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（BM）是最常见的中枢神经系统肿瘤类型，更多 比颅内肿瘤频繁。过去的各种疗法的进展已经加速 通过正在进行的临床试验和BM患者的历史不良结局的十年 明显改善。对比增强的T1加权MRI通常适用于描绘BM的大小 增强的病变评估治疗反应。由于血脑的破坏而导致的病变增强 屏障是脑肿瘤功能的非特异性。研究最多的MRI灌注方法 测量是动态敏感性对比度灌注加权成像（DSC-PWI），它测量 脑血流（CBF）和脑血体积（CBV）。 CBV是广泛采用的灌注度量 肿瘤血管的敏感标记。但是，其在BM研究中的临床适用性受到缺乏的影响 绝对定量，对比度的效果和频繁的敏感性伪像。动脉自旋标记 （ASL）是频繁的非侵入性纵向监测肿瘤血管性的理想选择。标准化在空间上 用于CBF映射的选择性ASL技术是使用单个后期的伪连续ASL（PCASL）方法 标记延迟，这可能会导致由于动脉流缓慢引起的过境时间延迟而导致CBF的低估 典型的老年患者。提出了速度选择性ASL（VSASL）来消除时间延迟的灵敏度。 我们的小组已经实施了第一个基于3D分段的基于VSASL的速度选择性反转（VSI） GRASE采集并证明了其对常规ASL方法对灌注信号的较高敏感性。 此外，我们的小组首先通过删除标签延迟来开发基于VSASL的CBV映射，该标签延迟已交付 SNR比基于ASL的CBF映射要高得多。此外，我们的初步数据表明VSASL 凭借3D基于刺激性的闪光获取可提供更好的灌注图像质量，而伪像更少 而不是使用GRASE和高时间分辨率，可以允许足够的回顾性运动校正。 这项研究的目的是：目标1，为基于VSASL的CBF和CBV进行进一步的技术发展 通过加速收购绘制协议；目标2，以评估两个优化VSASL的灵敏度 放射治疗后一个月内，CBF和CBV的方案发生了变化，并评估其早期预测 治疗结果； AIM 3，比较VSASL派生的CBF和CBV值的特异性 转移性复发与辐射诱导的作用的区别；目标4，以确保高可重现性 具有不同供应商和现场强度的多个扫描仪之间的VSASL协议。通过完成 提出的目的，基于高级VSASL的CBF和CBV映射方法将证明 监测BM中监测治疗反应的重要值将容易用于大规模临床研究， 并可以对体内所有原发性和转移性肿瘤的研究受益。