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

描述(申请人提供)：非侵入性超声弹性成像(UEI)治疗克罗恩病虽然目前的成像系统，如计算机断层扫描(CT)可以识别克罗恩病的炎症，但还没有成像工具来确定哪些患者有明显的肠道纤维化。炎症爆发之间的愈合允许肠道重建其上皮，但这种愈合过程会导致纤维瘢痕组织的沉积。反复的红斑和愈合周期通常会导致临床上显著的肠道纤维化和狭窄，20%的患者在确诊后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有很大影响。当克罗恩的病人有腹痛和呕吐时，这表明小肠严重狭窄。这可能是由于炎症，可以用药物治疗，也可能是由于慢性纤维化，需要手术。患者使用类固醇治疗有许多副作用，是经验性的。如果我们能确定哪些患者确实患有严重的肠道纤维化，导致他们的肠道狭窄，许多患者会得到更好的手术治疗。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处理的潜力。这种方法可以对改变的局部组织弹性特性和局部肠道力学进行完整的表征。此外，它还具有高空间分辨率，提供了出色的灵敏度、特异度、准确性和精确度。肠的机械性能是直接根据肠壁内应变来估计的，而不是根据肠壁厚度和/或直径的变化来推断的。测量过程的直接性是局部评估炎症性肠病过程中随着纤维化发展而发生的组织力学变化的理想方法。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，因为它基于可以用商业扫描仪获得的超声数据的新处理。这一建议的基本假设是：1.UEI可以测量与纤维化进展相关的肠壁弹性性质的局部变化。2.UEI测定的肠壁局部力学变化可预测既往炎症引起的肠壁局部纤维化的严重程度和程度。3.斑点追踪的UEI可以无创地测量啮齿动物高度局部性的肠道顺应性变化，并且很容易转化为人类的临床诊断工具。必须调查广泛的技术和科学问题，以充分利用所提议的技术的能力。因此，这项应用的两个特定目的是：1.确定非侵入性UEI是否能够区分长期使用三硝基苯磺酸(TNBS)灌肠治疗的大鼠纤维化结肠和正常结肠的机械特性；2.确定UEI是否能够检测和测量克罗恩病患者的纤维化程度和程度。公共卫生相关性：反复的炎症循环通常会导致临床上显著的肠道纤维化和狭窄，20%的患者在确诊后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有很大影响。当克罗恩的病人有腹痛和呕吐时，这表明小肠严重狭窄。这可能是由于炎症，可以用药物治疗，也可能是由于慢性纤维化，需要手术。患者使用类固醇治疗有许多副作用，是经验性的。如果我们能确定哪些患者确实患有严重的肠道纤维化，导致他们的肠道狭窄，许多患者会得到更好的手术治疗。虽然目前的成像系统，如计算机断层扫描(CT)可以识别克罗恩病的炎症，但还没有成像工具来识别哪些患者有明显的肠道纤维化。建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处理的潜力。这种方法可以对改变的局部组织弹性特性和局部肠道力学进行完整的表征。这种方法还可以快速地转化为临床实践，因为它基于可以用商业扫描仪获得的超声数据的新处理。

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.