Novel Approaches for Hyperpolarized Xenon-129 Magnetic Resonance Imaging

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Hyperpolarized xenon-129 Magnetic Resonance Imaging (MRI) provides the ability to non-invasively and repeatedly measure regional changes in lung microanatomy and function associated with pulmonary diseases. Xenon-129 MRI has been shown to be useful for early detection and diagnosis of chronic obstructive pulmonary disease, asthma and lung injury, all representing a significant health-care burden to Canadians. Furthermore, we have shown in rodents that unique functional measures of ventilation, exchange and blood flow (i.e. perfusion) are possible using the dynamics of the different signals arising from xenon-129 dissolved in lung tissues and red blood cells compared to the gas phase within the lung. Despite these very exciting pre-clinical results, xenon-129 MRI in humans remains challenging, mainly due to the limited signal available for 3D imaging using a single breath-hold, especially for the dissolved phases which are complicated by the effects of transverse relaxation, airway geometry (eg. branching) and exchange between the gas and dissolved phases.The objectives of the proposed research are: (i) to develop novel MRI hardware and software to improve the efficiency of xenon-129 image acquisition, (ii) to develop computational models to describe the effects of relaxation, diffusion and exchange on the xenon-129 signal in realistic lung geometries and (iii) to measure relevant xenon-129 biomarkers in rodent and human lungs including: ADC, ventilation, perfusion and gas exchange. The proposed research will take place in the Imaging Research Laboratories of the Robarts Research Institute of Western University. MRI software and hardware will initially be tested using a custom-built, low-field, animal imaging system developed with previous NSERC Discovery funding and then be translated to animal and human protocols on a clinical MRI platform (3 T). Development of the novel hyperpolarized xenon-129 MRI methods described in this proposal will provide significant opportunities for training, knowledge generation, both basic and applied as well as translation to the healthcare setting.