R01HL153606

Pet-MR Imaging of Pulmonary Fibrosis - Project Summary/Abstract

The goal of this project is to use quantitative PET-MR imaging of the lung to accurately quantify molecular abnormalities associated with pulmonary fibrosis, to predict disease progression, and to provide an early indication of whether anti-fibrotic therapy is likely to be effective.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a median survival of less than 4 years from the time of diagnosis. The treatment options remain limited due to highly variable clinical course and poorly understood pathogenic mechanisms.

Current strategies to diagnose and monitor IPF include lung biopsy, pulmonary function tests that measure global lung function, and anatomic imaging tools such as high-resolution computed tomography (HRCT). Yet these methods are limited in their ability to detect disease early, determine disease activity at any one measure, or monitor the therapeutic response.

Molecular imaging may be an alternative approach that is more sensitive to detect early fibrosis and potentially capable of distinguishing new, active fibrosis from stable disease – urgent and unmet clinical needs.

Our group recently developed a type I collagen-specific positron emission tomography (PET) probe, 68GA-CBP8, which was shown in animal models to detect pulmonary fibrosis at an early stage and was capable of monitoring treatment response. Preliminary data with this probe in healthy volunteers and IPF patients demonstrated that 68GA-CBP8 had significantly higher uptake in IPF lungs than in normal lungs. This data also showed that in addition to probe uptake in regions of lung with fibrosis as established by HRCT, there were additional areas of probe uptake in radiographically "normal" lung suggesting that the probe may be sensitive to lower levels of fibrosis than HRCT and/or sensitive to disease activity, i.e. newly formed collagen.

Magnetic resonance imaging (MRI) on the other hand can provide multiple readouts of morphology, physiology, and function. Preliminary data from our lab using dynamic contrast-enhanced MRI (DCE-MRI) in healthy controls and IPF subjects indicated that DCE parameters can distinguish abnormal from normal lung, and that these measures may predict disease progression.

Quantitative MRI-PET in lung has been historically limited because of low proton density and the fast signal decay due to susceptibility artifacts at air-tissue interfaces for MRI, while PET quantification remains challenging due to respiratory motion, photon attenuation, and regional variations in tissue, air, and blood fractions. However, combining the two modalities holds great potential to overcome some of these limitations.

Our central hypothesis is that non-invasive molecular imaging of collagen accumulation will allow us to capture the extent of ongoing lung injury in IPF patients and that a bi-modal imaging approach using collagen-targeted PET augmented by DCE-MRI will enable more accurate detection of disease activity and treatment response.

The General Hospital Corporation

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Charlestown, Massachusetts 02129 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 392% from $829,704 to $4,079,636.