Preterm brain injury remains an important complication of premature birth. Both hemodynamic abnormalities and alterations of cerebral blood flow have been associated with injury, but reliable methods for prospective identification of imminent injury are not available. To identify prospective physiologic risk factors, three aspects of the relationship among of oscillations of heart rate, oscillations of blood pressure, and oscillations of cerebral blood flow will be quantified: the arterial baroreflex, cerebral autoregulation, and the relation of the arterial baroreflex to cerebral autoregulation. These measurements will be obtained from a population of preterm neonates of birthweight less than 1000 grams. Measurements will be obtained at 8 hours, 24 hours, and one week of life. Oscillations of cerebral blood flow will be detected and quantified by near Infrared spectroscopy.
Specific Aim number 1: Arterial baroreflex. Transfer functions analysis will quantify the response of heart rate to changes in arterial blood pressure. Hypothesis: Neonates who are subsequently found by head ultrasound to have severe brain injury will fail to exhibit normal baroreflex activity. This will be indicated by a lesser response of heart rate to changes in arterial blood pressure, and a response time that is lengthened.
Specific Aim number 2: Cerebral autoregulation. Transfer function analysis will quantify cerebral autoregulation, defined as the normal buffering of changes in arterial blood pressure, so that passive relationships between arterial blood pressure and cerebral blood flow are enhanced. Hypothesis: Neonates who are subsequently found by head ultrasound to have severe brain injury will fail to exhibit normal cerebral autoregulation. This will be indicated by a greater response of cerebral blood flow to changes in arterial blood pressure, and a response time that is shortened.
Specific Aim number 3. Arterial baroreflex vs. Cerebral autoregulation. Spectral coherence of the arterial baroreflex relation will be compared to the spectral coherence of cerebral autoregulation. Correlation between these two coherences will serve as a measure of association between them. Hypothesis: Enhanced baroreflex activity is a physiologic marker for better cerebral autoregulation. This will be indicated by a negative correlation between the coherence of the baroreflex and the coherence of cerebral autoregulation. This proposal will combine novel measurement of oscillations in cerebral blood flow with advanced signal processing techniques to quantify the relationship among oscillations of heart rate, oscillations of blood pressure, and oscillations of cerebral blood flow. By representing heart rate, blood pressure, and cerebrovascular blood flow as dynamic quantities, if may be possible to model their relation to each other in a more useful way. This approach may provide the necessary and thus far unavailable foundation for an effective neuroprotective clinical strategy.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD001233-03
Application #
6343119
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Hanson, James W
Project Start
1999-01-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2002-12-31
Support Year
3
Fiscal Year
2001
Total Cost
$107,164
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Butte, A J; Bao, L; Reis, B Y et al. (2001) Comparing the similarity of time-series gene expression using signal processing metrics. J Biomed Inform 34:396-405