Imaging of Hematologic and Oncologic Disorders

 描述(申请人提供)：癌症患者在全身放疗或大剂量化疗后需要进行造血干细胞移植(HCT)，可能会获得严重的医疗并发症，不仅降低生活质量，还会增加发病率。肺部并发症可能是传染性和非传染性的，然而，闭塞性毛细支气管炎综合征(BOS)的发生和发展是一个可怕的临床情景，因为如果不进行挽救生命的肺移植，患者的肺功能破坏可能会导致死亡。早期诊断为BOS的癌症患者是可以治疗的，但由于目前的临床标准要求患者没有肺部感染(病毒、真菌、细菌)，及时诊断受到了阻碍。因此，即使在存在感染的情况下，也需要一种能够提供BOS早期诊断的生物标记物，这是临床上尚未满足的主要需求。我的研究活动历来专注于使用扩散加权磁共振成像和基于体素的分析方法分析肿瘤图像(功能扩散图)来早期检测肿瘤反应。这项研究的进展是因为我们能够将其扩展到其他方式，包括基于灌注的MR成像度量，以及最近的计算机断层扫描(CT)。最近，我的实验室开发了一种名为参数响应图(PRM)的CT方法，它能够同时量化正常肺实质、非肺气肿空气滞留(以前CT扫描看不见)，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疾病(COPD)患者。COPD的应用是胸部成像领域的一项重大临床突破，该领域于2014年9月获得了IMBIO LLC的批准，该公司从我们机构获得了该技术的许可。在此，我建议通过扩展和利用这些先前的发现来开辟新的领域，开发一种新的生物标记物来检测实质性疾病，努力将肺部感染与BOS区分开来。我的申请集中在一个主要的未得到满足的临床需求上，目的是在该奖项的资助期间改变临床护理。我们的调查团队非常有动力和热情，希望看到这一成功完成。在初步研究中，我们获得了支持我们的PRM生物标记物方法用于早期BOS诊断的原则证明结果。这一奖项将迅速推进用于HCT治疗的癌症患者管理的成像生物标记物的开发。前瞻性试验的回溯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。这一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调查团队合作，改变目前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提交的申请，以寻求批准PRM作为早期BOS诊断的生物标记物。我毫不怀疑，该奖项的资助将直接拯救许多未来接受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.