Development of Novel Ultra-short Echo Time - Magnetic Resonance Fingerprinting for the Assessment of Chronic Lung Disease

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PROJECT SUMMARY / ABSTRACT Chronic lung disease is one of the leading causes of mortality in the U.S. placing a significant burden on the health care system (>$30 billion currently for COPD). Unfortunately, clinical measurements of lung disease lack sensitivity to early regional disease (spirometry), are invasive (bronchoalveolar lavage), or expose patients to high doses of radiation (computed tomography (CT)). Therefore, a new non-invasive way to safely measure regional lung disease is an important tool for the care and investigation of chronic lung disease. Quantitative MRI can provide sensitive measurements of lung disease in a non-invasive fashion without ionizing radiation. For example, MR specific parameters (T1, T2*) and perfusion measurements have been shown to be associated with chronic lung disease and declining pulmonary function. The success in clinical imaging of lung disease has created an opportunity to explore animal models of lung disease with quantitative MRI. One major barrier to application of current clinical techniques to preclinical research is the significantly smaller amount of signal available for quantification in mouse lungs due to the ~1000 fold increase in spatial resolution, low spin density in the lungs, and increased magnetic susceptibility on high-field MRI scanners. Overcoming this decrease in signal relies on high field (>7T) MRI systems, small radiofrequency coils for efficient signal detection, and multiple signal averages to provide accurate quantification. The result is impractically long scan times for in vivo quantification of multiple MRI parameters. Therefore, there are currently no methods able to provide multi-parametric MRI measurements in animal models of lung disease. The MRI research group at CWRU has developed a wholly new platform of imaging techniques termed Magnetic Resonance Fingerprinting (MRF, Nature 2013). In the initial clinical study MRF simultaneously mapped T1, T2, and M0 in a human brain in ~10 seconds. Prior work has recently extended the MRF methodology to high-field preclinical MRI scanners. In this project, the MRF methodology will be expanded by incorporating ultra-short echo time (UTE) strategies to provide simultaneous multi-parametric MRI quantification (T1, T2, M0) in the lungs of mice in ~1 hour. These UTE-MRF assessments will be validated in in vitro phantoms as well as in established mouse models of lung infection and pulmonary fibrosis. A validated method for making quantitative multi-parametric MRI measurements in mouse models of lung disease will create opportunities for additional studies in a variety of mouse models of lung disease as well as rapid clinical translation to studies in patients.