The goal of the present project is to develop a clinically practical technique to quantify oxygen utilization in neonatal brain. Oxidative metabolism is the primary form of energy production in the human brain. Therefore, cerebral metabolic rate of oxygen (CMRO2) is an important index of brain function and tissue viability. Neonatal stage is particularly susceptible to disruptions in oxygen supply and metabolism, for example in the case of hypoxic ischemic encephalopathy (HIE) which is a consequence of oxygen deprivation in neonates due to birth asphyxia. Therefore, the availability of a non-invasive technique to determine CMRO2 in neonates may find immediate application in the diagnosis of HIE as well as in the treatment monitoring of HIE using hypothermia, which aim to reduce the brain's metabolic rate and preserve ATP. At present, there exist no practical techniques to determine CMRO2 in human neonates, because the conventional method of Positron Emission Tomography (PET) is not applicable due to radiation concerns. In this project, we will develop MR based techniques to measure CMRO2 in neonates. Our goal is to provide the clinical community a CMRO2 tool for neonatal applications that is completely non-invasive (no exogenous agent), rapid (<5 min of scan time), and can be performed on a standard 3 Tesla MRI. The PI's previous work has demonstrated that this goal is feasible in adult brain. Thus, the present project will benefit from our extensive experiences of developing this technique in adults. We have two Specific Aims.
Aim 1 will focus on in vivo studies of developing MR imaging protocols for the measurement of global CMRO2 in human neonatal subjects. We will conduct separate sub-studies to optimize several technical aspects of the venous oxygenation (TRUST MRI) and blood flow (phase-contrast MRI) techniques, including developing an automated, individualized labeling-slab positioning, comparison between triggered and non-triggered phase- contrast MRI, and determining optimal spatial resolution for neonatal imaging.
Aim 2 will focus on in vitro studies of neonatal blood T2 relaxometry, conducted on fresh cord blood of human neonates. This will allow us to obtain a calibration plot specifying blood T2 dependence on oxygenation, which is needed for calibrating the in vivo data. We clarify that, once the calibratio plot is established, it can be used for all future in vivo data, not just data collected in Aim 1. he neonatal T2 relaxometry will also provide important reference for many other MRI pulse sequences in neonates beyond the techniques in the proposed study, such as T2-prepared angiogram and susceptibility weighted imaging (SWI). Upon finishing this project, we will be able to provide researchers and clinicians with a set of MRI techniques for CMRO2 measurements that are ready for immediate applications in brain development and neonatal brain disorders.
Brain's energy utilization can be an important biomarker of neural development and brain tissue viability in neonates. The present project aims to develop non-invasive MR imaging techniques to evaluate the brain's energy utilization in neonates.
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