A dendrimer-based nanosized contrast agent dual-labeled for magnetic resonance and optical fluorescence imaging to localize the sentinel lymph node in mice

PURPOSE: To preoperatively and intraoperatively localize the sentinel lymph node (SLN), a single hybrid probe for MR and near infrared (NIR) optical imaging was synthesized and tested. MATERIALS AND METHODS: A macromolecular MR/NIR optical contrast agent was synthesized based on a approximately 191 gadolinium-labeled contrast agent using generation-6 polyamidoamine dendrimer (G6), which is also labeled with 2 Cy5.5, an NIR fluorophore. After establishing the optimal dose, the agent was injected into mammary glands of 10 normal mice to examine the lymphatic drainage from the breast using a 3T clinical scanner. Immediately after the MRI scan, NIR optical imaging and image-guided surgery were performed to compare the two imaging modalities. RESULTS: To consistently identify the SLNs, we needed to inject 25 microL of 30 mM [Gd] G6-Cy5.5. All SLNs could be easily identified and resected under NIR optical imaging-guided surgery. Although external NIR optical imaging failed to identify SLNs close to the injection site due to shinethrough, MR lymphography (MRL) consistently identified all SLNs regardless of their location. CONCLUSION: We have successfully synthesized and tested a dual labeled MR/NIR optical hybrid contrast agent, G6-Cy5.5 for reoperative and intraoperative localization of SLNs.     

Near-infrared fluorescence imaging of lymph nodes using a new enzyme sensing activatable macromolecular optical probe

The aim of this study was to validate the use of near infrared fluorescence imaging (NIRF) using enzyme-sensitive optical probes for lymph node detection. An optical contrast probe that is activated by cystein proteases, such as cathepsin B, was used to visualize lymph nodes by NIRF reflectance imaging. In order to quantitate the uptake of the optical probe in lymphatic tissue, the biodistribution was assessed using the Indium-111 labeled optical probe. Sixteen Balb-c mice were injected either intravenously (i.v.) or subcutaneously (s.c.) with the NIRF-probe (2 mol cyanine (Cy)/animal; i.v., n=10; s.c., n=6) and imaged 24 h after injection. Signal intensities and target-to-background ratios of various lymph nodes were measured by manual regions of interest (ROIs). Additional signal intensity measurements were performed of excised lymph nodes (n=21) from i.v. injected mice (24 h after injection) and compared with excised lymph nodes (n=8) of non-injected mice. The probe employed in this study was lymphotropic with approximately 3–4% accumulation in lymph nodes (3.4±0.8% ID/g). Measurements of the excised lymph nodes (after i.v. injection) confirmed a significant increase in lymph node fluorescence signal from baseline 26±7.6 arbitary units (AU) to 146±10.9 AU (p<0.0001). A significant increase in lymph node fluorescence signal was also seen in vivo throughout the body after i.v. injection (96±7.8 AU) and/or regionally after s.c. injection (141±11.5 AU) in comparison with baseline autofluorescence (26±7.6 AU). Target-to-background ratio was significantly higher after s.c. injection (6.6%±0.81) compared with i.v. injection (4.8±0.67%). Detection and visualization of lymph nodes is feasible by NIRF imaging using a cystein-protease sensitive optical probe.     

Multimodal fusion imaging ensemble for targeted sentinel lymph node management: initial results of an innovative promising approach for anatomically difficult lymphatic drainage in different tumour entities

Purpose There are situations where exact identification and localisation of sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand-held gamma probe and vital dye, either a priori or a posteriori. We developed a new method using a simultaneous injection of two lymphotropic agents for exact topographical tomographic localisation and biopsy of draining SLNs. The purpose of this prospective pilot study was to investigate the feasibility and efficacy of this method ensemble. Methods Fourteen patients with different tumour entities were enrolled. A mixture of ^99mTc-nanocolloid and a dissolved superparamagnetic iron oxide was injected interstitially. Dynamic, sequential static lymphoscintigraphy and SPECT served as pathfinders. MR imaging was performed 2 h after injection. SPECT, contrast MRI and, if necessary, CT scan data sets were fused and evaluated with special regard to the topographical location of SLNs. The day after injection, nine patients underwent SLN biopsy and, in the presence of SLN metastasis, an elective lymph node dissection. Results Twenty-five SLNs were localised in the 14 patients examined. A 100% fusion correlation was achieved in all patients. The anatomical sites of SLNs detected during surgery showed 100% agreement with those localised on the multimodal fusion images. SLNs could be excised in 11/14 patients, six of whom had nodal metastasis. Conclusion Our novel approach of multimodal fusion imaging for targeted SLN management in primary tumours with lymphatic drainage to anatomically difficult regions enables SLN biopsy even in patients with lymphatic drainage to obscure regions. Currently, we are testing its validity in larger patient groups and other tumour entities.     

Interstitial magnetic resonance lymphography using a polymeric t1 contrast agent: initial experience with Gadomer-17

RATIONALE AND OBJECTIVES: The detection of lymph node metastases is an important step in tumor staging and is significant for therapy planning. Lymph node-specific contrast agents can raise the sensitivity and specificity of modern diagnostic methods. This study investigated the suitability of the dendritic contrast agent Gadomer-17 in magnetic resonance (MR) lymph node imaging and compared three different dosages in such an application. METHODS: Doses of 1.0, 2.5, and 10.0 micromol Gd/kg body weight were interstitially injected into the hind legs of dogs; the signal intensities of two successive lymph node groups (inguinal and iliacal) were then recorded up to 120 minutes after injection. RESULTS: Gadomer-17 induced a strong increase in signal intensity of the examined lymph node groups. At 15 minutes postinjection, the enhancement increased by 120% to 680%, depending on the dose. The maximum enhancement was 450% to 960% at 60 to 90 minutes postinjection. Doses of 2.5 and 10.0 micromol Gd/kg showed comparable results; even the lowest dose (1.0 micromol Gd/kg) enhanced the contrast of the inguinal lymph nodes in 4 of 5 animals and the iliacal lymph nodes in three of five animals. Therefore, the minimum effective dose of Gadomer-17 in this study was approximately 2.5 micromol Gd/kg. CONCLUSION: This study revealed the excellent suitability of the dendritic contrast agent Gadomer-17 for MR imaging of the lymphatic system (lymph nodes and lymph vessels).     

MR淋巴管造影显示VX2兔乳腺癌前哨淋巴结

目的:探讨钆剂增强的MR淋巴管造影(MR- LG)用于VX2兔乳腺癌前哨淋巴结(SLN)显像的可行性.方法:采用VX2肿瘤软组织块悬液注射法建立30只兔原位乳腺癌动物模型.实验兔在肿瘤接种前后共行2次MR- LG检查(包括对比剂注射前的STIR序列扫描).图像3D重建后,淋巴管引流通路上距离原发肿瘤最近的淋巴结定义为SLN,且成像效果根据3D图像上有无淋巴结和淋巴管显像分成良好和较差两个等级;记录STIR序列扫描和MR- LG显示的所有淋巴结,并与前哨淋巴结病理对照.结果:80％ (24/30)的荷瘤兔完成第二次MR- LG检查,良好3D图像为79.2％ (19/24).在MR - LG图像上,淋巴结信噪比(SNR)均高于其引流淋巴管和同层肌肉(P值均＜ 0.05),SLN与n-SLN、引流淋巴管与同层肌肉之间的SNR无统计学差异.MR- LG图像上可清晰显示SLN和n-SLN(共26枚)的17只荷瘤兔,其STIR图像上共有28枚淋巴结,且两者淋巴结的大小无明显差异(t=0.124,P=0.902);其SLNB检查获得32枚淋巴结(SLN18枚,n- SLN 14枚),且淋巴结大小与MR- LG图像上和STIR序列扫描所显示的淋巴结无统计学差异.结论:钆剂增强MR-LG可较好地显像VX2兔乳腺癌SLN.     

Development of nanoparticle‐based magnetic resonance colonography

This study was to develop a novel method of nanoparticle‐based MR colonography. Two types of solid lipid nanoparticles (SLNs) were synthesized with loading of (a) gadolinium (Gd) diethylenetriaminepenta acetic acid to construct Gd‐SLNs as an MR T1 contrast agent and (b) otcadecylamine‐fluorescein‐isothiocyanate to construct Gd‐fluorescein isothiocyanate (FITC)‐SLNs for histologic confirmation of MR findings. Through an in vitro experiment, we first evaluated the size distribution and gadolinium diethylenetriaminepenta acetic acid entrapment efficiency of these SLNs. The SLNs displayed a size distribution of 50–300 nm and a gadolinium diethylenetriaminepenta acetic acid entrapment efficiency of 56%. For in vivo validation, 30 mice were divided into five groups, each of which was administered a transrectal enema using: (i) Gd‐SLNs (n = 6); (ii) Gd‐FITC‐SLNs (n = 6); (iii) blank SLNs (n = 6); (iv) gadolinium diethylenetriaminepenta acetic acid (n = 6); and (v) water (n = 6). T1‐weighted fluid‐attenuated inversion‐recovery MRI was then performed on mice after transrectal infusion of Gd‐SLNs or Gd‐FITC‐SLNs, which demonstrated bright enhancement of the colonic walls, with decrease in T1 relaxation time. When Gd‐FITC‐SLNs were delivered, green fluorescent spots were visualized in both the extracelluar space and the cytoplasm through colonic walls under confocal microscopy and fluorescence microscopy. This study establishes the “proof‐of‐principle” of a new imaging technique, called “nanoparticle‐based MR colonography,” which may provide a useful imaging tool for the diagnosis of colorectal diseases. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Limited pelvic lymphadenectomy using the sentinel lymph node procedure in patients with localised prostate carcinoma: a pilot study

Purpose The purpose of this study was to determine the potential role of the sentinel lymph node (SLN) procedure in limited lymph node dissection in patients with apparently localised prostate carcinoma.Methods In 27 patients with organ-confined prostate cancer, a single injection of 0.3 ml/30 MBq ^99mTc-rhenium sulphur colloid was injected transrectally into the peripheral zone of each lobe of the prostate (total 0.6 ml/60 MBq) under ultrasound guidance. Two hours after injection, scintigraphy was performed. The first step in surgery was the detection and dissection of lymph nodes identified as SLNs. Then, standard lymphadenectomy was performed, consisting in a limited dissection that included all lymph nodes from the obturator fossa and along the external iliac vein. Lymphatic tissue along the hypogastric artery was not systematically removed, except in the presence of SLNs.Results Mean patient age was 66 years (48–77); the mean serum prostate-specific antigen value was 10.6 ng/ml. In a high proportion of patients (21/27, 77.8%) an SLN was located along the initial centimetres of the hypogastric artery. The second most frequent site of SLNs was in the obturator fossa (11/27 patients, 40.7%), followed by the external iliac area (5/27 patients, 18.5%). Four patients had lymph node metastases, all in SLNs: two in the hypogastric area and two in the obturator fossa. Conclusion The SLN procedure revealed the individual variability in the lymphatic drainage of the prostate. The main site of SLNs was the hypogastric area, and two of the four metastatic nodes were located at this site. A limited standard pelvic lymphadenectomy, excluding the hypogastric lymph nodes, would have missed half of the lymph node metastases in this study. A radionuclide SLN procedure could assist in the correct staging of patients with early prostate cancer, especially when performing limited lymphadenectomy.     

MR lymphography with superparamagnetic iron oxide for sentinel lymph node mapping of N0 early oral cancer: A pilot study

Objectives:The purpose of this pilot study was to evaluate the usefulness of magnetic resonance lymphography (MRL) with superparamagnetic iron oxide (SPIO) in sentinel lymph node (SLN) mapping of clinically N0 early oral cancer, and to conduct a comparative study of this MRL with CT lymphography (CTL).Methods:CTL and MRL were performed for SLN mapping before surgery for 20 patients with clinically N0 early oral cancer. The detection rate, number, and location of SLNs in CTL and MRL were evaluated. Furthermore, optimal scanning/imaging timing in MRL was examined.Results:SLNs were detected by CTL in 18 (90%) patients, and the total and mean number of SLN were 35 and 1.8, respectively. All SLNs could be detected 2 min and 3.5–5 min after contrast medium injection. In all patients, SLNs were detected by MRL at 10 min after SPIO injection, and the total and mean number of SLN was 53 and 2.7, respectively. MRL at 30 min after the injection showed additional 18 secondary lymph nodes.Conclusion:MRL with SPIO is safe and useful imaging for the detection of SLNs in clinically N0 early oral cancer, and the optimal imaging timing is 10 min after SPIO injection.     

Breast sentinel lymph node mapping at CT lymphography with iopamidol: preliminary experience

PURPOSE: To evaluate sentinel lymph node (SLN) mapping with interstitial computed tomographic (CT) lymphography with small volumes of iopamidol for direction of SLN biopsy in breast cancer. MATERIALS AND METHODS: Thin-section transverse and three-dimensional CT images that included the breast and axilla were acquired at multi-detector row helical CT in 17 patients with operable breast cancer before subcutaneous injection of 2 mL of undiluted iopamidol into peritumoral and periareolar areas and 1-5 minutes after massage of injection sites. Location and size of SLNs were assessed at CT lymphography and were compared with SLNs at standard axillary lymph node dissection with blue dye staining. RESULTS: CT lymphography allowed localization of SLNs in all patients by means of visualization of a direct connection between an SLN and its afferent lymphatic vessels draining from the injection sites. Afferent vessels were joined and drained into a single axillary SLN, except in four patients with two or three SLNs, including a parasternal one. SLNs did not enhance because of rerouting of lymph flow in four patients. At surgery, SLNs that were stained or not stained with blue dye were easily found with CT lymphographic guidance. Tumoral infiltration was not evident in any resected nodes, except for infiltration in one patient with micrometastasis in SLN alone and infiltration in four patients with massive metastasis in both SLN and distant nodes. CONCLUSION: Because preoperative CT lymphography-guided SLN mapping provides SLN position with detailed lymphatic anatomy, it may be useful for the direction of breast SLN biopsy.     

Use of radiotracer for sentinel lymph node mapping in breast cancer optimizes staging independent of site of administration

PURPOSE: In an effort to optimize sentinel lymph node (SLN) mapping for breast cancer, sites of mapping agent administration and types of mapping agents used continue to be evaluated. This study compares SLN mapping using peritumoral (PT) or subareolar (SA) injection of radiolabeled colloid and examines the relative contributions of radiotracer and blue dye to SLN identification. MATERIALS AND METHODS: A retrospective review was performed of 456 patients with breast cancer and clinically negative axillae who underwent SLN mapping. Sequential groups of patients were injected with filtered Tc-99m SC, 326 peritumorally (group 1) and 130 subareolarly (group 2). All patients had intraoperative SA injection of 1% isosulfan blue dye. RESULTS: The SLN identification and isotope success rates were 97% and 96% in group 1 and 98% and 98% in group 2, respectively. Eighty-one patients (25%) in group 1 and 44 patients (34%) in group 2 had positive SLNs. Of these patients, 15% from group 1 and 14% from group 2 had only positive nodes detected by radiotracer, and 9 of these patients (6 from group 1 and 3 from group 2) had other nodes identified by both radiotracer and blue dye that were negative for metastases. Six percent of patients with positive SLNs were upstaged because of use of radiotracer. CONCLUSIONS: PT and SA injection of radiotracer have comparable success rates for axillary SLN identification. Given that 15% of patients in group 1 and 14% in group 2 had only positive SLNs detected by radiotracer, independent of site of administration, radiotracer remains essential for optimizing breast SLN mapping.     

Lymphoscintigraphy of melanoma: Lymphatic channel activity guides localization of sentinel lymph nodes, and gamma camera imaging/counting confirms presence of radiotracer in excised nodes

Lymphoscintigraphy has become a standard preoperative procedure to map the cutaneous lymphatic channel for progression of nodal metastasis of melanoma of the skin. Lymphoscintigraphy was employed to visualize lymphatic channels as a guide to identify sentinel lymph nodes (SLNs). Excised tissue was imaged with a gamma camera to verify the findings of presurgical lymphoscintigraphy. Percent counts of SLN(s) among the total counts of the excised melanoma tumor or scar tissue and SLN(s) were calculated. METHODS: Eleven patients with cutaneous melanoma received four to ten intradermal injections of Tc-99m sulfur colloid at elual distances around the melanoma site. Images were made immediately after injection: 1 minute per image for 15 min; and then 5 minutes or 1,000,000 counts per image for 30 min. After surgery, the excised melanoma tumor or scar and SLN(s) were imaged/counted with a gamma camera. Percent counts of SLNs among the total counts of the excised melanoma tumor or scar tissue and SLNs were calculated. To validate the specimen count accuracy, an experimental phantom study was done. RESULTS: Linear lymphatic channels were identified between the injected sites and the SLNs in each patient. Gamma camera images demonstrated radioactivity in the SLNs of all patients, verifying the lymphoscintigraphy findings. Uptake in the SLNs of ten of the eleven patients ranged from 0.4 to 7.2% (mean 2.2%) of the total counts in excised tissue. We noted that a node with lower uptake should not be ignored because a lower percent of SLN activity does not necessarily rule out existing metastasis. In two of eleven patients, histopathologic showed metastases. One patient's melanoma on the middle back had lymphatic channel activity directed to both axillae. The results of the phantom study validated accuracy of our specimen counts. CONCLUSIONS: Because linear lymphatic channels existed between lymph nodes and the injected sites in all eleven patients, these lymphatic channels could be used as a guide for localizing SLNs. The SLNs indicated by presurgical lymphoscintigraphy were verified by postoperative gamma camera imaging, and radiotracer localization in the SLNs averaged 2.2%.     

Reproducibility of lymphoscintigraphy in cutaneous melanoma: can we accurately detect the sentinel lymph node by expanding the tracer injection distance from the tumor site?

The aim of the study was to determine whether the sentinel lymph node (SLN) can be accurately detected in cutaneous melanoma patients when the injection distance from the tumor site is expanded. METHODS: In 100 patients with cutaneous melanoma, lymphoscintigraphy was performed twice. First, we injected 37 MBq (99m)Tc nanocolloid intracutaneously at a 2- to 5-mm distance from either the melanoma or the biopsy scar. The injection was followed by dynamic imaging, which continued until the SLN became visible. On another day, we repeated the investigation, injecting the radiopharmaceutical intracutaneously exactly 10 mm from the previous injection site. The detected SLNs of both investigations were compared to determine the number and location of SLNs for each patient. RESULTS: The SLN identification rate was 94% with close injection and 100% with 10-mm-distant injection. All SLNs detected with close injection were visible with distant injection. In 84 of 100 patients, the images of both investigations showed the same number and location of SLNs. In the remaining 16 patients, an additional SLN was detected with the distant injection. CONCLUSION: The reproducibility of lymphoscintigraphy using different injection distances was 84%. The discordance in the remaining 16% was caused by detection of a lymph node in addition to the original SLN with distant injection. Diagnostic excision of the primary tumor before lymphoscintigraphy was possible without preventing detection of the original SLN. However, in 16% of our patients, excision of an additional lymph node had to be considered when lymphoscintigraphy was performed after diagnostic excision.     

Contrast-assisted ultrasound for sentinel lymph node detection in spontaneously arising canine head and neck tumors

OBJECTIVES: We sought to evaluate a minimally invasive contrast-assisted ultrasound (US) technique for sentinel lymph node (SLN) localization. METHODS: Microbubble contrast medium was injected into peritumoral tissues in 10 dogs with spontaneous head or neck tumors. Regional lymph nodes (LNs) were imaged up to 20 minutes after contrast administration using power Doppler US. Comparative lymphoscintigraphy studies were performed in all dogs by peritumoral injection of 99mTc-sulfur colloid administered around the primary lesion. RESULTS: US contrast enhancement of SLN revealed sentinel nodes and associated lymphatics in 8 of 10 dogs. In each instance in which contrast-enhanced LN was identified with US, a corresponding SLN was detected by lymphoscintigraphy. Multiple SLNs were present in 2 dogs. Regional lymph nodes were positive for metastasis in 1 dog and reactive in 9 dogs. CONCLUSIONS: Contrast-assisted US is effective in localizing SLN. This technique could reduce or eliminate many of the limitations of current SLN detection procedures.     

Localization of breast sentinel lymph nodes by MR lymphography with a conventional gadolinium contrast agent. Preliminary observations in dogs and humans

Purpose: 
To test the capability of an indirect MR lymphography (MRLG) using a conventional extracellular gadolinium (Gd)-based contrast agent for localizing breast sentinel lymph node (SLN). Methods: 
A total of 1 and 0.5 ml of undiluted gadopentetate dimeglumine were injected subcutaneously into the two periareolar areas overlying each caudal mammary gland in 10 female dogs. Contiguous 2-mm-thick fast gradient echo MR images were acquired through the upper breast and axilla before and for 60 min after gentle massage at the injection sites, yielding 3D displays. The localized SLN was resected from the living animals, followed by post mortem examinations. MRLG (1 ml contrast agent injected) was also attempted in 5 female volunteers. Results: 
Even with 0.5-ml contrast agent, the MRLG clearly visualized the connection of SLN and lymphatic vessels directly draining from the injection sites, and the remaining distant nodes, with the maximal enhancement peaks within 10 min after massage. The 3D images provided comprehensive anatomy of these lymphatic pathways in each axilla. Of the 20 SLN and 128 distant nodes visualized on the MRLG, all the SLN (100%) and 107 (83.5%) distant nodes could be resected pre- and post mortem, in good correlation with the locations and sizes on the MR images. MRLG also effectively localized SLN in the volunteers, without significant adverse effects. Conclusion: 
An indirect MRLG using small volumes of conventional Gd-based contrast agent may have potential for accurate identification and surgical biopsy of breast SLN.     

乳腺癌前哨淋巴结CT淋巴管造影的可行性分析

目的 初步评价CT淋巴管造影(LG)显示早期乳腺癌前哨淋巴结(SLN)的可行性.方法 选取25例穿刺证实且腋窝触诊为阴性的乳腺癌患者行CT-LG检查.自注射部位指向腋窝方向的引流淋巴管上最先显像的1个或数个淋巴结为SLN,与前哨淋巴结活检(SLNB)结果相对照,数目相等者为符合,多于和少于分别为高估和低估.显像质量根据容积重组后有无淋巴管显像分为Ⅰ和Ⅱ级;并以体质量指数(BMI)≥25时为肥胖.对所得结果行Fisher精确检验.结果 (1)25例患者中,5例有局部切除手术史;BMI＜25者20例,≥25者5例.(2)25例患者CT-LG均见SLN显像,其中84.0%(21例)患者图像质量为Ⅰ级,16.0%(4例)为Ⅱ级.肥胖患者CT-LG显像质量较差,两者差异有统计学意义(P＜0.05).(3)25例患者共显示56枚SLN和45条淋巴管.与SLNB对照,36.0%(9例)患者两种结果符合,而高估和低估者分别为28.0%(7例)和36.0%(9例).造成两种结果不一致的原因主要与肥胖因素和局部切除手术有关,两者差异均有统计学意义(P＜0.05).(4)SLNB证实18例(52枚)阴性SLN,7例(15枚)阳性SLN,对应CT-LG共56枚SLN显像,其中阴性43枚,阳性13枚.形状为圆形在阴性和阳性SLN的比例分别为32.6%(14/43)和76.9%(10/13),二者差异有统计学意义(P＜0.05).中央区出现充盈缺损在阴性和阳性SLN中的比例分别为9.3%(4/43)和23.1%(3/13),但边缘区表现为不规则充盈缺损只在30.8%(4/13)的阳性SLN中出现.3枚(2例)SLN周围伴有多发小淋巴结,组织学显示有癌细胞浸润.结论 CT-LG可有效显示乳腺癌的SLN,但其准确性易受患者肥胖因素及患侧乳房手术的影响.SLN为圆形,边缘出现虫蚀样充盈缺损,以及伴有多发小淋巴结者均可提示痛细胞浸润.     

Lymphatic drainage from esophagogastric tract: feasibility of endoscopic CT lymphography for direct visualization of pathways

PURPOSE: To evaluate the feasibility of an endoscopic computed tomographic (CT) lymphography technique with submucosal injection of iopamidol for direct visualization of lymphatic drainage pathways in dogs and in patients with operable esophageal cancer. MATERIALS AND METHODS: With institutional animal committee approval, a total of 2 mL of undiluted iopamidol was injected into the esophageal (n = 6) or gastric (n = 3) submucosa in nine dogs by using a flexible endoscope. Multi-detector row CT images (section thickness, 1.25 mm) were obtained before contrast material injection and during the 10 minutes after injection. The animals were euthanized so that their lymphatic anatomy could be examined. With ethical committee approval and patient informed consent, nine patients with esophageal cancer also underwent CT lymphography with peritumoral injection of 2 mL of iopamidol, followed by esophagectomy and regional lymph node dissection with CT lymphographic guidance. The histopathologic features of dissected nodes, including sentinel lymph nodes (SLNs), were examined. RESULTS: CT lymphography depicted the direct connection of lymphatic drainage vessels with enhanced and/or unenhanced nodes (ie, SLNs) as early as within 5 minutes after contrast material injection in all subjects. All 13 SLNs in dogs (1.4 nodes per animal) and 18 SLNs in patients (two nodes per patient) were found and dissected at the correct location by using CT lymphographic guidance. In patients, histopathologic examination revealed the high predictive value of CT lymphographic-guided SLN biopsy: Only one of the preoperatively identified SLNs in three patients and both SLNs and adjacent nodes in two patients were positive for metastasis; all resected nodes in the remaining four patients were negative. CONCLUSION: Endoscopic CT lymphography is a feasible method for visualizing the direct connection between and the accurate anatomic location of SLNs and lymphatic drainage vessels.     

3D重建及CPR技术在乳腺癌腋窝前哨淋巴结CT淋巴管造影检查中的实验研究

目的 探讨多层螺旋CT 3D重建及曲面重建(CPR)技术在乳腺癌腋窝前哨淋巴结(SLN)CT淋巴管造影(CT-LG)检查中的应用价值.方法 采用VX2肿瘤组织块悬液皮下注射法制作VX2乳腺癌大白兔动物模型,对其行CT-LG检查.所有原始数据传至后处理工作站,运用3D重建及CPR技术显示显影的淋巴管及淋巴结,CT-LG图像上SLN定义为自对比剂注射部位至腋窝方向最先引流的淋巴结,并与SLN活检结果对照.结果 (1)20只荷瘤兔行CT-LG检查后,3D重建及CPR可显示SLN及其引流淋巴管;且70%(14/20)的实验兔成像效果良好,CT-LG共显示22条引流淋巴管,16枚SLN,7枚非SLN.(2)3D图像显示连续且对比剂充填均匀的8条淋巴管在CPR图像上均显示为均匀、连续的线管状高密度影;3D图像大部分显示对比剂充盈良好,局部中断或模糊的14条淋巴管,在CPR图像上均见自对比剂注射部位至腋窝SLN方向的连续的密度不均的线管状高密度影.余6只实验兔CT-LG检查显像效果较差,其中3只SLN显影淋巴管未显影,其CPR图像见自对比剂注射部位至SLN方向显影浅淡的线管状略高密度影,密度不均匀;而2只仅淋巴管起始段显影及1只SLN和淋巴管均未显影的实验兔,CPR图像与3D图像显像效果类似.(3)前哨淋巴结活检(SLNB)共摘取SLN 24枚,病理为转移性18枚,阴性6枚.淋巴结长径及CT-LG显像SLN出现充盈缺损在转移性和阴性SLN中有统计学差异(P=0.041和P=0.001);淋巴结短径、形状及边缘清晰与否在二者间无统计学意义(均P>0.05).结论 CT-LG检查中3D重建及CPR技术均可有效显示腋窝SLN及淋巴管的形态,且CPR技术显示更清楚、细致;淋巴结长径及CT-LG显像SLN的充盈缺损有助于鉴别转移性和阴性SLN.     

MR Lymphography with a Lymphotropic T1-Type MR Contrast Agent: Gd-DTPA-PGM

A model system of a paramagnetic lymphotropic MR contrast agent (Gd-DTPA labeled polyglucose associated macrocomplex, PGM) for T¹-weighted MR imaging of lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) and MR imaging data (optimal dose and timing parameters) were obtained in normal rats (n = 88) after subcutaneous (SC) injection of paramagnetic, radiolabeled [111In]Gd-DTPA-PGM. A rabbit model of lymph node metastases (n = 8) was ultimately used to demonstrate the potential of MR imaging with Gd-DTPA-PGM for nodal tumor detection. Maximum concentrations of Gd-DTPA-PGM were found in popliteal and paraaortic lymph nodes within 24 h after SC administration, and highest lymph node SNR values were obtained by MR imaging at this time point. The optimum imaging dose was 6–12 μmol Gd/kg. Tumor-lymph node contrast increased from 0.0 ± 1.2 precontrast to 19.2 ± 6.5 (spoiled gradient echo sequence, TR 50/TE 7/flip angle 60°) postcontrast and conspicuity of nodal metastases was improved. Gd-DTPA-PGM accumulates in lymph nodes after SC administration and significantly enhances lymph node signal intensity of normal animals but not metastatic lymph nodes.     

The Clinical Value of Hybrid Sentinel Lymphoscintigraphy to Predict Metastatic Sentinel Lymph Nodes in Breast Cancer

Purpose

Hybrid imaging techniques can provide functional and anatomical information about sentinel lymph nodes in breast cancer. Our aim in this study was to evaluate which imaging parameters on hybrid sentinel lymphoscintigraphy predicted metastatic involvement of sentinel lymph nodes (SLNs) in patients with breast cancer.

Methods

Among 56 patients who underwent conventional sentinel lymphoscintigraphy, 45 patients (age, 53.1 ± 9.5 years) underwent hybrid sentinel lymphoscintigraphy using a single-photon emission computed tomography (SPECT)/computed tomography (CT) gamma camera. On hybrid SPECT/CT images, we compared the shape and size (long-to-short axis [L/S] ratio) of the SLN, and SLN/periareolar injection site (S/P) count ratio between metastatic and non-metastatic SLNs. Metastatic involvement of sentinel lymph nodes was confirmed by pathological biopsy.

Results

Pathological biopsy revealed that 21 patients (46.7 %) had metastatic SLNs, while 24 (53.3 %) had non-metastatic SLNs. In the 21 patients with metastatic SLNs, the SLN was mostly round (57.1 %) or had an eccentric cortical rim (38.1 %). Of 24 patients with non-metastatic SLNs, 13 patients (54.1 %) had an SLN with a C-shape rim or eccentric cortex. L/S ratio was 2.04 for metastatic SLNs and 2.38 for non-metastatic SLNs. Seven (33 %) patients had T1 primary tumors and 14 (66 %) had T2 primary tumors in the metastatic SLN group. In contrast, 18 (75 %) patients had T1 primary tumors and six (25 %) had T2 tumors in the non-metastatic SLN group. S/P count ratio was significantly lower in the metastatic SLN group than the non-metastatic SLN group for those patients with a T1 primary tumor (p = 0.007).

Conclusions

Hybrid SPECT/CT offers the physiologic data of SPECT together with the anatomic data of CT in a single image. This hybrid imaging improved the anatomic localization of SLNs in breast cancer patients and predicted the metastatic involvement of SLNs in the subgroup of breast cancer patients with T1 primary tumors.     

Early MR lymphography with gadofluorine M in rabbits

PURPOSE: To investigate the dose and time dependency of gadofluorine M for lymph node imaging and the detection of lymph node metastases in an animal model and to compare gadofluorine M with Gadomer (both, Schering, Berlin, Germany) for lymph node enhancement. MATERIALS AND METHODS: Enhancement of popliteal and iliac lymph nodes was studied in VX2 tumor-bearing rabbits before injection and at 5-120 minutes and 24 hours after intravenous bolus injection of 0.025, 0.05, and 0.1 mmol gadolinium per kilogram of body weight gadofluorine M (six rabbits) or 0.5 mmol/kg Gadomer (eight rabbits). Effects of treatment and time point at enhancement were evaluated with repeated measures analysis of variance. Means were separated with all-pairs comparison with Tukey-Kramer adjustment. After 1.5-T magnetic resonance (MR) imaging, lymph nodes were removed, and prepared sections were stained with hematoxylin-eosin for microscopic examination. RESULTS: MR images in VX2 tumor-bearing rabbits revealed rapid and strong signal intensity increase in the functional lymph node tissue by 15 minutes after intravenous injection of gadofluorine M. Maximum enhancement of 165%-309% was observed 60-90 minutes after injection (enhancement with 0.05 and 0.1 mmol/kg significantly different from that with 0.025 mmol/kg, P < or =.05). Metastatic tissue showed only slight enhancement at early time points, resulting in high-contrast differentiation between functional and metastatic tissue. Intravenous injection of the blood-pool agent Gadomer induced only short and inhomogeneous lymph node enhancement (enhancement significantly lower [P < or =.05] than that with gadofluorine M). CONCLUSION: Findings in the study showed that gadofluorine M produces rapid lymph node accumulation. Diagnosis of lymph node metastases was shown with intravenous injection of gadofluorine M with a minimum effective diagnostic dose of 0.025 mmol/kg.