Development and Evaluation of Advanced Non-Contrast Perfusion MRI for Monitoring Treatment Response in Brain Metastases

用于监测脑转移治疗反应的先进非对比灌注 MRI 的开发和评估

• 批准号: 10716949
• 负责人: Qin Qin
• 金额: $ 65.84万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716949
• 关键词: 3-Dimensional; Acceleration; Adopted; Base Sequence; Blood Vessels; Brain; Brain Neoplasms; Central Nervous System Neoplasms; Cerebrovascular Circulation; Clinical; Clinical Research; Clinical Trials; Data; Development; Diagnosis; Early treatment; Enhancing Lesion; Ensure; Evaluation; Extravasation; Glioma; Image; Immunotherapy; Intracranial Neoplasms; Label; Magnetic Resonance Imaging; Maps; Measurement; Measures; Metastatic malignant neoplasm to brain; Metastatic/Recurrent; Methodology; Methods; Monitor; Morphologic artifacts; Motion; Multi-site clinical study; Neoplasm Metastasis; Nervous System Physiology; Operative Surgical Procedures; Outcome; Patient-Focused Outcomes; Patients; Perfusion; Prediction of Response to Therapy; Predisposition; Primary Brain Neoplasms; Primary Neoplasm; Protocols documentation; Radiation; Radiation therapy; Radiosurgery; Recurrence; Reproducibility; Signal Transduction; Site; Specificity; Standardization; Techniques; Time; Treatment outcome; Tumor Markers; Vendor; arterial spin labeling; blood-brain barrier disruption; cerebral blood volume; clinical application; clinical examination; contrast enhanced; cost effective; detection sensitivity; diagnostic accuracy; follow-up; healthy volunteer; imaging biomarker; improved; individualized medicine; older patient; perfusion imaging; prospective; radiation effect; reconstruction; response; targeted treatment; temporal measurement; treatment response; tumor; tumor progression

Project Abstract Brain metastases (BM) are the most commonly diagnosed type of central nervous system tumor, more frequent than primary intracranial neoplasms. Progress on various therapies have accelerated over the past decade through ongoing clinical trials, and the historically poor outcomes for patients with BM have been markedly improved. Contrast-enhanced T1-weighted MRI is routinely applied to depict BM with the size of the enhanced lesions for assessing treatment response. Lesion enhancement due to the disruption of blood-brain barrier is rather nonspecific of the functions of brain tumors. The most studied MRI methodology for perfusion measurement is dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI), which measures cerebral blood flow (CBF) and cerebral blood volume (CBV). CBV is the widely adopted perfusion measure as a sensitive marker of tumor vascularity. However, its clinical applicability in BM studies is hampered by its lack of absolute quantification, the contrast-leakage effect, and frequent susceptibility artifacts. Arterial spin labeling (ASL) is ideal for frequent non-invasive longitudinal monitoring of tumor vascularity. The standardized spatially selective ASL technique for CBF mapping is the pseudo-continuous ASL (PCASL) method using a single post- labeling delay, which may render underestimation of CBF due to transit time delay caused by slow arterial flow typical in elderly patients. Velocity-selective ASL (VSASL) was proposed to remove the time-delay sensitivity. Our group has implemented the first velocity-selective inversion (VSI) based VSASL with 3D segmented GRASE acquisition and demonstrated its higher sensitivity to perfusion signal over conventional ASL methods. Additionally, our group first developed VSASL based CBV mapping by removing labeling delay, which delivered much higher SNR than ASL based CBF mapping. Furthermore, our preliminary data showed that VSASL with 3D stack-of-spiral based FLASH acquisition delivered better perfusion image quality with less artifacts than using GRASE, and high temporal resolution potentially allowing adequate retrospective motion correction. The purpose of this study is: Aim 1, to conduct further technical developments for VSASL based CBF and CBV mapping protocols with accelerated acquisitions; Aim 2, to evaluate the sensitivity of the two optimized VSASL protocols to CBF and CBV changes within a month after the radiation therapy, and assess their early prediction to treatment outcomes; Aim 3, to compare the specificity of VSASL derived CBF and CBV values in the distinction of metastatic recurrence from radiation-induced effects; Aim 4, to ensure high reproducibility of the VSASL protocols between multiple scanners with different vendors and field strength. By completing the proposed aims, the advanced VSASL based CBF and CBV mapping methods are expected to demonstrate important values for monitoring treatment response in BM, will be readily available for large-scale clinical studies, and can benefit for studies of all primary and metastatic tumors in the body.

项目摘要 脑转移瘤（BM）是最常见的中枢神经系统肿瘤类型， 比原发性颅内肿瘤更常见。过去，各种治疗方法的进展加快了 十年来，通过正在进行的临床试验，BM患者的历史不良结局一直是 明显改善。常规应用对比增强T1加权MRI来描述BM， 用于评估治疗反应的增强的病变。由于血脑破坏导致的病变强化 屏障是脑肿瘤功能的非特异性。研究最多的灌注MRI方法 测量是动态磁化率对比灌注加权成像（DSC-PWI），其测量 脑血流量（CBF）和脑血容量（CBV）。CBV是广泛采用的灌注测量， 肿瘤血管分布的敏感标志物。然而，其在BM研究中的临床适用性受到其缺乏的阻碍。 绝对量化、对比度泄漏效应和频繁的磁化率伪影。动脉自旋标记 (ASL)是肿瘤血管分布频繁无创纵向监测的理想选择。空间标准化 用于CBF映射的选择性ASL技术是使用单个后处理的伪连续ASL（PCASL）方法， 标记延迟，由于动脉血流缓慢导致的通过时间延迟，可能导致低估CBF 典型的老年患者。速度选择性ASL（VSASL）被提出来消除时延敏感性。 我们的小组已经实现了第一个基于速度选择性反演（VSI）的VSASL， GRASE采集，并证明其对灌注信号的灵敏度高于传统ASL方法。 此外，我们的小组首先通过消除标记延迟开发了基于VSASL的CBV标测， SNR比基于ASL的CBF映射高得多。此外，我们的初步数据显示，VSASL 使用基于3D螺旋堆叠的FLASH采集，可提供更好的灌注图像质量，伪影更少 与使用GRASE相比，高时间分辨率可能允许充分的回顾性运动校正。 本研究的目的是：目标1，对基于VSASL的CBF和CBV进行进一步的技术开发 加速采集的标测方案;目的2，评价两种优化VSASL的灵敏度 放射治疗后一个月内CBF和CBV的变化，并评估其早期预测 目的3，比较VSASL导出的CBF和CBV值在治疗结局中的特异性。 转移复发与辐射诱导效应的区别;目的4，确保高重复性的 不同供应商和场强的多台扫描仪之间的VSASL协议。通过完成 提出的目标，先进的基于VSASL的CBF和CBV映射方法有望证明 监测BM治疗反应的重要值，可随时用于大规模临床研究， 并且可以有益于体内所有原发性和转移性肿瘤的研究。