CEREBRAL BLOOD FLOW AND METABOLISM IN NEWBORN INFANTS

尽管新生儿重症监护取得了进展，但围产期脑损伤 仍然是发病率和死亡率的主要原因。了解 脑血流动力学和能量代谢的发育性变化 发生在人类新生儿身上是设计合理治疗方案的关键 确保对大脑至关重要的充足营养供应的策略 功能和发展，同时最大限度地减少有害副作用 治疗性干预。这个项目的目的是提炼和 应用现有方法对脑血进行定量测量 危重新生儿的血流(CBF)和葡萄糖代谢(CMRGlu) 婴儿。需要检验的假设是：(1)葡萄糖转运到 新生儿大脑对血浆CMRGlu的反应不受速率限制 血糖浓度>2 mmoL/L(36 mg/dl)。(2)近红外 近红外光谱(NIR)可用于脑血流量的定量测量 新生儿准确度在正负10%以内。具体目标是： 1.测量环境血浆中血到脑的葡萄糖转运和CMRGlu 不同胎龄新生儿血糖水平的变化 在新生儿重症监护病房接受1-11C-葡萄糖和 使用我们开发的方法进行正电子发射断层扫描(PET) 并在非人类灵长类动物中得到验证。2.收集近红外数据 新生儿进行正电子发射计算机断层扫描时脑血流量的测定 测量特定目标1所需的CBF并确定效果 不同处理算法对近红外测量精度的影响 与正电子发射断层扫描(PET)相比。血糖浓度的测定 在这种情况下，内流成为大脑葡萄糖代谢的限速 患病的人类新生儿将建立一个与生物相关的水平 需要治疗的低血糖，从而使临床医生能够减少 降低低血糖脑损伤的危险，最大限度地减少任何危害 不必要的高血糖的影响。近红外光谱准确度的验证 在床边对脑血流量进行定量测量将确定这一点 新生儿脑血流量快速重复性监测技术 婴儿用于进一步的研究和临床研究。

In spite of advances in neonatal intensive care, perinatal brain damage remains a major cause of morbidity and mortality. Understanding the developmental changes in cerebral hemodynamics and energy metabolism that occur in human neonates is critical for designing rational treatment strategies that ensure an adequate supply of nutrients critical for brain function and development while minimizing deleterious side effects of therapeutic interventions. The purpose of this project is to refine and apply existing methodology for quantitative measurement of cerebral blood flow (CBF) and glucose metabolism (CMRGlu) to critically ill newborn infants. The hypotheses to be tested are (1) Glucose transport into the brain of newborn infants is not rate limiting for CMRGlu at plasma glucose concentrations above 2 mmol/L (36 mg/dl). (2) Near infrared spectroscopy (NIRS) can be used for quantitative measurement of CBF in newborn infants within plus/minus 10% accuracy. The specific aims are: 1. Measure blood-to-brain glucose transport and CMRGlu at ambient plasma glucose concentrations in newborn infants of different gestational ages hospitalized in the Neonatal Intensive Care Unit with 1-11C-glucose and positron emission tomography (PET) using a method that we have developed and validated in non-human primates. 2. Collect NIRS data for measurement of CBF from newborn infants at the time that they undergo PET measurements of CBF required for specific aim 1 and determine the effect of different processing algorithms on the accuracy of NIRS measurements as compared with PET. Determination of the plasma glucose concentration at which influx becomes rate limiting for cerebral glucose metabolism in ill newborn human infants will establish a biologically relevant level of hypoglycemia requiring treatment, thus enabling clinicians to reduce the danger of hypoglycemic brain damage and minimize any deleterious effects of unnecessary hyperglycemia. Validation of the accuracy of NIRS for quantitative measurements of CBF at the bedside will establish this technology for rapid and repetitive monitoring of CBF in ill newborn infants for further research and clinical studies.