Measuring Extracellular pH in a Lung Fibrosis Model with acidoCEST MRI

A feed-forward loop involving lactic acid production may potentially occur during the formation of idiopathic pulmonary fibrosis. To provide evidence for this feed-forward loop, we used acidoCEST MRI to measure the extracellular pH (pHe), while also measuring percent uptake of the contrast agent, lesion size, and the apparent diffusion coefficient (ADC). We developed a respiration-gated version of acidoCEST MRI to improve the measurement of pHe and percent uptake in lesions. We also used T-2-weighted MRI to measure lesion volumes and diffusion-weighted MRI to measure ADC. The longitudinal changes in average pHe and % uptake of the contrast agent were inversely related to reduction in lung lesion volume. The average ADC did not change during the time frame of the study. The increase in pHe during the reduction in lesion volume indicates a role for lactic acid in the proposed feed-forward loop of IPF.