新型MR对比剂长循环超顺磁氧化铁脂质体纳米微粒的体内外实验研究

目的 评价自制新型MR对比剂:长循环超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)脂质体纳米微粒的药代动力学.方法 以加入SPIO为对照组,加入长循环SPIO脂质体纳米微粒为实验组.(1)巨噬细胞的体外吞噬实验:将巨噬细胞株RAW 264.7经复苏、培养,细胞达到80%～90%融合后,以每孔2.5×105个细胞接种于培养板,对照组和实验组细胞与不同浓度药物孵化后,分别测定细胞中Fe浓度和Fe染色情况,并用析因设计的方差分析对结果进行统计学处理.(2)小鼠体内药物分布实验:C57BL/6J雄性小鼠6只,每组2只,设为空白对照组、对照组、实验组,经尾静脉分别注射生理盐水、SPIO以及长循环SPIO脂质体后牺牲动物,经病理检查观察2组药物在体内的分布情况.(3)荷肺癌裸鼠MR成像实验:建立20只BALB/c裸鼠移植型肺癌模型,分为对照组和实验组,每组10只,分别经尾静脉注入SPIO和长循环SPIO脂质体纳米微粒后行MR扫描,测量增强前后2组实验动物各时间点肝脏和肿瘤ROI的信号强度,绘制信噪比(SNR)时间动态变化曲线,采用协方差分析比较2组动物肝脏及肿瘤增强12 h 后SNR差异有无统计学意义.(4)细胞毒性实验(噻唑蓝,MTT法):检查2种药物对人肝细胞株HL-7702细胞的毒性作用,用析因设计的方差分析对结果进行统计学处理.结果 (1)巨噬细胞的体外实验:析因分析结果表明,对照组细胞内Fe含量明显高于实验组,差异有统计学意义(F=296 839.9,P=0.000).普鲁士蓝染色显示对照组巨噬细胞染色较深,实验组巨噬细胞染色较浅.(2)小鼠体内药物分布实验:对照组肝、脾、肺、肾组织内蓝染颗粒多于实验组.(3)荷肺癌裸鼠MR成像实验:平扫对照组肝脏SNR为31.47±0.56,实验组为30.89±1.41;增强扫描12 h后对照组为17.00±0.96,实验组为22.29±0.73.平扫对照组肿瘤SNR为58.41±0.61,实验组为58.44±1.08;增强扫描12 h后对照组为58.50±0.63,实验组为52.47±1.18.经协方差分析表明增强12 h后对照组肝脏SNR显著低于实验组(F=167.022,P=0.000);而实验组肿瘤 SNR显著低于对照组(F=266.106,P=0.000).(4)细胞毒性实验:随着培养液中Fe浓度的增加,HL-7702细胞生存率均有下降趋势,但析因分析结果表明,实验组药物的细胞毒性较对照组低(F=2256.204,P=0.000).结论 长循环SPIO脂质体纳米微粒在体内外均有较好的抗巨噬系统吞噬功能,在体内实现了长循环,对非网状内皮系统的肿瘤也具有良好的T2负性被动靶向强化效果;同时还降低了SPIO对细胞的毒性作用.

Abstract：

Objective To evaluate pharmacodynamics of prepared long-circulating superparamagnetic iron oxide (SPIO) liposomes. Methods Control and experimental groups were established after adding SPIO or long-circulating SPIO liposomes as agents. (1)Macrophages experiment in vitro: the RAW 264.7 macrophage cell strains were recovered, cultured and seeded in the culture plate at a density of 2.5×105 cells/well until they reached 80%-90% confluence. The intracellular Fe uptake of control and experimental group cells were quantified by Ferrozine assay after incubation with different concentrations of drugs. Factorial design analysis of variance was used as statistics method. Prussian blue staining method was used to detect staining of experimental cells.(2)Drug biodistribution in mice: C57BL/6J(n=6) were classified into blank control group (n=2), control group(n=2) and experimental group(n=2).Saline, SPIO and long circulating SPIO were injected via the tail vein in the blank control group, control group and experimental group respectively. Then distribution of drugs in the body was observed by pathological examination.(3) MR imaging of tumor-bearing nude mice: 20 BALB/c nude mice bearing lung cancer models were established and classified into control group and experimental group. After administration of drugs, all animals underwent MR scanning. Signal intensities of livers and tumors were measured, SNR-time dynamic curves were drew. Covariance analysis was used to compare post-enhanced SNR at the 12th hour. (4)Cytotoxicity studies (MTT): cytotoxicity of both drugs on human liver cell line HL-7702 was studied, and statistically analyzed using factorial design analysis of variance. Results (1) Macrophages experiment in vitro: The nanoparticle uptake by macrophage cells evaluated by ferrozine assay showed the uptake of blank SPIO was higher than long-circulating SPIO liposomes. Compared with the blank control group, there was strong blue staining in the macrophages with Prussian staining in the control group and little blue staining in the experimental group. (2) Drug biodistribution in mice: for blue stained cells composed of iron particles, the amounts in the liver, spleen, lung, kidney of the control group were more than those in the experimental group. (3) MR imaging of tumor-bearing nude mice: the non-enhanced SNR of livers and tumors in the control group and experimental group were 31.47 ± 0.56, 30.89 ± 1.41, 58.41 ± 0.61, 58.44 ± 1.08, respectively. After injecting of contrast agents, SNR of livers and tumors in the control group and experimental group were 17.00 ± 0.96, 22.29 ± 0.73, 58.50 ± 0.63, 52.47 ± 1.18, respectively. The covariance analysis showed that SNR of the livers in the control group after 12 hours was significantly lower than the experimental group (F=167.022, P=0.000); while the SNR of the tumors in the experimental group was significantly lower than the control group (F=266.106, P=0.000).(4) Cytotoxicity of nanoparticles by MTT method: the viability of HL-7702 cells tend to decrease with the increase of Fe concentration. Cytotoxicity in the long-circulating SPIO liposomes was lower than the SPIO(F=2256.204,P=0.000). Conclusions Long-circulating SPIO liposomes we prepared reveal suitable sizes, even distribution, and good anti-macrophage ability in vitro and in vivo. They have long circulation characteristic and T2 negative enhancement effect in the transplanted lung cancers, while they still maintain low cytotoxicity.     

脾脏血管肉瘤的CT表现（附1例报告）

脾脏原发性恶性肿瘤非常少见。脾脏原发性血管肉瘤,又称恶性血管内皮细胞瘤,是一种高度恶性的血管源性肿瘤。迄今为止,据文献报告约140余例。我院偶遇一例,现报告如下: 病例资料:患者,女必,40岁。自觉上腹部疼痛不适,伴乏力、心悸、消瘦二月余。体检:左中上腹扪及一包块,表面光滑,质偏硬,活动性差。实验室检查提示中度贫血。     

孤立性肺结节病灶CT分析

孤立性肺内病灶的鉴别诊断是影像学一个难点,本文就103例孤立性肺内病灶CT检查,重点从形态学角度进行分析。 材料与方法 103例病人,男82例,女21例,年龄16～75岁(平均54岁)。诊断均经手术和穿刺活检病理证实。病灶直径为1～6cm。肺癌66例,结核瘤17例,炎性假瘤5例,肺段性炎症3例,机化性肺炎3例,肺隔离症1例,肺梗死1例,     

四肢肌间海绵状血管瘤的MRI诊断

目的：探讨MRI对四肢肌间海绵状血管瘤的诊断价值。方法：经手术病理证实的四肢肌间海绵状血管瘤13例,术前行MRSET1WI、T2WI及动态增强扫描。回顾性分析其MRI表现并总结其特征。结果：13例中3例肿瘤位于上肢,10例位于下肢,其中有4例位于膝关节附近。12例表现为单发的团块状病灶,1例为多个病灶。病灶大小不等,最长径1.5～20.1cm。T2WI上瘤灶呈均匀或混杂高信号;T1WI上5例呈低信号,5例呈等信号,3例呈稍高信号。增强扫描示病灶呈不均匀明显强化。近关节者与远离关节者表现有较大差异,1例位于膝关节附近者导致膝关节广泛受损,另1例位于腘窝者导致邻近软骨组织增生并致膝关节挛缩畸形,余11例无周围组织明显受累征象。结论：四肢肌间海绵状血管瘤的MRI表现有一定特征性,结合临床症状及体征,可对其做出定位及定性诊断。     

放射治疗后肝脏损伤的动态增强MRI表现

目的探讨立体定向放射治疗后肝脏损伤的MRI表现及动态增强的强化特点。资料与方法回顾性分析26例原发性肝癌经立体定向放射治疗后行MRI平扫及动态增强复查的患者,分别观察T1WI、T2WI放射性肝损伤区域的信号特点和动态增强的强化方式并计算其放射治疗后的间隔时间,对动态增强强化方式的间隔时间进行统计学分析。结果在平扫T1WI上,放射性肝损伤区域呈低信号49人次,平均间隔时间为(82±38)d,呈等信号5人次,平均间隔时间为(28±12)d;T2WI上,放射性肝损伤区域呈等信号8人次,平均间隔时间为(26±18)d,呈高信号46人次,平均间隔时间(98±43)d。在T1WI动态增强上,动静脉期无强化(Ⅰ型)10人次,平均间隔时间为(32±18)d;在动脉期轻度强化,呈低或稍高信号,静脉期有强化呈等或稍高信号(Ⅱ型)12人次,平均间隔时间为(92±35)d;动静脉期明显强化都呈高信号(Ⅲ型)32人次,平均间隔时间为(110±72)d,Ⅰ型与Ⅱ型、Ⅲ型的间隔时间相比有显著性差异,Ⅱ型与Ⅲ型的间隔时间无显著性差异。结论放射性肝损伤因时间不同而呈不同的强化特点,推测是对放射性肝损伤动态演变不同阶段的反映,这对鉴别放射性肝损伤不同阶段有重要意义。     

肝局灶性病变CT与MRI动态增强对照研究

目的:探讨肝局灶性病变在CT和MRI动态增强中的影像差异及其原因,以提高对CT及MRI各自动态增强表现的认识。方法:搜集17例肝脏局灶性病变患者的临床资料,其中7例肝细胞肝癌,5例海绵状血管瘤,2例腺瘤,2例局灶结节性增生,1例转移瘤。全部病例均分别行CT及MRI的平扫和三期动态增强扫描;MRI采用SE序列加快速扰相梯度回波序列,将CT和MR动态增强图像进行对照观察,包括动态增强各期的强化范围、强化方式和强化幅度,强化幅度的比较用病灶密度(信号)与肝脏密度(信号)的比值进行比较。结果:肝癌、腺瘤和局灶结节性增生在CT与MRI上强化范围相似。1例肝癌动脉期强化幅度MRI大于CT,3例肝癌和2例局灶结节性增生门脉期及延迟期强化幅度MRI大于CT,2例腺瘤增强各期强化幅度MRI均大于CT,以动脉期差异最大。5例海绵状血管瘤强化范围动脉期及门脉期MRI大于CT,延迟期则相仿。1例转移瘤CT增强各期均未见明显强化,MRI门脉期及延迟期可见环状强化。结论:肝局灶性病变CT与MRI动态增强表现存在一定的差异,主要表现为部分病变增强各期强化幅度MRI大于CT,尤以动脉期差异最大;部分病变增强范围MRI大于CT。     

甲状腺病变的CT诊断及鉴别诊断

目的:分析甲状腺病变的CT表现,探讨各种甲状腺病变CT诊断及鉴别诊断要点。方法:回顾性分析经手 术病理证实的32例甲状腺病变的CT资料。所有病例均行CT平扫,26例行CT增强扫描。结果:本组32例甲状腺病变 的CT表现,可分为三大类型:①单结节型16例,包括甲状腺腺瘤8例、结节性甲状腺肿4例、甲状腺癌4例;②多结节型 13例,包括结节性甲状腺肿7例、甲状腺癌6例;③弥漫肿大型3例,包括Graves病1例、桥本病2例。CT对甲状腺恶性 病变的诊断符合率达88.5%,对良性病变的诊断符合率达78.3%。结论:掌握各种甲状腺病变的CT表现特点及分型,对 病变的定性诊断及鉴别诊断具有重要意义。     

MRI动态增强鉴别复发性肝癌和放射性肝损伤

目的 :探讨立体定向放射治疗原发性肝癌后MRI在鉴别复发性肝癌和放射性肝损伤的诊断价值。方法 :12名原发性肝癌立体定向放射治疗后怀疑复发的患者行MRT1WI、T2 WI和T1WI动态增强检查 ,分别测量复发性肝癌和放射性肝损伤的T1WI、T2 WI的信噪比及强化程度 ,并进行统计学分析。结果 :复发性肝癌和放射性肝损伤在T1WI和T2 WI上信号表现相似 ,两者SNR对比差异无显著性意义。增强扫描后 ,复发性肝癌在动脉期强化 ,静脉期及延迟期呈低信号 ,强化持续时间短 ;放射性肝损伤动脉期强化 ,强化持续时间长 ,静脉期及延迟期亦呈高信号 ,两者明显不同。结论 :MRI动态增强可有效的鉴别复发性肝癌和放射性肝损伤     

婴幼儿胸壁错构瘤的影像诊断

目的：探讨婴幼儿胸壁错构瘤（MHCW）的临床影像特征。方法：回顾性分析2例病理确诊为MHCW婴儿的临床影像资料。2例患儿临床表现为发热、咳嗽,均行胸部X线正侧位片及CT增强扫描。结果：2例患儿胸片均表现为左侧胸腔类圆形密度不均肿块,受累肋骨受压变形。CT显示肿物源自肋骨,境界清晰,内见高密度钙化样密度影,中心肋骨膨胀变形,增强后肿物部分区域轻度强化。结论：MHCW的影像表现具有一定特征性,确诊需依靠组织病理学检查。