Prediction and assessment of COPD lung volume reduction outcomes with polarized MRI

University Of Pennsylvania, Philadelphia PA

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Abstract

? DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is an increasingly urgent public health concern on both the national and global levels. Not only is the disorder a major cause of mortality, but the dyspnea, reduced capacity for physical exertion, and periodic exacerbations that it causes result in tremendous disability and cost. Treatment options for established COPD remain limited in number, diversity, and effectiveness. However, in recent years, significant innovation has been accomplished in the field of lung volume reduction (LVR), which seeks to enhance global lung function through the removal, occlusion, or obliteration of hyperinflated, emphysematous regions. While LVR has traditionally been implemented through surgical resection, the development of less invasive bronchoscopic techniques (BLVR) is ongoing and represents an extremely promising arena of COPD therapy. This application proposes to develop a hyperpolarized 129Xe magnetic resonance imaging (HP 129Xe MRI) approach for planning BLVR intervention and assessing its pulmonary effects. The core problem faced by all LVR approaches is that they have demonstrated highly variable outcomes; it consequently remains unclear exactly what types of patient will benefit most from this therapy and why. Clinicians currently base their decisions of whether to carry out LVR and which regions to target using high-resolution computed tomography (HRCT) to measure the extent of emphysema and its distribution. While HRCT is highly capable of accurately assessing these features, it does not provide the functional information necessary to gain a comprehensive understanding of an individual patient's regional pulmonary status. We thus posit that the incorporation of functional parameters obtained with HP 129Xe MRI will allow for more informed decision-making in regards to which patients should undergo LVR and how the procedure should be tailored according to the lung health of the particular patient. In applying HP 129Xe MRI to this medical area of need, a corollary goal will be achieved: the refinement of this hyperpolarized technique such that it can extract pulmonary information with the sensitivity of the more well-established HP 3He MRI approach. 3He has become drastically more expensive in recent years due to its scarcity, and the hyperpolarized community recognizes that a shift to the much less expensive and more easily obtainable 129Xe is necessary to ensure the translational applicability of this important technology. We seek here to use Xe to derive three lung parameters-specific ventilation (SV), alveolar oxygen tension (pAO2), 129 and apparent diffusion coefficient (ADC)-with approximately the same sensitivity and efficiency that we have previously attained using 3He. This development will enhance the clinical future of hyperpolarized MRI not only in the area of LVR, but also in the non-invasive assessment of COPD and lung diseases more broadly.