Metabolic imaging in newborns has proven useful for clinical assessment of children with brain injuries, extrinsic and inborn errors of metabolism, and disorders of brain maturation. As the brain matures, the metabolic profiles also change. ?-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mature brain, is an excitatory mediator during early brain development, and showed difference between preterm and term infants. Single voxel spectroscopic (SVS) acquisition is the most commonly available methodology for non-invasively investigating brain metabolism but covering multiple anatomical regions is challenging because each of the acquisitions takes approximately 5 minutes. In this proposed project, we will leverage the most recent advances in multi-channel phased arrays with RF technology to develop multi-slice GABA-edited 2D MR spectroscopy imaging (MRSI) with high spatial resolution that is acquired simultaneously at multiple locations in under 5 minutes of scan time. Metabolite accuracy compared to standard SVS and test- retest reliability will be conducted on scans from 10 healthy adult volunteers with one week apart. We will recruit 30 preterm patients. They will undergo their imaging exams when they are clinically stable and before discharge, and will return for follow-up visits at the 6-month corrected age. Metabolic profiles, along with the convention and advanced MR imaging parameters, will be correlated to the clinical outcome measures. The fast MRSI data acquisition being developed will provide capabilities for evaluating preterm infants and will also be important for diagnosis and assessment of a much broader range of neurological diseases. According to CDC, there are more than 500,000 babies in the US each year that are born prematurely (less than 37 weeks gestation). Babies born between 24 and 31 weeks gestation are five times as likely as full-term infants to have a birth defect, and infants born even a few weeks early are three times higher. Those who survive face the risk of life long health consequences, including difficulties in breathing and feeding, cerebral palsy, and problems in learning. Developing criteria of evaluating and identifying temporal and spatial changes in metabolites are critical for evaluating brain development in preterm infants. The proposed simultaneous multi-slice MRSI acquisition will enable assessment of a wider area of the brain within a clinical feasible time, allow longitudinal detection of the metabolic profiles in the same locations after voxel shift, and provide averaged spectra in irregular shapes, which will improve patient evaluation. The targeted patient population of newborns would benefit immediately from the increased mapping of metabolic information, while maintaining scan time, minimizing the time spent outside of NICU and reducing potential risk.

Public Health Relevance

According to the CDC, more than 500,000 babies in the US are born each year prematurely and over 25,000 with some form of birth injuries. The economic cost is tens of billions of dollars annually for additional healthcare and educational needs of the affected children, superimposed upon profound, unquantifiable emotional distress on the immediate family and surrounding communities. The proposed study will improve our understanding of localized and long-term metabolite changes in this newborn population, which would presumably offer treatment strategies to improve the outcome of these newborns.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD092660-02
Application #
9527167
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Higgins, Rosemary
Project Start
2017-07-15
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118