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Diagrammatic representation of axillary lymph node levels. Lymph nodes were classified as Level 1, Level 2, or Level 3 based on anatomic location. Level I: latissimus dorsi to lateral pectoralis minor; level II: posterior to pectoralis minor; level III: medial pectoralis minor to thoracic inlet.
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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.
32 patients with unilateral breast cancer...
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Citations
... Moreover, MR lymphography does not involve radiation exposure or require radioisotopes, making it a safer and more accessible option, especially in settings where nuclear medicine facilities are limited [8][9][10]. Recent studies have demonstrated the potential of interstitial contrast-enhanced magnetic resonance imaging (MRI) with extracellular gadolinium-based contrast agents for SLN mapping in patients with breast cancer and OSCC [11][12][13]. In a pioneering study involving OSCC patients, MR lymphography using a small volume (1 mL) of peritumorally administered gadobutrol consistently visualized SLNs in all 26 patients, with the majority (81%) also showing draining lymphatic vessels [11]. ...
Objectives: To assess the efficacy of magnetic resonance (MR) lymphography with gadobutrol contrast for sentinel lymph node (SLN) mapping in early-stage oral squamous cell carcinoma (OSCC). Methods: This pilot study compared the identification of SLNs by MR lymphography using a gadolinium-based contrast agent (gadobutrol) to conventional [99mTc]Tc-nanocolloid lymphoscintigraphy (including single-photon emission computed tomography/computed tomography (SPECT/CT)) in 10 early-stage OSCC patients undergoing SLN biopsy. The patients initially underwent conventional lymphoscintigraphy following the peritumoral administration of indocyanine green [99mTc]Tc-nanocolloid (120 megabecquerel; ~0.5 mL). Subsequently, 0.5–1.0 mL gadobutrol was peritumorally injected, and MR imaging was acquired for 30 min. The following day, the identified SLNs were harvested and subjected to a histopathological assessment. The MR lymphography and [99mTc]Tc-nanocolloid lymphoscintigraphy results were evaluated and compared with respect to those of the SLN identification. The reference standard consisted of a histopathological evaluation of the harvested SLNs, complementary neck dissection specimens, and follow-up data. Results: The MR lymphography detected 16 out of 27 SLNs identified by [99mTc]Tc-nanocolloid lymphoscintigraphy, revealing an additional SLN that did not harbor metastasis. MR lymphography failed to identify any SLNs in one patient. Of the seven histopathologically positive SLNs detected by [99mTc]Tc-nanocolloid lymphoscintigraphy, three were identified by MR lymphography. All patients remained disease-free after a median follow-up of 16 months. Compared to [99mTc]Tc-nanocolloid lymphoscintigraphy, MR lymphography using gadobutrol achieved an SLN identification rate of 59%, a sensitivity of 75%, and a negative predictive value of 86%. Conclusions: MR lymphography using gadobutrol demonstrates limited reliability for SLN mapping in early-stage OSCC.
... Neoadjuvant (i.e., preoperative) assessment of ALNs is of extreme importance to complete breast TNM staging. Current neoadjuvant non-invasive detection and diagnosis of ALNs using X-ray mammography, Ultrasound-Guided Biopsy, Magnetic Resonance Imaging, Positron Emission Tomography and Computed Tomography are often inconclusive [5][6][7]. The state-of-the-art procedure to evaluate axillary metastases is an intraoperative sentinel node biopsy which is a time-consuming surgical procedure limited to the first level nodes, which can result in the unnecessary removal of ALNs in upper levels [8,9]. ...
Breast cancer is the most common and the fifth deadliest cancer worldwide. In more advanced stages of cancer, cancer cells metastasize through lymphatic and blood vessels. Currently there is no satisfactory neoadjuvant (i.e., preoperative) diagnosis to assess whether cancer has spread to neighboring Axillary Lymph Nodes (ALN). This paper addresses the use of radar Microwave Imaging (MWI) to detect and determine whether ALNs have been metastasized, presenting an analysis of the performance of different artifact removal and beamformer algorithms in distinct anatomical scenarios. We assess distinct axillary region models and the effect of varying the shape of the skin, muscle and subcutaneous adipose tissue layers on single ALN detection. We also study multiple ALN detection and contrast between healthy and metastasized ALNs. We propose a new beamformer algorithm denominated Channel-Ranked Delay-Multiply-And-Sum (CR-DMAS), which allows the successful detection of ALNs in order to achieve better Signal-to-Clutter Ratio, e.g., with the muscle layer up to 3.07 dB, a Signal-to-Mean Ratio of up to 20.78 dB and a Location Error of 1.58 mm. In multiple target detection, CR-DMAS outperformed other well established beamformers used in the context of breast MWI. Overall, this work provides new insights into the performance of algorithms in axillary MWI.
... Magnetic resonance (MR) lymphography with peritumoral administration of a paramagnetic gadolinium [Gd 3+ ]-based contrast agent has been recently introduced in breast and cervical cancer, as an alternative method for preoperative visualization of SLNs and lymphatics [36][37][38]. These studies showed that paramagnetic gadolinium [Gd 3+ ]-based contrast agents, conventionally administered intravenously for contrast-enhanced MRI or MR angiography [39], are safe and useful for peritumoral administration and SLN mapping in humans. ...
Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [99mTc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.
... Conversely, SLNB may result in false negative results which can lead to an incorrect breast cancer staging and negatively impact further important therapeutic decisions [5]. Currently, the above mentioned imaging modalities and procedures are still unsatisfactory in terms of sensitivity and specificity [6][7][8]. ...
... Effective in-vivo detection of optically semitransparent lymphatic microvasculature has proven to be extremely challenging. For example, radioactive (lymphoscintigraphy), magneto-chromatic (magnetic resonance lymphography), fluorescent (indocyanine green (ICG) lymphography) dyes or microbubbles (ultrasound lymphography) [4][5][6][7] have been injected into the tissue at the particular anatomical site of interest to image the local draining lymphatic network, a rather limited clinical approach. In animal models, high resolution intravital ICG fluorescence microscopy is commonly used to visualize the lymphatic vessels and lymph nodes in greater detail, albeit within a limited depth range (up to 0.3-0.4 ...
Analysis of semi-transparent low scattering biological structures in optical coherence tomography (OCT) has been actively pursued in the context of lymphatic imaging, with most approaches relying on the relative absence of signal as a means of detection. Here we present an alternate methodology based on spatial speckle statistics, utilizing the similarity of a distribution of given voxel intensities to the power distribution function of pure noise, to visualize the low-scattering biological structures of interest. In a human tumor xenograft murine model, we show that these correspond to lymphatic vessels and nerves; extensive histopathologic validation studies are reported to unequivocally establish this correspondence. The emerging possibility of OCT lymphangiography and neurography is novel and potentially impactful (especially the latter), although further methodology refinement is needed to distinguish between the visualized lymphatics and nerves.
... After assessment with the QUADAS-2 checklist, two primary studies were found to be at high risk for bias [6,7], four studies were found to be at unclear risk for bias [5,8,9,11], and only one study was classified at low risk for bias [10]; all of them scored well in terms of applicability (Figure 1). The most common problem the authors encountered performing the assessment was a lack of information regarding the domain. ...
... The sensitivity, specificity, PPV, NPV values, and MRI modality used per included study are shown in Table 1. The included studies are quite heterogeneously divided concerning MRI modality [5][6][7][8][9][10]12] . DWI was the most prevalent modality among the included studies. ...
Staging of the axillary lymph nodes is an essential step to determine the appropriate treatment for breast cancer. Sentinel lymph node
biopsy (SLNB) is currently the first step in staging and the gold standard. However, if the sentinel node is positive, a full dissection of
the axillary lymph nodes should be performed (axillary lymph node dissection or ALND). This technique used to be the gold standard
but had considerable sequelae which diminished quality of life. SLNB still has sequelae but the incidence is much lower. The goal of
this systematic review is to assess whether MRI can replace or assist the current gold standard for axillary lymph node staging in breast
cancer. With the use of these non-invasive techniques, the risk of morbidity could be reduced even more. A comprehensive search and
an additional brief search in several databases has been performed using PRISMA. Studies were selected based on titles and abstracts
and were included or excluded using predetermined criteria. The studies were assessed for validity and applicability using the QUADAS2 tool by two readers. Data of three studies using diffusion-weighted imaging (DWI) were pooled and statistical analysis was performed. A total of seven studies were included for review. Three studies used DWI, others used T2-weighted imaging, contrast-enhanced
imaging, T1-weighted imaging or an MRI scoring system. Due to the heterogeneously divided MRI modalities, a small meta-analysis
of DWI was performed. Other studies were evaluated qualitatively. DWI reached a sensitivity of 87.67% (95% CI 77.88-94.20) and a
specificity of 59.31% (95% CI 50.85-67.38), a positive predictive value (PPV) of 52.03% (95 CI 42.84-61.12), and a negative predictive value (NPV) of 90.53% (95% CI 82.78-95.58). MRI can aid in the detection of axillary lymph node metastasis, but it cannot replace the current gold standard (SLNB/ALND).
... Meme kanseri hastalarında ALN tutulumu hastalığın prognozunu olumsuz yönde etkilediği gibi klinik ve cerrahi yaklaşımı belirleyen önemli bir faktördür. Malign meme tümörünün aksiller lenf nodlarına yayılımı, 10 yıllık rekürrens oranını %20-30'dan %70'lere çıkarmaktadır [2]. Bu nedenle, yeni tanı almış tüm meme kanseri hastalarında ALN tutulumunun değerlendirilmesi çok önemli bir zorunluluktur. ...
... Level-2 veya orta aksiller lenf nodları pektoralis minör kasının arkasında yer alır ve patolojik boyut ya da ekojenitede olmadığı takdirde kolayca saptanamayabilir. Level 3, yani apikal aksiller lenf nodları pektoralis minör kasının medialinde infraklaviküler bölgede yer alır [2,5]. Rotter (interpektoral) nodları, level-2 orta aksiller lenf nodlarının pektoralis majör ve minör kasları arasında yer alan bir bölümüdür [5]. ...
... Rotter nodu metastazının özel bir prognostik önemi vardır; eğer Rotter nodunda metastaz mevcut ise bu durum göğüs duvarı invazyonu riskinin yüksek olduğunun bir göstergesi olabilir [5]. Sentinel lenf nodu (SLN), tümörden orjin alan lenfatik sıvının ilk drene olduğu lenf nodu olarak tanımlanabilir (2). Mammografi (MG), ultrasonografi (US), meme manyetik rezonans görüntüleme (MRG) veya lenfosintigrafi, aksiller lenf nodu metastazı, özellikle sentinel lenf nodu (SLN) saptanmasında önemli modalitelerdir. ...
... Fink et al. introduced gadobutrol with its high T1-relaxivity as contrast agent for interstitial MRL in rats and investigated the contrast kinetics in lymph nodes, kidney, liver, muscle, and blood [9]. Furthermore, the use of gadolinium based contrast agents for MRL in patients with breast cancer has previously been reported by Lu et al. [10]. However, gadolinium-(Gd-) based MRL does not provide quantitative data to evaluate the functionality of lymphatics. ...
Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)- α , α ′, α ′′, α ′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2′,2′′-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas.
... Here, we demonstrated that breast tumors lacking VEGF-D expression do not exhibit a defect in primary tumor or lymph nodes lymphangiogenesis, but have a reduced amount of dilated lymphatic vessels associated with an inhibition of metastasis. Our findings suggested that this process is restricted to breast cancer, in agreement with previous studies showing a correlation between metastases and dilated lymphatic vessels in breast cancer patients (40). ...
The vascular endothelial growth factor VEGF-D promotes metastasis by inducing lymphangiogenesis and dilatation of the lymphatic vasculature, facilitating tumor cell extravasion. Here we report a novel level of control for VEGF-D expression at the level of protein translation. In human tumor cells, VEGF-D colocalized with eIF4GI and 4E-BP1, which can program increased initiation at IRES motifs on mRNA by the translational initiation complex. In murine tumors, the steady-state level of VEGF-D protein was increased despite the overexpression and dephosphorylation of 4E-BP1, which downregulates protein synthesis, suggesting the presence of an IRES in the 5' UTR of VEGF-D mRNA. We found that nucleolin, a nucleolar protein involved in ribosomal maturation, bound directly to the 5'UTR of VEGF-D mRNA, thereby improving its translation following heat shock stress via IRES activation. Nucleolin blockade by RNAi-mediated silencing or pharmacological inhibition reduced VEGF-D translation along with a subsequent constriction of lymphatic vessels in tumors. Our results identify nucleolin as a key regulator of VEGF-D expression, deepening understanding of lymphangiogenesis control during tumor formation.
... MRI lymphography has been used for SLN detection mainly in breast [57], and pelvic tumors [58]. One feature of these techniques is the possibility of differentiating between benign and malignant nodes depending on the node's imaging pattern. ...
Sentinel lymph node biopsy is an extensively explored diagnostic mean for reducing surgical risks while improving staging in different human malignancies. Several different techniques have been introduced to clinical use during last two decades. Methods as ink lymphography and lymphoscintigraphy have already established their position in sentinel nodes mapping. Novel approaches as CT, MRI-lymphography, contrast enhanced ultrasound and near-infrared fluorescence imaging possesses prominent potential advantages and demand further experience gaining. A review of the clinically utilized techniques is presented a special attention is drawn to their usefulness in the head and neck carcinomas work-up.
