Quantitative MRSI for the prediction of response to chemoradiation therapy in GBM

定量 MRSI 用于预测 GBM 放化疗反应

• 批准号: 9016499
• 负责人: James Scott Cordova
• 金额: $ 1.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9016499
• 关键词: Accounting; Adjuvant; Aftercare; Algorithms; Alkylating Agents; Architecture; Bioinformatics; Biological Markers; Brain; Brain Neoplasms; Caliber; Cell Death; Chemicals; Classification; Classification Scheme; Clinical; Clinical Trials; Coupling; Data; Data Analyses; Data Set; Deterioration; Development; Diffusion; Disease; Effectiveness; Epigenetic Process; Excision; Exhibits; Future; Glioblastoma; Goals; Health; Heterogeneity; Histone Deacetylase Inhibitor; Human; Image; Imaging technology; Incidence; Individual; Infiltration; Location; MRI Scans; Magnetic Resonance Imaging; Magnetism; Malignant - descriptor; Maps; Measurement; Measures; Metabolic; Metabolism; Methods; Modeling; Molecular; Monitor; Necrosis; Newly Diagnosed; Operative Surgical Procedures; Outcome; Outcome Measure; Patient-Focused Outcomes; Patients; Permeability; Pharmaceutical Preparations; Physicians; Physiological; Prediction of Response to Therapy; Procedures; Process; Progression-Free Survivals; Property; Protocols documentation; Radiation; Radiation therapy; Recurrence; Residual Tumors; Resolution; Sampling; Scientist; Signal Transduction; Spatial Distribution; Stable Disease; Steroids; Technical Expertise; Techniques; Technology; Testing; Therapeutic Effect; Tissues; Training; Tumor Debulking; Tumor Volume; Universities; University Hospitals; Validation; Vorinostat; Water; Weight; Work; base; blood product; cancer imaging; career; chemoradiation; computerized data processing; contrast enhanced; cytotoxicity; density; design; early experience; image guided radiation therapy; image guided therapy; imaging software; indexing; interest; magnetic resonance spectroscopic imaging; neuroimaging; personalized management; response; restoration; spectroscopic imaging; standard of care; targeted treatment; temozolomide; treatment response; tumor; tumor progression; two-dimensional; vector

DESCRIPTION (provided by applicant): The current standard for monitoring glioblastoma multiforme (GBM) progression relies heavily on the changes of enhancing tumor regions on contrast-enhanced, T1-weighted MRI using the Macdonald Criteria (MC). However, the inherent heterogeneity of GBM along with the volume and physiological changes associated with surgical resection make this two-dimensional assessment strategy problematic. Moreover, the addition of temozolomide (TMZ) to radiation therapy significantly increases the incidence of pseudo progression, further complicating response determination. It has become apparent that in the present era of molecularly-targeted therapy, when cytotoxicity may not be the primary therapeutic effect, contrast- enhanced MRI is inadequate for monitoring response and progression. More sophisticated and reliable techniques are desperately needed. Proton magnetic resonance spectroscopic imaging (1H-MRSI) is a promising technique that offers a non-invasive means to differentiate tumor progression from post-treatment changes based on the unique magnetic properties of molecular species within tissues. Furthermore, 1H-MRSI can be used to monitor response to therapies that cause widespread metabolic alterations -like suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor -if 1H-MRS biomarkers are quantified and standardized. As such, this work proposes to implement state-of-the-art 1H-MRSI technology to generate three-dimensional metabolite maps of the entire brain that can be co-registered with other imaging studies in a clinically useful fashion. By analyzing numerous data sets from clinical trials at Emory University processed in this fashion, 1) a segmentation algorithm for determining tumor volume and intracellular signal density will be developed, and 2) the spatial coherence of 1H-MRS-visible metabolites with standard MR image volumes will be determined. These standardized algorithms will then be used 3) to produce response vectors that will be tested against currently used response criteria and observed clinical outcomes to evaluate their effectiveness in determining tumor response to TMZ, radiation, and SAHA therapy. The intended outcome of this work is to make 1H-MRSI and the associated bioinformatic techniques practical for clinical use and a part of the standard assessment of brain tumor patients. Lastly, the proposed project will serve as a framework for the applicant's training plan, which is specifically designed to integrate basic analytical techniques and tumor imaging technology to assist the applicant in achieving the career goal of becoming a physician-scientist with a focus in image-guided therapy planning for malignant disease.

描述（由申请人提供）：当前监测多形胶质细胞瘤（GBM）进展的标准在很大程度上取决于使用MacDonald标准（MC）在对比增强的T1加权MRI上增强肿瘤区域的变化。但是，GBM的固有异质性以及与手术切除相关的体积和生理变化使这一二维评估策略有问题。此外，在放射疗法中添加替莫唑胺（TMZ）可显着增加伪进展的发生率，从而进一步复杂化反应测定。显然，在当今的分子靶向疗法时代，当细胞毒性可能不是主要治疗效果时，对比度增强的MRI不足以监测反应和进展。迫切需要更复杂和可靠的技术。质子磁共振光谱成像（1H-MRSI）是一种有前途的技术，它提供了一种非侵入性手段，可以根据组织内分子物种的独特磁力来区分肿瘤进展与治疗后变化。此外，1H -MRSI可用于监测对引起广泛代谢改变的疗法的反应，例如类似的suberoylanilide羟氨酸（SAHA），组蛋白脱乙酰基酶抑制剂-IF 1H -MRS生物标记物被量化和标准化。因此，这项工作建议实施最先进的1H-MRSI技术，以生成整个大脑的三维代谢图，这些图可以以临床上有用的方式与其他成像研究共同注册。通过分析以这种方式处理的埃默里大学临床试验中的许多数据集，1）将开发用于确定肿瘤体积和细胞内信号密度的分割算法，并且将确定具有标准MR图像量的1H-MRS可视代谢物的空间相干性。然后将使用这些标准化算法3）产生响应向量，这些反应向量将根据当前使用的响应标准进行测试，并观察到临床结果，以评估其在确定对TMZ，辐射和SAHA治疗的肿瘤反应方面的有效性。这项工作的预期结果是使1H-MRSI和相关的生物信息学技术可用于临床用途，并且是对脑肿瘤患者的标准评估的一部分。最后，拟议的项目将作为申请人培训的框架 计划是专门设计的，旨在整合基本的分析技术和肿瘤成像技术，以帮助申请人实现成为一名医师科学家的职业目标，重点是针对恶性疾病的图像引导治疗计划。