Imaging of Hematologic and Oncologic Disorders

血液和肿瘤疾病的影像学

• 批准号: 9923442
• 负责人: Brian D. Ross
• 金额: $ 85.32万
• 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/9923442
• 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; Respiratory physiology; 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; 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（由适用提供）：全身照射或高剂量化学疗法后需要造血干细胞移植（HCT）的癌症患者可获得严重的医疗并发症，这不仅降低了生活质量，还可以增加发病率。肺部并发症本质上可能是传染性和非感染性的，但是，闭塞性细支气管炎的发作和进展是一种令人恐惧的临床情况，因为破坏患者肺功能会导致死亡而无需肺部延长肺部移植。可以治疗早期诊断为BOS的癌症患者，但及时的诊断受到当前临床标准的阻碍，该标准要求患者没有肺部感染（病毒，真菌，细菌）。对于生物标志物的主要未满足的临床需求，即使在感染存在下，也可以早期诊断BOS。我的研究活动历史上一直集中在使用扩散加权MRI和基于体素的分析方法的早期检测到肿瘤反应的早期检测，以分析肿瘤学图像（功能扩散图）。这项研究进展了，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CT方法，称为参数响应图（PRM），该方法可以简单地定量正常的肺实质，非异性空气诱捕（以前是CT扫描看不见的），我们称为功能性小型气道疾病，并用来用于诊断性慢性慢性肺部疾病（COPD）患者（COPD）患者。 COPD申请是胸腔成像领域的主要临床突破，该领域于2014年9月获得了FDA批准，Imbio LLC是一家从我们机构获得该技术的公司。我本文提议通过扩展和利用这些先前的发现来开发一种新的生物标志物来检测实质性疾病，以将肺部感染与BOS区分开来，从而破裂新的立场。我的申请专注于重大未满足的临床需求，目的是在此奖项的资助期间改变临床护理。我们的调查团队充满积极性和热情地看到这一成功完成。在一项初步研究中，我们获得了原则证明结果，支持了我们的PRM生物标志物方法，用于早期BOS诊断。该奖项将迅速提高成像生物标志物的开发，以管理经HCT治疗的癌症患者的管理。前瞻性试验的回顾性数据分析和设计将提供验证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研究人员团队一起工作所需的灵活性和人员，以改变该癌症患者人群的当前临床管理。从该奖项获得的数据将用于支持FDA申请，以寻求PRM作为早期BOS诊断的生物标志物的批准。毫无疑问，该奖项的资金将直接挽救许多未来HCT治疗的癌症患者的生命。