Imaging of Hematologic and Oncologic Disorders

 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医学并发症，不仅降低生活质量，还增加发病率。肺部并发症可能是感染性和非感染性的，然而，闭塞性细支气管炎综合征（BOS）的发作和进展是一个可怕的临床情况，因为患者肺功能的破坏可能导致死亡，而无需救生肺移植。早期诊断为BOS的癌症患者可以接受治疗，但由于目前的临床标准要求患者无肺部感染（病毒、真菌、细菌），因此无法及时诊断。因此，即使在存在感染的情况下也可以提供BOS的早期诊断的生物标志物存在重大的未满足的临床需求。我的研究活动历来集中在早期检测肿瘤反应使用扩散加权MRI和基于体素的分析方法分析肿瘤图像（功能扩散图）。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，最近还扩展到计算机断层扫描（CT）。最近，我的实验室开发了称为参数响应图（PRM）的CT方法，该方法能够同时定量正常肺实质、非气肿性空气滞留（以前CT扫描不可见），我们将其称为功能性小气道疾病和肺气肿，用于诊断慢性阻塞性肺疾病（COPD）患者。COPD应用是胸部成像领域的一项重大临床突破，于2014年9月获得FDA批准，由Imbio LLC（一家从我们机构获得该技术许可的公司）批准。我在此建议通过扩展和利用这些先前的发现来开发一种新的用于检测实质疾病的生物标志物，以区分肺部感染和BOS。我的申请集中在一个主要的未满足的临床需求，其目标是在该奖项的资助期间改变临床护理。我们的调查团队是高度积极性和热情，看到这一成功完成。在一项初步研究中，我们获得了支持我们的PRM生物标志物方法用于早期BOS诊断的原理验证结果。该奖项将迅速推进用于HCT治疗癌症患者管理的成像生物标志物开发。回顾性数据分析和前瞻性试验的设计将提供验证PRM作为临床BOS诊断生物标志物所需的临床数据。该奖项将为我提供所需的灵活性和人员配备，与高度专业的多学科研究人员团队合作，以改变目前对癌症患者群体的临床管理。从该奖项获得的数据将用于支持FDA申请，以寻求批准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许多未来接受HCT治疗的癌症患者的生命。

 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.