High-fidelity brain perfusion MRI in newborns less than one week of age - Project Summary/Abstract: Cerebral perfusion can now be measured in patients of virtually all ages. Across the lifespan, the only remaining challenge is the measurement of cerebral perfusion during the first week after birth, the early neonatal period. Newborns 0-7 days of age have a brain size of approximately one-third of the adult and cerebral blood flow (CBF) that is as low as 10% of the adult values, making imaging perfusion in these patients particularly challenging. On the other hand, the first few weeks after birth is the most vulnerable period in one’s life, with 2.3 million newborns dying in 2022. Both preterm and full-term neonates can suffer from a number of pathological conditions related to abnormal cerebral perfusion, such as hypoxic-ischemic encephalopathy, perinatal ischemic stroke, and congenital heart disease. Therefore, there is an urgent need to develop a clinically feasible perfusion imaging technique for the early neonatal period. Some perfusion techniques involve exogenous tracer, thus are less desirable for use in neonates. ASL MRI is an excellent noninvasive tool to study cerebral perfusion in neonates, because it does not require exogenous agents, can be repeated multiple times, and allows quantitative measurements. However, the low intrinsic SNR and presence of several confounding factors have currently limited the use of ASL MRI in neonates. To the best of our knowledge, no studies have conducted systematic development of ASL perfusion MRI in healthy neonates. One of the main reasons is that, unlike conducting technical studies in adults, enrollment and access to healthy neonates for technical studies is extremely challenging. As a result, the vast majority of ASL studies on neonates have been conducted as an add-on to clinical MRI scans, on neonates who have certain clinical indications (to require them to receive an MRI). A novel aspect of the present application is that we will leverage unique resources at our institution that allow us to recruit healthy early neonates for research- dedicated MRI, which provides the necessary scan time to conduct systematic sequence development studies. Therefore, the primary goal of this application is to develop non-invasive ASL MRI for perfusion imaging in early neonates (<1 week after birth). This project consists of two aims, a technical aim and an initial application aim. Aim 1 will develop non-invasive perfusion MRI techniques in healthy neonates, which is in turn divided into four sub-aims covering distinctive components of the technical development. These components include MRI pulse sequence and acquisition development, expansion of the sequence to multiple post-labeling delay (PLD) scheme, on-scanner processing and kinetic modeling of the MRI data, and development of a toolbox for automatic and standardized quantification of perfusion parameters. Aim 2 will conduct a feasibility study to evaluate the clinical utility of perfusion MRI in neonates with hypoxic ischemic encephalopathy (HIE). Upon the successful completion of this project, we will have developed a reliable and turnkey perfusion imaging technique that is ready for broad use in both clinical and research settings.
