Assessment of lung function in neonates and infants Lung disease is the most common chronic disease of childhood, but methods for assessing lung disease such as spirometry cannot be performed by young children. Thus clinicians have only parental reports of patient symptoms upon which to base treatment decisions. Further, clinical trials of treatments for lung disease are difficult to perform in the absence of a quantitative outcome. Therefore many treatments for lung disease have not been tested in young children. Hyperpolarized (HP) noble gas magnetic resonance imaging is a technique for imaging the lung functional microstructure that provides a quantitative evaluation of lung disease severity in three-dimensions with high resolution. Ventilation imaging depicts regional patency of the airway tree, even down to the smallest airways. Ventilation abnormalities reveal the earliest signs of obstructive disease, such as cystic fibrosis and asthma. Diffusion weighted imaging quantifies the Brownian-motion length-scale of gas atoms. By mapping out acinar dimension regionally, diffusion weighted imaging is exquisitely sensitive to underdeveloped or injured alveolar tissues. Since hyperpolarized gas MRI does not use ionizing radiation, it is well-suited for use in children and infants. What is needed are safe and effective devices and methods for administering and imaging hyperpolarized noble gas in neonates and infants. We propose to develop a simple and elegant method for administering hyperpolarized helium-3 (HHe) to neonates and infants. New MR-compatible gas flow technologies will be developed, compared, and incorporated into a novel pass-though junction box which can substitute a small bolus of HHe for an equal amount of air. Its mostly passive and intrinsically safe design features will allow its use with either fre- breathing infants or with neonates on a mechanical ventilator. We will test the device by imaging free-breathing healthy adults while they are simulating the breathing volumes and patterns of infants. We further propose to adapt our 32-element chest coil which we successfully employed for accelerated structure-function imaging in adults. First we down-size it for subjects 13kg and under, and in year 2 optimize a second chest coil design for neonates under 4.5kg. We will submit IRB filings for these devices as non-significant medical risk devices. Working with our academic collaborators, we will first acquire accelerated hyperpolarized helium-3 images in free-breathing 1-2 year old infants, five who are healthy normals and two with chronic lung disease of prematurity (bronchopulmonary dysplasia, BPD). We will compare accelerated spiral and Cartesian imaging protocols exploiting the parallel coil. After regulatory review, we will proceed to imaging two neonates on ventilators just before they are extubated. One subject will be a neonate born prematurely who has early BPD. The second subject will be a neonate under care due to an hypoxic ischemic event. This subject's lungs should be structurally normal.

Public Health Relevance

Due to improvements in perinatal and antenatal care, as many as 50,000 very low birth weight infants are surviving in the US annually, many suffering from chronic lung disease of prematurity or bronchopulmonary dysplasia. Optimal management of pulmonary disease in neonates is hindered by the lack of a diagnostic imaging modality that could 1) guide acute care of infants born prematurely, and 2) evaluate outcomes to retrospectively determine which therapies preserve the greatest degree of lung function. Hyperpolarized noble gas MRI, a new safe non-ionizing method for assessing lung function is ideally suited to quantitative lung function measurements in infants. We propose development of a device for administering hyperpolarized noble gases to infants, sensing coils and protocols for MR imaging, and a step-by-step safety review strategy that will demonstrate feasibility by assessing lung function in the neonatal intensive care unit.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43HL117337-02
Application #
8531345
Study Section
Special Emphasis Panel (ZRG1-SBIB-V (90))
Program Officer
Blaisdell, Carol J
Project Start
2012-08-15
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$241,662
Indirect Cost
Name
Xemed, LLC
Department
Type
DUNS #
152959891
City
Durham
State
NH
Country
United States
Zip Code
03824