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

描述（由申请人提供）：克罗恩病的无创超声弹性成像（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有明显的肠道纤维化。炎症发作之间的愈合允许肠道重建其上皮，但这种愈合过程导致纤维化瘢痕组织的沉积。复发和愈合的反复循环经常导致临床显著的肠纤维化和狭窄，20%的患者在诊断3年内需要手术，57%的患者在患病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，这表明小肠严重变窄。这可能是由于炎症，这可以通过药物治疗，或由于慢性纤维化，这需要手术。患者是经验性地使用类固醇治疗，但有许多副作用。如果我们能够确定哪些患者确实有严重的肠道纤维化导致肠道狭窄，那么许多患者将通过手术得到更好的治疗。局部超声弹性成像（UEI）提供了从根本上改善克罗恩病肠道纤维化的诊断和及时管理的潜力。这种方法可以完全表征改变的局部组织弹性特性和局部肠力学。此外，它还具有高空间分辨率，具有出色的灵敏度、特异性、准确性和精密度。肠的力学特性是直接从肠内应变估计，而不是从肠的厚度和/或直径的变化推断。测量过程的直接性质对于炎症性肠病过程中随着纤维化的发展而发生的组织力学变化的局部评估是理想的。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，因为它是基于可以用市售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特性的局部变化。2. UEI测量的肠壁局部力学变化可以预测先前炎症引起的肠道局部纤维化的严重程度和程度。3. 带有斑点跟踪的UEI可用于无创测量啮齿类动物高度局部肠道顺应性变化，并且很容易转化为人类的临床诊断工具。必须研究范围广泛的技术和科学问题，以充分利用所建议的技术的能力。因此，这个应用程序的两个具体目标是：1。观察非侵入性UEI能否区分慢性三硝基苯磺酸灌肠大鼠纤维化结肠和正常结肠的力学特性；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程度。公共卫生相关性：反复的炎症循环经常导致临床显著的肠纤维化和狭窄，20%的患者在诊断3年内需要手术，57%的患者在患病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，这表明小肠严重变窄。这可能是由于炎症，这可以通过药物治疗，或由于慢性纤维化，这需要手术。患者是经验性地使用类固醇治疗，但有许多副作用。如果我们能够确定哪些患者确实有严重的肠道纤维化导致肠道狭窄，那么许多患者将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有明显的肠道纤维化。提出的局部超声弹性成像（UEI）提供了从根本上改善克罗恩病肠道纤维化的诊断和及时管理的潜力。这种方法可以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，因为它是基于超声数据的新处理，可以用市售扫描仪获得。

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.