磁共振间质淋巴造影实验研究

目的:探讨间质MR淋巴造影对肢体淋巴水肿的诊断价值。方法:用改良的Danese手术方法在13只新西兰大白兔后肢一侧形成淋巴水肿模型,另一侧作为对照。在每只大白兔双侧后肢足背部趾蹼处注射0.2ml欧乃影,按摩注射部位30秒钟。分别于造影剂注射前后进行三维MR淋巴造影及延迟淋巴造影成像。结果:实验侧淋巴管阻塞早期为渗出性改变及淋巴管侧支开放,晚期出现淋巴管扩张、迂曲、皮肤逆流。引流远端淋巴结显影较对照侧明显延迟。对照侧欧乃影吸收迅速,引流区域各组淋巴结、淋巴管及胸导管显示清晰。结论:间质MR淋巴造影可以在解剖背景下很好地显示引流区域淋巴管、淋巴结的解剖形态、功能及其异常表现。     

磁共振淋巴造影技术方法研究

目的：评估欧乃影介导的磁共振间质淋巴造影在诊断前列腺癌盆腔淋巴转移的可行性和安全性。方法：所有30例病理确诊前列腺癌患者,采用1.5T菲利浦超导型磁共振成像仪检查。先完成盆腔前列腺平扫,接着皮下注射造影剂欧乃影行三维增强磁共振淋巴造影术（3D CE-MRL）,最后欧乃影静脉注射盆腔前列腺增强扫描。结果：皮下注射后,欧乃影迅速吸收进入淋巴系统,引流区域各组淋巴结、淋巴管显示清晰。结论：皮下注射＂欧乃影＂行磁共振间质淋巴造影术诊断前列腺癌患者盆腔淋巴转移是可行和安全的。     

纳米探针BaGdF_5-PEG作为MR淋巴显像剂的实验研究

目的:CT或MR淋巴显像技术(CT/MR-LG)对前哨淋巴结(SLN)性质的评估还存在不足之处,而如果将这两种技术结合起来则有可能提高评估的准确性。在前期研究中我们已经验证纳米探针BaGdF_5-PEG可以作为CT-LG造影剂。在本研究中,我们将继续探讨纳米探针BaGdF_5-PEG作为MR-LG新型造影剂显像兔乳腺SLN的可行性。方法:采用水热法制备具有良好水溶性及生物相容性的纳米探针BaGdF_5-PEG。采用6只健康雌性新西兰白兔作为实验对象,于每只兔右侧第2乳晕皮下注射0.1 mL BaGdF_5-PEG,所有实验兔均行两次T1加权成像,分别为造影剂注射前以及注射后20 min;将从注射点至腋窝方向上的淋巴引流通路中最先增强的淋巴结定义为SLN,记录MR-LG图像显示的所有SLN,并将MR-LG结果与前哨淋巴结活检(SLNB)对照。结果:皮下注射BaGdF_5-PEG后20 min对实验兔行MR-LG,所获图像显示从注射点至腋窝方向上的淋巴引流通路中均可见明显增强的SLN,每只实验兔各显像一枚SLN,且MR-LG结果与SLNB结果一致。结论:纳米探针BaGdF_5-PEG作为兔乳腺SLN的MR淋巴显像剂是可行的。     

肢体淋巴水肿磁共振淋巴造影技术方法的实验研究

目的：研究肢体水肿演变过程中不同时期的胍淋巴造影影像特征夏其病理基础,探讨MR淋巴造影在肢体淋巴水肿方面的诊断价值。方法：用改良的Danese手术方法在20只新西兰大白兔后肢一侧形成淋巴水肿模型,另一侧作为对照。在每只大白兔双侧后肢足背部趾硅处注射0.2ml欧乃影,于淋巴水肿演变过程的不同时期进行三维胍淋巴造影。结果：胍淋巴造影能准确地确定淋巴管阻塞的部位,反映淋巴管形态、功能的状况。肢体淋巴水肿的不同时期,由于其病理基础不同。产生不同的MR淋巴造影表现。结论：间质MR淋巴造影可以在解剖背景下敏感而又可靠地显示各期肢体淋巴水肿。     

超微超顺磁性氧化铁纳米粒检测良恶性淋巴结的实验研究

目的:研究超微超顺磁性氧化铁纳米粒(USPIO)增强MRI检测正常、反应性增生淋巴结和肿瘤转移淋巴结的价值.方法:新西兰免24只,静脉注射0.2mmolFe/kg的USPIO,原子吸收光谱仪检测兔体内脏器铁含量.另取4只兔,作为正常淋巴结组.4只兔双侧后腿肌肉注射蛋黄乳胶,用于建立腘窝反应性增生淋巴结模型,4只兔后腿肌肉接种VX2肉瘤,用于建立腘窝肿瘤转移淋巴结模型.3组动物均静注0.2mmolFe/kg的USPIO,于注射前、注射后12h分别行MRI扫描,观察淋巴结信号强度变化.扫描后取出淋巴结,行HE染色、普鲁士蓝染色观察淋巴结结构变化,铁颗粒的存在,原子吸收光谱仪检测铁含量.结果:USPIO在兔体内血循环时间较长(>12h),除脾肝肺外,其主要分布至淋巴结等网状内皮细胞和吞噬细胞.MRI平扫时,正常、反应性增生淋巴结和肿瘤转移淋巴结T2信号强度无显著差异,静注USPIO后,正常、反应性增生淋巴结中心T2信号强度明显降低,肿瘤转移淋巴结信号强度无明显变化.HE染色、普鲁士蓝染色和原子吸收光谱仪检测显示,正常、反应性增生淋巴结均舍有USPIO铁颗粒,而肿瘤转移性淋巴结淋巴结结构丧失,未见铁颗粒.结论:静脉注射USPIO后MR成像可用来鉴别良恶性淋巴结.     

兔VX2肝癌模型微波消融后磁共振灌注成像的可行性与应用价值

目的通过兔VX2模型探讨肿瘤消融治疗后动态变化过程中,磁共振灌注成像动态量化研究的可行性及其价值。方法16只新西兰大白兔分为实验组12只,对照组4只。实验组在兔肝脏种植VX2肿瘤后,观察肿瘤直径超过2.0 cm时行微波消融治疗。对比术后当天7、d、14 d及28 d实验组与对照组磁共振灌注成像量化指标—最大增强斜率（MSI）的动态变化差异,并与病理结果对照分析。结果对照组兔及实验组兔术后当天肝实质灌注MSI差异无显著性;实验组兔术前肿瘤与术后当天残留肿瘤的平均MSI差异无显著性;实验组兔残留肿瘤与良性强化组织的MSI差异有显著性。残留肿瘤的时间-信号强度曲线表现为快速上升型;良性强化组织的时间-信号强度曲线表现为缓慢上升型。结论磁共振灌注成像的动态量化研究是可行的,量化指标MSI与消融治疗后各种组织的病理结果相吻合,可更为准确地量化表达病变组织的病理状态的改变。     

家兔盲肠和阑尾淋巴管的研究

用色素穿刺注入法、动脉内墨汁硝酸银水溶液注入法研究了家兔盲肠和阑尾淋巴管的起始、走向及所属淋巴结。盲肠和阑尾的毛细淋巴营均起始于固有膜,后依次穿过肠壁各层移行为系膜内淋巴管。后者经阑尾、盲肠淋巴结与肠系膜上淋巴结群中的相应淋巴结相联系。盲肠粘膜下层淋巴管内开始出现瓣膜;阑尾淋巴管瓣膜则在阑尾系膜缘内才出现。     

肢体淋巴水肿磁共振淋巴造影技术方法的实验研究

目的:研究肢体水肿演变过程中不同时期的MR淋巴造影影像特征及其病理基础,探讨MR淋巴造影在肢体淋巴水肿方面的诊断价值。方法:用改良的Danese手术方法在20只新西兰大白兔后肢一侧形成淋巴水肿模型,另一侧作为对照。在每只大白兔双侧后肢足背部趾蹼处注射0.2ml欧乃影,于淋巴水肿演变过程的不同时期进行三维MR淋巴造影。结果:MR淋巴造影能准确地确定淋巴管阻塞的部位,反映淋巴管形态、功能的状况。肢体淋巴水肿的不同时期,由于其病理基础不同,产生不同的MR淋巴造影表现。结论:间质MR淋巴造影可以在解剖背景下敏感而又可靠地显示各期肢体淋巴水肿。     

CpG加入脂质体疫苗配方的效果

<正>已经证明,脂质体疫苗配方中含有靶向天然免疫受体的刺激物会明显增加疫苗的免疫力。疫苗接种后,天然细胞群对免疫刺激物发生反应、吞噬和加工抗原,通过淋巴输入管道从注射点进入局部淋巴结。在这样的终端接受到的信号推动并塑造适应性免疫应答。然后效应淋巴细胞通过淋巴输出管离开淋巴结以执行其系统功能。作者直接将导管插入绵羊的淋巴管以详细研究疫苗用加入了Cp G的基于脂质体投递系统接种后,在局部淋巴引流网络中发     

正常山羊腰椎间盘营养途径的DCE-MRI观察

目的 研究正常山羊腰椎间盘软骨终板营养途径.方法 选取健康24月龄山羊8只,每只山羊观察4个腰椎间盘,共32个腰椎间盘.麻醉后,行磁共振动态增强扫描,观察感兴趣区的信号变化特点.分别测量增强前及增强后0 min、5 min、10 min、30 rain、1 h、1.5 h、2 h,2.5 h、3 h、3.5 h感兴趣区信号强度值,分析时间-信号强度曲线及峰值出现时间.结果 椎体磁共振信号强度在0 min时达到高峰后迅速下降;软骨终板区在30 min时缓慢达到第一高峰后轻度下降,于2 h上升达到第二高峰;髓核在5 min内为负值,之后缓慢上升于2 h达到高峰,随后逐渐下降.结论 正常山羊腰椎椎间盘主要通过软骨终板途径进行营养代谢.     

Dynamic imaging of lymphatic vessels and lymph nodes using a bimodal nanoparticulate contrast agent

BACKGROUND: Evaluation of lymphedema and lymph node metastasis in humans has relied primarily on invasive or radioactive modalities. While noninvasive technologies such as magnetic resonance imaging (MRI) offer the potential for true three-dimensional imaging of lymphatic structures, invasive modalities, such as optical fluorescence microscopy, provide higher resolution and clearer delineation of both lymph nodes and lymphatic vessels. Thus, contrast agents that image lymphatic vessels and lymph nodes by both fluorescence and MRI may further enhance our understanding of the structure and function of the lymphatic system. Recent applications of bimodal (fluorescence and MR) contrast agents in mice have not achieved clear visualization of lymphatic vessels and nodes. Here the authors describe the development of a nanoparticulate contrast agent that is taken up by lymphatic vessels to draining lymph nodes and detected by both modalities. METHODS: A unique nanoparticulate contrast agent composed of a polyamidoamine dendrimer core conjugated to paramagnetic contrast agents and fluorescent probes was synthesized. Anesthetized mice were injected with the nanoparticulates in the hind footpads and imaged by MR and fluorescence microscopy. High resolution MR and fluorescence images were obtained and compared to traditional techniques for lymphatic visualization using Evans blue dye. RESULTS: Lymph nodes and lymphatic vessels were clearly observed by both MRI and fluorescence microscopy using the bimodal nanoparticulate contrast agent. Characteristic tail-lymphatics were also visualized by both modalities. Contrast imaging yielded a higher resolution than the traditional method employing Evans blue dye. MR data correlated with fluorescence and Evans blue dye imaging. CONCLUSION: A bimodal nanoparticulate contrast agent facilitates the visualization of lymphatic vessels and lymph nodes by both fluorescence microscopy and MRI with strong correlation between the two modalities. This agent may translate to applications such as the assessment of malignancy and lymphedema in humans and the evaluation of lymphatic vessel function and morphology in animal models.     

Enhanced lymph node retention of subcutaneously injected IgG1-PEG2000-liposomes through pentameric IgM antibody-mediated vesicular aggregation

An efficient strategy for enhancing the lymph node deposition of rapidly drained liposomes from the interstitial injection site is described. Subcutaneously injected small-sized immuno-poly(ethyleneglycol)-liposomes (immuno-PEG-liposomes), containing 10 mol% mPEG350-phospholipid and 1 mol% PEG2000-phospholipid in their bilayer and where IgG1 is coupled to the distal end of PEG2000, not only drain rapidly from the interstitial spaces into the initial lymphatic system, but also accumulate efficiently among the lymph nodes draining the region when compared with non-PEG-bearing immunoliposomes where IgG is directly coupled to the phospholipid. Liposome deposition among the draining lymph nodes, however, was further enhanced dramatically following an adjacent subcutaneous injection of a pentameric IgM against the surface attached IgG molecules (IgM:IgG, 10:1) without compromising vesicle drainage from the interstitium. This is suggested to arise either as a result of formation of large immuno-aggregates within the lymphatic vessels with subsequent transport to and trapping among the regional lymph nodes and/or following IgM binding to Fc receptors of the lymph node sinus macrophages forming a platform for subsequent trapping of drained IgG-coupled liposomes. This lymph node targeting approach may be amenable for the design and surface engineering of any rapidly drained nanoparticulate system bearing peptides and proteins that can be aggregated with a desired monoclonal pentameric IgM.     

Enhanced lymph node retention of subcutaneously injected IgG1-PEG2000-liposomes through pentameric IgM antibody-mediated vesicular aggregation

An efficient strategy for enhancing the lymph node deposition of rapidly drained liposomes from the interstitial injection site is described. Subcutaneously injected small-sized immuno-poly(ethyleneglycol)-liposomes (immuno-PEG-liposomes), containing 10 mol% mPEG₃₅₀-phospholipid and 1 mol% PEG₂₀₀₀-phospholipid in their bilayer and where IgG1 is coupled to the distal end of PEG₂₀₀₀, not only drain rapidly from the interstitial spaces into the initial lymphatic system, but also accumulate efficiently among the lymph nodes draining the region when compared with non-PEG-bearing immunoliposomes where IgG is directly coupled to the phospholipid. Liposome deposition among the draining lymph nodes, however, was further enhanced dramatically following an adjacent subcutaneous injection of a pentameric IgM against the surface attached IgG molecules (IgM:IgG, 10:1) without compromising vesicle drainage from the interstitium. This is suggested to arise either as a result of formation of large immuno-aggregates within the lymphatic vessels with subsequent transport to and trapping among the regional lymph nodes and/or following IgM binding to Fc receptors of the lymph node sinus macrophages forming a platform for subsequent trapping of drained IgG-coupled liposomes. This lymph node targeting approach may be amenable for the design and surface engineering of any rapidly drained nanoparticulate system bearing peptides and proteins that can be aggregated with a desired monoclonal pentameric IgM.     

Imaging Lymphatic System in Breast Cancer Patients with Magnetic Resonance Lymphangiography

Objective

To investigate the feasibility of gadolinium (Gd) contrast-enhanced magnetic resonance lymphangiography (MRL) in breast cancer patients within a typical clinical setting, and to establish a Gd-MRL protocol and identify potential MRL biomarkers for differentiating metastatic from non-metastatic lymph nodes.

Materials and Methods

32 patients with unilateral breast cancer were enrolled and divided into 4 groups of 8 patients. Groups I, II, and III received 1.0, 0.5, and 0.3 ml of intradermal contrast; group IV received two 0.5 ml doses of intradermal contrast. MRL images were acquired on a 3.0 T system and evaluated independently by two radiologists for the number and size of enhancing lymph nodes, lymph node contrast uptake kinetics, lymph vessel size, and contrast enhancement patterns within lymph nodes.

Results

Group III patients had a statistically significant decrease in the total number of enhancing axillary lymph nodes and lymphatic vessels compared to all other groups. While group IV patients had a statistically significant faster time to reach the maximum peak enhancement over group I and II (by 3 minutes), there was no other statistically significant difference between imaging results between groups I, II, and IV. 27 out of 128 lymphatic vessels (21%) showed dilatation, and all patients with dilated lymphatic vessels were pathologically proven to have metastases. Using the pattern of enhancement defects as the sole criterion for identifying metastatic lymph nodes during Gd-MRL interpretation, and using histopathology as the gold standard, the sensitivity and specificity were estimated to be 86% and 95%, respectively.

Conclusion

Gd-MRL can adequately depict the lymphatic system, can define sentinel lymph nodes, and has the potential to differentiate between metastatic and non-metastatic lymph nodes in breast cancer patients.     

Anatomy of lymph nodes situated adjacent to the axilla in adult humans]

In 50 right and 50 left upper extremities examined in adult persons of both sex at the age of 28-90 years, delto-thoracic lymph nodes were revealed in 30% (right) and in 22% (left), and interthoracic lymph nodes--in 6% (right) and in 12% (left). The lymph nodes in question were revealed by the method of section after interstitial injection of Gerota's blue intradermally to fingers, palm, back of the hand deltoid area, lateral thoracic surface (at the level of the 6th intercostal space) and to the external part of the mammary gland. Injection was also performed into lymphatic vessels revealed by means of the interstitial injection. The delto-thoracic nodes were stated to situate in both the delto-thoracic sulcus and the delto-thoracic triangle. These vessels are situated along the course of the lateral collector of the free upper extremity. Deferent vessels of the delto-thoracic nodes flow into the apical axillary lymph nodes, into the deep and superficial cervical nodes, into the interthoracic lymph nodes and also into the subclavicular or into the jugular vein near a corresponding venous angle. Interthoracic lymph nodes, situated between musculus pectoralis major and minor, get their lymphatic vessels from lateral, inferior and central axillary nodes, from delto-thoracic nodes and also those lymphatic vessels that go from the mammary gland area. Deferent vessels of the interthoracic nodes flow into the apical axillary nodes.     

The lymphatic system in body homeostasis: physiological conditions

The lymphatic system is an organized network composed of functionally interrelated lymphoid tissue, and transportation pathways of tissue fluid/lymph and lymphoid cells. Its main components are 1. migrating dendritic cells, macrophages and lymphocytes, organized lymphoid tissue such as lymph nodes, thymus, spleen, bone marrow, and lymphoid tissue in gut and lungs, liver lymphoid cells, and the dendritic cell network of nonlymphoid organs; 2. vessels (intercellular space, lymphatics, and perivascular spaces); 3. fluids (tissue fluid and lymph). The lymphatic system can be divided into the following compartments: peripheral (from the interstitial space to and within the nearest lymph node), and central (efferent lymphatics, cysterna chyli, and thoracic duct, all lymphoid organs). Organs and tissues with the most active afferent arm of the lymphatic system are skin, gut, and lungs. These are the body structures exposed to the external environment. All other nonlymphoid bodily tissues are also percolated by tissue fluid/lymph, and contain a network of dendritic cells and macrophages. Data obtained from normal human subjects on lymph composition and flow are presented. Future trends in lymphatic research are outlined.     

Anatomy and topography of the common iliac lymph nodes in human beings in the 1st period of maturity

The investigation of common iliac lymph nodes has been performed in 20 corpses of the first mature age of both sex (5 male and 5 female corpses) of persons died from causes not connected with the lymphatic system diseases, the lower extremities and the pelvic organs. The common iliac lymph nodes with their afferent and efferent lymphatic vessels are revealed by means of interstitial injection into the lower extremities and the pelvic organs and with direct injection into the lymphatic vessels. The form, amount, size and topography of the common iliac lymphatic vessels have been studied. The lymphatic vessels, that go from certain body parts and organs to various subgroups of the common iliac lymph nodes, as well as the lymphatic vessels that connect the nodes both within the subgroup and also between the subgroups. The amount and size of the lymphatic nodes of the lateral subgroup predominate over the nodes of other subgroups of the common iliac lymph nodes; the amount of the common iliac lymph nodes predominates in men, and their size--in women. Amount of these nodes in the right and their size in the left predominate in both sex. Among the common iliac lymph nodes there are no teniform nodes, and efferent lymphatic vessels of the lateral and medial subgroup of the common iliac lymph nodes in 15% of cases run towards the lumbar nodes in the opposite side.     

Adrenergic innervation of lymph nodes and the thoracic duct

By means of incubation of slices in 2% solution of glyoxylic acid distribution of adrenergic fibers in the rabbit lymph nodes and in the thoracic lymphatic duct has been studied. Adrenergic fibers get into parenchyma of the lymph nodes via two ways. The first--the perivascular, when the nervous fibers make a plexus and get into the node along the blood vessels, the second--diffuse nervous fibers get together with trabecules in between the lymphoid nodules. The distribution density of the adrenergic fibers is not the same in different groups of the lymph nodes. In the lumbar nodes it is the highest. In the lymph nodes of the cervical part the density of the sympathetic fibers is, as a rule, lower than in the lumbar, but higher than in the axillary nodes. The lowest density of th adrenergic fibers is in the mesenteric, superficial inguinal lymph nodes and in the lymph nodes, situating near the thoracic part of the aorta. In the lymphatic duct wall small amount of adrenergic fibers are revealed, they form a plexus, predominantly in the cranial part.     

The influence of afferent lymphatic vessel interruption on vascular addressin expression

Tissue-selective lymphocyte homing is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. These vessels, the post capillary high endothelial venules (HEV), are found in organized lymphoid tissues, and at sites of chronic inflammation. Lymphocytes bearing specific receptors, called homing receptors, recognize and adhere to their putative ligands on high endothelial cells, the vascular addressins. After adhesion, lymphocytes enter organized lymphoid tissues by migrating through the endothelial cell wall. Cells and/or soluble factors arriving in lymph nodes by way of the afferent lymph supply have been implicated in the maintenance of HEV morphology and efficient lymphocyte homing. In the study reported here, we assessed the influence of afferent lymphatic vessel interruption on lymph node composition, organization of cellular elements; and on expression of vascular addressins. At 1 wk after occlusion of afferent lymphatic vessels, HEV became flat walled and expression of the peripheral lymph node addressin disappeared from the luminal aspect of most vessels, while being retained on the abluminal side. In addition, an HEV-specific differentiation marker, defined by mAb MECA-325, was undetectable at 7-d postocclusion. In vivo homing studies revealed that these modified vessels support minimal lymphocyte traffic from the blood. After occlusion, we observed dramatic changes in lymphocyte populations and at 7-d postsurgery, lymph nodes were populated predominantly by cells lacking the peripheral lymph node homing receptor LECAM-1. In addition, effects on nonlymphoid cells were observed: subcapsular sinus macrophages, defined by mAb MOMA-1, disappeared; and interdigitating dendritic cells, defined by mAb NLDC-145, were dramatically reduced. These data reveal that functioning afferent lymphatics are centrally involved in maintaining normal lymph node homeostasis.