Advanced Perfusion MRI of Treatment Response and Progression in Glioblastoma

描述（由申请人提供）：多形性胶质母细胞瘤（GBM）是最常见的原发性脑恶性肿瘤，其预后极差。术后，同步化疗和放疗最近被证明可以延长生存期，但这种强化治疗已导致认识到“假进展”（PsP）作为一个高度成问题的混淆治疗监测和临床试验设计。在PsP中，阳性治疗反应在常规MRI上模拟疾病进展（PD）。PsP使早期进展性疾病（ePD）与阳性治疗反应的区分变得复杂，影响了治疗干预的决定，并可能使反应患者处于错误停止化疗的致命风险中。考虑到与活检或再切除以确定复发诊断相关的成本、潜在发病率和采样误差，迫切需要临床上可靠的非侵入性方法来区分PsP和ePD。抗血管生成治疗的应用产生了进一步的模糊性，抗血管生成治疗被认为使渗漏的肿瘤血管系统正常化，从而几乎立即降低T1增强（假反应）。这额外地使疾病进展的评估复杂化，并且限制了常规MRI用于优化个体化治疗方案的效用。动态磁敏感对比（DSC）-PWI是临床PWI的流行标准，并已显示出区分肿瘤进展与治疗效果的前景。不幸的是，目前最先进的DSC-PWI技术具有严重的技术局限性，严重阻碍了其临床实用性，包括低空间分辨率，频繁的几何失真和敏感性 相关的伪影，尤其是在手术后的大脑中，以及由于渗漏的肿瘤血管的造影剂外渗的混杂效应而导致的估计误差。其中大多数是动态MRI固有的，因为需要高的空间和时间分辨率。不幸的是，试图纠正其中一个缺陷不可避免地会扩大其他缺陷。将MRI加速一个数量级的创新方法对于将DSC-PWI建立为临床环境中实用、相关和稳健的方法是必要的。本研究的总体目标是通过开发先进的PWI方法，生成肿瘤进展和治疗反应的敏感、特异和临床相关的成像生物标志物。我们的团队开创了几种加速成像技术，这些技术利用了欠采样、非笛卡尔、数据采集轨迹与基于模型和压缩感知的重建的共生关系。我们假设，这种协同作用也可以被利用来提供所需的加速，以提高分辨率和最大限度地减少标准DSC-PWI固有的伪影，以及实现所需的后处理，以最大限度地减少外渗效应。我们的目标是开发动态成像采集和重建方法，提供高分辨率，高精度的DSC-PWI，最大限度地减少伪影，同时提供高可靠性。这些方法将应用于GBM患者接受术后MRI监测肿瘤进展的初步研究。该项目将利用几个独特的资源和能力，在广泛的MR成像和神经肿瘤学研究计划在威斯康星大学麦迪逊分校。如果成功，这些技术不仅将改变脑肿瘤患者的护理和治疗发展，而且还将有助于其他疾病的研究，诊断和临床管理，包括急性中风，痴呆和神经退行性疾病。

DESCRIPTION (provided by applicant): Prognosis for glioblastoma multiforme (GBM), the most common primary brain malignancy, is extremely poor. Post-operative, concurrent chemo- and radiotherapy was recently shown to prolong survival but this intensification of therapy has led to the recognition of "pseudoprogression" (PsP) as a highly problematic confound to treatment monitoring and clinical trial design. In PsP a positive treatment response mimics progressive disease (PD) on conventional MRI. PsP complicates the differentiation of early progressive disease (ePD) from a positive treatment response affecting decisions about therapeutic intervention and potentially putting responsive patients at fatal risk of errant discontinuation of chemotherapy. Given the cost, potential morbidity, and sampling errors associated with biopsy or re-resection to establish a diagnosis of recurrence, clinically reliable non-invasive means of distinguishing PsP from ePD are critically needed. Further ambiguities arise with the application of anti-angiogenic therapy, which is thought to normalize leaky tumor vasculature to produce an almost immediate decrease in T1 enhancement (pseudo-response). This additionally complicates the assessment of disease progression and limits the utility of conventional MRI for the optimization of individualized treatment regimes. Dynamic susceptibility contrast (DSC)-PWI is the prevailing standard for clinical PWI and has shown promise in discriminating tumor progression from treatment effects. Unfortunately, current state-of-the-art DSC-PWI techniques have important technical limitations that critically impede their clinical utility including low spatial resolution, frequent geometric distortion and susceptibility related artifacts, especially in the post-operative brain, and estimation errors because of the confounding effects of contrast extravasation from leaky tumor vessels. Most of these are inherent to dynamic MRI because of the need for both high spatial and temporal resolution. Unfortunately, attempts to correct one of these deficiencies inevitably amplify others. Innovative approaches to accelerate MRI by an order of magnitude are necessary to establish DSC-PWI as a practical, relevant, and robust method in a clinical setting. The overarching aim of this research is to generate sensitive, specific, and clinically relevant imaging biomarkers of tumor progression and treatment response through the development of advanced PWI approaches. Our group pioneered several accelerated imaging techniques that exploit symbiosis of undersampled, non-Cartesian, data-acquisition trajectories with model-based and compressed-sensing-like reconstruction. We hypothesize that this synergy can also be exploited to provide the acceleration required to improve resolution and minimize artifacts inherent to standard DSC-PWI, as well as enable post-processing required to minimize extravasation effects. We aim to develop dynamic imaging acquisition and reconstruction methods that deliver high resolution, high accuracy DSC-PWI with minimized artifacts while providing high reliability. These methods will be applied in a pilot study of GBM patients undergoing post-operative MRI for monitoring of tumor progression. The project will leverage several unique resources and capabilities in broad MR imaging and Neuro-oncology research programs at UW-Madison. If successful, the techniques will not only change care and treatment development in brain tumor patients, but will also be useful for the study, diagnosis, and clinical management of other diseases including acute stroke, dementias, and neurodegenerative diseases.