Treatment-related CNS Injury in Children with Brain Tumors

脑肿瘤儿童治疗相关的中枢神经系统损伤

• 批准号: 9107250
• 负责人: Mary Baron Nelson
• 金额: $ 13.13万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-26 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9107250
• 关键词: Acute; Adjuvant Therapy; Adult; Affect; Aftercare; Age; Analysis of Covariance; Anisotropy; Anxiety; Area; Attention; Behavioral; Brain; Brain Injuries; Brain Neoplasms; Child; Childhood Brain Neoplasm; Childhood Injury; Chronic; Cognition; Control Groups; Cranial Irradiation; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Emotional; Emotions; Employment; Enrollment; Executive Dysfunction; Fiber; Future; Gender; Globus Pallidus; Goals; Health; Health Care Costs; High Dose Chemotherapy; Imaging Techniques; Individual; Infratentorial Neoplasms; Injury; Intervention; Intervention Studies; Language; Lead; Location; Long-Term Effects; Magnetic Resonance Imaging; Maps; Measures; Memory; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Modality; Moods; Neuroanatomy; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neuropsychological Tests; Nurses; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Pattern; Performance; Physically Handicapped; Physiology; Pilot Projects; Pontine structure; Population; Posterior Fossa; Prevention; Process; Quality of life; Quality-of-Life Assessment; Radiation; Recording of previous events; Recruitment Activity; Research; Research Personnel; Role; Schools; Siblings; Structure; Survivors; Techniques; Testing; Thalamic structure; Tissues; United States National Institutes of Health; Visuospatial; aged; base; brain tissue; career; central nervous system injury; chemotherapy; childhood cancer survivor; cognitive function; design; disability; executive function; experience; gray matter; improved; indexing; irradiation; knowledge base; morphometry; neuroimaging; neuropsychological; patient oriented; processing speed; putamen; social; standard of care; treatment effect; treatment group; tumor; water diffusion; white matter; white matter injury; young adult

DESCRIPTION (provided by applicant): This is a K23 award re-submission proposal for Dr. Mary Baron Nelson to provide her with the mentored support needed to accomplish the following goals: 1) become expert at using neuro-imaging research to determine mechanisms underlying injury to the brain; 2) further her understanding of neuroanatomy and physiology and neuropsychological assessment; 3) design and submit an R01 proposal; and 4) develop a career as an independent patient-oriented nurse researcher. Many childhood brain tumor survivors experience detrimental consequences, including neurocognitive deficits, physical disabilities and poor quality of life. Magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging (DTI) and tensor-based morphometry (TBM) allow for examination of structural integrity and volume in a non-invasive manner. Preliminary research of this investigator revealed evidence of chronic injury to multiple brain structures (pons, thalamus, mammillary bodies, caudate, putamen and globus pallidus) a mean of 5 years after treatment with systemic high dose chemotherapy in children with brain tumors. These structures are essential in transmitting information throughout the brain, and interaction between them is an inherent basis for cognition. The patients in the study also had deficits in executive functioning and poor quality of life (QOL). The purpose of this study is to further investigate this pattern o injury by comparing regional white and gray matter, specific brain structural volumes and diffusion indices between 50 children with posterior fossa brain tumors ages 10-16 years and 10 healthy sibling controls, and to determine the relationship of structural injury to neurocognitive, behavioral and QOL outcome. The patient group will consist of 20 patients who were treated with surgery, 10 treated with surgery and chemotherapy, and 20 treated with surgery/chemotherapy/cranial irradiation at least one year prior to study enrollment. All subjects will undergo brain MRI with DTI sequences, a full battery of neuropsychological, behavioral, emotional and QOL assessment. Individual DTI maps will be calculated, normalized and smoothed, and compared between patients and controls using analysis of covariance, with age at diagnosis and treatment as covariates. Post- processing multivariate tensor-based morphometry (mTBM) will compare white and gray matter volumes, and specific structural volumes. Additional analyses will be conducted among the 3 treatment groups to investigate differences in brain tissue injury patterns, neurocognitive and QOL outcomes, using multiple analysis of covariance, with age at diagnosis, current age and gender as covariates. This study will provide new information about patterns of injury and related outcomes in children with brain tumors treated with different modalities, creating a base of knowledge upon which to build interventional research.

描述（由申请人提供）：这是玛丽·巴伦·纳尔逊（Mary Baron Nelson）博士为她提供实现以下目标所需的指导支持的K23奖励重新提出建议：1）成为使用神经成像研究的专家，以确定对大脑受伤的机制； 2）进一步了解神经解剖学，生理学以及神经心理学评估； 3）设计并提交R01提案； 4）发展职业为独立的以患者为导向的护士研究员。 许多儿童脑肿瘤幸存者经历了有害后果，包括神经认知缺陷，身体残疾和生活质量差。磁共振成像（MRI）技术，例如扩散张量成像（DTI）和基于张量的形态计量学（TBM），可以以非侵入性方式检查结构完整性和体积。对该研究者的初步研究揭示了对多个脑结构（PON，Thalamus，乳腺体，尾状体，尾状，鬼核馆和Globus Pallidus）的慢性损伤的证据，平均为5年，治疗全身性高剂量化学疗法的脑肿瘤儿童。这些结构对于在整个大脑中传输信息至关重要，它们之间的相互作用是认知的固有基础。研究中的患者在执行功能和生活质量差（QOL）方面也有缺陷。 这项研究的目的是通过比较区域白物和灰质，特定的大脑结构体积和扩散指数，进一步研究这种模式损伤，50名患有10-16岁后窝脑肿瘤的儿童和10个健康的兄弟姐妹对照，并确定结构性损伤与神经认知的关系，并确定神经认知的关系， 行为和质量结果。该患者组将由20例接受手术治疗的患者组成，10例接受了手术和化学疗法治疗，并且至少在研究入学人群前一年接受了手术/化学疗法/颅骨辐射治疗的患者。所有受试者都将使用DTI序列（全部神经心理学，行为，情感和QOL评估）进行大脑MRI。将计算单个DTI图，并使用协方差分析，并在患者之间进行计算，归一化和平滑，并在患者和对照组之间进行比较，并在诊断和治疗时作为协变量进行比较。加工后多元张量的形态计（MTBM）将比较白物质和灰质体积以及特定的结构体积。将在这三个治疗组之间进行其他分析，以研究脑组织损伤模式，神经认知和QOL结果的差异，使用协方差的多次分析，以及诊断，当前年龄和性别作为协方差时的年龄。这项研究将提供有关以不同方式治疗的脑肿瘤儿童的损伤模式和相关结果的新信息，从而创造了建立介入研究的知识基础。