Perinatal brain injury remains a significant cause of infant mortality and morbidity, occurring in over 6 out of every 1,000 live births. It is a common cause of cerebral palsy, seizures, complex behavioral disorders and intellectual impairment. It is now believed that the majority of perinatal brain injury is due to impairment of oxidative metabolism, with neuronal injury due to ischemia followed by reperfusion or inherited defects in metabolic pathways expressed in the perinatal period. With neuronal activity closely linked in time to the metabolism or consumption of oxygen direct measures of cerebral oxygen consumption likely provide the most direct measure of neuronal health. We believe that a measure of oxygen consumption during the first week of life has the potential to improve early stratification of brain injury and better predict outcome. Positron Emission Tomography (PET) can provide direct information on oxygen consumption but the radiation exposure and lack of availability make routine use impractical. Our goal is to establish a safe, noninvasive multimodal method to estimate newborn regional cerebral oxygen consumption. We propose to combine Frequency Domain Near Infrared Spectroscopy (FD-NIRS) and the Magnetic Resonance (MR) technique of Arterial Spin Labeling (ASL) to estimate newborn cerebral oxygen consumption noninvasively and in real time. To do achieve this goal, technical advances are needed: 1) build a multichannel MRI coil tailored to the newborn head to optimize the SNR and reduce the scanning time;2) build a compatible optical probe to measure hemoglobin oxygen saturation simultaneously with MRI;3) take advantage of the MRI structural information for optimization of the algorithms used to quantify brain optical parameters and estimate oxygen consumption. To validate our measurement of oxygen consumption as an indicator of brain injury we will test our measure of oxygen consumption in 20 infants at risk for perinatal brain injury and correlate oxygen consumption with brain volume at 3 months.

Public Health Relevance

The metabolic rate of oxygen consumption (CMRO2) is the best measure of brain health after injury yet there are no non-invasive methods available. Combined 32-chanel MRI and frequency domain near infrared spectroscopy offer the potential to safely perform fast noninvasive estimates of absolute CMRO2 in one of our most vulnerable and difficult to assess populations: 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 #
5R21HD058725-02
Application #
7943092
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (90))
Program Officer
Vitkovic, Ljubisa
Project Start
2009-09-30
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$214,286
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Karmacharya, S; Gagoski, B; Ning, L et al. (2018) Advanced diffusion imaging for assessing normal white matter development in neonates and characterizing aberrant development in congenital heart disease. Neuroimage Clin 19:360-373
Roche-Labarbe, Nadege; Fenoglio, Angela; Radhakrishnan, Harsha et al. (2014) Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates. Neuroimage 85 Pt 1:279-86
Dehaes, Mathieu; Aggarwal, Alpna; Lin, Pei-Yi et al. (2014) Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia. J Cereb Blood Flow Metab 34:87-94
Lin, Pei-Yi; Roche-Labarbe, Nadège; Dehaes, Mathieu et al. (2013) Regional and hemispheric asymmetries of cerebral hemodynamic and oxygen metabolism in newborns. Cereb Cortex 23:339-48
Lin, Pei-Yi; Roche-Labarbe, Nadege; Dehaes, Mathieu et al. (2013) Non-invasive optical measurement of cerebral metabolism and hemodynamics in infants. J Vis Exp :e4379
Roche-Labarbe, Nadège; Fenoglio, Angela; Aggarwal, Alpna et al. (2012) Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain. J Cereb Blood Flow Metab 32:481-8
Dehaes, Mathieu; Grant, P Ellen; Sliva, Danielle D et al. (2011) Assessment of the frequency-domain multi-distance method to evaluate the brain optical properties: Monte Carlo simulations from neonate to adult. Biomed Opt Express 2:552-67
Keil, Boris; Alagappan, Vijay; Mareyam, Azma et al. (2011) Size-optimized 32-channel brain arrays for 3 T pediatric imaging. Magn Reson Med 66:1777-87