度回波（GRE）序列T2＊WI行磁标记干细胞成像。结果普鲁士蓝染色显示细胞质内大量铁颗粒存在，标记率100％；随细胞分裂增殖，细胞内铁颗粒逐渐减少。干细胞磁标记后24h及1、2、3周的台盼蓝拒染率分别为91．00％、93．00％、91．75％和92．50％，与未标记细胞相比较差异无统计学意义（P〉0．05）。10^3、10^4、10^5个磁标记干细胞T2WI信号降低分别为63．75％、82．31％、91．92％，T2＊WI信号降低分别为68．24％、83．01％、93．94％。10^5个干细胞磁标记后24h及1、2、3周T2＊WI信号降低分别为93．75％、75．92％、41．75％、8．83％。结论应用菲立磁-多聚左旋赖氨酸复合物标记大鼠间充质干细胞安全、有效；T2＊WI对磁标记干细胞的显示最敏感；MR信号改变与干细胞数目及分裂增殖状态相关。     

Comparison of in vitro RBC labeling with the UltraTag RBC kit versus in vivo labeling

This study compared cardiac-gated equilibrium blood-pool imaging studies using in vitro technetium-99m- (99mTc) labeled red blood cells (RBCs) prepared with the UltraTag RBC kit to in vivo labeling with stannous (pyro- and trimeta-) phosphates. The in vitro labeling procedure takes approximately 25 min and does not require centrifugation to separate free from bound 99mTc. Imaging studies were performed in 30 patients using the in vitro labeling procedure and in 30 patients with in vivo labeling. Regions of interest were placed over the center of the left ventricle, inferior and lateral to the left ventricle (background), and over the right midlung. The mean +/- s.e. in vitro RBC labeling efficiency was 98.5 +/- 0.2%. The heart-to-background ratios were significantly higher with in vitro labeling. The heart-to-background ratios, averaged among two blinded reviewers, were 4.6 and 3.4 for the in vitro and in vivo methods, respectively. The heart-to-lung ratio was generally higher with the in vitro procedure (3.6) than that observed with the in vivo method (3.2) but failed to attain statistical significance (p = 0.059). These results demonstrate the superiority of the in vitro labeling procedure over in vivo labeling for gated equilibrium blood-pool imaging.     

Hepatic MRI with SPIO: detection and characterization of focal liver lesions

A variety of parenterally administered iron oxides have been developed for contrast-enhanced MRI of the liver. Two different classes of iron oxides are currently clinically approved or in phase 3 trials: superparamagnetic iron oxides (SPIO) with a high R2/R1 relaxivity ratio and short blood half-life (AMI-25 and SH U 555 A), and ultrasmall paramagnetic iron oxides (USPIO) with a lower R2/R1 relaxivity ratio and longer blood half-life (AMI-227). All iron oxides significantly increase tumor-to-liver contrast and allow detection of more lesions than unenhanced MRI on T2-weighted images at a field strength of 0.2–1.5 T. Malignant lesions without phagocytic cells exhibit constant signal on T2-weighted accumulation phase images with all three iron oxides. All iron oxides cause a signal decrease of benign lesions with either phagocytic cells or a significant blood pool on T2-weighted accumulation phase images. The signal decrease of benign lesions is proportional to the Kupffer cell activity or tumor vascularity and is useful for lesion characterization. Another enhancement feature for the differentiation of benign from malignant lesions is ring enhancement of malignant lesions (metastases) on T1-weighted enhanced images either during the perfusion phase with SH U 555 A or during the accumulation phase with AMI-227, which is attributed to the blood pool effects of the compounds. Differentiation of lesions and vessels is easier on enhanced images with angiographic effects than on unenhanced images. Iron oxides improve the quality of two-dimensional MR angiography techniques of the portal venous system by decreasing background signal (liver tissue with all iron oxides) and increasing intravascular signal (AMI-227). The use of iron oxides for hepatic MRI provides an alternative to the existing multistep diagnosis with CT, CT portography, MRI and biopsy. Received: 24 September 1997; Revision received: 12 November 1997; Accepted: 14 November 1997     

MR动脉质子自旋标记与动态磁敏感对比增强灌注技术在脑胶质瘤分级中的价值

目的 探讨动脉质子自旋标记（ASL）与动态磁敏感对比增强（DSC）灌注技术用于脑胶质瘤分级的可行性。方法 经病理证实的28例脑胶质瘤患者，按世界卫生组织2000年规定的胶质瘤分级标准分为高级15例，低级13例。使用3．0TMR扫描仪进行Q2TIPS的ASL检查和静脉团注钆喷替酸葡甲胺（Gd-DTPA）的DSC灌注检查。所得数据经两独立样本秩和检验分析，P〈0．05为差异有统计学意义；并用直线回归的方法分析两种灌注方法的相关性。结果 ASL法测得的脑胶质瘤血流量（TBF）／对侧脑白质相对血流量（CBF）：高、低级别胶质瘤分别为（5．5±1．8）、（2．1±1．4），DSC法测得的值分别为（4．3±1．0）、（2．0±1．1），差异均有统计学意义（Z值分别为-3．824、-3．939，P〈0．01）；ASL法测得的TBF／对侧半球CBF值，高、低级别胶质瘤分别为（2．2±0．8）、（0．8±0．5），DSC法测得的值分别为（2．1±0．8）、（1．0±0．6），差异均有统计学意义（Z值分别为-3．987、-3．386，P〈0．01）；ASL法测得的TBF／对侧灰质CBF值，高、低级别胶质瘤分别为（1．7±0．6）、（0．7±0．5），DSC法测得值分别为（1．6±0．5）、（0．8±0．4），差异均有统计学意义（Z值分别为-3．894、-3．754，P〈0．01）。两种方法测得的上述比值均密切相关（r分别为0．91、0．93、0．91，P〈0．01）。结论 ASL可用于胶质瘤微血管灌注的评估，有助于区分低级别和高级别脑胶质瘤。     

兔动脉粥样硬化斑块:USPIO增强MR与Gd-DTPA增强MR对比实验研究

目的 在MR连续观察下,采用自制超小超顺磁性氧化铁(ultrasmall superparamagnetic iron oxide,US-PIO),与钆喷酸葡胺(Gd-DTPA)对比,分别对动脉粥样硬化(AS)兔行增强MR检查,旨在探讨USPIO增强MR对AS兔的价值.材料与方法35只雄性新西兰大白兔随机分为两组,25只给予高脂饮食诱导动脉粥样硬化,10只给予正常饮食作为对照组.所有扫描均在1.5 T磁共振扫描仪上进行,采用Cardiac线圈.扫描序列包括:T1WISE,T1WI SE脂肪抑制,T2WI FSE,T2*WI GRE.所有动物于喂养10周时测血清总胆固醇量,并进行平扫及USPIO增强24 h扫描,1周后行Gd-DTPA增强扫描,完成Gd-DTPA增强扫描当天处死不同喂养阶段模型兔及同期对照组正常兔,整个过程每2周重复一次.USPIO使用剂量为0.05 mmolFe/kg体重,Gd-DTPA使用剂量为0.25 mmol/kg体重.MR所见与病理相对照.结果 喂养10周时模型兔血清总胆固醇值明显高于正常组(P＜0.05),且所有模型兔大体标本均发生肉眼可见动脉粥样硬化样改变,除5只模型兔喂养中途死亡,其余兔均完成全程扫描.病理证实斑块内巨噬细胞吞噬USPIO.USPIO增强MR较Gd-DTPA增强能更好识别斑块内各种成分.结论 US-PIO增强MR对识别斑块成分具有独特价值,并能反映斑块内炎性浸润,因此对判断斑块易损性优于Gd-DTPA增强MR.     

肾功能损害肾脏肿瘤病人的动脉自旋标记MRI特性:初步经验

目的回顾性评价动脉自旋标记(ASL)MRI对肾功能损害病人的肾脏肿瘤血管评估的可行性。方法 2007年5月—2008年11月,对67例中的11例因中度至重度慢性或急性肾功能衰竭的连续病人行未增强ASL-MRI检查,以评     

Arterial spin labeling MR imaging for characterisation of renal masses in patients with impaired renal function: initial experience

Objectives  

To retrospectively evaluate the feasibility of arterial spin labeling (ASL) magnetic resonance imaging (MRI) for the assessment of vascularity of renal masses in patients with impaired renal function.     

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.     

Comparison of 111In-oxine and 111In-Acetylacetone for the labeling of cells: in vivo and in vitro biological testing

We have compared several complexes of indium as cell labels: indium-111-acetylacetone, indium-111-oxine, and indium-111-chloride complexed with 8-hydroxyquinoline (oxine) immediately prior to use. In labelling with acetylacetone, it was shown that the labeling efficiency is directly proportional to the amount of acetylacetone present, but the cell viability (as measured by in vitro aggregation studies), is inversely proportional to the amount of acetylacetone present. Biological studies were carried out in dogs using indium-111-labeled platelets; survival times and recovery values obtained with platelets labeled using all three techniques were similar. The same solutions were also used to label white blood cells; labeling efficiencies of greater than 80% were obtained in all cases, and the viability (as measured by trypan blue exclusion) was high in all cases. Chemotactic ability of the white cells labeled with indium-111-oxine is higher than that of unlabeled control cells; however, cells labeled with indium-111-acetylacetone were the same as the unlabeled control cells.     

Comparison of oxine and tropolone methods for labeling human platelets with indium-111

The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.     

Comparison of different types of blood pool agents (P792, MS325, USPIO) in a rabbit MR angiography-like protocol

RATIONALE AND OBJECTIVES: The objective of this study is to determine the influence of the pharmacokinetic behaviors of different classes of blood pool agents (BPA) on a rabbit experimental model that mimics a magnetic resonance angiographic protocol. BPA were as follows: P792, a macromolecular agent (RCBPA), USPIO, an ultrasmall superparamagnetic iron oxide particle agent (SCBPA), and MS-325, a small gadolinium chelate that expresses intravascular behavior by reversible albumin binding. METHODS: The 2 main phases of early distribution following contrast agent injection, that is, the bolus phase and the steady-state phase, are investigated by measuring Gd or Fe blood concentrations in the first 5 minutes postinjection. T1 relaxation times and r1 relaxivity were calculated at each time point of blood sampling. Furthermore, in the case of MS-325, the concentrations of the free and bound forms were calculated, according to the measured concentrations and the apparent r1 relaxivities. RESULTS: Injected under similar conditions, the 3 BPA have, during the bolus phase, a comparable profile to Gd-DOTA. Signal enhancement was maximum during this short bolus phase, as were the T1 relaxation times under 30 ms for all agents. At 1 minute postinjection, P792 (r1 = 39 seconds(-1) x mmol/L(-1), 20 MHz) demonstrated the same pharmacokinetic behavior as USPIO (r1 = 33 seconds(-1) x mmol/L(-1), 20 MHz): C1 minute/C0 values were 91 +/- 6% and 92 +/- 12%, respectively. Immediately after the injection at clinical dose, 74% of MS-325 was in free form, resulting in an apparent r1 relaxivity of only 13 seconds(-1) x mmol/L(-1) (20 MHz); 1 minute postinjection, the C1 minute/C0 value of 61 +/- 4% was the lowest as compared with P792 and USPIO and the bound form represented 75% of the MS-325 molecules. CONCLUSIONS: The BPA P792 and USPIO have favorable properties that result from their intravascular retention and their lack of extravasation, allowing optimal contrast between the vessel and the adjacent tissue for several minutes postinjection. Combining a rapid body clearance and a marked T1 effect, P792 presents optimal blood pool characteristics for angiographic applications. During the bolus phase, MS-325 is mainly in free form, which presents the disadvantage of increasing the tissue signal background, due to extravasation of the free form.     

Patellar cartilage lesions: in vitro detection and staging with MR imaging and pathologic correlation

Fourteen freshly disarticulated knee specimens were studied to assess the usefulness of magnetic resonance (MR) imaging in the detection and correct staging of patellar chondral lesions. Axial and sagittal images were obtained; T1-weighted spin-echo sequences were found satisfactory for defining cartilage morphology. Specimens were sectioned and examined grossly for cartilage changes such as softening, blistering, fibrillation, fissuring, and frank subchondral bone exposure. In a side-by-side comparison, all lesions classified grossly in the Shahriaree system as stage II or higher showed MR changes. Stage I changes could not be identified in disarticulated specimens. Stage III lesions showed cartilage irregularity (ulceration) or a loss of the normal, sharply defined margin between coapted cartilage, which represented "crabmeat" fibrillation. Stage IV lesions showed ulceration to bone, sometimes with subchondral bone changes. In this in vitro, preliminary study, MR imaging was found to be an accurate means for detecting and staging moderate and advanced patellar cartilage lesions.     

肿瘤靶向性MR分子探针的标记及研究进展

使用MR分子成像技术对肿瘤细胞进行标记、显像的关键在于MR分子探针的运用。运用不同的分子识别系统合成靶向性探针,从肿瘤的基因、分子水平特异性地诊断肿瘤的发生是肿瘤成像的基础。针对肿瘤细胞的各种MR靶向分子探针标记方法进行综述。     

肿瘤靶向性MR分子探针的标记及研究进展

使用MR分子成像技术对肿瘤细胞进行标记、显像的关键在于MR分子探针的运用。运用不同的分子识别系统合成靶向性探针,从肿瘤的基因、分子水平特异性地诊断肿瘤的发生是肿瘤成像的基础。针对肿瘤细胞的各种MR靶向分子探针标记方法进行综述。     

A novel potential application for 99mTc-HMPAO: endothelial cell labeling for in vitro investigation of cell-biomaterial interactions.

Good adherence of endothelial cells (ECs) seeded on vascular prostheses and cell retention under flow conditions are important factors to consider in the use of functionalized prostheses in vascular surgery. Because 111In-oxine radiolabeling presents disadvantages, we wondered whether, because of its well-known physical properties, 99mTc-hexamethyl propyleneamine oxime (HMPAO or exametazime) could be used. Methods: The cytotoxicity of unlabeled HMPAO and 99mTc-HMPAO at increasing concentrations and activities was tested on monolayers of the EC line EA-hy-926. The influence of temperature and time on tracer incorporation into cells was also tested. The optimal labeling conditions were applied to evaluate the retention of ECs seeded on polyester grafts under flow conditions by gamma camera detection. Results: The activity of 10 MBq/10(6) cells corresponding to 4.5 microg/10(6) cells of unlabeled HMPAO, applied for 3 h at 37 degrees C (cellular uptake = 18%), was the best compromise between the maintenance of cell viability and metabolic activity and efficient detection by the gamma camera. Spontaneous leakage was observed and analyzed by high-performance liquid chromatography. A cell loss of 13% after 180-min exposure to shear stress was obtained. CONCLUSION: Our data thus indicate the feasibility of using such a radiolabeling technique to investigate EC-biomaterial interactions.