MRI Assessment of Tumor Perfusion, Permeability and Cellularity

肿瘤灌注、渗透性和细胞结构的 MRI 评估

• 批准号: 10062866
• 负责人: Christopher Chad Quarles
• 金额: $ 39.95万
• 依托单位: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062866
• 关键词: Adopted; Adult; Aftercare; Animal Model; Architecture; Biophysics; Biopsy; Biopsy Specimen; Blood Vessels; Brain Neoplasms; Cellularity; Characteristics; Childhood; Clinical; Clinical Management; Clinical Trials; Combined Modality Therapy; Contrast Media; Data; Development; Diagnosis; Diagnostic radiologic examination; Dose; Early treatment; Echo-Planar Imaging; Excision; Exhibits; Gadolinium; Genetic; Glioma; Goals; Grant; Health Care Costs; Healthcare; Histologic; Histopathology; Image; Image Guided Biopsy; Imaging Techniques; Individual; MRI Scans; Magnetic Resonance Imaging; Malignant neoplasm of brain; Measures; Medical Care Costs; Methodology; Methods; Modification; Molecular Profiling; Monitor; Morbidity - disease rate; Noise; Operative Surgical Procedures; Patient Care; Patients; Perfusion; Permeability; Physiologic pulse; Ploidies; Predisposition; Primary Neoplasm; Progression-Free Survivals; Protocols documentation; Radiation therapy; Recurrence; Recurrent tumor; Research; Resources; Scanning; Site; T2 weighted imaging; Techniques; The Cancer Genome Atlas; Time; Tissues; Tumor Burden; Universities; Vascular Permeabilities; Vision; base; biophysical properties; brain tumor imaging; clinically relevant; contrast enhanced; genetic profiling; hemodynamics; image guided; imaging approach; imaging biomarker; imaging modality; imaging study; improved; mortality; novel; personalized therapeutic; pre-clinical; precision oncology; preclinical study; radiation effect; response; standard of care; success; trait; treatment effect; treatment planning; treatment response; tumor; tumor DNA

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.

该项目的长期目标是通过开发和验证来改善脑癌患者护理 肿瘤的晚期动态敏感性对比度对比度磁共振成像（DSC-MRI）方法 表征和治疗反应评估。改善大脑的生物物理表征 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 用于检测原发性和复发性肿瘤并评估所有脑肿瘤的治疗反应的方法 患者。尽管使用了广泛使用，但CE-MRI的准确性仍然有限，因为它无法划定 在肿瘤类型之间，受到治疗效果的混淆，可能需要几个月才能辨别真正的治疗 回复。我们认为，高级和临床优化的DSC-MRI技术可以克服这些 局限性并可能影响射线照相诊断，反应评估和图像引导的活检。期间 我们在临床前动物模型中开发和验证了这笔赠款的第一阶段，新型DSC- 用于定量和同时成像脑肿瘤血流动力学，血管完整性的MRI技术 和细胞结构。鉴于这些技术在临床前研究中证明了这些技术的有效性，我们现在正在寻找 优化和验证其在脑肿瘤患者中的效用。我们的第一个目的是开发和优化临床 实用的，同时基于螺旋的自旋和梯度回声（SAGE）DSC-MRI策略，用于映射总和 微血管血流动力学，血管大小，血管结构，血管渗透性和细胞划分。 这样的序列克服了许多降低当前DSC-MRI扫描质量的障碍， 需要较低剂量的基于Gadolinium的对比剂，可以采取更可靠的灌注措施，并 提高DSC-MRI数据和用于手术计划的常规图像之间的注册精度。 下一个目标是为基于鼠尾草的指标建立阈值值，以准确区分高级 胶质瘤从治疗后辐射效应中复发，并通过直接相关与图像引导组织验证 组织病理学。这将使临床医生能够做出较早的治疗决策并启动二线 疗法更快。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 在增强和非增强组织中的内容。我们将确定基于圣人的指标，是否 单独或组合，可以鉴定富含肿瘤的活检抽样位点，从而提供 经过验证的基于生物标志物的图像指导活检方法，可以改善组织学和基因分析。 基于鼠尾草的肿瘤灌注，渗透性和细胞的度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特征，定位并提早提供 更具体的治疗反应指标。

项目成果

Hypoxia Imaging With PET Correlates With Antitumor Activity of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) in Rodent Glioma Models.

• DOI: 10.18383/j.tom.2016.00259
• 发表时间: 2016-09
• 期刊: Tomography (Ann Arbor, Mich.)
• 作者: Stokes AM;Hart CP;Quarles CC
• 通讯作者: Quarles CC

A simplified spin and gradient echo approach for brain tumor perfusion imaging.

• DOI: 10.1002/mrm.25591
• 发表时间: 2016-01
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Stokes AM;Quarles CC
• 通讯作者: Quarles CC

Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging.

• DOI: 10.1016/j.mri.2014.08.027
• 发表时间: 2014-12
• 期刊: MAGNETIC RESONANCE IMAGING
• 影响因子: 2.5
• 作者: Stokes, Ashley M.;Skinner, Jack T.;Quarles, C. Chad
• 通讯作者: Quarles, C. Chad

Characterizing the Influence of Preload Dosing on Percent Signal Recovery (PSR) and Cerebral Blood Volume (CBV) Measurements in a Patient Population With High-Grade Glioma Using Dynamic Susceptibility Contrast MRI.

• DOI: 10.18383/j.tom.2017.00004
• 发表时间: 2017-06
• 期刊: Tomography (Ann Arbor, Mich.)
• 作者: Bell LC;Hu LS;Stokes AM;McGee SC;Baxter LC;Quarles CC
• 通讯作者: Quarles CC

Development of a spiral spin- and gradient-echo (spiral-SAGE) approach for improved multi-parametric dynamic contrast neuroimaging.

• DOI: 10.1002/mrm.28933
• 发表时间: 2021-12
• 期刊: MAGNETIC RESONANCE IN MEDICINE
• 影响因子: 3.3
• 作者: Stokes, Ashley M.;Ragunathan, Sudarshan;Robison, Ryan K.;Fuentes, Alberto;Bell, Laura C.;Karis, John P.;Pipe, James G.;Quarles, C. Chad
• 通讯作者: Quarles, C. Chad