Light-Based Brain Functional Imaging in the Premature Infant

Implementation of a Non-Invasive, Bedside Functional Imaging System

Susan R. Hintz, M.D.

Stanford University, Stanford, CA

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

November 2001, for 3 years

Funding Amount:

$100,000

Abstract

Light-Based Brain Functional Imaging in the Premature Infant: Implementation of a Non-Invasive, Bedside Functional Imaging System

The premature infant is at very high risk for brain injury resulting in poor neurodevelopmental outcome. Brain injury in these infants may be diagnosed by techniques such as ultrasound or MRI that reveal damage after it has already been done. There are no known early indicators by which to reliably predict poor outcome in the premature infant. However, it is likely that changes in blood flow and oxygenation to specific areas of the brain play a role in the cerebral insult. Data from a non-invasive and continuous cerebral monitoring system and their correlation to traditional radiologic findings as well as to results of long-term neurodevelopmental exams are essential components to the study of brain injury in the critically ill newborn.

The Diffuse Optical Tomography System (DOTS) is a portable continuous-wave diffuse optical tomography system that uses lasers at 780 nm and 830 nm to provide real-time, non-invasive bedside assessments. Preliminary studies in preterm infants with DOTS during passive motor stimulation resulted in reproducible focal and contralateral change in cerebral absorption. Further, these initial studies indicate an increase in blood volume, as well as an overall increase in deoxyhemoglobin concentration to the activated area suggestive of an inverse BOLD response.

We propose to perform non-invasive, bedside optical functional imaging studies of the premature infant brain over a range of gestational ages (25-32 weeks EGA) daily for the first 7 days of life. We will compare observed changes in regional brain blood volume and oxygenation across gestational and actual ages in order to evaluate potential differences with advancing maturation. These early functional cerebral data will then be analyzed with respect to 1) white matter damage as seen by brain MRI at hospital discharge, and 2) neurodevelopmental outcome by Bayley Scales of Infant Development and neurologic exam at 18-22 months. Specific functional imaging patterns may be found to correlate with specific abnormal findings on MRI or, more importantly, long-term neurodevelopmental outcomes such as cerebral palsy. Optical functional imaging, a beside, real-time technology, could then be used to prospectively identify those infants at highest risk for adverse outcomes.

As neuroprotective strategies develop further, optical functional imaging may play an important role in directing therapy.

Investigator Biographies

Susan R. Hintz, M.D.

Assistant Professor of Pediatrics, Stanford University

Hypothesis

Hypothesis:
1. Optical functional images of the premature infant brain 25-32 weeks estimated gestational age (EGA), obtained at the bedside and in real-time, will reveal blood volume and oxygenation changes with passive sensorimotor stimulation.
2. Optical functional images of the infant brain will change with gestational and actual age.
3. Differences in functional images early in the premature infant's clinical course may correlate with differences in brain MRI at discharge and/or 18-22 month neurodevelopmental follow-up.

Goals:
1. To perform non-invasive, bedside optical functional imaging studies of the premature infant brain over a range of gestational ages (25-32 weeks EGA) daily for the first 7 days of life and to compare observed changes in regional brain blood volume and oxygenation across gestational and actual ages in order to evaluate potential differences with advancing maturation.
2. To embark upon studies correlating specific early functional patterns with later traditional radiologic findings (brain MRI at discharge) and neurodevelopmental outcome (at 18-22 months), thus identifying populations at highest risk for developmental delay and cerebral palsy early in the clinical course.
3. To further the understanding of the function and development of the premature infant brain by creating the first real-time, non-invasive "library" of functional images, thus developing optical imaging methodology so that it may be easily used in other hospitals, facilitating multicenter studies and disseminating this potentially diagnostic tool.

Methods:
Over a three year study period, the researchers will use the Diffuse Optical Tomography System (DOTS) to obtain daily brain functional images in premature infants (25 to 32 weeks gestational age, which is 8 to 15 weeks premature) over the first week of life. At the time of discharge from the hospital, brain MRI's will be performed; at 18 to 22 months of age, the patients will undergo follow-up neurodevelopmental exams to assess for developmental delay or neurologic consequences such as cerebral palsy.

Selected Publications

Mirmiran M., Barnes P., Keller K., Constantinou J., Fleisher B.E., Hintz S.R., and Ariagno R.L. Neonatal brain MRI before discharge is better than head ultrasound in predicting cerebral palsy in VLBW preterm infants. Pediatrics. 2004 Oct;114(4):992-8 .