Non-invasive Ultrasound Elasticity Imaging (UEI) in Crohn's Disease

描述（由申请人提供）：克罗恩病的非侵入性超声弹性成像（UEI）虽然目前的成像系统，如计算机断层扫描（CT）扫描可以识别克罗恩病的炎症，但没有成像工具来识别哪些患者具有显著的肠纤维化。炎症发作之间的愈合允许肠重建其上皮，但该愈合过程导致纤维化瘢痕组织的沉积。反复发作和愈合的周期往往导致临床上显著的肠纤维化和狭窄，20%的患者在诊断后3年内需要手术，57%的患者在疾病10年后需要手术。这对生活质量和医疗费用产生了重大影响。当克罗恩病患者出现腹痛和呕吐时，这表明小肠严重狭窄。这可能是由于炎症，可以用药物治疗，或由于慢性纤维化，这需要手术。患者凭经验用类固醇治疗，有许多副作用。如果我们能够确定哪些患者确实患有严重的肠纤维化导致肠狭窄，那么许多患者可以通过手术得到更好的治疗。局部超声弹性成像（UEI）提供了从根本上提高克罗恩病肠纤维化的诊断和及时管理的潜力。该方法允许完全表征改变的局部组织弹性特性和局部肠力学。此外，它具有高空间分辨率，提供出色的灵敏度，特异性，准确性和精密度。肠的机械特性直接从壁内应变估计，而不是从肠厚度和/或直径变化推断。测量程序的直接性质非常适合局部评估炎症性肠道疾病过程中随着纤维化发展而发生的组织机械变化。如果我们的假设是正确的，这种方法可以迅速转化为临床实践，因为它是基于新的处理超声数据，可以获得与商业可用的扫描仪。该方案的基本假设是：1. UEI可以测量与纤维化进展相关的肠壁弹性特性的局部变化。2.通过UEI测量的肠壁的局部机械变化可以预测由先前炎症引起的肠局部纤维化的严重程度和范围。3.具有斑点跟踪的UEI可用于非侵入性地测量啮齿动物的高度局部化的肠道顺应性变化，并且可容易地转化为人类的临床诊断工具。必须对广泛的技术和科学问题进行调查，以充分利用所提出的技术的能力。因此，本申请的两个具体目的是：1.确定非侵入性UEI是否可以区分长期用TNBS（三硝基苯磺酸）灌肠剂治疗的大鼠中纤维化结肠和正常结肠的机械特性;和2.确定UEI是否能够检测和测量克罗恩病患者纤维化的严重程度和范围。公共卫生相关性：反复的炎症循环经常导致临床上显著的纤维化和肠狭窄，20%的患者在诊断后3年内需要手术，57%的患者在疾病10年后需要手术。这对生活质量和医疗费用产生了重大影响。当克罗恩病患者出现腹痛和呕吐时，这表明小肠严重狭窄。这可能是由于炎症，可以用药物治疗，或由于慢性纤维化，这需要手术。患者凭经验用类固醇治疗，有许多副作用。如果我们能够确定哪些患者确实患有严重的肠纤维化导致肠狭窄，那么许多患者可以通过手术得到更好的治疗。虽然目前的成像系统，如计算机断层扫描（CT）扫描可以识别克罗恩病的炎症，但没有成像工具来识别哪些患者患有严重的肠道纤维化。拟议的局部超声弹性成像（UEI）提供了从根本上改善克罗恩病肠纤维化的诊断和及时管理的潜力。该方法允许完全表征改变的局部组织弹性特性和局部肠力学。这种方法也可以迅速转化为临床实践，因为它是基于新的处理超声数据，可以获得与商业可用的扫描仪。

DESCRIPTION (provided by applicant): Non-invasive Ultrasound Elasticity Imaging (UEI) in Crohn's Disease While current imaging systems such as computed tomography (CT) scanning can identify inflammation in Crohn's disease, there are no imaging tools to identify which patients have significant intestinal fibrosis. Healing between flares of inflammation allows the intestine to reconstitute its epithelium, but this healing process results in the deposition of fibrotic scar tissue. Repeated cycles of flares and healing often lead to clinically significant fibrosis and stenosis of the intestine, requiring surgery in 20% of patients within 3 years of diagnosis, and in 57% of patients after 10 years of disease. This has a substantial impact on quality of life and medical costs. When Crohn's patients have abdominal pain and vomiting, this indicates severe narrowing of the small intestine. This can be due to inflammation, which can be treated with medical therapy, or due to chronic fibrosis, which requires surgery. Patients are treated empirically with steroids with their many side effects. Many patients would be better treated with surgery if we could identify which patients truly have severe intestinal fibrosis causing their intestinal strictures. Local ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and timely management of intestinal fibrosis in Crohn's disease. This method allows complete characterization of the altered local tissue elastic properties and local intestine mechanics. Furthermore, it does so with high spatial resolution, offering excellent sensitivity, specificity, accuracy and precision. The mechanical properties of the intestine are estimated directly from intramural strain rather than inferred from intestine thickness and/or diameter changes. The direct nature of the measurement procedure is ideal for local assessment of tissue mechanical changes that occur with the development of fibrosis in the course of inflammatory bowel disease. If our hypotheses are correct, this method can be rapidly translated into clinical practice since it is based upon novel processing of ultrasound data that can be obtained with commercially available scanners. The fundamental hypotheses of this proposal are: 1.UEI can measure local changes in the elastic properties of the intestinal wall associated with the progression of fibrosis. 2. Local mechanical changes of the intestine wall as measured by UEI can predict the severity and extent of local fibrosis of the intestine resulting from previous inflammation. 3. UEI with speckle tracking can be used to non-invasively measure highly localized intestinal compliance changes in rodents, and is readily translatable into a clinical diagnostic tool in humans. A wide range of technical and scientific issues must be investigated to fully exploit the capabilities of the techniques proposed. Therefore, the two specific aims of this application are: 1. to determine whether noninvasive UEI can distinguish between the mechanical properties of fibrotic colon and normal colon in rats treated chronically with TNBS (trinitrobenzenesulfonic acid) enemas; and 2. To determine whether UEI is able to detect and measure the severity and extent of fibrosis in patients with Crohn's disease. PUBLIC HEALTH RELEVANCE: Repeated cycles of inflammation often lead to clinically significant fibrosis and stenosis of the intestine, requiring surgery in 20% of patients within 3 years of diagnosis, and in 57% of patients after 10 years of disease. This has a substantial impact on quality of life and medical costs. When Crohn's patients have abdominal pain and vomiting, this indicates severe narrowing of the small intestine. This can be due to inflammation, which can be treated with medical therapy, or due to chronic fibrosis, which requires surgery. Patients are treated empirically with steroids with their many side effects. Many patients would be better treated with surgery if we could identify which patients truly have severe intestinal fibrosis causing their intestinal strictures. While current imaging systems such as computed tomography (CT) scanning can identify inflammation in Crohn's disease, there are no imaging tools to identify which patients have significant intestinal fibrosis. The proposed local ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and timely management of intestinal fibrosis in Crohn's disease. This method allows complete characterization of the altered local tissue elastic properties and local intestine mechanics. This method also can be rapidly translated into clinical practice since it is based upon novel processing of ultrasound data that can be obtained with commercially available scanners.