MRI Assessment of Tumor Perfusion, Permeability and Cellularity

这个项目的长期目标是通过开发和验证来改善脑癌患者的护理 先进的肿瘤动态磁化率对比磁共振成像(DSC-MRI)方法 表征和治疗反应评估。改善脑的生物物理特性 肿瘤仍然是一个高度相关的临床目标。目前，对比剂增强磁共振成像(CE-MRI)是主要的 检测原发和复发肿瘤并评估对基本上所有脑肿瘤的治疗反应的手段 病人。然而，尽管被广泛使用，CE-MRI的准确性仍然有限，因为它不能描绘 在肿瘤类型之间，治疗效果令人困惑，可能需要几个月的时间才能辨别出真正的治疗方法 回应。我们相信，先进的和临床优化的DSC-MRI技术可以克服这些 这可能会受到限制，并可能影响放射诊断、反应评估和影像引导活检。在.期间 在这笔赠款的第一期支持中，我们开发并在临床前动物模型中验证了新型DSC- 脑肿瘤血流动力学、血管完整性定量同步成像的MRI技术 和细胞结构。鉴于这些技术在临床前研究中的有效性，我们现在寻求 以优化和验证其在脑肿瘤患者中的有效性。我们的首要目标是开发和优化一种临床 实用的同步螺旋自旋和梯度回波(SAGE)DSC-MRI方法 微血管血流动力学，血管大小，血管结构，血管通透性和细胞结构。 这种序列克服了降低当前DSC-MRI扫描质量的许多障碍， 需要较低剂量的基于Gd的造影剂，可实现更可靠的灌注测量和 提高了DSC-MRI数据和用于外科计划的常规图像之间的配准精度。 我们的下一个目标是为基于SAGE的指标建立阈值，以准确区分高级 脑胶质瘤治疗后复发的放射效应及与影像引导组织的直接相关性验证 组织病理学。这将使临床医生能够更早地做出治疗决定，并启动二线 更快地接受治疗。我们的最终目标是验证基于SAGE的参数对组织肿瘤的敏感性 增强组织和非增强组织中的含量。我们将确定基于SAGE的指标、 单独或联合使用，能够识别富含肿瘤的活检取样点，从而提供 经过验证的基于生物标记物的图像引导活检方法可以改善组织学和遗传学特征。 基于SAGE的肿瘤灌注、渗透性和细胞密度的测量将有助于克服许多 CE-MRI的局限性，因为它们更有可能改善肿瘤的定性、定位并提供早期和 更具体的治疗反应指标。

The long-term goal of this project is to improve brain cancer patient care by developing and validating advanced dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) methods for tumor characterization and therapeutic response assessment. Improving the biophysical characterization of brain tumors remains a highly relevant clinical objective. Currently, Contrast-Enhanced MRI (CE-MRI) is the primary means to detect primary and recurrent tumors and assess therapeutic response for essentially all brain tumor patients. Yet despite widespread use, CE-MRI accuracy remains limited, as it is incapable of delineating between tumor types, is confounded by treatment effects and can require months to discern true therapeutic response. We believe that advanced and clinically optimized DSC-MRI techniques can overcome these limitations and could impact radiographic diagnosis, response assessment and image-guided biopsies. During the first period of support of this grant we developed and validated, in pre-clinical animal models, novel DSC- MRI techniques for quantitative and simultaneous imaging of brain tumor hemodynamics, vascular integrity and cytoarchitecture. Given the demonstrated validity of these techniques in pre-clinical studies we now seek to optimize and validate their utility in brain tumor patients. Our first Aim is to develop and optimize a clinically practical, simultaneous spiral-based spin and gradient echo (SAGE) DSC-MRI strategy for mapping total and microvascular hemodynamics, vessel size, vessel architecture, vascular permeability and cytoarchitecture. Such a sequence overcomes many of the obstacles that reduce the quality of current DSC-MRI scans, requires lower doses of Gadolinium based contrast agents, enables more reliable perfusion measures and improves registration accuracy between DSC-MRI data and conventional images used for surgical planning. We next aim to establish threshold values for SAGE based metrics that accurately differentiate high-grade glioma recurrence from post treatment radiation effect and validate by direct correlation to image-guided tissue histopathology. This would enable clinicians to make earlier treatment decisions and initiate second-line therapies sooner. Our final aim is to validate the sensitivity of SAGE-based parameters to histologic tumor content both within enhancing and non-enhancing tissue. We will determine whether SAGE based metrics, individually or combined, enable the identification of tumor rich biopsy sampling sites, thereby providing a validated biomarker-based image guided biopsy approach that could improve histologic and genetic profiling. SAGE-based measures of tumor perfusion, permeability and cellularity would help overcome many of the limitations of CE-MRI as they are more likely to improve tumor characterization, localization and offer early and more specific indicators of treatment response.