快速液体衰减反转回复序列在颅脑肿瘤诊断中的应用价值

１２６例颅脑肿瘤同时行快速液体反转回复序列成像和常规ＦＳＥＴ２Ｗ成像。通过比较分析两者显示病变的能力，探讨ＦＬＩＡＲ对颅脑肿瘤的诊断价值。结果显示示ＦＬＡＩＲ序列ＭＲＩ较Ｔ２ＷＩ有更高的对比度，在显示病变的部位，大小，轮廓，范围和数目方面具有更好的敏感性。     

Development of Bifunctional Gadolinium-Labeled Superparamagnetic Nanoparticles (Gd-MnMEIO) for In Vivo MR Imaging of the Liver in an Animal Model

Liver tumors are common and imaging methods, particularly magnetic resonance imaging (MRI), play an important role in their non-invasive diagnosis. Previous studies have shown that detection of liver tumors can be improved by injection of two different MR contrast agents. Here, we developed a new contrast agent, Gd-manganese-doped magnetism-engineered iron oxide (Gd-MnMEIO), with enhancement effects on both T1- and T2-weighted MR images of the liver. A 3.0T clinical MR scanner equipped with transmit/receiver coil for mouse was used to obtain both T1-weighted spoiled gradient-echo and T2-weighted fast spin-echo axial images of the liver before and after intravenous contrast agent injection into Balb/c mice with and without tumors. After pre-contrast scanning, six mice per group were intravenously injected with 0.1 mmol/kg Gd-MnMEIO, or the control agents, i.e., Gd-DTPA or SPIO. The scanning time points for T1-weighted images were 0.5, 5, 10, 15, 20, 25, and 30 min after contrast administration. The post-enhanced T2-weighted images were then acquired immediately after T1-weighted acquisition. We found that T1-weighted images were positively enhanced by both Gd-DTPA and Gd-MnMEIO and negatively enhanced by SPIO. The enhancement by both Gd-DTPA and Gd-MnMEIO peaked at 0.5 min and gradually declined thereafter. Gd-MnMEIO (like Gd-DTPA) enhanced T1-weighted images and (like SPIO) T2-weighted images. Marked vascular enhancement was clearly visible on dynamic T1-weighted images with Gd-MnMEIO. In addition, the T2 signal was significantly decreased at 30 min after administration of Gd-MnMEIO. Whereas the effects of Gd-MnMEIO and SPIO on T2-weighted images were similar (p = 0.5824), those of Gd-MnMEIO and Gd-DTPA differed, with Gd-MnMEIO having a significant T2 contrast effect (p = 0.0086). Our study confirms the feasibility of synthesizing an MR contrast agent with both T1 and T2 shortening effects and using such an agent in vivo. This agent enables tumor detection and characterization in single liver MRI sections.     

MR Imaging Evaluation of Intracerebral Hemorrhages and T2 Hyperintense White Matter Lesions Appearing after Radiation Therapy in Adult Patients with Primary Brain Tumors

The purpose of our study was to determine the frequency and severity of intracerebral hemorrhages and T2 hyperintense white matter lesions (WMLs) following radiation therapy for brain tumors in adult patients. Of 648 adult brain tumor patients who received radiation therapy at our institute, magnetic resonance (MR) image data consisting of a gradient echo (GRE) and FLAIR T2-weighted image were available three and five years after radiation therapy in 81 patients. Intracerebral hemorrhage was defined as a hypointense dot lesion appearing on GRE images after radiation therapy. The number and size of the lesions were evaluated. The T2 hyperintense WMLs observed on the FLAIR sequences were graded according to the extent of the lesion. Intracerebral hemorrhage was detected in 21 (25.9%) and 35 (43.2) patients in the three- and five-year follow-up images, respectively. The number of intracerebral hemorrhages per patient tended to increase as the follow-up period increased, whereas the size of the intracerebral hemorrhages exhibited little variation over the course of follow-up. T2 hyperintense WMLs were observed in 27 (33.3%) and 32 (39.5) patients in the three and five year follow-up images, respectively. The age at the time of radiation therapy was significantly higher (p < 0.001) in the patients with T2 hyperintense WMLs than in those without lesions. Intracerebral hemorrhages are not uncommon in adult brain tumor patients undergoing radiation therapy. The incidence and number of intracerebral hemorrhages increased over the course of follow-up. T2 hyperintense WMLs were observed in more than one-third of the study population.     

Automated classification of atherosclerotic plaque from magnetic resonance images using predictive models

The information contained within multicontrast magnetic resonance images (MRI) promises to improve tissue classification accuracy, once appropriately analyzed. Predictive models capture relationships empirically, from known outcomes thereby combining pattern classification with experience. In this study, we examine the applicability of predictive modeling for atherosclerotic plaque component classification of multicontrast ex vivo MR images using stained, histopathological sections as ground truth. Ten multicontrast images from seven human coronary artery specimens were obtained on a 9.4 T imaging system using multicontrast-weighted fast spin-echo (T1-, proton density-, and T2-weighted) imaging with 39-mum isotropic voxel size. Following initial data transformations, predictive modeling focused on automating the identification of specimen's plaque, lipid, and media. The outputs of these three models were used to calculate statistics such as total plaque burden and the ratio of hard plaque (fibrous tissue) to lipid. Both logistic regression and an artificial neural network model (Relevant Input Processor Network-RIPNet) were used for predictive modeling. When compared against segmentation resulting from cluster analysis, the RIPNet models performed between 25 and 30% better in absolute terms. This translates to a 50% higher true positive rate over given levels of false positives. This work indicates that it is feasible to build an automated system of plaque detection using MRI and data mining.     

The Utility of Gadoxetic Acid-Enhanced MR Imaging to Characterize Atypical Cirrhotic Nodules Detected on Dynamic CT Images

Purpose

To evaluate whether gadoxetic acid (Gd-EOB-DTPA)-enhanced MR images of tumors taken during the hepatocyte-specific phase can aid in the differentiation between hepatocellular carcinoma (HCC) and dysplastic nodules (DNs) in patients with atypical cirrhotic nodules detected on dynamic CT images.

Materials and Methods

Seventy-one patients with 112 nodules showing atypical dynamic enhancement on CT images underwent gadoxetic acid-enhanced MR imaging (MRI) studies. Using a reference standard, we determined that 33 of the nodules were DNs and that 79 were true HCCs. Tumor size, signal intensity on precontrast T1-weighted images (T1WI) and T2WI, and the pattern of dynamic enhancement on MR images taken in the hepatocyte-phase were determined.

Results

There were significant differences in tumor size, hyperintensity on T2WI, hypointensity on T1WI, typical HCC enhancement pattern on dynamic MR images, or hypointensity on hepatocyte-phase images between DNs and HCC. The sensitivity and specificity were 60.8% and 87.9% for T2WI, 38.0% and 87.9% for T1WI, 17.7% and 100% for dynamic MR imaging, 83.5% and 84.9% for hepatocyte-phase imaging, and 60.8% and 87.9% for tumor size (threshold of 1.7 cm).

Conclusion

Gd-EOB-DTPA-enhanced hepatocyte-phase imaging is recommended for patients at high risk of HCC who present with atypical lesions on dynamic CT images.     

Magnetic Resonance Imaging Assessment of Effective Ablated Volume following High Intensity Focused Ultrasound

Under magnetic resonance (MR) guidance, high intensity focused ultrasound (HIFU) is capable of precise and accurate delivery of thermal dose to tissues. Given the excellent soft tissue imaging capabilities of MRI, but the lack of data on the correlation of MRI findings to histology following HIFU, we sought to examine tumor response to HIFU ablation to determine whether there was a correlation between histological findings and common MR imaging protocols in the assessment of the extent of thermal damage. Female FVB mice (n = 34), bearing bilateral neu deletion tumors, were unilaterally insonated under MR guidance, with the contralateral tumor as a control. Between one and five spots (focal size 0.5 × 0.5 × 2.5 mm³) were insonated per tumor with each spot receiving approximately 74.2 J of acoustic energy over a period of 7 seconds. Animals were then imaged on a 7T MR scanner with several protocols. T1 weighted images (with and without gadolinium contrast) were collected in addition to a series of T2 weighted and diffusion weighted images (for later reconstruction into T2 and apparent diffusion coefficient maps), immediately following ablation and at 6, 24, and 48 hours post treatment. Animals were sacrificed at each time point and both insonated/treated and contralateral tumors removed and stained for NADH-diaphorase, caspase 3, or with hematoxylin and eosin (H&E). We found the area of non-enhancement on contrast enhanced T1 weighted imaging immediately post ablation correlated with the region of tissue receiving a thermal dose CEM43 ≥ 240 min. Moreover, while both tumor T2 and apparent diffusion coefficient values changed from pre-ablation values, contrast enhanced T1 weighted images appeared to be more senstive to changes in tissue viability following HIFU ablation.     

小鼠肺腺癌模型的建立及肿瘤病理分析

目的用乙基亚硝脲（ENU）在BABL/c小鼠建立肺腺癌模型并对ENU所诱发的肺腺癌进行病理观察。方法妊娠17d的SPF级母鼠腹腔接受ENU或缓冲液注射,在子代鼠的鼠龄满32周时收获其全肺标本,对肺组织进行常规石蜡半连续切片,HE染色,镜下观察肿瘤病理。结果 ENU经胎盘一次性诱发子代鼠多发性肺肿瘤形成,病理显示这些肿瘤为处于不同发展阶段的腺瘤和腺癌,腺癌的类型有细支气管肺泡癌样腺癌（雌性：5/6,雄性：4/6）和分化不等的腺癌（雌性：4/6,雄性：5/6）,诱癌频率在雌、雄性小鼠均为5/6,癌变频率在雌性16/43,雄性12/31。结论成功建立了小鼠肺腺癌模型,肿瘤病理的多样性提示癌变机制在分子水平的复杂性。     

Inhibition of inducible nitric oxide synthase in murine visceral larva migrans: effects on lung and liver damage

The roles of nitric oxide production and oxidative process were studied in mice infected with Toxocara canis and treated with aminoguanidine which is a specific inhibitor of inducible nitric oxide synthase (iNOS). Relations of nitric oxide synthase inhibition and tissue pathology were assessed by biochemical, histological and immunohistochemical methods. In experiments, Balb/c albino mice were inoculated with T. canis eggs either with or without aminoguanidine treatment or alone, at 24th, 48th hours and on 7th days. LPx and SOD values in liver tissue and plasma were measured. Liver and lung tissues were evaluated for the pathological lesions. The expression of eNOS and iNOS in both tissues were studied with immunohistochemistry in the same intervals. We observed significant differences between T. canis infected and aminoguanidine treated animals. Larval toxocarosis led to oxidative stress elevation in plasma. Microscopic examination of the liver histological sections revealed pathological lesions in the hepatic parenchyma in infected mice. In the mice received T. canis eggs plus aminoguanidine, the sinusoidal areas were enlarged. Histological lesions were more severe at 48 hours after infection. Numbers of eNOS and iNOS expressing epithelial cells were increased in the T. canis infected mice. The activities of eNOS and iNOS were also observed in the body of the larvae which have migrated to lung and liver. As a result, we have demonstrated that in vivo production of eNO and iNO during T. canis infection cause direct host damages and it is strongly related to the oxidative stress. We propose that larval NO can also be effective in larval migration, but it needs further investigation on distribution of NO in larvae.     

腱鞘巨细胞瘤的影像学诊断

目的:分析腱鞘巨细胞瘤的影像学表现以提高对该病的认识。方法:回顾性分析10例经手术病理证实的腱鞘巨细胞瘤的X线平片及MRI表现,其中10例行X线平片检查,8例行MRI平扫及增强扫描。结果:X线平片显示局部稍高密度软组织肿块影,邻近骨质未见明显异常或轻度侵蚀破坏。MRI表现为相应部位软组织肿块影,T1WI多呈较低信号,内可见条片状更低信号影,增强后强化明显;T2WI呈高低混杂信号影;病灶与邻近肌腱关系密切,其中一例包绕指屈肌腱蔓状生长;局部骨皮质可受侵。结论:腱鞘巨细胞瘤的影像学表现具有一定的特征性。     

IFN和PDS合剂体内抗流感病毒的作用

观察了IFN与PDS合剂的体内抗病毒效果。首先排除IFN和PDS对动物的毒性作用 ,再以不同剂量的单剂和合剂给小鼠用药。用流感强毒株对小鼠进行攻击 ,同时以利巴韦林和正常小鼠作为对照。通过对动物死亡率、肺部病变的病理组织学检查结果进行比较 ,合剂组效果明显好于单剂组 ,且有剂量效应关系。上述结果表明 ,IFN和PDS合剂可明显减轻流感病毒感染过程中的肺组织病变 ,可用于流行性感冒的治疗。     

Monitoring in vivo changes in lung microstructure with ³He MRI in Sendai virus-infected mice

Recently, a Sendai virus (SeV) model of chronic obstructive lung disease has demonstrated an innate immune response in mouse airways that exhibits similarities to the chronic airway inflammation in human chronic obstructive pulmonary disease (COPD) and asthma, but the effect on distal lung parenchyma has not been investigated. The aim of our study is to image the time course and regional distribution of mouse lung microstructural changes in vivo after SeV infection. (1)H and (3)He diffusion magnetic resonance imaging (MRI) were successfully performed on five groups of C57BL/6J mice. (1)H MR images provided precise anatomical localization and lung volume measurements. (3)He lung morphometry was implemented to image and quantify mouse lung geometric microstructural parameters at different time points after SeV infection. (1)H MR images detected the SeV-induced pulmonary inflammation in vivo; spatially resolved maps of acinar airway radius R, alveolar depth h, and mean linear intercept Lm were generated from (3)He diffusion images. The morphometric parameters R and Lm in the infected group were indistinguishable from PBS-treated mice at day 21, increased slightly at day 49, and were increased with statistical significance at day 77 (p = 0.02). Increases in R and Lm of infected mice imply that there is a modest increase in alveolar duct radius distal to airway inflammation, particularly in the lung periphery, indicating airspace enlargement after virus infection. Our results indicate that (3)He lung morphometry has good sensitivity in quantifying small microstructural changes in the mouse lung and that the Sendai mouse model has the potential to be a valid murine model of COPD.     

Pulmonary tumors inefficiently prime tumor-specific T cells

The lung is a common site of metastatic and primary tumor growth, and has been shown to be an immunosuppressive environment. We tested the impact of the lung environment on the development of tumor-specific T cell responses against the CMS5 fibrosarcoma, and found a deficit in the efficacy of naive tumor-specific DUC18 T cells against tumors established in the lung. One hundred-fold more naive tumor-specific T cells were required to protect against tumor development or reject established tumors in the lung than an identical tumor challenge delivered s.c. in the flank. Importantly, CMS5 growing in the flank facilitated the rejection of tumors present in the lungs. In the presence of flank tumors, transferred T cells were not phenotypically altered but were present in much greater numbers in the parabronchial lymph nodes, bronchoalveolar lavage, and lung parenchyma than in mice bearing lung tumors alone. We hypothesized that APC present in the lung and skin draining lymph nodes were differentially initiating T cell proliferation, leading to differences in the size of the final effector populations. A direct comparison of DUC18 T cell proliferation against APC from flank or lung draining lymph nodes showed profoundly greater proliferation to flank draining lymph node APC. The impaired stimulation of naive T cell proliferation by lung draining APC provides one mechanistic explanation for the lower overall immune response, and inability to effectively reject tumors, in the lung.     

腮腺腺淋巴瘤的MRI诊断（附12例分析）

目的：探讨腮腺腺淋巴瘤的MR表现特征。方法：回顾性分析12例经病理证实的腺淋巴瘤患者MR及临床资料,男性10例,女性2例,平均年龄59.1岁。观察病灶的数目、部位、形态、边界、大小以及MR信号特点等。结果：12例中,单发9例,多发3例,共17个病灶。其中12个病灶位于腮腺浅叶后下部,13个病灶为纵向生长椭圆形。T1WI上16个病灶为等或稍高于肌肉信号,1个含有高信号。STIR序列中等稍高信号者7个,10个含有大小不等的明显高信号。增强扫描轻到中度强化者15个,明显强化2个。9个病例颈部可见中等大小淋巴结。结论：50岁以上吸烟男性,发现腮腺浅叶后下方边界清楚、纵向生长椭圆占位,STIR序列信号欠均匀,高度提示腺淋巴瘤。     

Evaluation of radiomic texture feature error due to MRI acquisition and reconstruction: A simulation study utilizing ground truth

The purpose of this study was to examine the dependence of image texture features on MR acquisition parameters and reconstruction using a digital MR imaging phantom. MR signal was simulated in a parallel imaging radiofrequency coil setting as well as a single element volume coil setting, with varying levels of acquisition noise, three acceleration factors, and four image reconstruction algorithms. Twenty-six texture features were measured on the simulated images, ground truth images, and clinical brain images. Subtle algorithm-dependent errors were observed on reconstructed phantom images, even in the absence of added noise. Sources of image error include Gibbs ringing at image edge gradients (tissue interfaces) and well-known artifacts due to high acceleration; two of the iterative reconstruction algorithms studied were able to mitigate these image errors. The difference of the texture features from ground truth, and their variance over reconstruction algorithm and parallel imaging acceleration factor, were compared to the clinical “effect size”, i.e., the feature difference between high- and low-grade tumors on T1- and T2-weighted brain MR images of twenty glioma patients. The measured feature error (difference from ground truth) was small for some features, but substantial for others. The feature variance due to reconstruction algorithm and acceleration factor were generally smaller than the clinical effect size. Certain texture features may be preserved by MR imaging, but adequate precautions need to be taken regarding their validity and reliability. We present a general simulation framework for assessing the robustness and accuracy of radiomic textural features under various MR acquisition/reconstruction scenarios.     

Respiratory Gating during Stereotactic Body Radiotherapy for Lung Cancer Reduces Tumor Position Variability

Purpose

We evaluated the effects of respiratory gating on treatment accuracy in lung cancer patients undergoing lung stereotactic body radiotherapy by using electronic portal imaging device (EPID) images.

Materials and Methods

Our study population consisted of 30 lung cancer patients treated with stereotactic body radiotherapy (48 Gy/4 fractions/4 to 9 days). Of these, 14 were treated with- (group A) and 16 without gating (group B); typically the patients whose tumors showed three-dimensional respiratory motion ≧5 mm were selected for gating. Tumor respiratory motion was estimated using four-dimensional computed tomography images acquired during treatment simulation. Tumor position variability during all treatment sessions was assessed by measuring the standard deviation (SD) and range of tumor displacement on EPID images. The two groups were compared for tumor respiratory motion and position variability using the Mann-Whitney U test.

Results

The median three-dimensional tumor motion during simulation was greater in group A than group B (9 mm, range 3–30 mm vs. 2 mm, range 0–4 mm; p<0.001). In groups A and B the median SD of the tumor position was 1.1 mm and 0.9 mm in the craniocaudal- (p = 0.24) and 0.7 mm and 0.6 mm in the mediolateral direction (p = 0.89), respectively. The median range of the tumor position was 4.0 mm and 3.0 mm in the craniocaudal- (p = 0.21) and 2.0 mm and 1.5 mm in the mediolateral direction (p = 0.20), respectively.

Conclusions

Although patients treated with respiratory gating exhibited greater respiratory tumor motion during treatment simulation, tumor position variability in the EPID images was low and comparable to patients treated without gating. This demonstrates the benefit of respiratory gating.     

Experimental nerve imaging at 1.5-T

Experimental lesions of the peripheral nerve system can be visualized in vivo by magnetic resonance imaging (MRI). Many studies of the rat peripheral nervous systems were performed on dedicated animal MR scanners with a high magnetic field strength for good spatial resolution. Here, we present an MR protocol to study experimental lesions of the rat nervous system with clinical 1.5-T MR scanners and commercially available coils. Using a three-sequence approach (T1-weighted imaging, fat-saturated T2-weighted imaging and fat-saturated T1-weighted imaging with Gd-DTPA in the same plane), the relevant signal changes of the lesioned nerve can be visualized and separated from other structures, e.g., blood vessels. Furthermore, we give an overview on different types of contrast agents used for peripheral nerve MR imaging and MR findings in selected experimental models of rat peripheral nerve injury.     

Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions

Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images.     

Applications cliniques de l’imagerie hybride TEP-IRM

This paper reports the results of a preliminary study evaluating the feasibility and performance of a first whole body hybrid PET/MR scanner allowing sequential acquisition of co-registered MR and PET images. Sixty-two patients underwent whole body PET/MR imaging immediately after a clinical PET/CT. The hybrid device consists of a 3T MR and a time-of-flight PET scanner sharing a single bed allowing sequential acquisition of co-registered MR and PET images. Imaging protocols included a whole body MR used for attenuation correction of PET followed by high-resolution diagnostic MR. Image analysis included visual identification of radiotracer uptake in tumors and measurement of standardized uptake values (SUV) in tumoral lesions and in normal organs. PET images acquired in the PET/MR with a delay of 85 ± 22 minutes (range 49–120 minutes) showed perfect correlation and identical diagnostic quality compared to PET/CT. In 42 patients (68%), additional high-resolution MR sequences were acquired for clinical diagnosis showing excellent quality without any visually detectable artifacts. SUV measurements of tumor lesions obtained after correction with MR attenuation maps showed an excellent correlation with PET/CT (R² = 0.89 and R² = 0.95 for mean and maximum tissue uptake respectively). Due to the delay between the two studies, changes in tracer uptake biodistribution of normal tissue were observed. Our preliminary data show that whole body PET/MR is clinically applicable in oncologic patients yielding a comparable diagnostic performance as PET/CT with respect to lesion detection and localization.     

Macrophages homing to metastatic lymph nodes can be monitored with ultrasensitive ferromagnetic iron-oxide nanocubes and a 1.5T clinical MR scanner

Background

Due to the ability of macrophages to specifically home to tumors, their potential use as a delivery vehicle for cancer therapeutics has been suggested. Tracking the delivery and engraftment of macrophages into human tumors with a 1.5T clinical MR scanner requires the development of sensitive contrast agents for cell labeling. Therefore, this study aimed to determine whether intravenously injected macrophages could target a primary tumor as well as metastatic LNs, and whether these cells could be detected in vivo by MRI.

Methodology

Peritoneal macrophages were obtained from BALB/c nude mice. The viability, phagocytotic capacity and migratory activity of the macrophages were assessed. MR imaging was performed using a clinical 1.5 T MR scanner and we estimated the T2* of the labeled macrophages. Metastatic lymph nodes were produced in BALB/c nude mice. We administrated 2×10⁶ macrophages labeled with 50 µg Fe/mL FIONs intravenously into the mice. In the 3D T2* GRE MR images obtained one day after the injection of the labeled macrophages or FION solution, the percentages of pixels in the tumors or LNs below the minimum normalized SI (signal intensity) threshold were summated and reported as the black pixel count (%) for the FION hypointensity. Tumors in the main tumor model as well as the brachial, axillary and inguinal lymph nodes in the metastatic LN models were removed and stained. For all statistical analyses, single-group data were assessed using t test or the Mann-Whitney test. Repeated measurements analysis of variance (ANOVA) with Tukey–Kramer post hoc comparisons were performed for multiple comparisons.

Conclusions

The FION-labeled macrophages, which could be non-invasively monitored using a 1.5 T clinical MR scanner, targeted both the main tumors and LN metastases. Overall, the results of this study suggest that the use of macrophages may have many future applications in the clinic for vectorizing therapeutic agents toward main tumors as well as LN metastases.