Neuroimaging insights into lung disease-related brain changes: from structure to function

Lung diseases induce changes in brain structure and function, leading to a range of cognitive, emotional, and motor deficits. The concept of the lung-brain axis has been proposed through neuroanatomy, endocrine, and immune pathway, while a considerable number of studies also explored the existence of the lung-brain axis from a neuroimaging perspective. This survey summarizes studies exploring the relationship between lung disease and brain structure and function from neuroimaging perspective, particular in magnetic resonance imaging (MRI). We have collated existing lung diseases studies and categorized them into four types: chronic obstructive pulmonary disease (COPD), coronavirus disease 2019 (COVID-19), lung cancer and other lung diseases. The observed structural and functional changes in the brain and cognitive dysfunction induced by lung diseases are discussed. We also present distinct pattern of brain changes in various lung diseases. Neuroimaging changes in COPD are concentrated in the frontal lobes, including gray matter atrophy, white matter damage, and reduced perfusion. Patients with COVID-19 exhibit extensive microhemorrhages and neuroinflammation, brain regions functionally connected to the primary olfactory cortex show greater changes. For lung cancer patients, brain changes are mainly attributed to the neurotoxicity of radiotherapy and chemotherapy, with damage concentrated in subcortical structures, patients with cancer pain demonstrate hyperconnectivity in motor and visual networks. The survey also discusses the pathological mechanisms revealed in neuroimaging studies and clinical significance of current studies. Finally, we analyzed current limitations, mainly in terms of small sample size, non-standardized criteria, reliance on correlation analyses, lack of longitudinal studies, and absence of reliable biomarkers. We suggest future research directions should include leveraging artificial intelligence for biomarker development, conducting longitudinal and multicenter studies, and investigating the systemic effects of lung disease on the brain and neuromodulation strategies.