MRI Assessment of Tumor Perfusion, Permeability and Cellularity

该项目的长期目标是通过开发和验证 用于肿瘤的先进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。改善脑的生物物理表征 肿瘤仍然是高度相关的临床目标。目前，对比增强MRI（CE-MRI）是主要的 检测原发性和复发性肿瘤并评估基本上所有脑肿瘤的治疗反应的方法 患者然而，尽管CE-MRI被广泛使用，但其准确性仍然有限，因为它无法描绘 肿瘤类型之间的差异，受到治疗效果的混淆，可能需要数月才能辨别出真正的治疗效果。 反应我们相信，先进的和临床优化的DSC-MRI技术可以克服这些问题， 局限性，并可能影响放射学诊断，反应评估和图像引导活检。期间 在这项资助的第一阶段，我们在临床前动物模型中开发和验证了新型DSC- MRI技术用于脑肿瘤血流动力学、血管完整性的定量和同步成像 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 以优化和验证它们在脑肿瘤患者中的效用。我们的第一个目标是开发和优化临床 实用的同步螺旋自旋和梯度回波（SAGE）DSC-MRI策略，用于标测总 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。 这种序列克服了许多降低当前DSC-MRI扫描质量的障碍， 需要更低剂量的钆基造影剂，能够实现更可靠的灌注测量， 提高了DSC-MRI数据和用于手术计划的传统图像之间的配准精度。 接下来，我们的目标是建立基于SAGE的指标的阈值，以准确区分高等级 治疗后放射效应导致胶质瘤复发，并通过与图像引导组织的直接相关性进行验证 组织病理学这将使临床医生能够更早地做出治疗决定， 治疗更早。我们的最终目的是验证基于SAGE的参数对组织学肿瘤的敏感性 增强组织和非增强组织内的含量。我们将确定是否基于SAGE的指标， 单独地或组合地，使得能够识别富含肿瘤的活检取样部位，从而提供 经验证的基于生物标志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、渗透性和细胞结构的测量将有助于克服许多肿瘤细胞的损伤。 CE-MRI的局限性，因为它们更有可能改善肿瘤表征、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.