The use of Advanced MRI techniques to evaluate antenatal lung development.

Inadequate development of the lungs (known as pulmonary hypoplasia) is a relatively common event, occurring in 1 in 1000 pregnancies. In 50% of these babies the lungs are too small for long term survival after birth. Risk factors include rupture of the membranes before twenty-four weeks with loss of the amniotic fluid surrounding the baby or the presence of a congenital abnormality of the baby's heart or chest

At present, in clinical practice, the size of the baby's lungs can be evaluated during the pregnancy using either ultrasound or basic magnetic resonance imaging (MRI). The latter are safe scans which use magnets to create images of the baby. Estimated size gives some information about whether a baby will survive after birth but neither of these assessments provide detailed information about alterations in lung development such as how the air spaces are forming or indicate how the lungs might function after birth. Advanced MRI techniques could provide more in depth information about both normal and abnormal lung development.

This study will use these advanced MRI techniques to see how babies' lungs develop in the womb during normal pregnancies (100 pregnancies). We will then assess 70 pregnancies at high risk of pulmonary hypoplasia to assess the specific alterations in lung development that occur in this condition.

All women will undergo an MRI scan during their pregnancy. In women with uncomplicated pregnancies this will be once during the pregnancy between 16 and 42 weeks. In women with pregnancies at risk of pulmonary hypoplasia we will perform two MRI scans, one when we identify them as high risk and another later in the pregnancy. We will collect information on the babies after birth such as if they survive, need oxygen or other treatments to help them breathe. After birth we will also assess how the lungs are functioning using a technique called helium dilution. During this safe test the baby breathes in helium (a non-harmful gas) which allows us to calculate the actual size of the babies' lungs.

In the future this new knowledge may help individualize counselling as to how a baby's lungs are likely to function after birth. Currently women who lose the waters around the baby early in the pregnancy or have other abnormalities with the chest or heart are given the option of termination of pregnancy due to the high risk of pulmonary hypoplasia however some children do survive although with varying qualities of life. These new MRI scans may also help to monitor potential treatments aimed at improving lung growth and development such as surgery or medications administered in the womb.

Pulmonary hypoplasia is a congenital condition in which development of the lungs is incomplete. This results in lungs that are too small for efficient gas exchange in postnatal life. It affects 1:1000 pregnancies and is lethal in over 50% of cases. It is associated with conditions such as second trimester premature rupture of membranes, congenital diaphragmatic hernia or certain congenital heart diseases. At present ultrasound and conventional MRI scans provide the mainstay of antenatal lung assessment and are used to prognosticate whether the child is likely to survive. However these scans only evaluate overall lung size and do not provide insight into tissue microstructure or function.

Advanced MRI techniques (deformable slice to volume reconstruction, motion corrected diffusion and T2* imaging) facilitate more accurate assessment of lung size and vasculature, and can assess tissue microstructure and oxygenation potentially reflecting alveolar structure and tissue perfusion. This project aims to evaluate lung development with advanced MRI techniques in uncomplicated pregnancies and those at high risk of pulmonary hypoplasia.

Methods
100 women with uncomplicated pregnancies and 70 with conditions at high risk of pulmonary hypoplasia will be recruited from four tertiary referral units. MRI imaging will be undertaken including T2, T2* and diffusion sequences. Outcome data including survival, surgical interventions, surfactant or supplemental oxygen therapy will be recorded. Pulmonary function tests will be performed at term equivalent age from three units. Data will be postprocessed to generate lung volumes, mean T2*, fractional anisotropy and apparent diffusion co-efficients. Normal ranges during gestation for each parameter will be generated and conditions at high risk of pulmonary hypoplasia will then be compared.

In the future we hope this knowledge may help improve and individualize counselling, and evaluate surgical and medical interventions.