Dual Energy CT Evaluation of Airway Inflammation

描述（由申请人提供）：本提案的目的是通过使用双能计算机断层扫描（DECT）直接测量碘造影剂给药后支气管壁增强，提供一种独特的、定量的、功能性的气道炎症生物标志物。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，以前需要侵入性血管造影或复杂的实验室技术，很少使用。大量的疾病，无论是获得性的还是遗传性的，都会导致慢性气道炎症，对于这些疾病的诊断，尤其是治疗，都是重要而共同的临床挑战。尽管高分辨率CT在诊断和监测这些疾病方面发挥着重要作用，但迄今为止，CT诊断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，通过强调气道炎症程度和严重程度的定量，功能评估，最终目的是将这种方法应用于气道炎症的广泛原因-具有准确评估常规治疗的重要意义，以及重要的是为潜在的新治疗方法提供生物标志物。这项建议的真正创新之处在于使用了最近推出的双能CT扫描仪，现在可以同时获取两个不同能级的CT数据，从而通过其独特的化学成分来区分材料。这包括单独绘制组织内碘分布的特定能力，从而定量测量段和亚段气道壁内的造影剂增强。为了验证我们的假设，我们建议研究有禽分枝杆菌复合体（MAC）肺部疾病的患者，将其作为慢性气道炎症相关疾病的合适模型。MAC越来越普遍，并与相当高的发病率和死亡率有关。虽然诊断标准明确，但治疗指征仍然存在很大争议，需要长时间的3-4药物治疗方案，造成许多副作用。最后，管理治疗的指南被证明是特别有问题的，缺乏具体和可靠的定量，功能标记。在这项研究中，我们建议评估总共60例MAC患者，其中30例需要治疗，通过连续的DECT来代替常规的随访CT检查，目的是记录DECT在慢性气道炎症患者中提供新的生物标志物的潜力。

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.