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Imaging of Lymphatic Anomalies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02744027
Recruitment Status : Completed
First Posted : April 20, 2016
Last Update Posted : March 21, 2018
University of Pennsylvania
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gorham Disease Lymphatic Diseases Lymphangiomatosis Other: Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL) Other: Heavy Weighted T2 Imaging (T2W) Other: Lymph Node Access Not Applicable

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Dynamic Contrast Enhanced MR Lymphangiogram Imaging of Lymphatic Anomalies (LA)
Study Start Date : April 2016
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 2017

Arm Intervention/treatment
Dynamic Contrast Enhanced Magnetic Contrast Imaging
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)
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.

Other: Heavy Weighted T2 Imaging (T2W)
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.

Other: Lymph Node Access

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.

Primary Outcome Measures :
  1. Describe lymphatic anatomy of participants with lymphatic anomalies (LA) [ Time Frame: 2 Days ]
    The primary endpoint will be the description of lymphatic anatomy assessing if participants have a single or branched Thoracic Duct.

Secondary Outcome Measures :
  1. Development of a classification system for lymphatic flow [ Time Frame: 2 days ]
    Development of a classification system based on retrograde or anterograde flow of lymphatic fluid.

  2. Description of Lymphatic malformations in participants with lymphatic anomalies [ Time Frame: 2 days ]
    Assessing if lymphatic malformation are present or absent in participants with lymphatic anomalies.

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Ages Eligible for Study:   2 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02744027

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United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
University of Pennsylvania
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Principal Investigator: Yoav Dori, MD, PhD Children's Hospital of Philadelphia
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Children's Hospital of Philadelphia Identifier: NCT02744027    
Other Study ID Numbers: 15-012331
First Posted: April 20, 2016    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Children's Hospital of Philadelphia:
Generalized Lymphatic Anomaly
Kaposiform Lymphangiomatosis
Dynamic Contrast Enhanced Magnetic Resonance Lymphangiogram
Magnetic Resonance Imaging
Additional relevant MeSH terms:
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Osteolysis, Essential
Lymphatic Diseases
Congenital Abnormalities
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Resorption