Hyperpolarized 129Xe MRI: Development of hardware, software and its PET-based validation.

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Non-invasive in-vivo inhaled hyperpolarized 129Xe MRI was proven to be useful for visualizing of the ventilated lung regions, obtaining regional information about the lung alveolar sizes, observing the oxygen-like exchange between a xenon "dissolved" in the lung tissue and red blood cells and also imaging of the brain blood supply on the xenon frequency. However, even after 20 years of developing hyperpolarized 129Xe MRI, the fundamental limitations specific to this imaging modality remain unresolvable. A good example of such limitation is the low signal-to-noise ratio (SNR) of 129Xe images, which impedes the development of many novel acquisition schemes that are highly sensitive to the SNR, such as isotropic voxel static ventilation imaging, accelerated multiple b-value diffusion-weighting MRI, accelerated simultaneous collection of 129Xe gas and 129Xe within lung tissue and blood, 129Xe brain perfusion imaging, and 129Xe biosensor imaging. There are three main reasons for low SNR of 129Xe images: the inefficient image acquisition methods that currently exist, due to the limited image acquisition time combined with non-optimal image reconstruction algorithms; low-sensitivity of the MRI transmit/receive coils; and the low level of 129Xe hyperpolarization in combination with the small volume production. By utilizing fundamental MRI principles, the proposed research program will solve decades of unresolved 129Xe MRI problems. This is unique for Canada and fully reflects my progress in the 129Xe MRI field. My extensive expertise, built over the last two decades, in developing acquisition methods along with my experience in building advanced hardware will allow my research team to overcome the current technological challenges in the field. This research plan is an excellent platform to develop, test and validate novel 129Xe MRI imaging methods and compare them to the gold standard perfusion imaging modality (PET). The feasibility of such measurements has been demonstrated by my research group in a single experiment in 2019. The success of this program will demonstrate the usefulness of lung and brain 129Xe MRI imaging to 129Xe researchers (6 sites in Canada and many abroad), industry (MRI hardware makers) and clinicians. Why does this matter now, more than ever? 129Xe lung MRI is extremely powerful and it is the only radiation free imaging tool for lung structure & function measurements, whose urgent need has emerged because of the damage Covid-19 does to the lung, requiring intensive research and development now and in the future. The proposed program will provide new tools for accurate lung damage assessment, therapy guidance, and treatment outcome evaluation. Furthermore, this research plan provides training for HQP in the fields of medical imaging, MRI pulse sequence development and hardware engineering, Deep Learning, quantum and thermodynamic modelling.