Low risk in vivo diagnosis of IPF with optical imaging

利用光学成像对 IPF 进行低风险体内诊断

基本信息

批准号：
9088547
负责人：
Lida P Hariri
金额：
$ 17.91万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9088547
关键词：
Address Adverse effects Advisory Committees Biomedical Engineering Biometry Biopsy Blinded Bronchoscopy Budgets Caliber Catheters Cessation of life Chest Chronic Clinical Clinical Management Clinical Medicine Clinical Research Collaborations Complement Data Decision Making Detection Diagnosis Diagnostic Diagnostic Procedure Diagnostic tests Disease Disease Progression Drug Prescriptions Drug usage Educational workshop Elements Engineering Enrollment Environment Evaluation Excision FDA approved Faculty Fibrosis Foundations Goals Guidelines Hamman-Rich syndrome Heterogeneity Histology Hospitalization Image Imagery Interstitial Pneumonia K-Series Research Career Programs Knowledge Laboratories Lead Libraries Lung Lung diseases Malignant neoplasm of lung Medical Imaging Melissa Mentors Mentorship Methods Microscope Microscopic Microscopy Morbidity - disease rate Operative Surgical Procedures Optical Coherence Tomography Optics Pathologist Pathology Patient Care Patients Peripheral Pharmaceutical Preparations Physicians Pilot Projects Pirfenidone Positioning Attribute Postdoctoral Fellow Progression-Free Survivals Pulmonary Fibrosis Research Research Design Research Personnel Research Training Resected Resolution Resources Risk Scientist Sensitivity and Specificity Solid Specialist Specimen Structure of parenchyma of lung Survival Rate Testing Therapeutic Time Tissues Training Translating Translational Research Translations Writing base career career development cost diagnostic accuracy effective therapy experience high risk imaging informatics improved in vivo innovation instructor lung imaging medical schools minimally invasive mortality novel novel therapeutics optical imaging outcome forecast patient oriented pre-clinical public health relevance response responsible research conduct skills tenure track tool

项目摘要

DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF) is a progressive, ultimately fatal form of idiopathic interstitial pneumonitis (IIP), with a 3 year survival rate of 0%. Diagnostic certainty of IPF is critical to patient management and therapeutic decision-making. Two new FDA-approved therapies, pirfenidone and nintedanib, have been shown to slow disease progression in IPF and brought new hope to IPF patients. Due to their high costs, side effects, and documented efficacy only in IPF, pulmonologists only prescribe these drugs to patients with a well- established diagnosis of IPF. Definitive IPF diagnosis can be made by chest CT alone in about half of cases when classic imaging features are present, which must include peripheral honeycombing. When CT does not visualize honeycombing, patients must undergo surgery to resect lung tissue and look for honeycombing microscopically to establish diagnostic certainty of IPF. Unfortunately, surgical lung resection has high risks of associated morbidity and mortality, including provoking further disease progression, and even death. There is a clear clinical need for a low risk method of microscopic IPF diagnosis. In this proposal, we take a hypothesis driven approach to determine whether bronchoscopic optical imaging can serve as a novel, low-risk, non- surgical paradigm for IPF diagnosis without surgery or tissue removal. Optical coherence tomography (OCT) provides rapid 3D visualization of large tissue volumes with microscopic resolutions (< 10 µm, comparable with low-power microscopy) well beyond the capabilities of CT. We have developed ultrathin bronchoscopic OCT catheters and conducted in vivo peripheral lung imaging in patients. We have shown in preliminary studies that endobronchial OCT can detect microscopic honeycombing (< 1 mm diameter) in IPF that is not visible with CT. We hypothesize that minimally invasive bronchoscopic OCT can detect microscopic honeycombing and diagnose IPF with high sensitivity and specificity. In Aim 1, we will develop and validate OCT diagnostic criteria to detect microscopic honeycombing and diagnose IPF. We will create a library of airway- based OCT with matched histology from ex vivo lung specimens from patients with suspected IIP. In Aim 2, we will conduct a pilot clinical study to test the translation of bronchoscopic OCT to identify microscopic honeycombing and diagnose IPF in vivo. If successful, these studies will result in the clinical translation of bronchoscopic OCT imaging as a minimally-invasive method for IPF diagnosis, mitigating the need for surgical diagnostic procedures. This proposal addresses a significant clinical problem in a way not previously achievable, and could lead to major innovations in IPF clinical management and therapeutic decision-making. CANDIDATE Dr. Hariri is an Instructor in Pathology on the tenure track at Harvard Medical School. Her long-term career goal is to become an independent physician-scientist using optical imaging to assess pulmonary disease such as IPF. She has a strong background in optical imaging research through her graduate training as a biomedical engineer and post-doctoral research, and is one of four specialist pulmonary pathologists at MGH. Her prior research experience and clinical knowledge of IIP have optimally positioned her to conduct the proposed studies. Dr. Hariri has spent a significant portion of her research training assessing OCT for disease detection, particularly in lung cancer, in controlled preclinical and ex vivo studies. She is now ready to translate this experience to clinical optical imaging that makes direct impacts on patient care. In order to achieve her long- term career goals, she must obtain further mentoring and experience in the translation of optical imaging to the clinical setting. This proposal will provide her with this essential training, and a solid foundation on which she will build her career as an independent researcher in patient-oriented pulmonary optical imaging. MENTORING ENVIRONMENT AND TRAINING PLAN Dr. Hariri will train in an exceptional environment at MGH with abundant intellectual and collaborative opportunities, and access to all the necessary resources to conduct her research. Her mentors, Drs. Melissa Suter and Andrew Tager, are luminaries in their respective fields of clinical optical imaging and pulmonary fibrosis. Drs. Tager and Suter both have ample mentoring experience, each having mentored 15 post-doctoral trainees, of whom many have obtained K awards or full faculty positions. They have an established mentoring relationship with Dr. Hariri, and ongoing collaborations with one another. They are fully dedicated to supporting Dr. Hariri in this proposal and her transition to independence. In addition, Drs. Brett Bouma and Thomas Colby will serve on Dr. Hariri's research advisory committee and provide further respective expertise in clinical translation of optical imaging and IPF diagnosis. To complement the expertise of her mentors and the proposed research, Dr. Hariri will complete courses in biostatistics, medical imaging informatics, translational research, and clinical study design through Harvard. Through mentorship from Drs. Suter and Tager and workshops/courses held at MGH and Harvard, Dr. Hariri will gain the necessary skills to successfully transition to an independent physician-scientist, including research planning, scientific writing, applying for an R01, laboratory and budget management, responsible conduct of research, and effective mentoring.

描述（由适用提供）：特发性肺纤维化（IPF）是一种进行性的，最终致命的特发性间质性肺炎（IIP），生存率为0％。 IPF的诊断确定性对于患者管理和治疗决策至关重要。已显示两种新的FDA批准疗法Pirfenidone和Nyntedanib已被证明会减慢IPF的疾病进展，并给IPF患者带来了新的希望。由于其高成本，副作用和仅在IPF中有效的有效性，脉冲学家仅向具有公认的IPF诊断的患者开出这些药物。当存在经典成像特征的情况下，大约一半的情况下，可以通过胸部CT进行确定的IPF诊断，这必须包括外围蜂窝。当CT不可视化蜂窝状时，患者必须接受手术才能切除肺组织，并在显微镜下寻找蜂窝状以确定IPF的诊断确定性。不幸的是，手术肺切除率具有相关发病率和死亡率的高风险，包括引起进一步的疾病进展，甚至死亡。明显的临床需要是微观IPF诊断的低风险方法。在此提案中，我们采用假设驱动方法来确定支气管镜光学成像是否可以用作新型，低风险的非手术范式，用于IPF诊断，而无需手术或去除组织。光学相干断层扫描（OCT）可快速3D可视化大型分辨率（<10 µm，与低功率显微镜相当）的大型组织体积，远远超出了CT的能力。我们已经开发了超薄的支气管OCT导管，并在患者的体内进行了体内外周肺成像。我们在初步研究中表明，支气管内OCT可以检测IPF中CT不可见的IPF中的微观蜂窝（<1 mm）。我们假设微创支气管镜OCT可以以高灵敏度和特异性检测微观蜂窝和诊断IPF。在AIM 1中，我们将制定并验证OCT诊断标准，以检测微观蜂窝和诊断IPF。我们将创建一个基于气道的OCT图书馆，该图书馆来自可疑IIP患者的离体肺样本的匹配的组织学库。在AIM 2中，我们将进行一项试验临床研究，以测试支气管镜OCT的翻译，以鉴定体内微观蜂窝和诊断IPF。如果成功，这些研究将导致支气管镜OCT成像作为IPF诊断的最小侵入性方法的临床翻译，从而减轻了对手术诊断程序的需求。该提案以以前未达到的方式解决了一个重大的临床问题，并可能导致IPF临床管理和治疗决策的重大创新。候选人Hariri博士是哈佛医学院任职曲目的病理学讲师。她的长期职业目标是使用光学成像来评估肺部疾病（例如IPF）成为独立的身体科学家。她通过毕业生具有强大的光学成像研究背景。培训是一名生物医学工程师和博士后研究，并且是MGH的四位专业肺病理学家之一。她先前的研究经验和IIP的临床知识最佳地定位了她进行拟议的研究。 Hariri博士在受控的临床前和离体研究中都花费了很大一部分研究培训评估OCT进行疾病检测，特别是在肺癌中。她现在准备将这种经验转化为临床光学成像，从而直接影响患者护理。为了实现她的长期职业目标，她必须在将光学成像转换为临床环境中获得进一步的心理和经验。该建议将为她提供这种基本培训，并扎实的基础，她将在其职业生涯中担任以患者为导向的肺光学成像的独立研究人员。指导环境和培训计划Hariri博士将在MGH的特殊环境中进行培训，并拥有丰富的知识和协作机会，并获得所有必要的资源来进行她的研究。她的导师博士。梅利莎·苏特（Melissa Suter）和安德鲁·塔格（Andrew Tager）是其各自的临床光学成像和肺纤维化领域的亮相。博士。塔格（Tager）和苏特（Suter）都有丰富的心理经验，每个人都有15名博士后学员的心理，其中许多人获得了K奖或完整的教职员工。他们与Hariri博士建立了既定的心理关系，并彼此之间进行了持续的合作。他们完全致力于支持Hariri博士在这项提案中，并过渡到独立。另外，博士。 Brett Bouma和Thomas Colby将在Hariri博士的研究咨询委员会任职，并在光学成像和IPF诊断方面提供进一步的相对专业知识。为了完成她的导师和拟议的研究的专业知识，Hariri博士将通过哈佛完成生物统计学，医学成像信息，翻译研究和临床研究设计课程。通过在MGH和Harvard举行的Suter和Tager博士以及讲习班/课程的指导下，Hariri博士将获得必要的技能，以成功地过渡到独立的身体科学家，包括研究计划，科学写作，申请R01，实验室和预算管理，负责任的研究，研究的行为以及有效的心理。