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）是间质性肺病（ILD）的一种进行性、致死性形式， 在美国，每年有10万例，3年生存率为50%，并带来巨大的社会经济医疗负担。 早期、准确的诊断对于确定治疗至关重要，IPF和其他疾病的治疗方法有很大不同。 传染病。尽早开始治疗是预防肺功能不可逆丧失的关键策略， 最大限度地提高患者疗效。当经典的IPF诊断时，约50%的病例可通过CT进行确诊。 存在影像学特征，其必须包括外周蜂窝。但是CT无法分辨 < 2 mm的特征，包括约50%病例中存在的显微镜下蜂窝样改变，其中包括几乎所有 早期IPF病例。当CT未能诊断IPF时，需要进行外科肺活检（SLBX）以获得组织， 显微镜检查，但具有高发病率和死亡率的风险。评估治疗反应也是至关重要的， 决定哪些患者应该继续接受昂贵的、耐受性差的治疗，哪些不应该。IPF 显微镜特征是疾病进展的指标，但不能随着时间的推移进行评估，无论是CT或 SLBX。我们的目标是通过临床验证支气管内光学 相干断层扫描（EB-OCT）用于早期显微镜IPF诊断和治疗反应 考核EB-OCT提供快速的3D成像，显微分辨率（< 10 μm）远远超过CT 能力的我们已经开发了薄的OCT导管，可以通过支气管镜进入胸膜下肺， 与SLBX相比，在更多不同部位评估100倍以上的肺容量，无相关风险。我们有 在18名ILD患者的初步研究中显示，体内EB-OCT可以检测到不可见的显微蜂窝样结构 用CT我们的数据表明，EB-OCT可以以近乎完美的准确度区分IPF和非IPF ILD， 与SLBX相比。为了最终验证这一点，我们将进行拟议的研究：在目标1中，我们 将使用我们的离体EB-OCT和匹配的组织学数据库来确定IPF离体诊断的准确性 在独立的多位阅片人中，进行盲态评估并验证量化个体IPF的自动化方法 组织学上已知表明疾病进展的显微镜特征。在目标2中，我们将翻译这些 一项多中心前瞻性临床研究的结果。我们将确定EB-OCT治疗IPF的准确性 在独立多位阅片师中接受诊断SLBX的非诊断性CT患者的诊断， 盲法评估。然后，我们将在6个月后对IPF患者在相同位置重复EB-OCT， 使用Aim 1中确认的自动化方法量化每个时间点的EB-OCT特征。我们将 比较接受和不接受治疗的患者之间的EB-OCT变化以及肺功能测试的变化 和生存这些研究的完成将通过验证EB-OCT消除IPF的主要障碍 作为一种微创、低风险的方法，用于早期、准确诊断和评估治疗反应。 这将允许更早开始治疗，更早评估疗效，并增加IPF患者的生存期。

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

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