Quantitative Ultrasound Imaging Biomarkers of Crohn's Disease

克罗恩病的定量超声成像生物标志物

• 批准号: 10078606
• 负责人: David Henry Bruining
• 金额: $ 42.74万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-11 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10078606
• 关键词: Affect; Agreement; American; Analysis of Variance; Anatomy; Area; Biological Markers; Categories; Chronic; Clinical; Clinical Research; Code; Comb animal structure; Crohn' s disease; Decision Making; Detection; Disease; Distal part of ileum; Doppler Ultrasound; Endoscopy; Evaluation; Excision; Fibrosis; Generations; Image; Imaging technology; Individual; Inflammation; Inflammatory; Intestines; Ionizing radiation; Length; Magnetic Resonance Imaging; Measurement; Medical; Modeling; Modification; Operative Surgical Procedures; Outcome; Pathology; Patient Schedules; Patients; Penetration; Prediction of Response to Therapy; ROC Curve; Randomized; Reference Standards; Reproducibility; Resolution; Sampling; Scanning; Source; Speed; Surgical Pathology; Technology; Testing; Thick; Time; Treatment outcome; Ultrasonography; angiogenesis; contrast enhanced; cost; cost effective; disorder control; elastography; imaging approach; imaging biomarker; imaging modality; improved; multimodality; new technology; novel; outcome prediction; quantitative ultrasound; recruit; responders and non-responders; virtual

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.

项目摘要 克罗恩病（CD）是一种慢性炎症性肠病，影响超过100万美国人， 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 指导治疗。超声安全、经济、广泛，因此提供了一种有吸引力的替代方法， 增强CT/MRI，以便频繁随访。在这里，我们提出了一种多参数超声成像 结合B模式、VesselQuest（一种灵敏度更高的新微血管成像方法）的方法 与常规多普勒相比），梳推超声剪切波弹性成像（CUSE） 评价CD炎症和纤维化负荷。 具体目标1：技术进步。使用编码虚拟源的合成发射孔径成像将 用于提高VesselQuestHD高清版的分辨率和穿透力。随机 奇异值分解（SVD）和随机空间下采样将用于加速SVD 用于实时VesselQuestRT成像。我们将改进CUSE的步进推束横波 产生和用于剪切波检测的谐波成像。将进行试点患者测试，以优化 这些技术，并为下面的临床研究铺平了道路。 具体目标2：与MRI的比较。我们将研究100名CD患者，以研究这种新的 疾病评估和治疗结果预测技术。患者开始新的药物治疗 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 基线、4周和6个月时的超声检查。超声参数与MRI评分的相关性， 将评估基线和6个月。超声区分轻度和重度疾病的功效 将通过ROC（受试者工作特征）分析进行评估。此外，将使用ROC分析 评估基线或4周时的超声参数是否可以预测6个月时的治疗反应。 具体目标3：生殖研究。两名超声医师将重复扫描45名CD患者。组内 将使用相关系数来评估超声参数的超声医师间一致性。 来自模型的患者内方差分量将提供超声医师间的估计值。 方差，代表纵向随访的最小可检测差异的下限。 具体目标4：与手术病理学比较。我们将研究50例CD患者， 使用手术病理学作为参考标准，评估这种新技术用于纤维化的有效性。的 超声参数与从病理学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分析将用于评估是否单独或组合 超声参数可以区分无至中度纤维化与重度纤维化。 该项目的成功完成将为克罗恩病的频繁随访带来新的技术。