Multimodality Neuroimaging Evaluation of Cognitive Functioning in Lower Grade Astrocytoma

低级别星形细胞瘤认知功能的多模态神经影像评估

• 批准号: 10701775
• 负责人: Jeremy William Gordon
• 金额: $ 65.39万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701775
• 关键词: Age; Anatomy; Astrocytoma; Biological Markers; Blood Volume; Brain; Brain Neoplasms; Carbon; Cell Respiration; Cerebrum; Clinical; Clinical Management; Clinical Research; Cognition; Creatine; Data; Decision Making; Diagnosis; Diffusion; Edema; Evaluation; Excision; Functional Magnetic Resonance Imaging; Glioma; Gliosis; Glutamates; Glycolysis; Grant; Image; Impaired cognition; Impairment; Infrastructure; Injury; Intervention; Lesion; Location; Magnetic Resonance Imaging; Measures; Metabolic; Metabolism; Modeling; Monitor; Mutation; N-acetylaspartate; Neurocognitive; Neurocognitive Deficit; Neurons; Operative Surgical Procedures; Patient-Focused Outcomes; Patients; Perfusion; Physiological; Positioning Attribute; Productivity; Protocols documentation; Protons; Publications; Pyruvate; Quality of life; Radiation therapy; Recording of previous events; Recurrence; Recurrent tumor; Reproducibility; Research; Research Design; Rest; Risk; Scanning; Schedule; Scientist; Severities; Technology; Testing; Time; Tissue Sample; Tissues; Treatment Protocols; Tumor Biology; Tumor Burden; Tumor Volume; United States National Institutes of Health; Work; brain abnormalities; clinical examination; cognitive function; early detection biomarkers; effective therapy; experience; first-in-human; image guided; imaging study; improved; interest; metabolic imaging; multimodal neuroimaging; multimodality; neoplastic cell; novel; pre-clinical; real-time images; regional difference; response; spectroscopic imaging; survival outcome; survival prediction; temozolomide; treatment effect; treatment response; treatment strategy; tumor; tumor growth; volunteer; white matter

PROJECT SUMMARY Survival outcomes for patients with lower grade gliomas continue to improve as diagnosis and treatment evolve. However, damage caused by tumor growth and by the consequences of treatment often leads to significantly impaired cognitive function. Our previous work has demonstrated that radiation therapy reduced ratios of N-acetyl-aspartate (a neuronal biomarker) levels to creatine derive from proton-1 MR spectroscopic imaging within the normal-appearing white matter. This steady state metabolic imaging also provides other metabolic parameters to differentiate tumor cells from normal brain, detect the presentence of IDH mutation and predict survival in lower grade glioma. In addition, stable and treatment-free lower grade glioma had impaired cognition and quality of life, with the severity associated with the history of treatment and the volume of T2 lesions. These results suggest that the use of multiparametric MRI could improve tumor delineation, identify patients at risk for specific deficits and provide an opportunity for intervention. The objective of this translational proposal is to utilize a novel multimodality MR protocol, which integrates dynamic and steady state MR metabolic imaging with diffusion, perfusion, and resting-state functional MRI to provide quantitative metrics on dynamic and steady-state metabolism, white matter integrity, blood volume, and functional networks, to evaluate cognitive functioning and quality of life in patients with lower grade astrocytoma. We will take advantage of our unique experience in proton-1 MR spectroscopic imaging, which has been implemented into routine clinical examinations, and hyperpolarized carbon-13 pyruvate imaging, where we performed the first-in-human [2-13C]pyruvate study to image real-time glycolysis and oxidative metabolism simultaneously, to assess tumor burden, cognitive functioning, and quality of life. Once the multimodality MR protocol has been established in Aim 1, we will evaluate the normal and abnormal brain changes during radiation therapy and then correlate these changes to impairments in cognitive functioning and quality of life in Aim 2. Aim 3 will examine signatures associated with recurrent tumors and evaluate the impact of tumor burden on cognition and quality of life. The results of the proposed study will be critical for assessing response to treatment, developing effective treatment strategies, and improving quality of life. Ultimately, it will provide effective clinical management of patients and aid neuro-oncologists in making timely decisions.

项目摘要 低级别胶质瘤患者的生存结局随着诊断和治疗的不断改善 进化然而，由肿瘤生长和治疗后果引起的损害通常导致 认知功能严重受损我们以前的工作已经证明，放射治疗减少了 N-乙酰基-天冬氨酸（神经元生物标志物）水平与肌酸的比率来自质子-1 MR光谱 在正常外观的白色物质内成像。这种稳态代谢成像还提供了其他 代谢参数，以区分肿瘤细胞与正常脑，检测IDH突变的存在 并预测低级别胶质瘤的存活率。此外，稳定和未经治疗的低级别胶质瘤， 认知和生活质量受损，严重程度与治疗史和治疗量相关 T2病变。这些结果表明，使用多参数MRI可以改善肿瘤的描绘， 识别存在特定缺陷风险的患者，并提供干预机会。的目的 翻译建议是利用一种新的多模态MR协议，它集成了动态和稳态 状态MR代谢成像与弥散、灌注和静息状态功能MRI，以提供定量 关于动态和稳态代谢、白色物质完整性、血容量和功能的指标 网络，以评估低级别星形细胞瘤患者的认知功能和生活质量。我们将 利用我们在质子-1磁共振波谱成像方面的独特经验， 常规临床检查和超极化碳-13丙酮酸成像，在那里我们进行了 首次在人体中进行[2- 13 C]丙酮酸盐研究，同时对糖酵解和氧化代谢进行实时成像， 评估肿瘤负荷、认知功能和生活质量。一旦多模态MR协议已经被 在目标1中，我们将评估放射治疗期间正常和异常的大脑变化， 然后将这些变化与目标2中认知功能和生活质量的损害相关联。目标3将 检查与复发性肿瘤相关的特征，并评估肿瘤负荷对认知的影响 和生活质量。拟议研究的结果对于评估治疗反应至关重要， 制定有效的治疗策略，提高生活质量。最终，它将提供有效的 患者的临床管理和帮助神经肿瘤学家及时做出决定。