Improving infant hydrocephalus outcomes in Uganda: Predicting developmental outcomes and identifying patients at risk for early treatment failure after ETV/CPC

改善乌干达婴儿脑积水的结局：预测发育结局并识别 ETV/CPC 后处于早期治疗失败风险的患者

• 批准号: 10428554
• 负责人: Pei-Yi Lin
• 金额: $ 51.54万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-13 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428554
• 关键词: Africa South of the Sahara; Aftercare; Age-Months; Boston; Brain; Brain Injuries; Caring; Cauterize; Cerebrovascular Circulation; Cerebrum; Cessation of life; Clinical; Collaborations; Combined Modality Therapy; Creation of ventriculo-peritoneal shunt; Custom; Dangerousness; Data Analyses; Dependence; Developing Countries; Development; Devices; Diffuse; Disease; Early treatment; Emergency Situation; Enrollment; Evolution; Failure; Fogarty International Center; Frequencies; Funding; Goals; Growth; Head; Health; Hydrocephalus; Infant; Infection; Infrastructure; Investments; Lead; Length of Stay; Life; Longterm Follow-up; Maintenance; Measurable; Measurement; Measures; Metabolism; Monitor; National Institute of Child Health and Human Development; Neonatal; Operative Surgical Procedures; Optics; Outcome; Oxygen; Patients; Pediatric Hospitals; Perfusion; Physiological; Physiology; Pilot Projects; Postoperative Period; Prediction of Response to Therapy; Property; Randomized Controlled Trials; Resource-limited setting; Rest; Risk; Scanning; Severities; Severity of illness; Shunt Device; Site; Spectrum Analysis; Structure; Structure of choroid plexus; Technology; Testing; Thick; Time; Toddler; Training; Treatment Failure; Treatment Step; Uganda; United States; United States National Institutes of Health; Ventriculostomy; X-Ray Computed Tomography; base; brain health; global health; high risk; improved; large scale data; longitudinal dataset; low and middle-income countries; neonatal infection; neurodevelopment; novel; peer; prognostic assays; prognostic tool; quality assurance; standard care; treatment response

Project Summary/Abstract Infant hydrocephalus is a serious global health problem, with an estimated 400,000 new cases annually. Nearly half of these occur in sub-Saharan Africa, with neonatal infection being the most common cause there. Untreated, hydrocephalus causes progressive brain injury and even death. The standard treatment has long been placement of a ventriculoperitoneal shunt (VPS) but these devices require life-long maintenance and nearly all fail multiple times. Because of this, shunt-dependence is more dangerous in LMIC where emergency access to neurosurgical care is difficult or impossible. CURE Children’s Hospital of Uganda (CCHU) developed an alternate treatment combining endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) to give patients a shunt-free life. An NIH-funded, randomized controlled trial of ETV/CPC vs VPS for infants with post- infectious hydrocephalus (PIH) at CCHU found no significant difference at one-year post-treatment in brain growth or developmental outcomes. Treatment failure is a significant problem for both, occurring in a third. Developmental outcomes were associated with the amount of brain growth, but not with traditional metrics of head or ventricle size. Treatment has always focused on controlling ventricle size, but this has little association with outcomes. Brain growth is a better indicator, and we hypothesize in PIH it depends in part on the integrity of the underlying brain matter after infection and in part on the cerebral circulation’s ability to support regrowth. Consequently, we hypothesize cerebral blood flow and metabolism are more representative of disease severity and treatment response. We developed a novel, combined frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS/DCS) technology to measure cerebral blood flow (CBF) and oxygen metabolism (CMRO2) non-invasively at the bedside. In pilot studies at BCH and CCHU, we found untreated hydrocephalus progressively impedes cerebral perfusion and depresses metabolism, while successful treatment immediately restores CBF and CMRO2. Moreover, greater CMRO2 immediately after surgery correlated with better brain growth six months later. We now propose validating these results in a larger group with the goal of leading hydrocephalus treatment away from targeting ventricle size and directing it instead towards measurable improvements in the brain’s physiological health. Such a paradigm shift will have substantial clinical impact in developing countries, the United States, and the rest of the world.

项目摘要/摘要 婴儿脑积水是一个严重的全球健康问题，估计每年有40万新病例。差一点 其中一半发生在撒哈拉以南非洲，新生儿感染是那里最常见的原因。未经治疗， 脑积水会导致进行性脑损伤，甚至死亡。长期以来，标准的治疗方法是 放置脑室腹膜分流术(VPS)，但这些装置需要终身维护，几乎所有 多次失败。正因为如此，在紧急接入LMIC的LMIC中，分流依赖更加危险 神经外科治疗是困难的或不可能的。乌干达治愈儿童医院(CCHU)开发了一种替代方案 内窥镜下第三脑室造瘘术联合脉络丛烧灼术(ETV/CPC) 病人过着无分流的生活.一项由美国国立卫生研究院资助的ETV/CPC与VPS治疗婴幼儿后遗症的随机对照试验 CCHU的感染性脑积水(PIH)在治疗后一年脑内没有显著差异 生长或发育结果。治疗失败对两者都是一个重大问题，发生在三分之一。 发育结果与大脑发育的数量有关，但与传统的 头部或脑室大小。治疗一直专注于控制脑室大小，但这一点几乎没有关联。 带着结果。大脑发育是一个更好的指标，我们假设在妊高征患者中，它在一定程度上取决于完整性 感染后潜在的大脑物质的变化，部分取决于大脑循环支持再生的能力。 因此，我们假设脑血流和新陈代谢更能代表疾病的严重程度。 和治疗反应。我们开发了一种新颖的、结合了频域近红外和漫反射的 相关光谱仪(FDNIRS/DCS)技术测量脑血流量和血氧 在床边无创的代谢(CMRO2)。在BCH和CCHU的试点研究中，我们发现未经治疗 虽然治疗成功，但脑积水进行性阻碍脑血流并抑制新陈代谢 立即恢复CBF和CMRO2。此外，术后即刻较大的CMRO2与 六个月后大脑发育更好。我们现在建议在一个更大的小组中验证这些结果，目标是 引导脑积水的治疗从以脑室大小为目标转向可测量的方向 改善大脑的生理健康。这种范式的转变将在临床上产生重大影响 发展中国家、美国和世界其他地区。

项目成果

Design of a sustainable prepolarizing magnetic resonance imaging system for infant hydrocephalus.

• DOI: 10.1007/s10334-018-0683-y
• 发表时间: 2018-10
• 期刊: Magma (New York, N.Y.)
• 作者: Obungoloch J;Harper JR;Consevage S;Savukov IM;Neuberger T;Tadigadapa S;Schiff SJ
• 通讯作者: Schiff SJ

Learning Based Segmentation of CT Brain Images: Application to Postoperative Hydrocephalic Scans.

• DOI: 10.1109/tbme.2017.2783305
• 发表时间: 2018-08
• 期刊: IEEE transactions on bio-medical engineering
• 作者: Cherukuri V;Ssenyonga P;Warf BC;Kulkarni AV;Monga V;Schiff SJ
• 通讯作者: Schiff SJ

DEEP MR IMAGE SUPER-RESOLUTION USING STRUCTURAL PRIORS.

使用结构先验的深度 MR 图像超分辨率。

• DOI: 10.1109/icip.2018.8451496
• 发表时间: 2018
• 期刊: Proceedings. International Conference on Image Processing
• 作者: Cherukuri,Venkateswararao;Guo,Tiantong;Schiff,StevenJ;Monga,Vishal
• 通讯作者: Monga,Vishal

Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage.

• DOI: 10.1038/srep25903
• 发表时间: 2016-05-16
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Lin PY;Hagan K;Fenoglio A;Grant PE;Franceschini MA
• 通讯作者: Franceschini MA

Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC.

改善乌干达的婴儿脑积水结局：一种预测发育效果的纵向前瞻性研究方案，并确定ETV/CPC后有早期治疗衰竭风险的患者。

• DOI: 10.3390/metabo12010078
• 发表时间: 2022-01-14
• 期刊: Metabolites
• 影响因子: 4.1
• 作者: Vadset TA;Rajaram A;Hsiao CH;Kemigisha Katungi M;Magombe J;Seruwu M;Kaaya Nsubuga B;Vyas R;Tatz J;Playter K;Nalule E;Natukwatsa D;Wabukoma M;Neri Perez LE;Mulondo R;Queally JT;Fenster A;Kulkarni AV;Schiff SJ;Grant PE;Mbabazi Kabachelor E;Warf BC;Sutin JDB;Lin PY
• 通讯作者: Lin PY