Imaging of Hematologic and Oncologic Disorders

血液和肿瘤疾病的影像学

• 批准号: 10159867
• 负责人: Brian D. Ross
• 金额: $ 83.27万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159867
• 关键词: Air; Award; Biological Markers; Bronchiolitis Obliterans; Cancer Patient; Cessation of life; Chest; Chronic Obstructive Airway Disease; Clinical; Clinical Data; Clinical Management; Data; Data Analyses; Detection; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Funding; Future; Goals; Hematology; Hematopoietic Stem Cell Transplantation; High Dose Chemotherapy; Image; Infection; Institution; Lead; Left; Lung; Lung Transplantation; Lung infections; Magnetic Resonance Imaging; Maps; Methodology; Modality; Morbidity - disease rate; Nature; Outcome; Patients; Perfusion; Pulmonary Emphysema; Quality of life; Research; Research Activity; Research Personnel; Scanning; Structure of parenchyma of lung; Syndrome; Technology; Time; Uncertainty; Viral; Whole-Body Irradiation; Work; X-Ray Computed Tomography; analytical method; base; biomarker development; cancer imaging; cancer survival; clinical care; design; diagnostic biomarker; early detection biomarkers; flexibility; imaging biomarker; medical complication; multidisciplinary; patient population; prospective; public health relevance; pulmonary function; response; small airways disease; tumor

 DESCRIPTION (provided by applicant): Cancer patients requiring hematopoietic stem cell transplantation (HCT) following whole-body irradiation or high dose chemotherapy can acquire severe medical complications which not only reduce quality of life but also increase morbidity. Pulmonary complications may be infectious and noninfectious in nature however, onset and progression of bronchiolitis obliterans syndrome (BOS) is a frightening clinical scenario as destruction of patient lung function can lead to death without lifesaving lung transplantation. Cancer patients in which an early diagnosis of BOS is made can be treated but timely diagnosis is hampered by current clinical criteria which require patients to be free of pulmonary infections (viral, fungal, bacterial). Thus there is a major unmet clinical need for a biomarker that can provide for the early diagnosis of BOS even in the presence of infection. My research activity has been historically focused on early detection of tumor response using diffusion-weighted MRI and voxel-based analytical methods for analysis of oncological images (functional diffusion maps). This research progressed as we were able to extend it to other modalities including perfusion- based MR imaging metrics and more recently to computed tomography (CT). Recently, my lab developed CT methodology termed the Parametric Response Map (PRM) that was capable of simultaneous quantification of normal lung parenchyma, non-emphysematous air trapping (previously invisible to CT scans) that we refer to as functional small airways disease and emphysema for diagnosing chronic obstructive pulmonary disease (COPD) patients. The COPD application was a major clinical breakthrough for the field of thoracic imaging which received FDA clearance in September 2014 by Imbio LLC, a company which licensed the technology from our institution. I am herein proposing to break new ground by extending and leveraging these previous findings to develop a new biomarker for the detection of parenchymal disease in an effort to distinguish pulmonary infections from BOS. My application is focused on a major unmet clinical need with the goal of changing clinical care during the funding of this Award. Our investigative team is highly motivated and passionate for seeing this to successful completion. In a preliminary study, we obtained proof-of-principle results supporting our PRM biomarker approach for early BOS diagnosis. This award will rapidly advance imaging biomarker development for the management of HCT-treated cancer patients. Retrospective data analysis and design of a prospective trial will provide the clinical data required to validate PRM as a clinical BOS diagnostic biomarker. This Award will provide me the flexibility and staffing required to work together with a highly professional team of multidisciplinary investigators to change the current clinical management of this cancer patient population. Data obtained from this Award will be used to support an FDA filing to seek approval of PRM as a biomarker of early BOS diagnosis. I have no doubt that the funding of this Award will directly save the lives of many future HCT-treated cancer patients.

 描述（由申请人提供）：全身照射或高剂量化疗后需要造血干细胞移植（HCT）的癌症患者可能会出现严重的并发症，这不仅会降低生活质量，还会增加发病率。肺部并发症可能是感染性和非感染性的。然而，实际上，闭塞性细支气管炎综合征 (BOS) 的发作和进展是一种令人恐惧的临床情况，因为如果不进行肺移植来挽救生命，患者肺功能的破坏可能会导致死亡。早期诊断为 BOS 的患者可以得到治疗，但当前的临床标准要求患者没有肺部感染（病毒、真菌、细菌），因此及时诊断受到阻碍，因此对生物标志物的临床需求尚未得到满足。即使存在感染，也可以提供 BOS 的早期诊断。我的研究活动历来侧重于使用扩散加权 MRI 和基于体素的分析方法来分析肿瘤图像（功能扩散图）来早期检测肿瘤反应。 .这项研究取得了进展因为我们能够将其扩展到其他模式，包括基于灌注的 MR 成像指标以及最近的计算机断层扫描 (CT)，最近，我的实验室开发了称为参数响应图 (PRM) 的 CT 方法，能够同时量化正常情况。肺实质、非肺气肿性空气滞留（以前 CT 扫描不可见），我们称之为功能性小气道疾病和肺气肿，用于诊断慢性阻塞性肺病COPD 患者的应用是胸部成像领域的一项重大临床突破，该技术于 2014 年 9 月获得 FDA 批准，该公司获得了我们机构的技术许可，我在此建议通过扩展来开辟新的领域。并利用这些先前的发现开发一种新的生物标志物来检测实质疾病，以区分肺部感染和 BOS。我的申请重点是未满足的主要临床需求，目标是在本奖项资助期间改变临床护理。我们的研究团队非常积极和热衷于看到这一成果的成功完成，在一项初步研究中，我们获得了支持我们用于早期 BOS 诊断的 PRM 生物标志物方法的原理验证结果。该奖项将迅速推进用于 HCT 管理的生物标志物成像开发。回顾性数据分析和前瞻性试验设计将提供验证 PRM 作为临床 BOS 诊断生物标志物所需的临床数据。该奖项将为我提供与高度专业的多学科团队合作所需的灵活性和人员配置。调查人员改变该奖项获得的数据将用于支持 FDA 申请批准 PRM 作为早期 BOS 诊断的生物标志物，我毫不怀疑该奖项的资助将直接挽救该癌症患者群体的临床管理。许多未来接受 HCT 治疗的癌症患者的生活。