Multi-parametric Perfusion MRI for Therapy Response Assessment in Brain Cancer

该计划的长期目标是通过优化和验证定量 磁共振成像方法用于早期预测脑癌对治疗的反应。目前， 对比增强MRI（CE-MRI）代表了指导脑肿瘤临床几乎所有方面的标准 管理，包括手术活检/切除、放射治疗计划和治疗后监测 进行响应评估。不幸的是，CE-MRI的准确性仍然有限，这造成了重大的临床意义。 挑战因此，临床决策通常需要手术活检以进行明确诊断，这增加了 医疗成本、患者发病率/死亡率和资源利用。为了克服CE-MRI的局限性， 动态磁化率对比（DSC）MRI和动态对比增强（DCE）MRI的使用越来越多 以评估肿瘤灌注和渗透性。研究表明，DSC/DCE参数与 肿瘤分级，可以预测治疗后肿瘤进展的可能性，并区分治疗相关 效果与肿瘤进展。然而，DSC-MRI的广泛临床采用和结合 由于可变的采集方法、造影剂剂量 方案和分析协议，迄今为止，尚未标准化和自动化用于临床使用。 已知这些问题会影响DSC-MRI指标的可重复性和解释。自旋和梯度 回波（SAGE）DSC-MRI序列能够使用较低剂量的Gd基造影剂， 扫描时间，对采集参数不太敏感，方法学上更可重复，产量更高 准确的灌注参数，提供DCE-MRI、血管尺寸和血管的同时测量 结构成像数据、氧气输送和对肿瘤细胞特征高度敏感的新指标。 因此，SAGE方法使得能够询问关于肿瘤的独特和互补的读数。 与临床结果相关的微观结构和功能，并可以识别患者对 疗法在临床试验可以从基于SAGE的DSC-MRI中受益之前， 需要优化、自动化和标准化。因此，我们建议：1）实施多供应商，SAGE- DSC-MRI协议，2）建立用于质量保证和分析的自动化和开源算法，3） 与Imaging Biometrics合作，开发一个商业集成的、供应商中立的图像分析平台 用于分析SAGE DSC-MRI数据和4）验证SAGE DSC-MRI工具用于预测胶质瘤对 贝伐单抗治疗。对医疗保健的影响：我们将为神经肿瘤学社区提供经过验证的， 用于识别早期治疗反应的定量图像采集和分析方法， 适用于常规和靶向脑肿瘤治疗的多中心临床试验，从而使 更快的药物发现和改善患者的个性化护理。

The long-term goal of this program is to improve patient care by optimizing and validating quantitative magnetic resonance imaging methods for the early prediction of brain cancer response to therapy. Currently, contrast-enhanced MRI (CE-MRI) represents the standard for guiding almost all aspects of brain tumor clinical management, including surgical biopsy/resection, radiation treatment planning, and post-treatment surveillance for response assessment. Unfortunately, CE-MRI’s accuracy remains limited, which creates significant clinical challenges. Thus, clinical decisions often require surgical biopsy for definitive diagnosis, which increases medical costs, patient morbidity/mortality, and resource utilization. To overcome the limitations of CE-MRI, dynamic susceptibility contrast (DSC) MRI and dynamic contrast enhanced (DCE) MRI are increasingly used to evaluate tumor perfusion and permeability. Studies have shown that DSC/DCE parameters correlate with tumor grade, can predict the likelihood of tumor progression after therapy, and differentiate treatment related effects versus tumor progression. However, the widespread clinical adoption and incorporation of DSC-MRI into multi-site clinical trials has been hindered due to variable acquisition methods, contrast agent dosing schemes and analysis protocols, which to date, have yet to be standardized and automated for clinical use. These issues are known to affect the repeatability and interpretation of DSC-MRI metrics. Spin and gradient echo (SAGE) DSC-MRI sequences enable the use of lower doses of Gd-based contrast agents, require less scan time, are less sensitive to acquisition parameters, are methodologically more reproducible, yield more accurate perfusion parameters, provide simultaneous measures of DCE-MRI, vessel size and vessel architectural imaging data, oxygen delivery and novel metrics highly sensitive to tumor cellular characteristics. Accordingly, SAGE methods enable the interrogation of unique and complementary readouts on tumor microstructure and function that correlate with clinical outcomes and can identify patients responding to therapy. Before clinical trials can benefit from SAGE based DSC-MRI the acquisition and analysis protocols need to be optimized, automated and standardized. Thus, we propose to: 1) implement multi-vendor, SAGE- DSC-MRI protocols, 2) establish automated and open source algorithms for quality assurance and analysis, 3) partner with Imaging Biometrics to develop a commercially integrated, vendor neutral image analysis platform for analyzing SAGE DSC-MRI data and 4) validate SAGE DSC-MRI tools for predicting glioma response to bevacizumab therapy. Impact on Healthcare: We will provide the neuro-oncology community with validated, quantitative image acquisition and analysis methods for identifying early therapeutic response that are appropriate for multi-site clinical trials of conventional and targeted brain tumor therapies, thereby enabling more rapid drug discovery and improved individualized care for patients.