Dual Energy CT Evaluation of Airway Inflammation

描述(由申请人提供)：这项建议的目的是通过使用双能量计算机断层扫描(DECT)直接测量碘化对比剂注射后支气管壁的增强，提供一种独特的、定量的、功能性的呼吸道炎症生物标志物。我们假设的关键是一个公认的事实，即炎症导致支气管动脉充血，以前需要有创血管造影术或很少使用的复杂实验室技术。大量的后天和遗传性疾病都会导致慢性呼吸道炎症，对这些疾病的诊断和治疗是临床上重要而常见的挑战。尽管高分辨率CT在建立和监测这些疾病方面发挥了重要作用，但迄今为止，CT解释完全依赖于形态学评估，而且往往是主观的。我们提出了一种新的诊断范式，强调对呼吸道炎症程度和严重程度的定量、功能性评估，最终目的是将这种方法应用于各种呼吸道炎症原因--对准确评估常规治疗以及为潜在的新治疗方法提供重要的生物标志物具有重要意义。这一提议的真正创新方面是使用了最近推出的双能量CT扫描仪，现在可以同时采集两个不同能级的CT数据，从而可以根据材料的独特化学成分进行区分。这包括单独绘制组织内碘分布的特殊能力，从而定量测量节段和亚段气道壁的对比度增强。为了验证我们的假设，我们建议研究记录在案的霉菌复合体(MAC)肺部疾病患者，作为与慢性呼吸道炎症相关的条件的APT模型。MAC越来越普遍，并与相当大的发病率和死亡率有关。虽然诊断标准已经明确，但治疗的适应症仍然存在很大争议，需要延长3-4个药物方案，导致许多副作用。最后，管理治疗的指导方针已被证明是特别有问题的，缺乏具体和可靠的定量和功能标记。具体地说，在这项研究中，我们建议评估总共60名MAC患者，其中30人需要治疗，用连续的DECT来代替常规获得的后续CT检查，目的是证明DECT为患有慢性呼吸道炎症的患者提供一种新的生物标记物的潜力。 公共卫生相关性：本研究的目的是评估我们开发的一种新的创新方法，该方法使用双能量计算机断层扫描(DECT)通过评估气道壁血管的变化来评估以慢性气道炎为特征的疾病的患者，从而提供一个定量的、功能性的疾病生物标志物。为了验证我们的方法，我们打算研究由分枝杆菌禽类复合体(MAC)引起的感染患者，将其作为一种日益常见的疾病的特别合适的代表，事实证明，这种疾病已被证明特别难以诊断和治疗，期望使用一种量化的、功能性的方法来评估疾病的范围和活动将对这一重要患者的日常管理产生深远的影响。进一步预计，同样的技术将被证明对几乎所有其他与慢性气道炎相关的疾病都有价值，从而为使用计算机断层扫描评估呼吸道提供了一个新的范例。

DESCRIPTION (provided by applicant): The purpose of this proposal is to provide a unique, quantitative, functional biomarker of airway inflammation by directly measuring bronchial wall enhancement following iodinated contrast administration using dual-energy computed tomography (DECT). Key to our hypothesis is the well established fact that inflammation leads to bronchial arterial hyperemia previously requiring either invasive angiography or sophisticated laboratory techniques rarely utilized. A large number of diseases, both acquired and inherited, result in chronic airway inflammation, conditions for which diagnosis and especially management represent important and common clinical challenges. Although high resolution CT plays an important role in establishing and monitoring these diseases, to date, CT interpretation has exclusively relied on morphologic assessment and is often subjective. We propose a new diagnostic paradigm by emphasizing quantitative, functional assessment of the extent and severity of airway inflammation with the ultimate aim of applying this approach to a wide range of causes of airway inflammation - with important implications for accurately assessing both routine treatment as well as importantly providing a biomarker for potential new therapeutic approaches . The truly innovative aspect of this proposal is the use of recently introduced dual energy CT scanners that now enable the simultaneous acquisition of CT data at two different energy levels allowing differentiation of materials by their unique chemical composition. This includes the specific ability to separately map the distribution of iodine within tissues, and hence quantitatively measure contrast enhancement within segmental and subsegmental airway walls. To validate our hypothesis, we propose to study patients with documented Mycobarterial avium complex (MAC) lung disease as an apt model of conditions associated with chronic airway inflammation. MAC is increasingly prevalent and is associated with considerable morbidity and mortality. While criteria for diagnosis are well defined, indications for treatment remain highly controversial, requiring a prolonged 3-4 drug regimen causing numerous side-effects. Finally, guidelines for managing therapy have proved especially problematic, lacking specific and reliable quantitative, functional markers. For this study, specifically, we propose to evaluate a total of 60 patients with MAC, 30 of whom will require therapy, with sequential DECT's obtained in place of routinely acquired follow-up CT exams, with the intent to document the potential of DECT to provide a novel biomarker in patients with conditions causing chronic airway inflammation. PUBLIC HEALTH RELEVANCE: The purpose of this study is to evaluate a new, innovative method that we have developed employing dual energy computed tomography (DECT) to evaluate patients with diseases characterized by chronic airway inflammation by assessing changes in airway wall vascularity, thereby providing a quantitative, functional biomarker of disease. To validate our approach we intend to study patients with infections due to Mycobacterial avium complex (MAC) as a particularly apt representative of an increasingly common disease that has proved especially difficult to diagnose and especially treat, with the expectation that use of a quantitative, functional method for assessing disease extent and activity will have a profound impact on daily management of this important group of patients. It is further anticipated that this same technique will prove of value for virtually all other diseases associated with chronic airway inflammation, hence providing a new paradigm for the use of computed tomography to evaluate the airways.