A lung scan that uses inhaled xenon gas instead of X-rays is revealing hidden damage in people with Long-COVID who struggle to catch their breath after even mild exertion. Many non-hospitalised patients with Post-COVID syndrome suffer from persistent shortness of breath despite having normal CT scans and standard lung function tests. This suggests that current imaging tools are missing the underlying problem. The EXPLAIN study will test whether hyperpolarised xenon MRI—a technique that tracks how gas moves from the lungs into the bloodstream—can detect damage to the alveolar membrane and pulmonary blood vessels that standard scans cannot see. If the technique proves effective, it could provide a reliable diagnostic test for a large group of Long-COVID patients who currently have no clear explanation for their symptoms. This would allow clinicians to distinguish lung damage from other causes of breathlessness, such as deconditioning or anxiety, and guide appropriate treatment. The research also aims to develop an AI algorithm that could help standard CT scans detect these same abnormalities, making the diagnostic tool more widely available without requiring specialised MRI equipment.
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We will examine the hypothesis that in a proportion of non-hospitalised patients with Post-COVID-19 syndrome (NHLC) and a normal CT scan, persistent exertional dyspnoea results from damage to the alveolar membrane/pulmonary vasculature identifiable by hyperpolarised Xenon MRI, including a perfusion MRI scan (HPX-pMRI). Using this technique we have demonstrated the presence of persistent abnormalities in dyspneoic post-hospitalised COVID-19 patients and in two NHLC patients. The work programme consists of: Recruiting 200 NHLC patients from dedicated Post-COVID clinics in Oxford/Sheffield with documented exertional dyspnoea without an identifiable cause on CT Recruiting 50 NHLC patients from the Post-COVID clinic who do not have symptoms of exertional dyspnoea. Recruiting 50 non-hospitalised patients with prior proven SARS-CoV-2 infection without symptoms of Long-COVID. Performing low dose CT (if not already performed) and HPX-pMRI on these patients Performing Lung function and exercise tests and validated questionnaires in study participants Taking a blood sample for future analysis A subset of each cohort will have combined HPX-pMRI and cardiac MRI We will: Test the hypothesis that exertional dyspnoea in NHLC is contributed by alveolar diffusion/perfusion defects detected on HPX-pMRI imaging, and assess the duration of the abnormalities detected Characterise and quantify the alveolar perfusion/diffusion abnormality caused by SARS-CoV-2 infection using HPX-pMRI Determine the specificity of the findings by comparing the imaging data in the three study cohorts, and to two already ongoing HPX-pMRI studies using the same scan protocols - 50 post-hospitalised patients in the C-MORE-POST study and to the NIHR funded Post COVID UK-ILD study. Determine whether a positive/negative HPX-pMRI is associated with an abnormal cardiac MRI Dependent upon whether HPX-pMRI differentiates these groups: develop a CT AI algorithm to improve detection of abnormalities on CT by mapping CT to the ground truth HPX-pMRI data, and perform immune profiling on the stored blood samples.
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