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.
Cancer patients requiring hematopoietic stem cell transplantation have significant morbidity due to pulmonary complications which include bronchiolitis obliterans syndrome (BOS). Early diagnosis is critical in order to effectively treat these patients as left uncheck, the patients lungs will be destroyed requiring lifesaving lung transplantation. This project will develop a robust and sensitive CT imaging biomarker capable of early detection of BOS even in the presence of other complications included pulmonary infections. The successful outcome will be a major advance in the clinical management and survival of this cancer patient population.
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