Precision MRI of Left Atrial Fibrosis for Patients with Atrial Fibrillation

项目总结/摘要：针对肺静脉和其他心房部位的导管消融已经出现 作为恢复和维持窦性心律的最佳干预措施;然而，1年成功率仅为60- 百分之七十由于消融术并不能使所有房颤（AF）患者受益， 对于预期的无应答者（30-40%），需要避免不必要的手术（成本> 20，000美元，风险约5%）。 从标准临床和影像学指标得出的房颤复发的潜在预测因子已被证明是 有限使用。左心房（LA）纤维化更有希望，因为纤维化在发展中起着核心作用， 可能是更广泛的疾病的标志物， 标准肺静脉隔离事实上，使用3D LA晚期钆增强（LGE）评估的LA纤维化 由犹他州团队率先开发的心血管磁共振（CMR）已显示出预测AF的前景 消融后复发。然而，LA纤维化的“犹他州”分类受到怀疑，因为 缺乏独立的验证和确认。这种重复性的缺乏源于两个基本的 方法缺陷：（a）空间分辨率（1.5 mm x 1.5 mm x 2.5 - 5 mm）和对比度不足， 噪声比（CNR）和1.5 T下的长扫描时间（~11 min）以及（B）不可靠的图像分析技术， 量化薄（约2 mm）LA壁中的纤维化。这些缺陷阻碍了LA的广泛采用 临床实践中的纤维化定量。 为了克服这些障碍，我们建议开发颠覆性技术， 通过整合以下先进技术定量LA纤维化：（1）自由呼吸3D LGE CMR 具有星堆k空间采样和压缩的平衡稳态自由进动（b-SSFP）读出 感测（CS）或超维黄金角RAdial稀疏并行（XD-GRASP）重建， 门控呼吸运动，以实现具有高空间分辨率（1.3）的前所未有的图像质量（即CNR mm x 1.3 mm x 1.5 mm）和1.5特斯拉下可接受的扫描时间（6 min），以及（2） 使用随机分析精确定量LA纤维化。建议签名的独特优势 优于标准分析技术技术包括：（2a）更精确的无阈值纤维化定义，（2b） 对LA分割不敏感，（2c）强度不均匀性的自校正，（2d）标准化，以及 患者特异性定量，以及（2 e）全自动化和快速（2分钟）处理。 本多中心研究的具体目标是：a）开发和验证稳健的3D LA LGE CMR 1.5特斯拉的采集和重建方法，（B）开发和验证一种新的LGE签名技术 用于定量LA纤维化，以及c）评价LA纤维化的预测准确性和再现性 两个网站的签名。该提案具有很高的潜在影响，因为它解决了两个基本问题 方法学缺陷妨碍了临床实践中广泛采用LA纤维化定量。

Project Summary/Abstract: Catheter ablation targeting the pulmonary veins and other atrial sites has emerged as the best intervention for restoring and maintaining sinus rhythm; however, 1-year success rates are only 60- 70%. Because ablation does not benefit all atrial fibrillation (AF) patients, a personalized medicine approach is needed to avoid an unnecessary procedure (cost >$20,000, risk ~5%) for expected non-responders (30-40%). Potential predictors of AF recurrence derived from standard clinical and imaging metrics have proven to be of limited use. Left atrial (LA) fibrosis is more promising, because fibrosis plays a central role in the development of an arrhythmogenic substrate for AF and may be a marker for more extensive disease less amenable to standard pulmonary vein isolation. In fact, LA fibrosis assessed with 3D LA late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), pioneered by the Utah group, has shown promise for predicting AF recurrence post-ablation. However, the “Utah” classification of LA fibrosis has garnered skepticism because of a lack of independent verification and validation. This lack of reproducibility stems from two fundamental methodologic deficiencies: (a) inadequate spatial resolution (1.5 mm x 1.5 mm x 2.5 to 5 mm) and contrast-to- noise ratio (CNR) and lengthy scan time (~11 min) at 1.5 Tesla and (b) unreliable image analysis techniques for quantification of fibrosis in the thin (~2 mm) LA wall. These deficiencies preclude widespread adoption of LA fibrosis quantification in clinical practice. To push the field of forward through these obstacles, we propose to develop disruptive technologies for quantification of LA fibrosis by integrating the following advanced techniques: (1) free-breathing 3D LGE CMR balanced steady state free precession (b-SSFP) readout with stack-of-stars k-space sampling and compressed sensing (CS) or eXtra-Dimensional Golden-angle RAdial Sparse Parallel (XD-GRASP) reconstruction with self- gating respiratory motion for achieving unprecedented image quality (i.e. CNR) with high spatial resolution (1.3 mm x 1.3 mm x 1.5 mm) and acceptable scan time (6 min) at 1.5 Tesla and (2) novel signatures technique for precise quantification of LA fibrosis using stochastic analysis. Unique advantages of the proposed signatures technique over standard analysis techniques include: (2a) more precise threshold-free fibrosis definition, (2b) insensitivity to LA segmentation, (2c) self-correction for intensity inhomogeneity, (2d) standardization and patient-specific quantification, and (2e) full automation and fast (2 min) processing. The specific objectives of this multi-center study are to: a) develop and validate robust 3D LA LGE CMR acquisition and reconstruction methods for 1.5 Tesla, (b) develop and validate a novel LGE signatures technique for quantification of LA fibrosis, and c) evaluate the prediction accuracy and reproducibility of LA fibrosis signatures across two sites. This proposal has high potential impact because it addresses two fundamental methodologic deficiencies precluding widespread adoption of LA fibrosis quantification in clinical practice.