“Near-Infrared Fluorescence Imaging of the Lymphatic System in Children with Chylous Pleural Effusion after Heart Surgery – A Feasibility Pilot Study”

Doctor's Name: 
Sevick, Eva PhD, MD
Hospital/Institution: 
University of Texas - Health Science Center

Congenital cardiovascular malformation (CVMs) affect 0.5 – 0.7% of all live births, with the prevalence for severe CVMs reported to be 1.5 cases per 1000 live births.  Repair of congenital heart defects can be complicated by contributions from the dysfunction of the lymphatic circulatory system.  The lymphatics serve to take up residual fluid from the tissue spaces as well as the lipid-laden fluid from the gastrointestinal system (termed chyle) and to return it to the blood vasculature near the area of the heart.  Chylothorax is a critical condition in which there is an accumulation of chyle around the lungs, a rare, but serious complication in children who undergo heart surgery.  We don’t know what exactly causes chylothorax and because of this, it is difficult to treat the condition. There are three suspected causes of chylothorax: 

During cardiac surgery there may be inadvertent damage to the main connection between the lymphatic system and the blood circulatory system, at a location known as the thoracic duct. The damage may result in a failure to return lymph and chyle to the blood and as a result a spillage of lymph or chyle into the chest area occurs. 

The venous blood vasculature near the heart into which the lymph/chyle drains is either obstructed, “plugged up,” or has a very high pressure that prevents lymph/chyle drainage into the blood circulatory system. 

Genetic defects that either are inherited or spontaneously occur in the womb (called de novo mutations) can cause heart defects and may also cause lymphatic defects which create a “plumbing problem” for the return of lymph/chyle to the blood vasculature.

While there are no diagnostic methods to determine the cause of pediatric chylothorax in each individual case, different causes of individual cases require different means to manage this critical condition.  For example, if there is damage to the thoracic duct, a surgical procedure called “thoracic duct ligation” is conducted in which the connection between the lymphatic and blood circulation is closed to stop spillage of chyle into the chest.  On the other hand, if there is no damage to the thoracic duct and instead an obstruction between lymph and blood circulatory systems, then a thoracic duct ligation can close off the only potential means to reverse spillage and return normal lymph/chyle drainage to the blood circulation.  This situation calls for more conservative treatment.  Finally, if there is a familial cause of the defect, families would like to know for future family planning and embark on conservative and most effective care of their child.  If there is a de novo or spontaneous genetic defect that occurs in the womb, knowing this genetic defect could help understand the molecular basis for the congenital heart and lymphatic defects possibly leading to effective drug therapies.

In this research program, we employ two translational technologies, (1) a minimally invasive, bedside imaging modality called near-infrared fluorescence lymphatic imaging (NIRFLI) in order to visualize the extent of thoracic duct damage (if any) and to determine whether there are congenital lymphatic vasculature defects that could aid in the management of chylothorax in these critically ill children; and (2) next generation sequencing (NGS) of DNA which could identify whether there are inherited or de novo mutations that could be causative of condition. Preliminary data involves (1) the FDA approved, compassionate use case of using NIRFLI to image the lymphatics in a 5 week old infant within the pediatric intensive care unit in order to help direct surgical management of chylothorax after heart surgery and (2) the use of NGS to show that a gene variant known to be associated with blood vasculature malformation in a young man was also responsible for his abnormal lymphatic malformations diagnosed with NIRFLI.  The preliminary data supports the long-suspected interactions between the blood circulatory system and the relatively forgotten lymphatic vasculature, which could be relevant for the care of children with congenital heart defects.

The  proposed study involves a collaborative team with an established record of translational research and with expertise in pediatric cardiology and intensive care (Dr. Balaguru, M.D.), near-infrared fluorescence imaging devices (Drs. Sevick, Ph.D and Tan, Ph.D), and next generation sequencing and bioinformatics (Dr. Gonzalez-Garay, Ph.D.).

Award Date 1: 
2014
Award Amount 1: 
$25,000
Award Date 2: 
2015
Award Amount 2: 
$61,056