An Early Imaging Marker of Emphysema

肺气肿的早期影像学标志

• 批准号: 10412100
• 负责人: Craig J Galban
• 金额: $ 47.45万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-28 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10412100
• 关键词: 3-Dimensional; Air; Airway Disease; Area; Bronchiolitis Obliterans; Cause of Death; Chronic Obstructive Pulmonary Disease; Classification; Clinical; Clinical Trials; Collaborations; Data; Development; Diagnosis; Disease; Disease Progression; Dose; Dyspnea; Engineering; Evaluation; Foundations; Freezing; Funding; Future; Health; Human; Image; Interdisciplinary Study; Lung; Lung Transplantation; Maps; Measures; Methods; Monitor; Morbidity - disease rate; Noise; Outcome; Patient Care; Patients; Pattern; Physicians; Population; Publishing; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Reporting; Sampling; Scanning; Severity of illness; Signal Transduction; Subgroup; Surface; Syndrome; System; Techniques; Testing; Tissues; Transplant Recipients; United States National Institutes of Health; Validation; Work; X-Ray Computed Tomography; alveolar destruction; base; clinically relevant; cohort; density; diagnostic value; disorder subtype; early onset; end stage disease; exercise capacity; imaging biomarker; improved; in vivo; indexing; lung volume; microCT; mortality; novel strategies; post-transplant; precision medicine; predictive marker; pulmonary function; radiologist; reconstruction; response; small airways disease

PROJECT SUMMARY/ ABSTRACT Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the US, with nearly 60 million confirmed cases world-wide. Emphysema and small airways disease (SAD) are two main components of COPD. Emphysema, associated with severe COPD, results in alveolar destruction and is a leading cause of mortality in this population. Considered at the tissue level an end-stage disease, there are limited treatment options once diagnosed. As such, there is a clear unmet clinical need to identify markers that predict the early onset of emphysema. Small airways disease, a treatable component of COPD, has been identified in recent studies as a potential precursor of emphysema. Although promising, clinical techniques were unable to measure SAD hindering its use as a marker. This limitation was overcome through our development of a 3D analytical technique called Parametric Response Mapping (PRM). When applied to computed tomography (CT) scans, PRM identifies non-emphysematous air trapping, an indirect measure of SAD, even in the presence of emphysema. In fact, we have demonstrated that the relative lung volume of PRM-derived functional SAD (%PRMfSAD) predicted spirometric decline in COPD patients, highlighting its potential as an indicator of COPD progression. Nevertheless, %PRMfSAD provides only a whole-lung assessment, limiting its potential at detecting the onset and local progression of emphysema. To fully realize PRMfSAD as a predictor of emphysema, we have advanced our PRM technique by applying topological methods, based on the Minkowski Functionals, to our 3D PRM classification maps. Referred to as topological PRM (tPRM), this method reported in Scientific Reports extracts and quantifies features from 3D PRMfSAD resulting in 3D maps of relative density (V; analogous to %PRMfSAD), surface area (S), mean breadth (B) and Euler-Poincaré statistic (χ). Our preliminary results have shown that tPRMfSAD correlated better to clinical measures than the %PRMfSAD. Based on these findings, we hypothesize that our approach will improve PRM sensitivity to disease progression while providing the spatial information needed to detect the onset of emphysema. We have set out three aims to test our hypothesis. In Aim 1, we will evaluate the sensitivity of our tPRM method to CT signal variability associated with scanner type, CT acquisition and reconstruction kernel, as well as corroborate correlations in tPRM to various clinical measures as previously reported. In Aim 2, we will determine distinctions in tPRM to contributions of emphysema and SAD as measured from microCT analysis of frozen explanted lung cores obtained from lung transplant recipients with end-stage COPD. Finally, in Aim 3, we will correlate longitudinal changes over a 5-yr interval in tPRM to clinically- relevant measures. These aims will be accomplished through support from the NIH-sponsored clinical trial COPDGene and continued multi-center and multi-disciplinary collaborations. Relevance: We anticipate that the successful outcome of this effort will improve the diagnostic capability of CT imaging through the realization of an early marker for the onset of emphysema, leading to improved patient care through precision medicine.

项目摘要/摘要 慢性阻塞性肺疾病（COPD）是美国第三大死亡原因，近60 百万在全球范围内确认案件。肺气肿和小气道疾病（SAD）是两个主要组成部分 COPD。与严重COPD相关的肺气肿会导致肺泡破坏，并且是 该人群的死亡率。在组织一级考虑的末期疾病，治疗有限 诊断后的选项。因此，明显未满足的临床需要识别预测早期的标记 肺气肿的发作。小型气道疾病是COPD的可治疗部分 研究是肺气肿的潜在前体。尽管很有希望，但临床技术无法测量 悲伤阻碍用作标记。通过我们开发3D分析，这种限制是克服的 技术称为参数响应映射（PRM）。当应用于计算机断层扫描（CT）扫描时 PRM识别非熟悉空气诱捕，即使存在的间接度量，即使存在 气肿。实际上，我们已经证明了PRM衍生功能SAD的相对肺体积 （％PRMFSAD）预测COPD患者的肺活量下降，强调了其作为COPD的指标的潜力 进展。但是，％prmfsad仅提供全肺评估，限制了其检测的潜力 肺气肿的发作和局部进展。为了完全实现PRMFSAD作为肺气肿的预测指标，我们有 通过根据Minkowski功能应用拓扑方法来提出PRM技术 PRM分类地图。该方法被称为拓扑PRM（TPRM），在科学报告中报道 提取和量化3D PRMFSAD的特征，导致相对密度的3D图（V；类似于类似 ％prmfsad），表面积，平均广度（b）和Euler-Poincaré统计（χ）。我们的初步结果 表明TPRMFSAD与临床指标的相关性比％PRMFSAD更好。基于这些发现，我们 假设我们的方法将提高PRM对疾病进展的敏感性，同时提供空间 检测肺气肿开始所需的信息。我们已经设定了三个目标来检验我们的假设。在 AIM 1，我们将评估TPRM方法对与扫描仪类型相关的CT信号变异性的敏感性， CT采集和重建内核，以及TPRM中与各种临床测量的证实相关性 如前所述。在AIM 2中，我们将确定TPRM对肺气肿和SAD贡献的区别 从从肺移植受者获得的冷冻外植入的肺核心的Microct分析中测得 末期COPD。最后，在AIM 3中，我们将在TPRM的5年间隔内将纵向变化与临床 - 相关措施。这些目标将通过NIH赞助的临床试验的支持来实现 Copdgene并继续进行多中心和多学科合作。相关性：我们预计 这项工作的成功结果将通过实现CT成像的诊断能力 肺气肿发作的早期标记，通过精确医学改善了患者护理。

项目成果

Implementation and evaluation of ultra-low dose CT in early cystic fibrosis lung disease.

• DOI: 10.1183/13993003.00286-2023
• 发表时间: 2023-07
• 期刊: EUROPEAN RESPIRATORY JOURNAL
• 影响因子: 24.3
• 作者: Bayfield, Katie J.;Weinheimer, Oliver;Boyton, Christie;Fitzpatrick, Rachel;Middleton, Anna;Kennedy, Brendan;Blaxland, Anneliese;Jayasuriya, Geshani;Caplain, Neil;Issa, Hana;Goetti, Robert;Wielpuetz, Mark O.;Yu, Lifeng;Galban, Craig J.;Robinson, Terry E.;Bartholmai, Brian;Fitzgerald, Dominic;Selvadurai, Hiran;Robinson, Paul D.
• 通讯作者: Robinson, Paul D.

Assessing small airways dysfunction in asthma, asthma remission and healthy controls using particles in exhaled air.

使用呼出空气中的颗粒评估哮喘中的小气道功能障碍、哮喘缓解和健康控制。

• DOI: 10.1183/23120541.00202-2019
• 发表时间: 2019
• 期刊: ERJ open research
• 影响因子: 4.6
• 作者: Carpaij,OrestesA;Muiser,Susan;Bell,AlexJ;Kerstjens,HuibAM;Galban,CraigJ;Fortuna,AleksaB;Siddiqui,Salman;Olin,Anna-Carin;Nawijn,MartijnC;vandenBerge,Maarten
• 通讯作者: vandenBerge,Maarten

Investigating the Incidence of Pulmonary Abnormalities as Identified by Parametric Response Mapping in Patients With Lung Cancer Before Radiation Treatment.

• DOI: 10.1016/j.adro.2022.100980
• 发表时间: 2022-07
• 期刊: ADVANCES IN RADIATION ONCOLOGY
• 影响因子: 2.3
• 作者: Owen, Daniel R;Sun, Yilun;Irrer, Jim C;Schipper, Matthew J;Schonewolf, Caitlin A;Galban, Stefanie;Jolly, Shruti;Haken, Randall K Ten;Galban, C J;Matuszak, M M
• 通讯作者: Matuszak, M M

An assessment of the correlation between robust CT-derived ventilation and pulmonary function test in a cohort with no respiratory symptoms.

在无呼吸道症状的队列中评估稳健 CT 衍生通气与肺功能测试之间的相关性。

• DOI: 10.1259/bjr.20201218
• 发表时间: 2021
• 期刊: The British journal of radiology
• 作者: Nair,GirishB;Galban,CraigJ;Al-Katib,Sayf;Podolsky,Robert;vandenBerge,Maarten;Stevens,Craig;Castillo,Edward
• 通讯作者: Castillo,Edward

MDCT-based longitudinal automated airway and air trapping analysis in school-age children with mild cystic fibrosis lung disease.

• DOI: 10.3389/fped.2023.1068103
• 发表时间: 2023
• 期刊: Frontiers in pediatrics
• 影响因子: 2.6
• 作者: Weinheimer O;Konietzke P;Wagner WL;Weber D;Newman B;Galbán CJ;Kauczor HU;Mall MA;Robinson TE;Wielpütz MO
• 通讯作者: Wielpütz MO