Calculating Wall Shear Stress in Infant Pulmonary Veins

The purpose of this study is to better understand pediatric pulmonary vein stenosis (PVS), which is the narrowing of blood vessels that connect the lungs to the heart. PVS is a life-threatening disease without a clear cause. The investigators think patients who develop PVS have an increased Wall Shear Stress (WSS) level in the pulmonary veins, which is the force placed on the walls of the veins. This study will determine if WSS can be calculated in the pulmonary veins of infants using Ferumoxytol enhanced Cardiac Magnetic Resonance Imaging (FcMRI). If possible, the investigators aim to use FcMRI to better screen patients at risk of PVS and to help guide therapy in patients with PVS.

Background:

The mechanism of pediatric intraluminal pulmonary vein stenosis (PVS) remains unknown. It is hypothesized that elevated wall shear stress (WSS) as a result of excessive pulmonary blood flow (left to right shunts) and/or pulmonary vein distortion from surrounding anatomy contributes to the neo-intimal proliferation. Calculating WSS in pediatric pulmonary veins using ferumoxytol enhanced cardiac magnetic resonance (FcMRI) has not been reported and would represent a novel method of evaluation.

Objectives:

The primary objective is to determine the feasibility of calculating WSS in infant pulmonary veins using FcMRI. The secondary objective is to determine the magnitude and variability of WSS in pulmonary veins among high-risk patients and normal controls.

Study Design:

Prospective, interventional, single center, feasibility study

Setting/Participants:

Single center study at The Children's Hospital of Philadelphia. High-risk infants (n = 10) will include two groups of patients; (1) infants with moderate to severe bronchopulmonary dysplasia (BPD) and (2) infants with postoperative repair of total anomalous pulmonary venous connection (TAPVC). Group 1 participants will be infants who are undergoing an MRI as part of clinical care for other issues (i.e., MRI brain for hypoxic ischemia encephalopathy), with the research FcMRI being performed following the clinical care MRI. Group 2 participants will be infants who are undergoing FcMRI as part of clinical care. Controls (n = 10) will be pediatric patients without intracardiac defects who are undergoing FcMRI as part of clinical care (i.e., evaluation of anomalous coronary, aortopathy, vascular ring).

Study Procedures, Interventions and Measures:

Participants will undergo FcMRI and have the WSS calculated in each pulmonary vein (right upper, right lower, left upper, left lower) using several methodologies. Patients will be followed for 12 months following cMRI monitoring for a new diagnosis of PVS.

Eligibility Criteria:
Normal (Controls) Subjects Inclusion Criteria

1. Males or Females less than 18 years of age.
2. Weight \> 3 kg.
3. Undergoing cMRI with ferumoxytol as part of clinical care.
4. Structurally normal heart (by echocardiography) with exception of small left to right shunts, isolated valve pathology, anomalous coronary arteries, extracardiac vascular anomalies such as arch anomalies.
5. Parental/guardian permission (informed consent).

Normal (Controls) Subjects Exclusion Criteria

1. Congenital heart disease (except small left to right shunts, isolated valve pathology, anomalous coronary arteries, extracardiac vascular anomalies such as arch anomalies).
2. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
3. Patient not receiving ferumoxytol as part of their cMRI due to a known hypersensitivity to the drug, or a known diagnosis of iron overload.

High-Risk Subject Inclusion Criteria

1. Males or Females less than 12 months of age.
2. Diagnosis of moderate to severe BPD (group 1) or TAPVC s/p repair (group 2).
3. Weight \> 3 kg.
4. Undergoing non-contrast MRI for clinical reasons (group 1) or undergoing cMRI with ferumoxytol as part of clinical care (group 2).
5. Parental/guardian permission (informed consent).

High-Risk Subject Exclusion Criteria

1. Congenital heart disease with single ventricle physiology.
2. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
3. Patient has a contraindication to ferumoxytol such as a known hypersensitivity to the drug, or a known diagnosis of iron overload.