In vivo endobronchial OCT for IPF diagnosis and therapy response assessment

用于 IPF 诊断和治疗反应评估的体内支气管内 OCT

• 批准号: 10620646
• 负责人: Lida P Hariri
• 金额: $ 78.21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620646
• 关键词: Affect; Anatomy; Biopsy; Blinded; Bronchoscopy; Catheters; Cessation of life; Clinical; Clinical Research; Correlative Study; Data; Databases; Diagnosis; Diagnostic; Disease; Disease Progression; Early Diagnosis; Early treatment; Elements; FDA approved; Fibrosis; Goals; Healthcare; High Resolution Computed Tomography; Histologic; Histology; Hospitalization; Hospitals; Image; Immunosuppression; Individual; Interstitial Lung Diseases; Libraries; Location; Lung; Lung diseases; Maps; Measures; Methods; Microscopic; Microscopy; Monitor; Morbidity - disease rate; Multicenter Studies; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Pathologist; Pathology; Patient-Focused Outcomes; Patients; Peripheral; Persons; Pilot Projects; Prognosis; Pulmonary function tests; Reader; Resolution; Rhode Island; Risk; Sampling; Sensitivity and Specificity; Site; Structure; Structure of parenchyma of lung; Survival Rate; Testing; Thinness; Three-Dimensional Imaging; Time; Tissues; Translating; Treatment Efficacy; Usual Interstitial Pneumonia; Visualization; X-Ray Computed Tomography; accurate diagnosis; adverse event risk; antifibrotic treatment; care burden; effective therapy; efficacy evaluation; feature detection; fibrotic interstitial lung disease; fibrotic lung disease; health care economics; high risk; idiopathic pulmonary fibrosis; imaging modality; improved; in vivo; individual patient; lung volume; minimally invasive; mortality; mortality risk; optimal treatments; prevent; prospective; pulmonary function; socioeconomics; three-dimensional visualization; tool; treatment response

Project Summary Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal form of interstitial lung disease (ILD), affecting 100,000 per year in the US, with a 3-year survival rate of 50% and a large socio-economic healthcare burden. Early, accurate diagnosis is essential to determine treatment, which differs drastically between IPF and other ILDs. Initiating treatment as early as possible is a key strategy to prevent irreversible loss of lung function and maximize patient outcomes. Definitive IPF diagnosis can be made by CT in ~50% of cases when classic imaging features are present, which must include peripheral honeycombing. However, CT is unable to resolve features < 2 mm, including microscopic honeycombing present in ~50% of cases, which includes nearly all cases of early IPF. When CT fails to diagnose IPF, surgical lung biopsy (SLBX) is required to obtain tissue for microscopy, but has high morbidity and mortality risks. Evaluating therapeutic response is also critical for deciding which patients should stay on expensive, poorly-tolerated therapy and which should not. IPF microscopic features are indicators of disease progression, but cannot be assessed over time with either CT or SLBX. Our objective is to meet this critical need by clinically validating endobronchial optical coherence tomography (EB-OCT) for early microscopic IPF diagnosis and therapy response assessment. EB-OCT provides rapid 3D imaging with microscopic resolutions (< 10 μm) well beyond CT capabilities. We have developed thin OCT catheters that can bronchoscopically access the subpleural lung, assessing 100x more lung volume at more distinct sites than SLBX without the associated risks. We have shown in a pilot study of 18 ILD patients that in vivo EB-OCT can detect microscopic honeycombing not visible with CT. Our data suggest that EB-OCT can differentiate IPF from non-IPF ILDs with near perfect accuracy as compared with SLBX. In order to validate this conclusively, we will conduct the proposed studies: In Aim 1, we will use our ex vivo EB-OCT and matched histology database to determine accuracy for IPF diagnosis ex vivo in an independent multi-reader, blinded assessment and validate automated methods to quantify individual IPF microscopic features known to indicate disease progression against histology. In Aim 2, we will translate these findings to a multi-centered prospective clinical study. We will determine the accuracy of EB-OCT for IPF diagnosis in patients with non-diagnostic CT undergoing diagnostic SLBX in an independent multi-reader, blinded assessment. We will then repeat EB-OCT in IPF patients, 6 months later, at the same locations and quantify EB-OCT features at each time point using the automated methods validated in Aim 1. We will compare EB-OCT changes amongst patients on and off therapy and against changes in lung function testing and survival. The accomplishment of these studies will eliminate a major obstacle in IPF by validating EB-OCT as a minimally-invasive, low-risk method for early, accurate diagnosis and assessment of therapy response. This will permit earlier therapy initiation, earlier assessment of efficacy, and increase survival for IPF patients.

项目摘要 特发性肺纤维化（IPF）是一种进行性致命形式的间质性肺疾病（ILD），影响 美国每年100,000，生存率为50％，社会经济保健伯恩（Burnen）的生存率为3年。 早期，准确的诊断对于确定治疗至关重要，这在IPF和其他方面截然不同 ILDS。尽早开始治疗是防止不可逆转的肺功能丧失和 最大化患者的预后。 CT可以在约50％的情况下进行确定的IPF诊断 存在成像功能，其中必须包括外围蜂巢。但是，CT无法解决 <2 mm的特征，包括〜50％的病例中存在的微观蜂窝，其中包括几乎所有 早期IPF病例。当CT无法诊断IPF时，需要手术肺活检（SLBX）才能获得组织 显微镜，但发病率和死亡率很高。评估治疗反应对于 确定哪些患者应保持昂贵，耐受性较差的治疗，哪些不应进行。 IPF 微观特征是疾病进展的指标，但不能随着CT或 Slbx。我们的目的是通过临床验证的支撑式光学来满足这一关键需求 早期微观IPF诊断和治疗反应的相干断层扫描（EB-OCT） 评估。 EB-OCT提供了远远超出CT的微观分辨率（<10μm）的快速3D成像 功能。我们已经开发了薄的OCT导管，可以支气管计进入胸膜下肺， 在没有相关风险的情况下，评估比SLBX更明显的位点的肺部体积多100倍。我们有 在一项针对18名ILD患者的试点研究中显示的，体内EB-OCT可以检测到微观蜂巢不可见 与CT。我们的数据表明，EB-OCT可以将IPF与非IPF ILD区分开，因为 与SLBX相比。为了最终验证这一点，我们将进行拟议的研究：在AIM 1中，我们 将使用我们的离体EB-O-OCT和匹配的组织学数据库来确定IPF诊断的准确性。 在独立的多阅读器，盲目的评估和验证自动化方法中，以量化单个IPF 显微镜特征已知表明针对组织学的疾病进展。在AIM 2中，我们将翻译这些 以多为中心的前瞻性临床研究的发现。我们将确定IPF的EB-OCT的准确性 在独立的多阅读器中接受诊断SLBX的非诊断CT患者的诊断， 盲目评估。然后，我们将在6个月后的同一位置重复IPF患者的EB-OCT 使用AIM 1中验证的自动方法在每个时间点量化EB-OCT的功能。我们将 比较治疗中和关闭治疗患者之间的EB-OCT变化与肺功能测试的变化 和生存。这些研究的实现将通过验证EB-OCT来消除IPF的主要障碍 作为一种最小侵入性的低风险方法，用于早期，准确的诊断和评估治疗反应。 这将允许较早的治疗计划，对效率的早期评估以及IPF患者的生存率提高。

项目成果

Speaking the Same Language: The Fleischner Society Glossary for Thoracic Imaging.

说同样的语言：弗莱施纳学会胸部影像术语表。

• DOI: 10.1148/radiol.240414
• 发表时间: 2024
• 期刊: Radiology
• 影响因子: 19.7
• 作者: Hariri,LidaP;Beasley,MaryBeth;Sholl,LynetteM;Wikenheiser-Brokamp,KathrynA
• 通讯作者: Wikenheiser-Brokamp,KathrynA

2023 American Thoracic Society BEAR Cage Winning Proposal. Endobronchial Optical Coherence Tomography: A Novel Imaging Technique for Early Microscopic Diagnosis and Monitoring of Interstitial Lung Disease.

2023 年美国胸科学会 BEAR Cage 获奖提案。

• DOI: 10.1164/rccm.202310-1869ed
• 发表时间: 2024
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Nandy,Sreyankar

Reply to Kalverda et al.: Endobronchial Optical Coherence Tomography: Shining New Light on Diagnosing Usual Interstitial Pneumonitis?

• DOI: 10.1164/rccm.202112-2737le
• 发表时间: 2022-04-15
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7

Practical application and validation of the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines for the diagnosis of idiopathic pulmonary fibrosis.

• DOI: 10.1186/s12931-021-01670-7
• 发表时间: 2021-04-26
• 期刊: Respiratory research
• 影响因子: 5.8
• 作者: Shih AR;Nitiwarangkul C;Little BP;Roop BW;Nandy S;Szabari MV;Mercaldo N;Mercaldo S;Montesi SB;Muniappan A;Berigei SR;Lynch DA;Sharma A;Hariri LP
• 通讯作者: Hariri LP

Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review.

• DOI: 10.1016/j.chest.2020.09.259
• 发表时间: 2021-01
• 期刊: Chest
• 影响因子: 9.6
• 作者: Hariri LP;North CM;Shih AR;Israel RA;Maley JH;Villalba JA;Vinarsky V;Rubin J;Okin DA;Sclafani A;Alladina JW;Griffith JW;Gillette MA;Raz Y;Richards CJ;Wong AK;Ly A;Hung YP;Chivukula RR;Petri CR;Calhoun TF;Brenner LN;Hibbert KA;Medoff BD;Hardin CC;Stone JR;Mino-Kenudson M
• 通讯作者: Mino-Kenudson M