Imaging of Lymphatic Anomalies

Study Overview
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Brief Summary
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Lymphatic Anomalies (LA) is characterized by proliferation of lymphatic tissue causing deterioration of pulmonary function. Understanding changes in lymphatic anatomy in these patients is hindered by the difficulty of imaging the lymphatic system. Dynamic Contrast Enhanced MR Lymphangiogram (DCMRL) may be useful in investigating pathological changes in the lymphatic system.

Detailed Description
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Lymphatic anomalies (LA) are a spectrum of rare diseases classified into lymphatic tumors and malformations. Complicated LA cases in the past have been called lymphangiomatosis because of varied disseminated involvement including soft tissue and viscera such as the spleen, liver and bone. Pleural effusions and pericardial effusions are often associated with these lesions. These are now classified into different phenotypes such as Generalized Lymphatic Anomaly (GLA), Gorham's Stout Disease (GSD) and Kaposiform Lymphangiomatosis (KLA). These complicated phenotypes can cause massive osteolysis causing a morbidity and mortality from infection or paralysis or worsening pulmonary function and effusions (GSD, GLA, KLA). The major cause of mortality and morbidity in these patients is the deterioration of pulmonary function by chronic chylous effusions and progressive interstitial lung disease. Unfortunately, little is known about biomarkers, risk stratification or the pathophysiology of this progression. The understanding of changes in patients' lymphatic anatomy with LA is hindered by the difficulty of imaging the lymphatic system. Dynamic Contrast Enhanced MR Lymphangiogram (DCMRL) is a technique that has recently been developed, allowing dynamic MR imaging of the lymphatic system by injecting gadolinium contrast agent in the groin lymph nodes. This technique has been previously used to identify pathological lymphatic perfusion of the lung parenchyma in patients with plastic bronchitis and neonatal chylothorax. Based on these imaging findings, a treatment algorithm has been designed and used to successfully treat the majority of those patients with these conditions.

Official Title
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Dynamic Contrast Enhanced MR Lymphangiogram Imaging of Lymphatic Anomalies (LA)

Conditions
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Gorham Disease, Lymphatic Diseases, Lymphangiomatosis

Intervention / Treatment
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* Other: Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL)
* Other: Heavy Weighted T2 Imaging (T2W)
* Other: Lymph Node Access


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with Lymphatic Anomalies (GLA, KL, Gorham disease) with radiological and or pathological confirmation of lung involvement will be considered for the study. Girls > 11 y.o. with a negative urine pregnancy test and contraception use. Registration in the International Lymphangiomatosis and Gorham's Disease Alliance (LGDA) Patient Registry or referral by a physician. Exclusion Criteria: Subjects with contraindications to contrast enhanced MRI: allergy to gadolinium imaging agents, impaired renal function (GFR<30) and presence of paramagnetic objects. Claustrophobia or contraindications to sedation/anesthesia Uncorrectable coagulopathy (bleeding disorders). Pregnant or lactating females.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Dynamic Contrast Enhanced Magnetic Contrast Imaging<br>Dynamic Contrast Enhanced Magnetic Resonance (MR) Lymphangiogram and heavy T2 Magnetic Resonance imaging data will be evaluated for abnormal lymphatic perfusion of the lung parenchyma. Abdominal and thoracic lymphatic malformations will be characterized by location, number, size, relationship to other organs and perfusion patterns in order to create a basis of imaging classification of lymphatic abnormalities (LA). Subjects will undergo both Dynamic Contrast Enhanced Magnetic Resonance Lymphangiogram (DCMRL) and Heavy Weighted T2 Imaging. | Other: Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL)<br>* Following completion of the T2 lymphatic mapping, contrast agent administered will be calculated based on weight. Investigators will use dosage of 0.1cc/kg of contrast which will be injected by hand simultaneously into each lymphatic node (LN) at a rate of 0.5-1 cc per min. One minute after the injection, scanning will be initiated using high spatial and temporal resolution magnetic resonance angiography (syngo time-resolved angiography with stochastic trajectories [TWIST]) sequence. The sequence parameters will be adjusted with a time delay such that a complete volume will be acquired approximately every 20-60 seconds. This will be followed by additional scans with a high-resolution navigator gated 3-dimensional flash inversion recovery (IR) sequence. In all subjects the scan area covered the neck, chest, and abdomen as caudal as feasible.<br>Other: Heavy Weighted T2 Imaging (T2W)<br>* Magnetic Resonance imaging (MRI) will be performed and T2W MRI lymphatic mapping will be performed using a respiratory navigated and cardiac gated 3 dimensional turbo spin echo sequence with pre-set parameters. Scan time varies from 2-5 min depending upon the size of the subject.<br>Other: Lymph Node Access<br>* The procedure will be performed under sedation and anesthesia if participants are aged 16 or under. The procedure will be performed with local anesthesia for participants aged over 16 years old. Using ultrasound guidance two inguinal lymph nodes (one each side) will be directly accessed with 25-gauge spinal needles attached to a short connector tubing. A shallow angle for puncture will be used to create a long subcutaneous tract to assist in stabilizing the needle. A small amount of an oil-based contrast or water soluble contrast will be injected under fluoroscopy guidance to confirm the correct position of the needles inside the lymph nodes. After stabilizing the needle, the subjects will be transferred into the MRI suite.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Describe lymphatic anatomy of participants with lymphatic anomalies (LA) | The primary endpoint will be the description of lymphatic anatomy assessing if participants have a single or branched Thoracic Duct. | 2 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of a classification system for lymphatic flow | Development of a classification system based on retrograde or anterograde flow of lymphatic fluid. | 2 days | 
| Description of Lymphatic malformations in participants with lymphatic anomalies | Assessing if lymphatic malformation are present or absent in participants with lymphatic anomalies. | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic Resonance Imaging, Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, Dynamic Contrast Enhanced Magnetic Resonance Lymphangiogram