Quantitative Ultrasound Imaging Biomarkers of Crohn's Disease

项目总结 克罗恩病(CD)是一种慢性炎症性肠道疾病，影响着100多万美国人和医疗费用 每年数十亿美元。频繁和准确地评估肠道炎症和纤维化对于 引导疗法。超声波是安全、经济、可广泛使用的，因此提供了一种有吸引力的替代方案。 增强的CT/MRI用于频繁的随访。在此，我们提出了一种多参数超声成像方法 结合B超、VesselQuest(一种具有更高灵敏度的新微血管成像方法)的方法 与常规多普勒相比)，以及梳状推进超声横波弹性成像(CUSE) CD炎症和纤维化负担的评估。 具体目标1：技术进步。具有编码虚拟信源的合成发射孔径成像将 用于提高高清版本VesselQuestHD的分辨率和穿透力。随机 奇异值分解(SVD)和随机空间下采样将被用来加速奇异值分解 用于实时VesselQuestRT成像。我们将改进用于横波的行进推梁的Cuse 产生，以及用于横波检测的谐波成像。将进行试点患者测试，以优化 这些技术为下文的临床研究铺平了道路。 具体目的2：与MRI对照。我们将对100名CD患者进行研究，以探讨这种新疗法的疗效。 疾病评估和治疗结果预测技术。患者开始一种新的药物治疗 将在基线和治疗后6个月进行对比增强MRI(用作参考标准)，以及 在基线、4周和6个月时进行超声检查。超声参数与头颅MRI评分的相关性 将对基线和6个月进行评估。超声在鉴别轻、重度疾病中的作用 将通过ROC(接收器工作特性)分析进行评估。此外，还将使用ROC分析 评估基线或4周的超声参数是否可以预测6个月后的治疗反应。 具体目标3：重复性研究。两名超声师将重复扫描45名CD患者。类内 相关系数将被用来评估超声参数的超声医师之间的一致性。 来自模型的患者内方差分量将提供对超声诊断员之间的估计 方差，表示纵向随访的最小可检测差异的下限。 具体目标4：与手术病理对照。我们将对50例CD患者进行研究，以调查 以外科病理学为参考标准，评价这项新技术在评估纤维化方面的有效性。这个 超声参数与从病理中获得的纤维化类别的关联将使用 斯皮尔曼等级相关。此外，ROC分析将用于评估单独或组合 超声参数可以区分非至中度和重度纤维化。 该项目的成功完成将为克罗恩病的频繁随访带来一种新的技术。

PROJECT SUMMARY Crohn's Disease (CD), a chronic inflammatory bowel condition, affects over 1 million Americans and costs billions of dollars annually. Frequent and accurate evaluation of bowel inflammation and fibrosis is critical to guide therapy. Ultrasound is safe, cost-effective, and widely available, thus provides an attractive alternative to contrast enhanced CT/MRI for frequent follow-ups. Here we propose a multi-parameter ultrasound imaging approach combining B-mode, VesselQuest (a new microvessel imaging method with much higher sensitivity than conventional Doppler), and Comb-push Ultrasound Shearwave Elastography (CUSE) for comprehensive evaluation of CD inflammation and fibrosis burden. Specific Aim 1: Technical Advancement. Synthetic Transmit Aperture imaging with coded virtual sources will be used to improve the resolution and penetration of the high definition version VesselQuestHD. Random Singular Value Decomposition (SVD) and randomized spatial down-sampling will be used to accelerate SVD for realtime VesselQuestRT imaging. We will improve CUSE with marching push beams for shear wave generation, and harmonic imaging for shear wave detection. Pilot patient tests will be conducted to optimize these technologies and pave the way for clinical studies below. Specific Aim 2: Comparison with MRI. We will study 100 CD patients to investigate efficacy of this new technology for disease evaluation and treatment outcome prediction. Patients starting a new medical therapy will have contrast enhanced MRI (used as reference standard) at baseline and 6-months post therapy, and ultrasound at baseline, 4-weeks, and 6-months. The correlation of ultrasound parameters with MRI scores at baseline and 6-months will be assessed. The efficacy of ultrasound for differentiating mild vs. severe disease will be assessed by ROC (Receiver Operating Characteristic) analysis. In addition, ROC analysis will be used to assess whether ultrasound parameters at baseline or 4-weeks can predict treatment response at 6-months. Specific Aim 3: Reproducibility Study. Two sonographers will repeatedly scan 45 CD patients. Intraclass correlation coefficients will be used to evaluate the inter-sonographer agreement for ultrasound parameters. The within patient variance component from the model will provide an estimate of the inter-sonographer variance, which represents a lower bound for the minimum detectable difference for longitudinal follow-ups. Specific Aim 4: Comparison with Surgical Pathology. We will study 50 CD patients to investigate the efficacy of this new technology for evaluating fibrosis, using surgical pathology as the reference standard. The association of ultrasound parameters with fibrosis category obtained from pathology will be assessed using Spearman rank correlation. In addition, ROC analysis will be used to assess whether individual or combined ultrasound parameters can distinguish between none-to-moderate versus severe fibrosis. Successful completion of this project will lead to a novel technology for frequent follow-ups of Crohn's disease.