Neurological Diseases Research in High Risk Newborns

描述（由申请人提供）：该提案旨在使Nehal Parikh博士，一位具有研究技能的新生儿学家，成为在高风险婴儿围产期脑损伤的方法学强临床研究方面的领导者。我们提出一个全面的5年职业发展计划，包括：1)两项极低出生体重儿脑损伤的重要临床研究：A)定量（体积）磁共振成像（MRI）的前瞻性队列研究，用于预测>= 18个月时的神经感觉障碍（一项研究评估定量MRI作为诊断测试的特性，相对于定性MRI和常规临床预测指标的增量预测价值，以及总脑容量和局部脑容量的预测价值）；B)在依赖呼吸机的婴儿（常规使用大剂量地塞米松治疗）中进行的一项随机试验，以评估低剂量氢化可的松治疗是否能预防这类婴儿常见的区域和总皮质体积减少。这些研究将传授神经诊断测试、神经保护策略和高危婴儿预后评估方面的研究技能。这些发现将引起极大的兴趣，并为K23资助结束时的R01资助铺平道路；2)强化师徒关系。

DESCRIPTION (provided by applicant): This proposal is designed to prepare Dr. Nehal Parikh, a neonatologist with demonstrated research skills, to become a leader in performing methodologically strong clinical studies of perinatal brain injury in high-risk infants. We propose a comprehensive 5-year career development program involving: 1) Two important clinical studies of brain injury in extremely low birth weight infants: A) A prospective cohort study of quantitative (volumetric) magnetic resonance imaging (MRI) performed at or near term to predict neurosensory impairments at >= 18 months (a study evaluating the properties of quantitative MRI as a diagnostic test, the incremental predictive value over qualitative MRI and routine clinical predictors, and the predictive value of total and regional brain volumes); B) A randomized trial among ventilator-dependent infants (who are conventionally treated with high-dose dexamethasone) to assess whether low-dose hydrocortisone therapy prevents the reduced regional and total cortical volumes common among such infants. These studies will impart research skills in neurodiagnostic tests, neuroprotective strategies, and prognostic assessments for high-risk infants. The findings will be of great interest and pave the way for R01 funding by the end of K23 funding; 2) Intensive mentorship. The primary mentor is a neonatologist and epidemiologist (Jon Tyson, MD, MPH), who is experienced in studies of brain injury, a PI in the NICHD Neonatal Research Network, a PI in the NHLBI Clinical Research Curriculum, Director of the Center for Clinical Research and Evidence Based Medicine, and a dedicated and successful mentor. For the above studies, Dr. Parikh will also have prominent co-mentors in neurology (lan Butler, MD), developmental psychology and quantitative MRI (Robert Lasky, PhD), and neonatology and investigator training (Kathleen Kennedy, MD, MPH, Director, Master's Degree Program in Clinical Research). Dr. Tyson's Center and the Pediatrics Department will support these studies; 3) Master's Degree in Clinical Research (matriculated by Dr. Parikh in Sept. 2003). Courses (36 credit hrs) include Research Ethics, Advanced Biostatistics, and Advanced Epidemiology. His thesis will be a major publication from the above research. Institutional strengths include one of the largest populations of high-risk infants in the US, a strong perinatal research program (1 of only 8 centers in both the NICHD Maternal-Fetal and Neonatal Networks), a neonatal ICU supportive of clinical research (with the largest number of infants randomized in Network trials last year), and a well functioning follow up program. The proposed program will provide Dr. Parikh the research experience, dedicated mentorship, and necessary coursework to become a leader in clinical research addressing perinatal brain injury.