SBIR-STTR Award

Clinical neonatal monitoring is also vital for diagnosis and prognosis of acute pathologies. One such pathology, neonatal intraventricular hemorrhage (IVH), is a common consequence of premature birth, with approximately 30 percent of infants weighing less than 1500 g having some degree of bleeding. While some neonates exhibit clear outward signs related to IVH such as apnea, pallor, seizures and metabolic acidosis, up to 50 percent of IVHs may be clinically silent. Large IVHs are associated with unfavorable neurologic outcomes. Adverse neurodevelopmental sequelae include cerebral palsy, seizures, posthemorrhagic hydrocephalus (which may require a ventriculoperitoneal shunt), blindness, deafness, and cognitive impairment (Hintz and O'Shea 2008, Goldenberg and Jobe 2001). Although ultrasound is almost universally employed as a retrospective screen at 7 days of life, 50 percent of IVHs occur during the first day of life (and 75 percent in the first 3 days). Further ultrasound is less sensitive to Grade II IVHs (Babcock et al 1982, Mack et al 1981), and its availability as a diagnostic tool is operator dependent, with limited hours of availability. The variation in clinical presentation and need to intervene early stresses the need for a simple to interpret device that can monitor and detect developing IVHs in real time, allowing administration of supportive therapies (blood products) or treatments (activated factor VII). While the clinical consequences of IVH are severe, little is known about its exact etiology. Many physiologic disturbances (e.g., loss of cerebral blood flow autoregulation, increased central venous pressure, hypotension) have been associated with IVHs through retrospective studies, but exact cause-effect relationships between these parameters do not exist (Ballabh 2010). Further, causal connections between the incidence of IVH and neuroelectric abnormalities observed in IVH such as positive rolandic sharps and seizures have not been established. In this project we propose developing a device that can be used in a future comprehensive investigation of the connections between circulatory and neuroelectric abnormalities in the context of IVH. If it is successful, this device may not only aid understanding of the underlying mechanisms leading to IVH, but also be of use in early identification of developing bleeds, and combined with appropriate therapies, limiting the extent of bleeding and other brain damage. Monitoring of premature infants poses unique challenges, one of these being the ideal of non-invasive bedside monitoring. We have previously developed an electrical imaging device that uses an EEG- like electrode array to continuously monitor and quantify small (< 0.5 ml) blood accumulations in the neonatal ventricles. We propose developing a monitoring device that can simultaneously gather EEG and bleeding status data using the same electrode array, with minimal impact on clinical management. Data from the device will be made available in a manner that also allows comparison with other physiological monitoring systems.

Public Health Relevance:
Premature birth accounts for roughly 12 percent of all live births annually in the United States. Despite advances in technologies and treatments in the past decade, the incidence of severe acute complications for very premature infants accompanied by risks for chronic medical conditions, such as cerebral palsy, have not markedly diminished since the mid-1990s. A majority of these neurodevelomental problems are associated with damage to the subventricular zone and subsequent intraventricular hemorrhage. Currently, detection of intraventricular hemorrhage is retrospective. The overall goal of this project is to develop a novel brain-monitoring device that will allow the bedside clinician to improve the delivery of care to these neonates in real time, thereby decreasing the extent of intraventricular hemorrhages and decreasing the severity of neurodevelopmental deficits.

Public Health Relevance Statement:
Premature birth accounts for roughly 12 percent of all live births annually in the United States. Despite advances in technologies and treatments in the past decade, the incidence of severe acute complications for very premature infants accompanied by risks for chronic medical conditions, such as cerebral palsy, have not markedly diminished since the mid-1990s. A majority of these neurodevelomental problems are associated with damage to the subventricular zone and subsequent intraventricular hemorrhage. Currently, detection of intraventricular hemorrhage is retrospective. The overall goal of this project is to develop a novel brain-monitoring device that will allow the bedside clinician to improve the delivery of care to these neonates in real time, thereby decreasing the extent of intraventricular hemorrhages and decreasing the severity of neurodevelopmental deficits.

NIH Spending Category:
Bioengineering; Brain Disorders; Cardiovascular; Cerebral Palsy; Clinical Research; Diagnostic Radiology; Infant Mortality/ (LBW); Lung; Neurosciences; Pediatric; Perinatal - Birth - Preterm (LBW); Perinatal Period - Conditions Originating in Perinatal Period; Stroke

Project Terms:
Accounting; Achievement; Acute; Apnea; Blindness; Blood; Blood Coagulation Factor; Blood Platelets; Blood Pressure; blood product; Blood Volume; Brain; Brain Injuries; Cardiovascular system; care delivery; Central venous pressure; Cerebral Palsy; Cerebrovascular Circulation; Chronic; Clinical; Clinical Management; Complex; Computer software; Creation of ventriculo-peritoneal shunt; Data; Deafness; design; Detection; Device or Instrument Development; Devices; Diagnosis; Diagnostic; disability; Early Diagnosis; Early identification; electric impedance; Electrodes; Electroencephalography; Ensure; Environment; Erythrocytes; Etiology; Exhibits; Factor VIIa; Future; Goals; Head; Hemorrhage; Homeostasis; Hospitals; Hour; Hydrocephalus; Hypercapnia; Hypotension; Image; Imaging Device; Impaired cognition; improved; Incidence; Infant; intraventricular hemorrhage; Investigation; Ischemic-Hypoxic Encephalopathy; Life; Liquid substance; Live Birth; Measurement; Mechanical ventilation; Medical; meetings; Metabolic acidosis; Methods; Modeling; Monitor; monitoring device; Morbidity - disease rate; Morphologic artifacts; Neonatal; Neonatal Brain Injury; Neonatal Intensive Care; neonate; Neurodevelopmental Deficit; Neurologic; Neurological outcome; novel; outcome forecast; Pallor; Pathology; Patients; Periventricular Leukomalacia; Pharmaceutical Preparations; phase 1 study; Physiologic Monitoring; Physiological; Physiology; pilot trial; premature; Premature Birth; Premature Infant; Prospective Studies; Research; respiratory; Retrospective Studies; Risk; Safety; Seizures; Severities; Speed (motion); Stress; subventricular zone; Supportive care; System; Technology; Testing; Time; tomography; tool; Ultrasonography; United States; Variant

Clinical neonatal monitoring is also vital for diagnosis and prognosis of acute pathologies. One such pathology, neonatal intraventricular hemorrhage (IVH), is a common consequence of premature birth, with approximately 30 percent of infants weighing less than 1500 g having some degree of bleeding. While some neonates exhibit clear outward signs related to IVH such as apnea, pallor, seizures and metabolic acidosis, up to 50 percent of IVHs may be clinically silent. Large IVHs are associated with unfavorable neurologic outcomes. Adverse neurodevelopmental sequelae include cerebral palsy, seizures, posthemorrhagic hydrocephalus (which may require a ventriculoperitoneal shunt), blindness, deafness, and cognitive impairment (Hintz and O'Shea 2008, Goldenberg and Jobe 2001). Although ultrasound is almost universally employed as a retrospective screen at 7 days of life, 50 percent of IVHs occur during the first day of life (and 75 percent in the first 3 days). Further ultrasound is less sensitive to Grade II IVHs (Babcock et al 1982, Mack et al 1981), and its availability as a diagnostic tool is operator dependent, with limited hours of availability. The variation in clinical presentation and need to intervene early stresses the need for a simple to interpret device that can monitor and detect developing IVHs in real time, allowing administration of supportive therapies (blood products) or treatments (activated factor VII). While the clinical consequences of IVH are severe, little is known about its exact etiology. Many physiologic disturbances (e.g., loss of cerebral blood flow autoregulation, increased central venous pressure, hypotension) have been associated with IVHs through retrospective studies, but exact cause-effect relationships between these parameters do not exist (Ballabh 2010). Further, causal connections between the incidence of IVH and neuroelectric abnormalities observed in IVH such as positive rolandic sharps and seizures have not been established. In this project we propose developing a device that can be used in a future comprehensive investigation of the connections between circulatory and neuroelectric abnormalities in the context of IVH. If it is successful, this device may not only aid understanding of the underlying mechanisms leading to IVH, but also be of use in early identification of developing bleeds, and combined with appropriate therapies, limiting the extent of bleeding and other brain damage. Monitoring of premature infants poses unique challenges, one of these being the ideal of non-invasive bedside monitoring. We have previously developed an electrical imaging device that uses an EEG- like electrode array to continuously monitor and quantify small (< 0.5 ml) blood accumulations in the neonatal ventricles. We propose developing a monitoring device that can simultaneously gather EEG and bleeding status data using the same electrode array, with minimal impact on clinical management. Data from the device will be made available in a manner that also allows comparison with other physiological monitoring systems.

Public Health Relevance Statement:
Premature birth accounts for roughly 12 percent of all live births annually in the United States. Despite advances in technologies and treatments in the past decade, the incidence of severe acute complications for very premature infants accompanied by risks for chronic medical conditions, such as cerebral palsy, have not markedly diminished since the mid-1990s. A majority of these neurodevelomental problems are associated with damage to the subventricular zone and subsequent intraventricular hemorrhage. Currently, detection of intraventricular hemorrhage is retrospective. The overall goal of this project is to develop a novel brain-monitoring device that will allow the bedside clinician to improve the delivery of care to these neonates in real time, thereby decreasing the extent of intraventricular hemorrhages and decreasing the severity of neurodevelopmental deficits.

NIH Spending Category:
Bioengineering; Brain Disorders; Cardiovascular; Cerebral Palsy; Clinical Research; Diagnostic Radiology; Infant Mortality/ (LBW); Lung; Neurosciences; Pediatric; Perinatal - Birth - Preterm (LBW); Perinatal Period - Conditions Originating in Perinatal Period; Stroke

Project Terms:
Accounting; Achievement; Acute; Apnea; Blindness; Blood; Blood Coagulation Factor; Blood Platelets; Blood Pressure; blood product; Blood Volume; Brain; Brain Injuries; Cardiovascular system; care delivery; Central venous pressure; Cerebral Palsy; Cerebrovascular Circulation; Chronic; Clinical; Clinical Management; Complex; Computer software; Creation of ventriculo-peritoneal shunt; Data; Deafness; design; Detection; Device or Instrument Development; Devices; Diagnosis; Diagnostic; disability; Early Diagnosis; Early identification; electric impedance; Electrodes; Electroencephalography; Ensure; Environment; Erythrocytes; Etiology; Exhibits; Factor VIIa; Future; Goals; Head; Hemorrhage; Homeostasis; Hospitals; Hour; Hydrocephalus; Hypercapnia; Hypotension; Image; Imaging Device; Impaired cognition; improved; Incidence; Infant; intraventricular hemorrhage; Investigation; Ischemic-Hypoxic Encephalopathy; Life; Liquid substance; Live Birth; Measurement; Mechanical ventilation; Medical; meetings; Metabolic acidosis; Methods; Modeling; Monitor; monitoring device; Morbidity - disease rate; Morphologic artifacts; Neonatal; Neonatal Brain Injury; Neonatal Intensive Care; neonate; Neurodevelopmental Deficit; Neurologic; Neurological outcome; novel; outcome forecast; Pallor; Pathology; Patients; Periventricular Leukomalacia; Pharmaceutical Preparations; phase 1 study; Physiologic Monitoring; Physiological; Physiology; pilot trial; premature; Premature Birth; Premature Infant; Prospective Studies; Research; respiratory; Retrospective Studies; Risk; Safety; Seizures; Severities; Speed (motion); Stress; subventricular zone; Supportive care; System; Technology; Testing; Time; tomography; tool; Ultrasonography; United States; Variant