Next-generation ultrafast functional 3D pulmonary imaging

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PROJECT SUMMARY Deadly diseases such as COPD, asthma, lung injury, constrictive bronchiolitis, and pulmonary fibrosis affect >300 million people worldwide and cause ~3 million annual deaths. There is currently no widespread clinical imaging modality to perform high-resolution functional lung imaging: CT, conventional MRI, and X-ray can only provide structural images of dense tissues—informing about pathologies like tumors and pneumonia—but yielding little or no information about lung ventilation, perfusion, alveoli size, etc. This state of affairs contrasts with cancer imaging, which includes MRI, CT, ultrasound, mammography, PET and others, which collectively enable early detection (via population screening), diagnoses, and monitoring response to treatment. Furthermore, CT scans expose the body to ionizing radiation, and thus cannot be performed frequently due to increased risk associated with cancer-inducing radiation. MRI of hyperpolarized noble gases (e.g. 129Xe) reports on lung function: ventilation and diffusion. Despite remarkable research breakthroughs in this field demonstrating the effectiveness and safety of hyperpolarized noble gas MRI to detect a wide range of lung diseases and monitor response to treatment, the prospects for widespread clinical adaptation of this imaging modality face major challenges, including (i) the high cost and complexity of the equipment for production of hyperpolarized 129Xe gas, and (ii) the requirement for a customized MRI scanner capable of 129Xe – note, all FDA-approved MRI scanners can image only protons. We have developed clinical-scale production of proton-hyperpolarized propane gas. The process of hyperpolarized propane gas production is remarkably simple, highly efficient and low-cost. A dose of contrast agents can be prepared in 2 seconds using disposable hyperpolarizer. Moreover, propane is already FDA-approved for unlimited safe use in foods. Therefore, hyperpolarized propane lung MRI can obviate the challenges of hyperpolarized 129Xe gas. Under this training award, I will be trained to develop next-generation 3D ultra-fast lung imaging capability using three spin isomers of hyperpolarized propane gas. I hypothesize that it may be possible to create highly symmetric hyperpolarized propane spin isomer capable of retaining hyperpolarized state for ~1 minute in the gas phase at clinically relevant conditions. Sub-second 3D MRI of these spin isomers can produce background-free functional lung images of gas diffusion and ventilation. In this project, I will develop clinical-scale production of these spin isomers and their ultrafast MRI in excised sheep lungs with the goal of systematic relaxation mapping for future in vivo studies. The clinical translation of this new fast and low-cost imaging modality will revolutionize pulmonary imaging and pulmonary care of a wide range of lung diseases—this is my long-term career goal.