Imaging of Hematologic and Oncologic Disorders

血液和肿瘤疾病的影像学

• 批准号: 10398131
• 负责人: Brian D. Ross
• 金额: $ 79.28万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10398131
• 关键词: Air; Award; Biological Markers; Bronchiolitis Obliterans; Cancer Patient; Cessation of life; Chest; Chronic Obstructive Pulmonary 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.

项目成果

Ocular Toxicity Profile of ST-162 and ST-168 as Novel Bifunctional MEK/PI3K Inhibitors.

ST-162 和 ST-168 作为新型双功能 MEK/PI3K 抑制剂的眼部毒性特征。

• DOI: 10.1089/jop.2017.0126
• 发表时间: 2018
• 期刊: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
• 作者: Smith,Andrew;Pawar,Mercy;VanDort,MarcianE;Galbán,Stefanie;Welton,AmandaR;Thurber,GregM;Ross,BrianD;Besirli,CagriG
• 通讯作者: Besirli,CagriG

Potential for Early Fracture Risk Assessment in Patients with Metastatic Bone Disease using Parametric Response Mapping of CT Images.

• DOI: 10.18383/j.tom.2015.00154
• 发表时间: 2015-12
• 期刊: Tomography (Ann Arbor, Mich.)
• 作者: Hoff BA;Toole M;Yablon C;Ross BD;Luker GD;VanPoznak C;Galbán CJ
• 通讯作者: Galbán CJ

Vascular Deformation Mapping (VDM) of Thoracic Aortic Enlargement in Aneurysmal Disease and Dissection.

• DOI: 10.18383/j.tom.2017.00015
• 发表时间: 2017-09
• 期刊: Tomography (Ann Arbor, Mich.)
• 作者: Burris NS;Hoff BA;Kazerooni EA;Ross BD
• 通讯作者: Ross BD

Discovery of Bifunctional Oncogenic Target Inhibitors against Allosteric Mitogen-Activated Protein Kinase (MEK1) and Phosphatidylinositol 3-Kinase (PI3K).

• DOI: 10.1021/acs.jmedchem.5b01655
• 发表时间: 2016-03-24
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: Van Dort ME;Hong H;Wang H;Nino CA;Lombardi RL;Blanks AE;Galbán S;Ross BD
• 通讯作者: Ross BD

Parametric Response Mapping of FLAIR MRI Provides an Early Indication of Progression Risk in Glioblastoma.

• DOI: 10.1016/j.acra.2020.08.015
• 发表时间: 2021-12
• 期刊: Academic radiology
• 影响因子: 4.8
• 作者: Hoff BA;Lemasson B;Chenevert TL;Luker GD;Tsien CI;Amouzandeh G;Johnson TD;Ross BD
• 通讯作者: Ross BD