Using Imaging to Define Risk Factors for Brain Injury Following Heart Surgery in Infants

Daniel Licht, M.D.

The Children's Hospital of Philadelphia

Department of Pediatrics and Neurology
Funded in January, 2008: $100000 for 2 years
LAY SUMMARY . ABSTRACT . HYPOTHESIS . SELECTED PUBLICATIONS .

LAY SUMMARY

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Using imaging to define risk factors for brain injury following heart surgery in infants

 Investigators will test the validity of using an optical non-invasive imaging technique, which continuously monitor cerebral blood flow and brain oxygenation, for determining which infants are at greatest risk of developing abnormal cerebral blood flow fluctuations after open heart surgery. Patients will then have a brain MRI to correlate this abnormal cerebral blood flow fluctuation with developing white matter damage in the brain.

Some children born with severe forms congenital heart defects (CHD) require open-heart surgery during their first week of life.  These infants undergo cardiopulmonary bypass, with or without cooling of their head and body to produce circulatory arrest during the surgery. These two strategies may alter the way cerebral arteries respond to signals from the body, including alteration of “autoregulation,” the process that normally protects the brain against blood pressure fluctuations. Normally, smaller blood vessels in the brain will either dilate or constrict in response to changes in systemic blood pressure. As a consequence of open heart surgery, however, infants’ cerebral blood flow fluctuates with changes in systemic blood pressure: low systemic blood pressure will result in low cerebral blood flow.  While 90 percent of infants survive the operation, more than 50 percent develop an injury to the brain’s white matter, called periventricular leukomalacia (PVL), which may result in learning disabilities.  Additionally, about 20 percent of the infants have already developed PVL prior to surgery, due to the heart condition itself.

The investigators hypothesize that disrupted autoregulation results in an increased risk of developing PVL following surgery. First, they will use MRI imaging pre-surgically, to quantify the extent of any existing PVL. Then they will identify those infants with disrupted autoregulation, using a non-invasive optical imaging technique, called Diffuse Optical Spectroscopy (DOS). This imaging technique can measure cerebral blood flow and oxygen saturations continuously through the scalp, without requiring chemical or radioactive dyes.  Brain MRI will be used thereafter to obtain pilot data on the effect of disrupted autoregulation on the risk for developing PVL (or worsening of existing PVL white matter damage) during the post-operative period. By correlating impaired autoregulation of cerebral blood flow with post-surgical MRI they will identify infants with the highest risk for post-operative PVL. 

Significance:  If DOS is found to be a valid means for identifying infants at risk for PVL post-surgically, DOS will become a vital tool for post-surgical monitoring to prevent brain injury. Furthermore, it’s use could be extended to the care of vulnerable infant populations such as the premature infant.

ABSTRACT

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Hemodynamic Monitoring of Postoperative Infants with CHD: Assessing Risk for White Matter Injury

Abstract: Brain injury in the form of periventricular leukomalacia (PVL) is common following infant heart surgery for severe forms of congenital heart defects (CHD) and affects over 50% of these infants. PVL is likely responsible for learning disabilities and cognitive delays seen in school aged children who have survived infant heart surgery. PVL occurs when the white matter is deprived of oxygen and blood flow during a developmental stage in which certain cells in the white matter (oligodendrocytes) are particularly prone to injury. Known risk factors for PVL in the population of infants with CHD include low postoperative blood pressures and oxygen saturations. <br>The conduct of these early heart surgeries is complex and requires cardiopulmonary bypass (CPB) with or without deep hypothermic circulatory arrest (DHCA). These two strategies may alter the way cerebral arteries respond to signals from the body, including alteration of autoregulatory function. Impaired autoregulation of cerebral blood flow (CBF) allows blood flow to the brain to fluctuate passively with systemic blood pressures. This abnormal physiology is termed perfusion-passive CBF.<br> Using diffuse optical spectroscopy (DOS), a novel, non-invasive, light-based instrument capable of measuring CBF and cerebral oxygenation continuously, we aim to study possible mechanisms that lead to brain injury in the form of PVL.

INVESTIGATOR BIOGRAPHIES

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Daniel Licht, M.D.

Dr. Licht is an Assistant Professor of Neurology and Pediatrics at the Children's Hospital of Philadelphia since 2004. Dr. Licht received his medical degree from New Jersey Medical School (UMDNJ – Newark) in 1997 and completed his pediatric residency at the Children's Hospital of Philadelphia. Neurology training with special qualification in child neurology was completed at the Hospital of the University of Pennsylvania and the Children's Hospital of Philadelphia in 2002. Dr. Licht specializes in neurological complications of congenital heart defects and pediatric stroke, though he maintains a general pediatric neurology outpatient clinic. His research involves the application and validation of non-invasive methods to image cerebral blood flow in infants and children.

 

HYPOTHESIS

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Hypothesis: The central hypothesis of this proposal is that postoperative, perfusion-passive CBF underlies the development of PVL in infants with CHD. To address this hypothesis, the following specific aims are proposed: Specific Aim 1: Adapt the existing all-optical, bedside monitor for longitudinal monitoring of the infant brain. Develop a fiber-optic probe that optimizes instrument comfort, hygiene, safety and physiologic quantification, particularly differentiation of the signals in extra-cerebral layers (scalp, skull) and cortex. Specific Aim 2: Investigate the utility of the resultant noninvasive bedside optical instrument for monitoring cerebral hemodynamics in infants during the immediate post-operative recovery period. Sub-aim 2a: Time-lock the diffuse optical spectroscopy (DOS) measurements of rCBF and oxymetry to continuous measurements of heart rate, systolic and diastolic blood pressure and temperature. Track short-term (minute-scales) fluctuations across methodologies. Sub-aim 2b: Time-lock the diffuse optical spectroscopy measurements of rCBF and oximetry to periodic (e.g. every 2 hours) measurements of pCO2 and hemoglobin in arterial blood gas samples. Track long-term (hour scales) fluctuations of baseline rCBF over time. Specific Aim 3: To obtain pilot clinical data to investigate the effect of perfusion-passive CBF on the risk for development of new or worsening PVL lesions in the postoperative period. Cranial MRI will be performed immediately before and 7 to 10 days after surgery. Methods: DOS will be employed to monitor infants with CHD in the immediate postoperative recovery period. Fluctuations of CBF will be cross-correlated with fluctuations in mean arterial blood pressure to detect infants in whom autoregulation of CBF is impaired. All infants participating in this study will receive an MRI prior to and after heart surgery to quantify PVL. Infants with the highest cross-correlation values will have the highest risk for postoperative PVL.

SELECTED PUBLICATIONS

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Cerebral Blood Flow 2013