Imaging of Lymphatic Anomalies

• ClinicalTrials.gov Identifier: NCT02744027
• Recruitment Status: Completed
• First Posted: April 20, 2016
• Last Update Posted: March 21, 2018
• Sponsor: Children's Hospital of Philadelphia
• Collaborator: University of Pennsylvania
• Information provided by (Responsible Party): Children's Hospital of Philadelphia

Study Description

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.

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Children's Hospital of Philadelphia

University of Pennsylvania

Investigators

• Principal Investigator: Yoav Dori, MD, PhD; Children's Hospital of Philadelphia

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Itkin M, Rabinowitz DA, Nadolski G, Stafler P, Mascarenhas L, Adams D. Abnormal Pulmonary Lymphatic Flow in Patients With Lymphatic Anomalies and Respiratory Compromise. Chest. 2020 Aug;158(2):681-691. doi: 10.1016/j.chest.2020.02.058. Epub 2020 Mar 24.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT02744027
• Other Study ID Numbers: 15-012331
• First Posted: April 20, 2016
• 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:

Osteolysis, Essential; Lymphatic Diseases; Congenital Abnormalities; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Osteolysis; Bone Resorption