Magnetic Resonance Lymphangiography Research Articles

Analysis on efficacy of magnetic resonance lymphangiography using INV-001 in healthy beagle dogs

We aimed to conduct a proof-of-concept study of INV-001 in visualizing lymphatic vessels and nodes without venous contamination and to determine the optimal dose condition of INV-001 for magnetic resonance lymphangiography (MRL) in healthy beagles. MRL was performed using a 3.0-Tesla (T) whole body clinical magnetic resonance imaging (MRI) scanner. A dose-finding study of INV-001 for MRL in beagles (N = 6) was carried out according to an adaptive optimal dose finding design. For the reproducibility study (N = 6), MRL was conducted at selected INV-001 doses (0.056 and 0.112 mg Fe/kg) with a 15 mM concentration. Additionally, an excretion study (N = 3) of INV-001 was conducted by analyzing T1, T2, and T2* maps of the liver and kidney 48 h post-administration. INV-001 administration at doses of 0.056 and 0.112 mg Fe/kg (concentration: 15 mM) consistently demonstrated the visualization of contrast-enhanced lymphatic vessels and nodes without venous contamination in the beagles. The contrast enhancement effect was highest at 30 min after INV-001 administration, then gradually decreasing. No toxicity-related issues were identified during the study. After 48 h, the T1, T2, and T2* values in the liver and both kidneys were found to be comparable to the pre-administration values, indicating thorough INV-001 excretion. The optimal dosing conditions of INV-001 for MRL for contrast-enhanced visualization of lymphatic vessels and nodes exclusively with no venous contamination in beagles was determined to be 0.056 mg Fe/kg with a 15 mM concentration.

Comparison of the Pharmacokinetics of Gadolinium-Based and Iron Oxide-Based Contrast Agents inside the Lymphatic Structure using Magnetic Resonance Lymphangiography.

Gadolinium (Gd)-based contrast agents are primarily used for contrast-enhanced magnetic resonance lymphangiography (MRL). However, overcoming venous contamination issues remains challenging. This study aims to assess the MRL efficacy of the newly developed iron-based contrast agent (INV-001) that is specially designed to mitigate venous contamination issues. The study further explores the optimal dosage, including both injection volume and concentration, required to achieve successful visualization of the popliteal lymph nodes and surrounding lymphatic vessels. All animals utilized in this study were male Sprague-Dawley (SD) rats weighing between 250 and 300g. The contrast agents prepared were injected intradermally in the fourth phalanx of both hind limbs using a 30-gauge syringe in SD rats. MRL was performed every 16min on a coronal 3D time-of-flight sequence with saturation bands using a 9.4-T animal machine. Contrary to Gd-DOTA, which exhibited venous contamination in most animals irrespective of injection dosages and conditions, INV-001 showed no venous contamination. For Gd-DOTA, the popliteal lymph nodes and lymphatic vessels reached peak enhancement 16min after injection from the injection site and then rapidly washed out. However, with INV-001, they reached peak enhancement between 16 and 32min after injection, with prolonged visualization of the popliteal lymph node and lymphatic vessels. INV-001 at 0.45μmol (15mM, 30 μL) and 0.75μmol (15mM, 50 μL) achieved high scores for qualitative image analysis, providing good visualization of the popliteal lymph nodes and lymphatic vessels without issues of venous contamination, interstitial space enhancement, or lymph node enlargement. In MRL, INV-001, a novel T1 contrast agent based on iron, enables prolonged enhancement of popliteal lymph nodes and lymphatic vessels without venous contamination.

Central conducting lymphatic anomaly: from bench to bedside.

Central conducting lymphatic anomaly (CCLA) is a complex lymphatic anomaly characterized by abnormalities of the central lymphatics and may present with nonimmune fetal hydrops, chylothorax, chylous ascites, or lymphedema. CCLA has historically been difficult to diagnose and treat; however, recent advances in imaging, such as dynamic contrast magnetic resonance lymphangiography, and in genomics, such as deep sequencing and utilization of cell-free DNA, have improved diagnosis and refined both genotype and phenotype. Furthermore, in vitro and in vivo models have confirmed genetic causes of CCLA, defined the underlying pathogenesis, and facilitated personalized medicine to improve outcomes. Basic, translational, and clinical science are essential for a bedside-to-bench and back approach for CCLA.

Assessment Modalities for Lower Extremity Edema, Lymphedema, and Lipedema: A Scoping Review.

Lower extremity swelling may be broadly characterized as due to edema, lymphedema, or lipedema. Differentiation between these three conditions is important for providing appropriate treatment. This review analyzes and compares different clinical diagnostic modalities for these conditions, with the aim of assisting in the process of choosing the most appropriate diagnostic modality by highlighting the advantages and limitations of each. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for a systematic search of peer-reviewed literature, the following diagnostic methods for lower extremity swelling were investigated: (1) ultrasound (US), (2) lymphoscintigraphy (LSG), (3) computed tomography (CT), (4) bioimpedance spectroscopy (BIS), (5) tissue dielectric constant (TDC), and (6) magnetic resonance imaging (MRI), including magnetic resonance lymphangiography (MRL). The databases used in the search were PubMed, ProQuest, CINAHL Complete, Web of Science, Embase, and Biomedical Reference Collection. After retrieving 115 studies based on predetermined inclusion criteria, a total of 31 studies were critically evaluated. The main results indicate the following: duplex US is the modality of choice to initially identify lower extremity edema such as deep venous thrombosis (DVT) and venous reflux due to its high sensitivity and specificity. CT venography of the lower extremity appears to bethe preferred option for gynecologic cancer patients with lower extremity swelling post-treatment, as it measures subcutaneous tissue volumes to look for DVTs, lymphoceles, and cancer recurrence. TDC is a recommended modality for a variety of conditions, including edema and lymphedema, in part, due to its noninvasive localized assessment capabilities and ease of use. LSG emerges as an effective imaging modality for lymphedema characterization with minimal invasiveness and high sensitivity and specificity. BIS is widely used to identify and monitor lower extremity lymphedema but has been reported to have low sensitivity and lacks the ability to account for changes in tissue composition such as fibrosis. US and MRL are favored for lipedema diagnosis, with MRL providing comprehensive anatomical and functional insights, albeit with cost and accessibility limitations compared to US. While CT, MRI, US, and TDC are all useful for differentiating lymphedema from lipedema, MRI is the preferred modality due to its anatomical and functional diagnostic capabilities. However, US is a pragmatic alternative for use with obese patients or when MRI is not an option.

Magnetic resonance lymphangiography: Establishing normal

BackgroundDespite an increased interest in visualizing the lymphatic vessels with magnetic resonance lymphangiography (MRL), little literature is available describing their appearance in nonlymphedematous individuals. To determine lymphatic abnormalities, an understanding of how healthy lymphatic vessels appear and behave needs to be established. Therefore, in this study, MRL of individuals without a history of lymphatic disease was performed. MethodsA total of 25 individuals (15 women) underwent MRL of their lower limbs using a 3.0 T Philips magnetic resonance imaging scanner (Philips Medical Systems). The first nine participants were recruited to establish the concentration of gadolinium-based contrast agent (GBCA) to administer, with the remainder imaged before and after interdigital forefoot GBCA injections at the optimized dose. Outcomes, including lymphatic vessel diameter, tortuosity, and frequency of drainage via particular drainage routes, were recorded. ResultsHealthy lymphatic vessels following the anteromedial pathway were routinely observed in post-contrast T1-weighted images (average tortuosity, 1.09 ± 0.03), with an average of 2.16 ± 0.93 lymphatic vessels with a diameter of 2.47 ± 0.50 mm crossing the anterior ankle. In six limbs, vessels following the anterolateral pathways were observed. No vessels traversing the posterior of the legs were seen. In a subset of 10 vessels, the lymphatic signal, measured at the ankle, peaked at 29 minutes, 50 seconds ± 9 minutes, 29 seconds after GBCA administration. No lymphatic vessels were observed in T2-weighted images. ConclusionsContrast-enhanced MRL reliably depicts the lymphatic vessels in the legs of healthy controls. Following interdigital contrast injection, anteromedial drainage appears dominant. Quantitative measures related to lymphatic vessel size, tortuosity, and drainage rate are readily obtainable and could be beneficial for detecting even subtle lymphatic impairment.

Identifying Functional Lymph Nodes in Lower Extremity Lymphedema Patients: The Role of High-frequency Ultrasound.

Lymph nodes may play a potential role in lymphedema surgery. Radiologic evaluation of nodes may reveal the status of pathologic conditions but with limited accuracy. This study is the first to evaluate the efficacy of ultrasound in detecting functioning nodes in lymphedema patients and presents a criterion for determining the functionality of the lymph nodes. This retrospective study reviews 30 lower extremity lymphedema cases which were candidates for lymph node to vein anastomosis. Lymphoscintigraphy and magnetic resonant lymphangiography (MRL) imaging were compared with ultrasound features which were correlated to intraoperative indocyanine green (ICG) nodal uptake as an indication of functionality. Majority were International Society of Lymphology stage 2 late (50.0%) and stage 3 (26.7%). ICG positive uptake (functioning nodes) was noted in 22 (73.3%), while 8 patients (26.6%) had negative uptake (nonfunctioning). Ultrasound had significantly the highest specificity (100%) for identifying functional nodes followed by lymphoscintigraphy (55%) and MRL (36%; p = 0.002, p < 0.001, respectively). This was associated with 100% positive predictive value compared against lymphoscintigraphy (44%) and MRL (36%; p < 0.001 for both). The identified ultrasound imaging criteria for functioning lymph node were oval lymph node shape (Solbiati Index), morphology, vascularity pattern, and vascularity quantification. The use of ultrasound in nodal evaluation was proven effective in different pathologic conditions and demonstrated the best prediction for functionality of the lymph node based on the new evaluation criteria.

MR Lymphangiography in Lymphatic Disorders: Clinical Applications, Institutional Experience, and Practice Development.

Lymphatic flow and anatomy can be challenging to study, owing to variable lymphatic anatomy in patients with diverse primary or secondary lymphatic pathologic conditions and the fact that lymphatic imaging is rarely performed in healthy individuals. The primary components of the lymphatic system outside the head and neck are the peripheral, retroperitoneal, mesenteric, hepatic, and pulmonary lymphatic systems and the thoracic duct. Multiple techniques have been developed for imaging components of the lymphatic system over the past century, with trade-offs in spatial, temporal, and contrast resolution; invasiveness; exposure to ionizing radiation; and the ability to obtain information on dynamic lymphatic flow. More recently, dynamic contrast-enhanced (DCE) MR lymphangiography (MRL) has emerged as a valuable tool for imaging both lymphatic flow and anatomy in a variety of congenital and acquired primary or secondary lymphatic disorders. The authors provide a brief overview of lymphatic physiology, anatomy, and imaging techniques. Next, an overview of DCE MRL and the development of an MRL practice and workflow in a hybrid interventional MRI suite incorporating cart-based in-room US is provided, with an emphasis on multidisciplinary collaboration. The spectrum of congenital and acquired lymphatic disorders encountered early in an MRL practice is provided, with emphasis on the diversity of imaging findings and how DCE MRL can aid in diagnosis and treatment of these patients. Methods such as DCE MRL for assessing the hepatic and mesenteric lymphatic systems and emerging technologies that may further expand DCE MRL use such as three-dimensional printing are introduced. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Three-dimensional non-contrast magnetic resonance lymphography severity stage for upper extremity lymphedema

PurposesNon-contrast magnetic resonance lymphography (NMRL) has recently shown the capability of evaluating anatomical fluid distribution in upper extremity lymphedema (UEL). However, there is still a lack of knowledge about the correlation between the characteristic three-dimensional (3D) NMRL findings and the indocyanine green lymphography (ICG-L) findings. Our goal was to clarify the relationship between the 3D NMRL findings and the ICG-L findings. MethodsMedical charts of patients with secondary UEL who underwent NMRL and ICG-L between January 2018 to October 2021 were reviewed. The upper extremities were divided into 6 regions; the hand, elbow, and the radial and ulnar aspects of the forearm and the upper arm. We investigated the prevalence of characteristic 3D NMRL patterns (Mist/Spray/Inky) in each region based on the ICG-L stage. We also examined the association between the 3D NMRL stage which we proposed and the ICG-L stage, and other clinical factors. ResultsA total of 150 regions of 25 patients with upper extremities lymphedema were enrolled in the study. All of the characteristic patterns increased significantly as the ICG-L stage advanced (p < 0.001, < 0.001, and < 0.001, respectively). The predominant NMRL patterns changed significantly from the Early pattern (Mist pattern) to the Advanced pattern (Inky/Spray pattern) as the ICG-L stage progressed (p < 0.001). The higher Stage of 3D NMRL was significantly associated with the progression of the ICG-L stage (rs = 0.80, p < 0.001). ConclusionsCharacteristic 3D NMRL patterns and the 3D NMRL Stage had a significant relationship with the ICG-L stage and other clinical parameters. This information may be an efficient tool for a more precise and objective evaluation of various treatments for UEL patients.

Kiosk 9Q-TA-05 - Central Conducting Lymphatic Anomaly: A Rare Cause of Chylopericardium in a Child Diagnosed on Magnetic Resonance Lymphangiography

Kiosk 9Q-TA-05 - Central Conducting Lymphatic Anomaly: A Rare Cause of Chylopericardium in a Child Diagnosed on Magnetic Resonance Lymphangiography

Introduction of Relationship Between the Vascular and Lymphatic Systems in Lymphedema Diagnosis and Treatment Research

In the past, the lymphatic and vascular systems were considered to be distinct circulatory systems. Consequently, diseases related to lymphatic and vascular circulation insufficiency were considered to have entirely different pathogenesis and treatment strategies. However, recent studies have reported a close interaction between these systems, revealing that dysfunction in lymphatic circulation can affect vascular insufficiency and vice versa. This new understanding has intimated the necessity of studying body fluid circulation from an integrated perspective that encompasses both capillaries and larger vessels in the lymphatic and vascular systems. In this review, we will introduce some cases observed in our research on lymphedema, a representative lymphatic insufficiency disease, focusing on the interrelation between the lymphatic and vascular systems identified in our findings. We studied lymphatic channel sheet (LCS), which is an artificial lymphatic scaffold for lymphangiogenesis, lymphangio-dynamics, which is a method to evaluate the lymphatic function, and quantified staging using magnetic resonance (MR) lymphangiography with gadolinium contrast agents. Although these studies were initiated to diagnose and treat lymphatic circulation disorders, we could observe associations with the vascular system. Based on these cases, we aim to discuss the intricate relationship between the lymphatic and vascular systems.

Massive Chylous Ascites in a 9-Year-Old Girl with Malrotation-A Case Report.

Malrotation leading to massive chylous ascites is rare. A 9-year-old girl was investigated for slowly increasing abdominal distension under a year. She had no vomiting, weight loss, or pain, but was bothered in social situations. Medical investigations, including ultrasound and computed tomography scans, revealed massive ascites. Laparocentesis yielded milk-colored fluid, confirmed as lymph through laboratory analysis. A complete blood count, liver function and hematologic parameters, chyle cytology, bacterial cultures, and polymerase chain reaction for tuberculosis were all within normal limits. She was referred to a tertiary center for vascular anomalies. A dynamic contrast-enhanced magnetic resonance lymphangiography showed normal lymphatic anatomy without leakage or flow obstruction. A whole-body magnetic resonance imaging revealed a central mesenteric rotation. She was referred to a tertiary center for pediatric surgery, where a laparoscopic Ladd's procedure was performed using a new 5 mm pediatric sealing device, along with an appendectomy using a 5 mm stapler. To derotate the bowel, fenestrations were created in compartments containing a substantial amount of chyle and ascites, resulting in the drainage of 2.4 L of fluid. She was discharged the day after surgery and has been in good health for 1 year. We present a video illustrating the Ladd's procedure steps in this patient.

CASE-FA-01 - Magnetic Resonance Lymphangiography for Evaluation of Lymphatic Pattern in Patients with Univentricular Physiology in a Tertiary Pediatric Center in Mexico

CASE-FA-01 - Magnetic Resonance Lymphangiography for Evaluation of Lymphatic Pattern in Patients with Univentricular Physiology in a Tertiary Pediatric Center in Mexico

Comparison of Magnetic Resonance Lymphangiography and Photoacoustic Lymphangiography in Preoperative Mapping of Lymphovenous Bypass

Comparison of Magnetic Resonance Lymphangiography and Photoacoustic Lymphangiography in Preoperative Mapping of Lymphovenous Bypass

Kiosk 11R-FB-05 - Experience with Dynamic Magnetic Resonance Lymphangiography in a Middle-income Country Entering a Stage of Maturation

Kiosk 11R-FB-05 - Experience with Dynamic Magnetic Resonance Lymphangiography in a Middle-income Country Entering a Stage of Maturation

Lymphangiogenesis after nonvascularized lymph node transplantation: Lymphangiographic findings in mice and minipigs

The establishment of new connections after NVLNT (non-vascularized lymph node transplantation) is still poorly understood. The purpose of this study was to investigate lymphatic connections after NVLNT using lymphangiography. In a mice model, 40 mice were allocated to undergo NVLNT or sham surgery. On day 21 after NVLNT, the lymphatic vessels were observed on near-infrared fluorescence imaging with indocyanine green. In a minipig model, 12 minipigs underwent NVLNT. On day 14 after NVLNT, the transplanted lymph node and donor site were checked by ultrasound, and minipigs with viable transplanted LNs were allocated to lipiodol lymphangiography or MR lymphangiography groups. Transplanted LN engraftment was examined with immunohistochemical staining. After NVLNT in mice, the signal intensities in the popliteal region at 3 minutes and 5 minutes were higher in the transplanted side than the control side (21.3 ± 8.1 vs. 11.0 ± 4.6 at 3 minutes, 26.7 ± 6.8 vs. 19.7 ± 5.9 at 5 minutes), while in the sham group, there were no significant differences between sides. In minipigs, lipiodol lymphangiography (n = 5) showed Lipiodol accumulation in transplanted LNs with innumerable newly formed lymphatic vessels and lymphovenous shunts. MR lymphangiography (n = 5) showed higher enhancement on the transplanted side compared to the control side. Histology showed successful engraftment of transplanted LNs in 16 out of 20 (80%) mice and 9 out of 12 (75%) minipigs. Omnidirectional lymphangiogenesis forming a dense lymphatic network and spontaneous formation of lymphovenous shunts were shown after NVLNT.

The Role of Imaging of Lymphatic System to Prevent Cancer Related Lymphedema.

Lymphedema is a progressive chronic condition affecting approximately 250 million people worldwide, a number that is currently underestimated. In Western countries, the most common form of lymphedema of the extremities is cancer-related and less radical surgical intervention is the main option to prevent it. Standardized protocols in the areas of diagnosis, staging and treatment are strongly required to address this issue. The aim of this study is to review the main diagnostic methods, comparing new emerging procedures to lymphoscintigraphy, considered as the golden standard to date. The roles of Magnetic Resonance Lymphangiography (MRL) or indocyanine green ICG lymphography are particularly reviewed in order to evaluate diagnostic accuracy, potential associations with lymphoscintigraphy, and future directions guided by AI protocols. The use of imaging to treat lymphedema has benefited from new techniques in the area of lymphatic vessels anatomy; these perspectives have become of value in many clinical scenarios to prevent cancer-related lymphedema.

Imaging Modalities for Evaluating Lymphedema.

Lymphedema is a progressive condition. Its therapy aims to reduce edema, prevent its progression, and provide psychosocial aid. Nonsurgical treatment in advanced stages is mostly insufficient. Therefore-in many cases-surgical procedures, such as to restore lymph flow or excise lymphedema tissues, are the only ways to improve patients' quality of life. Imaging modalities: Lymphoscintigraphy (LS), near-infrared fluorescent (NIRF) imaging-also termed indocyanine green (ICG) lymphography (ICG-L)-ultrasonography (US), magnetic resonance lymphangiography (MRL), computed tomography (CT), photoacoustic imaging (PAI), and optical coherence tomography (OCT) are standardized techniques, which can be utilized in lymphedema diagnosis, staging, treatment, and follow-up. Conclusions: The combined use of these imaging modalities and self-assessment questionnaires deliver objective parameters for choosing the most suitable surgical therapy and achieving the best possible postoperative outcome.

Lymphoscintigraphy Findings are Associated with Outcome in Children with Chylothorax After Cardiac Surgery.

Postoperative chylothorax in patients with congenital heart diseases (CHD) results in poor outcomes if anatomical and functional abnormalities of the lymphatic system are present. While these abnormalities are typically diagnosed by intranodal lymphangiography and dynamic contrast magnetic resonance lymphangiography, the usefulness of lymphoscintigraphy in these patients has not been evaluated. Between January 2019 and December 2021, 28 lymphoscintigraphies were performed in our institution for investigating prolonged pleural effusion after cardiac surgery. The images were assessed by three board-certified pediatric cardiologists retrospectively to determine the likelihood of a central lymphatic flow disorder. The likelihood was scored (range 1-3) based on structural abnormalities and congestive flow in the lymphatic system. Those scores were summed and the likelihood was categorized as low to intermediate (< 8 points) or high (8 or 9 points). Median age at lymphoscintigraphy was 129days (IQR, 41-412days), it was performed at a median of 22days (IQR, 17-43) after surgery, and median score was 6 points (IQR, 4-7.5). Kendall's coefficient of concordance (0.867; p < 0.05) indicated high inter-rater reliability. Overall survival at 6months after surgery was 92.5% in the low-to-intermediate group but 68.6% in the high group (p < 0.05), and duration of postoperative thoracic drainage was 27 and 58days, respectively (p < 0.05). Lymphatic abnormalities detected by lymphoscintigraphy were associated with poorer outcomes. Lymphoscintigraphy was thought to be useful in assessing anatomic and functional lymphatic abnormalities, despite its minimal invasiveness.

Lymphedema Surgical Treatment Using BioBridgeTM: A Preliminary Experience

Lymphedema treatment has traditionally been based on conservative therapies. In recent years, the introduction of two microsurgical techniques—venolymphatic anastomoses and lymph-node transplantation—have revolutionized the therapeutic approach to this disease. However, these surgical techniques only provide a partial volume reduction, and thus, they require further improvement. A new device called BioBridgeTM, an implantable biocompatible and biodegradable mesh, made up of aligned nanofibrillar collagen scaffolds that mimic the collagen matrix, could significantly improve the benefits of these surgical strategies, favoring lymphatic regeneration. In this article, we describe our experience with three patients affected by primary lymphedema, two treated with a lymph-node transplant, and one with venolymphatic anastomosis. All interventions involved the placement of nanocollagen scaffolds. With each patient, non-contrast magnetic resonance lymphography was performed for surgical planning and there was an imaging and a clinical follow-up at 1 year. All patients showed a significant reduction in the affected areas with the demonstration of new lymphatic vessels at MR imaging follow-up. This was a preliminary experience, and it showed the potential benefit of positioning nonfibrillar scaffolds in combination with other microsurgical therapies for lymphedema.

Non-Contrast MR Lymphography and Intranodal Dynamic Contrast MR Lymphangiography in Children with Congenital Heart Disease-Imaging Findings as well as Impact on Patient Management and Outcome.

Lymphatic flow disorders are rare but devastating complications in children with congenital heart disease. T2-weighted magnetic resonance lymphography and intranodal dynamic contrast magnetic resonance lymphangiography are imaging modalities that can depict central lymphatic anatomy and flow pattern. Our objective was to describe the technical aspects and our imaging findings of central lymphatic abnormalities and their impact on patient management and outcomes: We conducted a retrospective review of 26 children with congenital heart disease who presented for lymphatic imaging between 2015 and 2020 at our institution. Eleven had postoperative chylothorax, six had plastic bronchitis, seven had protein-losing enteropathy and three had Noonan syndrome. Our lymphatic imaging demonstrated severely abnormal lymphatic flow in all of the children, but only minor abnormalities in protein-losing enteropathy. No major procedure-related complication occurred. Lymphatic interventions were performed in six patients, thoracic duct decompression in two patients and chylothorax revision in three patients. This led to symptomatic improvements in all of the patients: Lymphatic imaging is safe and essential for the diagnosis of lymphatic flow disorders and therapy planning. Our intranodal lymphangiography depicts an abnormal lymphatic flow pattern from the central lymphatics but failed to demonstrate an abnormal lymphatic flow in protein-losing enteropathy. These imaging techniques are the basis for selective lymphatic interventions, which are promising to treat lymphatic flow disorders.