Tumor-induced alterations in lymph node lymph drainage identified by contrast-enhanced MRI.
Ontology highlight
ABSTRACT:
SUBMITTER: Ruddell A
PROVIDER: S-EPMC5357140 | biostudies-literature | 2015 Jul
REPOSITORIES: biostudies-literature
Publications
Tumor-induced alterations in lymph node lymph drainage identified by contrast-enhanced MRI.
Ruddell Alanna A Kirschbaum Sara B SB Ganti Sheila N SN Liu Cheng-Liang CL Sun Ryan R RR Partridge Savannah C SC
Journal of magnetic resonance imaging : JMRI 20140925 1
<h4>Background</h4>To use high resolution MRI lymphography to characterize altered tumor-draining lymph node (TDLN) lymph drainage in response to growth of aggressive tumors.<h4>Methods</h4>Six mice bearing B16-F10 melanomas in one rear footpad were imaged by 3.0 Tesla (T) MRI before and after subcutaneous injection of Gadofosveset trisodium (Gd-FVT) contrast agent into both rear feet. Gd-FVT uptake into the left and right draining popliteal LNs was quantified and compared using Wilcoxon signed- ...[more]
Similar Datasets
Project description:Contrast-enhanced MRI lymphography shows potential to identify alterations in lymph drainage through lymph nodes (LNs) in cancer and other diseases. MRI studies have typically used low molecular weight gadolinium contrast agents, however larger gadolinium-loaded nanoparticles possess characteristics that could improve the specificity and sensitivity of lymphography. The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection. Mice bearing B16-F10 melanoma footpad tumors were imaged to assess tumor-induced alterations in lymph drainage through tumor-draining popliteal and inguinal LNs versus contralateral uninvolved drainage. Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective. All of the contrast agents distributed in foci around the cortex and medulla of tumor-draining popliteal LNs, while they were restricted to the cortex of non-draining LNs. Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage. These characteristics of tumor-induced lymph drainage could be useful for diagnosis of LN pathology in cancer and other diseases. The preferential uptake of nanoparticle contrasts into tumor-draining LNs could also allow selective targeting of therapies to tumor-draining LNs.
| S-EPMC4620490 | biostudies-literature
Project description:The growth of metastatic tumors in mice can result in markedly increased lymph flow through tumor-draining lymph nodes (LNs), which is associated with LN lymphangiogenesis. A dynamic magnetic resonance imaging (MRI) assay was developed, which uses low-molecular weight gadolinium contrast agent to label the lymphatic drainage, to visualize and quantify tumor-draining lymph flow in vivo in mice bearing metastatic melanomas. Tumor-bearing mice showed greatly increased lymph flow into and through draining LNs and into the bloodstream. Quantitative analysis established that both the amount and the rate of lymph flow through draining LNs are significantly increased in melanoma-bearing mice. In addition, the rate of appearance of contrast media in the bloodstream was significantly increased in mice bearing melanomas. These results indicate that gadolinium-based contrast-enhanced MRI provides a noninvasive assay for high-resolution spatial identification and mapping of lymphatic drainage and for dynamic measurement of changes in lymph flow associated with cancer or lymphatic dysfunction in mice. Low-molecular weight gadolinium contrast is already used for 1.5-T MRI scanning in humans, which should facilitate translation of this imaging assay.
| S-EPMC2435006 | biostudies-literature
Project description:Purpose To develop a radiomics model based on preoperative dynamic contrast-enhanced MRI (DCE-MRI) to identify sentinel lymph node (SLN) metastasis in breast cancer (BC) patients. Materials and Methods The MRI images and clinicopathological data of 142 female primary BC patients from January 2017 to December 2018 were included in this study. The patients were randomly divided into the training and testing cohorts at a ratio of 7:3. Four types of radiomics models were built: 1) a radiomics model based on the region of interest (ROI) of breast tumor; 2) a radiomics model based on the ROI of intra- and peri-breast tumor; 3) a radiomics model based on the ROI of axillary lymph node (ALN); 4) a radiomics model based on the ROI of ALN and breast tumor. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to assess the performance of the three radiomics models. The technique for order of preference by similarity to ideal solution (TOPSIS) through decision matrix analysis was used to select the best model. Results Models 1, 2, 3, and 4 yielded AUCs of 0.977, 0.999, 0.882, and 1.000 in the training set and 0.699, 0.817, 0.906, and 0.696 in the testing set, respectively, in terms of predicting SLN metastasis. Model 3 had the highest AUC in the testing cohort, and only the difference from Model 1 was statistically significant (p = 0.022). DCA showed that Model 3 yielded a greater net benefit to predict SLN metastasis than the other three models in the testing cohort. The best model analyzed by TOPSIS was Model 3, and the method’s names for normalization, dimensionality reduction, feature selection, and classification are mean, principal component analysis (PCA), ANOVA, and support vector machine (SVM), respectively. Conclusion ALN radiomics feature extraction on DCE-MRI is a potential method to evaluate SLN status in BC patients.
| S-EPMC9207247 | biostudies-literature
Project description:We explored the prognostic impact of the dynamic contrast enhanced MR imaging (DCE-MRI) parameter ABrix in cervical cancer combined with global gene expression data to reveal the underlying molecular phenotype of the parameter and construct a gene signature that reflected ABrix. Based on 78 cervical cancer patients subjected to curative chemoradiotherapy, we identified a prognostic ABrix parameter by pharmacokinetic analysis of DCE-MR images based on the Brix model, where tumors with low ABrix appeared to be most aggressive. Gene set enrichment analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between ABrix and the hypoxia gene sets, whereas gene sets related to proliferation, radioresistance, and wound healing were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including targets of the hypoxia inducible factor (HIF1M-NM-1) and the unfolded protein response (UPR), were the most significant. In the remaining 32 tumors, low ABrix was associated with upregulation of HIF1M-NM-1 protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. Based on the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low ABrix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients. Gene expression correlating with the DCE-MRI parameter ABrix were identified in 46 patients (DCE-MRI cohort) and used to find a hypoxia gene signature. The prognsotic impact of the gene signature was validated in an independent cohort of 109 patients (validation chort). Cell culture experiments were performed to generate cervical cancer specific gene lists associated with hypoxia (GSM897799 - GSM897804).
2012-08-16 | E-GEOD-36562 | biostudies-arrayexpress
Project description:We explored the prognostic impact of the dynamic contrast enhanced MR imaging (DCE-MRI) parameter ABrix in cervical cancer combined with global gene expression data to reveal the underlying molecular phenotype of the parameter and construct a gene signature that reflected ABrix. Based on 78 cervical cancer patients subjected to curative chemoradiotherapy, we identified a prognostic ABrix parameter by pharmacokinetic analysis of DCE-MR images based on the Brix model, where tumors with low ABrix appeared to be most aggressive. Gene set enrichment analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between ABrix and the hypoxia gene sets, whereas gene sets related to proliferation, radioresistance, and wound healing were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including targets of the hypoxia inducible factor (HIF1α) and the unfolded protein response (UPR), were the most significant. In the remaining 32 tumors, low ABrix was associated with upregulation of HIF1α protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. Based on the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low ABrix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients.
2012-08-16 | GSE36562 | GEO
Project description:Introduction The impact of hypothermia on the impaired drainage function of the glymphatic system in traumatic brain injury (TBI) is not understood. Methods Male Sprague–Dawley rats undergoing controlled cortical impact injury (CCI) were subjected to hypothermia or normothermia treatment. The rats undergoing sham surgery without CCI were used as the control. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with intrathecal administration of low- and high-molecular-weight contrast agents (Gd-DTPA and hyaluronic acid conjugated Gd-DTPA) was performed after TBI and head temperature management. The semiquantitative kinetic parameters characterizing the contrast infusion and cleanout in the brain, including influx rate, efflux rate, and clearance duration, were calculated from the average time-intensity curves. Results and discussion The qualitative and semiquantitative results of DCE-MRI obtained from all examined perivascular spaces and most brain tissue regions showed a significantly increased influx rate and efflux rate and decreased clearance duration among all TBI animals, demonstrating a significant impairment of glymphatic drainage function. This glymphatic drainage dysfunction was exacerbated when additional hypothermia was applied. The early glymphatic drainage reduction induced by TBI and aggravated by hypothermia was linearly related to the late increased deposition of p-tau and beta-amyloid revealed by histopathologic and biochemical analysis and cognitive impairment assessed by the Barnes maze and novel object recognition test. The glymphatic system dysfunction induced by hypothermia may be an indirect alternative pathophysiological factor indicating injury to the brain after TBI. Longitudinal studies and targeted glymphatic dysfunction management are recommended to explore the potential effect of hypothermia in TBI.
| S-EPMC9932501 | biostudies-literature
Project description:Lymph node (LN) stromal cells, particularly fibroblastic reticular cells (FRCs), provide critical structural support and regulate immunity, tolerance and the transport properties of LNs. For many tumors, metastasis to the LNs is predictive of poor prognosis. However, the stromal contribution to the evolving microenvironment of tumor-draining LNs (TDLNs) remains poorly understood. Here we found that FRCs specifically of TDLNs proliferated in response to tumor-derived cues and that the network they formed was remodeled. Comparative transcriptional analysis of FRCs from non-draining LNs and TDLNs demonstrated reprogramming of key pathways, including matrix remodeling, chemokine and/or cytokine signaling, and immunological functions such as the recruitment, migration and activation of leukocytes. In particular, downregulation of the expression of FRC-derived chemokine CCL21 and cytokine IL-7 were accompanied by altered composition and aberrant localization of immune-cell populations. Our data indicate that following exposure to tumor-derived factors, the stroma of TDLNs adapts on multiple levels to exhibit features typically associated with immunosuppression.
| S-EPMC4994871 | biostudies-literature
Project description:The intestinal immune system has the challenging task of tolerating foreign nutrients and the commensal microbiome, while excluding or eliminating ingested pathogens. Failure of this balance leads to conditions such as inflammatory bowel diseases, food allergies and invasive gastrointestinal infections1. Multiple immune mechanisms are therefore in place to maintain tissue integrity, including balanced generation of effector T (TH) cells and FOXP3+ regulatory T (pTreg) cells, which mediate resistance to pathogens and regulate excessive immune activation, respectively1-4. The gut-draining lymph nodes (gLNs) are key sites for orchestrating adaptive immunity to luminal perturbations5-7. However, it is unclear how they simultaneously support tolerogenic and inflammatory reactions. Here we show that gLNs are immunologically specific to the functional gut segment that they drain. Stromal and dendritic cell gene signatures and polarization of T cells against the same luminal antigen differ between gLNs, with the proximal small intestine-draining gLNs preferentially giving rise to tolerogenic responses and the distal gLNs to pro-inflammatory T cell responses. This segregation permitted the targeting of distal gLNs for vaccination and the maintenance of duodenal pTreg cell induction during colonic infection. Conversely, the compartmentalized dichotomy was perturbed by surgical removal of select distal gLNs and duodenal infection, with effects on both lymphoid organ and tissue immune responses. Our findings reveal that the conflict between tolerogenic and inflammatory intestinal responses is in part resolved by discrete gLN drainage, and encourage antigen targeting to specific gut segments for therapeutic immune modulation.
| S-EPMC6587593 | biostudies-literature
Project description:Purpose: The intestine's main function is to digest and absorb dietary nutrients, with help from the absorptive epithelium and underlying vasculature and lymphatic system, as well as the microbiome. The intestine also houses the largest immune cell population in the body, tasked with providing resistance to toxins and invading pathogens while maintaining tolerance to dietary and microbial antigens, either by local action or lymphatic trafficking to the gut-draining lymph nodes (gLNs) to mount adaptive responses. While previous studies revealed the drainage map to various gLNs along the murine gut, and described immunological differences between gLNs, the underlying cellular components and the functional consequences of gut segment-specific drainage have not been systematically addressed. We sought to understand how compartmentalized lymphatic drainage of the intestinal milieu contributes to immune responses towards luminal antigens. Results: Here we report that gLNs are immunologically unique according to the functional gut segment they drain. Stromal and dendritic cell gene signatures, as well as adaptive T cell polarization against the same luminal antigen, differed between gLNs along the intestine, the proximal small intestine–draining gLNs preferentially giving rise to tolerogenic and the distal gLNs to pro-inflammatory T cell responses. This compartmentalized dichotomy could be perturbed by duodenal infection, surgical removal of select distal gLNs, dysbiosis, or ectopic antigen delivery, impacting both lymphoid organ and tissue immune responses. Conclusions: Our findings reveal that the conflict between tolerogenic and inflammatory adaptive responses is in part resolved by discrete gLN drainage, and encourage gut segment-specific antigen targeting for therapeutic immune modulation.
2019-04-10 | GSE121811 | GEO
Project description:BackgroundThe objective of this paper is to explore the value of a delta-radiomic model of the axillary lymph node (ALN) using dynamic contrast-enhanced (DCE) MRI for early prediction of the axillary pathological complete response (pCR) of breast cancer patients after neoadjuvant chemotherapy (NAC).MethodsA total of 120 patients with ALN-positive breast cancer who underwent breast MRI before and after the first cycle of NAC between October 2018 and May 2021 were prospectively included in this study. Patients were divided into a training (n = 84) and validation (n = 36) cohort based on the temporal order of their treatments. Radiomic features were extracted from the largest slice of targeted ALN on DCE-MRI at pretreatment and after one cycle of NAC, and their changes (delta-) were calculated and recorded. Logistic regression was then applied to build radiomic models using the pretreatment (pre-), first-cycle(1st-), and changes (delta-) radiomic features separately. A clinical model was also built and combined with the radiomic models. The models were evaluated by discrimination, calibration, and clinical application and compared using DeLong test.ResultsAmong the three radiomic models, the ALN delta-radiomic model performed the best with AUCs of 0.851 (95% CI: 0.770-0.932) and 0.822 (95% CI: 0.685-0.958) in the training and validation cohorts, respectively. The clinical model yielded moderate AUCs of 0.742 (95% CI: 0.637-0.846) and 0.723 (95% CI: 0.550-0.896), respectively. After combining clinical features to the delta-radiomics model, the efficacy of the combined model (AUC = 0.932) in the training cohort was significantly higher than that of both the delta-radiomic model (Delong p = 0.017) and the clinical model (Delong p < 0.001) individually. Additionally, in the validation cohort, the combined model had the highest AUC (0.859) of any of the models we tested although this was not statistically different from any other individual model's validation AUC. Calibration and decision curves showed a good agreement and a high clinical benefit for the combined model.ConclusionThis preliminary study indicates that ALN-based delta-radiomic model combined with clinical features is a promising strategy for the early prediction of downstaging ALN status after NAC. Future axillary MRI applications need to be further explored.
| S-EPMC9817310 | biostudies-literature