QUANTITATIVE ULTRASOUND TO DETECT APOPTOSIS IN THE NEONATAL BRAIN

Millions of human infants sustain brain injury each year. Our means to visualize cell death in their brains are limited. Magnetic resonance imaging (MRI) may detect nervous tissue injury but its true sensitivity is unknown. There is great need for non-invasive, safe and easy to implement imaging modalities which can be performed repeatedly and safely at the bedside, and detect evolving cell death in the brain during the period of injury.
Apoptosis, or programmed cell death, is a prominent form of cell death in the developing mammalian brain. It occurs in response to hypoxia/ischemia, trauma, exposure to sedative/anesthetic (SADs) or antiepileptic drugs (AEDs). It is characterized by distinct structural changes, compaction and segregation of nuclear material in the earliest stage, fragmentation of the nucleus and budding of membrane-bound apoptotic bodies at the late stages. These changes in morphology generate scattering sources that can reflect ultrasound differently from viable cells. Quantitative ultrasound (QUS) has been used to detect the unique scattering properties of apoptotic cells in cancer in vitro and in vivo. QUS can be used to evaluate early treatment responses to radiation and/or chemotherapy and provide guidance for suitable future direction of treatment. The low cost, portability, lack of need of contrast agents, and rapid image acquisition and processing makes QUS appealing for the in vivo detection of cell death.
The overall plan is to apply QUS to human infants and evaluate for changes indicative of apoptosis in neonates undergoing cardiac surgery with cardiopulmonary bypass (CB) and deep hypothermic circulatory arrest (DHCA) and those with perinatal asphyxia.
The significance of this research is immense. If successful, this methodology will become invaluable in helping clarify when and where apoptosis occurs in the infant human brain and will allow address several fundamental questions that arise from preclinical research. At the same time, it will provide invaluable means of bedside neuromonitoring in neonatal and pediatric neurocritical care.