Quantitative susceptibility mapping for stroke risk prediction of vulnerable carotid plaques

我们的主要目的是使用定量磁敏感性映射（QSM）建立可靠的非侵入性MRI 用于不稳定颈动脉粥样硬化斑块的识别和危险分层。目前，关于 预防中风的颈动脉血管重建术，如颈动脉内膜切除术或颈动脉支架植入术， 是否有？50%颈动脉狭窄。然而，这种策略只使用了脆弱的一个特征， 斑块和经常错误分类的病人。使用成像技术识别易破裂颈动脉的其他特征 血栓栓塞性卒中高风险的斑块，结合狭窄评估，被证明是一种 更有效的风险评估方法。在这些特征中，斑块内出血（IPH）与 中风风险增加4到6倍，而钙化与中风风险降低50%相关。在 传统的方法，IPH和钙化分别被定义为高信号和低信号，在一个 作为多对比MRI（mcMRI）方案的一部分采集的T1加权（T1w）图像上的斑块区域。 然而，T1w高信号仅捕获短暂的高铁血红蛋白出血相。在随后的 在含铁血黄素相，IPH出现低信号，这是由于强磁化诱导的去相位效应， 超顺磁性含铁血黄素（磁化率> 150 ppm），可能被误解为钙化， 尽管钙化是强抗磁性的（~2.3ppm）。这一提议的关键科学前提是， QSM可以根据T1w低信号与IPH含铁血黄素和钙化的不同， 磁性，因此将显著改善成像表征和风险分层。 颈动脉粥样硬化斑块患者。我们率先开发了QSM，并展示了 QSM对颈动脉斑块出血和钙化敏感性高。在这个项目中，我们将进一步 通过开发多对比QSM，提高颈动脉斑块QSM在常规临床成像中的应用 （mcQSM）方法，其不仅可以在5分钟扫描时间内提供QSM，还可以提供传统的mcMRI对比。 我们将开发一种非线性QSM重建算法，该算法对噪声和运动具有鲁棒性， 分离共存的IPH和钙化，以改善钙化血管中的IPH检测。然后我们将建立 mcQSM检测患者IPH和钙化的诊断准确性优于mcMRI 安排做颈动脉内膜切除术最后，我们将测试mcQSM将提供 与mcMRI相比，对卒中的区分度显著更高。这一提议的成功结果将使 颈动脉斑块QSM准备在个性化的新兴时代广泛和常规的临床使用 减少中风的个人和社会负担。

Our main objective is to use quantitative susceptibility mapping (QSM) in establishing reliable noninvasive MRI for identification and risk stratification of unstable carotid atherosclerotic plaques. Currently, decisions about carotid revascularization to prevent stroke, such as carotid endarterectomy or carotid artery stenting, are based on whether there is ?50% carotid artery stenosis. However, this strategy uses only one feature of vulnerable plaque and frequently misclassifies patients. Using imaging to identify other features of rupture-prone carotid plaques with high risk for thromboembolic stroke, in combination with stenosis assessment, proves to be a more effective approach for risk evaluation. Of these features, intraplaque hemorrhage (IPH) is associated with a 4 to 6-fold higher risk of stroke, while calcification is associated with a 50% lower stroke risk. In the conventional approach, IPH and calcification are defined as hyperintensity and hypointensity, respectively, in a plaque region on the T1-weighted (T1w) image acquired as part of the multi-contrast MRI (mcMRI) protocol. However, T1w hyperintensity only captures the transient methemoglobin phase of hemorrhage. In the ensuing hemosiderin phase, IPH appears hypointense due to the strong susceptibility-induced dephasing effects of the superparamagnetic hemosiderin (susceptibility>150 ppm), which can be misinterpreted as calcification, although calcification is strongly diamagnetic (-2.3 ppm). The key scientific premise of this proposal is that QSM can reliably resolve T1w hypointensity into IPH hemosiderin versus calcification based on their different magnetic property, and therefore will significantly improve imaging characterization and risk stratification of patients with atherosclerotic carotid plaques. We have pioneered QSM development and demonstrated the exquisite sensitivity of QSM for hemorrhage and calcification in carotid plaque. In this project, we will further improve the utility of carotid plaque QSM for routine clinical imaging by developing a multi-contrast QSM (mcQSM) approach which can provide not only QSM but also traditional mcMRI contrasts in 5 min scan time. We will develop a nonlinear QSM reconstruction algorithm which is robust against noise and motion and can separate co-existing IPH and calcification to improve IPH detection in calcified vessels. We will then establish the improvement in diagnostic accuracy of mcQSM over mcMRI for detecting IPH and calcification in patients who are scheduled for carotid endarterectomy. Finally, we will test the hypothesis that mcQSM will provide significantly higher discrimination for stroke than mcMRI. A successful outcome of this proposal will make carotid plaque QSM ready for widespread and routine clinical use in the emerging era of personalized medicine to reduce the individual and societal burden of stroke.