Establishing the validity of brain tumor perfusion imaging

摘要 这次竞争性更新的主要目标是建立临床脑肿瘤灌注成像协议 为高精度、生理灵敏度和临床适用性而设计。动态磁敏感 对比度（DSC）MRI是神经肿瘤学中最广泛使用的先进成像技术之一， 据报道，在美国和欧洲的所有常规脑肿瘤扫描中使用了85%。前一 该项目的唯一目标是确定最准确的DSC-MRI采集协议 通过开发，验证和应用基于人口的数字参考对象（DRO），然后验证 这些治疗方案在脑肿瘤患者中的应用这项工作最重要的发现是， 准确的单次造影剂剂量和单回波DSC-MRI方案的临床验证，目前已 已被脑肿瘤成像界采纳为共识建议。另一个关键结果是， 该项目是使用DRO和前瞻性患者研究对单剂量双回波DSC进行验证， MRI序列，一种能够同时评估DSC和动态对比增强的方法 （DCE）-MRI数据，作为具有最高准确度的协议，即使在可变脉冲序列参数和 组织特性。在先前工作成功的基础上，我们现在的目标是克服两个仍然限制 DSC-MRI的临床实用性、准确性和多部位一致性：i）依赖于基于回波平面成像（EPI）的 破坏几何保真度、灌注和解剖图像的可靠共定位的脉冲序列 和准确性的推导DCE-MRI数据，和ii）缺乏验证，和基准，脑肿瘤DSC/DCE- MRI后处理算法和软件，用于单回波和双回波采集。这些限制 代表了迫切需要解决的关键和临床相关挑战。为了解决这些问题， 我们建议：1）建立一个用于验证脑肿瘤DSC DCE-MRI分析的拟人基准 工具和2）开发用于同时DSC/DCE MRI的三维双回波脉冲序列。在这 我们将为神经肿瘤学社区提供经过验证的图像采集和分析方法， 准确、生理敏感和临床适用的脑肿瘤患者DSC/DCE-MRI标测方法。 我们将提供第一个DSC/DCE-MRI拟人基准，可用于验证现有的 未来的算法和软件，从而提高多中心和临床试验的一致性。最终，经过验证 DSC-MRI技术将提高其可靠性和相关性，包括肿瘤 定位，治疗反应评估，手术和活检指导，以及多中心临床试验， 常规和靶向脑肿瘤治疗。

ABSTRACT The principal goal of this competitive renewal is to establish clinical brain tumor perfusion imaging protocols strategically designed for high accuracy, physiologic sensitivity and clinical applicability. Dynamic susceptibility contrast (DSC) MRI is one of the most widely used advanced imaging techniques in neuro-oncology, with a reported use of 85% in all routine brain tumor scans at sites across the US and Europe. During the previous funding cycle, the singular aim of the project was to identify the most accurate DSC-MRI acquisition protocol(s) by developing, validating and applying a population-based digital reference object (DRO) and then verifying these protocols in patients with brain tumors. The most significant finding of this effort was the identification and clinical validation of an accurate single contrast agent dose and single-echo DSC-MRI protocol, which has now been adopted as the consensus recommendation by the brain tumor imaging community. Another key result of this project was the validation, using the DRO and a prospective patient study, of a single-dose, dual-echo DSC- MRI sequence, an approach that enables simultaneous assessment of DSC and dynamic contrast enhanced (DCE)-MRI data, as the protocol with highest accuracy, even across variable pulse sequence parameters and tissue properties. Building on the success of this prior work, we now aim to overcome two obstacles that still limit DSC-MRI’s clinical utility, accuracy, and multi-site consistency: i) a reliance on echo planar imaging (EPI) based pulse sequences that undermine the geometric fidelity, reliable colocalization of perfusion and anatomic images and accuracy of derived DCE-MRI data, and ii) lack of validation of, and a benchmark for, brain tumor DSC/DCE- MRI post-processing algorithms and software, for both single- and dual-echo acquisitions. These limitations represent critical and clinically relevant challenges that urgently need to be addressed. To address these issues, we propose to: 1) establish an anthropomorphic benchmark for validating brain tumor DSC DCE-MRI analysis tools and 2) develop a three-dimensional, dual-echo pulse sequence for simultaneous DSC/DCE MRI. In this project we will provide the neuro-oncology community with validated image acquisition and analysis methods for accurate, physiologic sensitive and clinically applicable DSC/DCE-MRI mapping methods in brain tumor patients. We will provide the first DSC/DCE-MRI anthropomorphic benchmark that can be used to validate existing and future algorithms and software, thereby improving multi-site and clinical trial consistency. Ultimately, validated DSC-MRI techniques will improve its reliability and relevancy across a range of clinical scenarios, including tumor localization, therapy response assessment, surgical and biopsy guidance, and multi-site clinical trials of conventional and targeted brain tumor therapies.