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Updated: Apr 24, 2026
Real-Time, Semi-Automated Fluorescent Measurement of the Airway Surface Liquid pH of Primary Human Airway Epithelial Cells
Published on: June 13, 2019
Measuring extracellular pH in a lung fibrosis model with acidoCEST MRI
Kyle M Jones1, Edward A Randtke, Christine M Howison
1Biomedical Engineering Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA.
Purpose:
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).
Procedures:
We developed a respiration-gated version of acidoCEST MRI to improve the measurement of pHe and percent uptake in lesions. We also used T2-weighted MRI to measure lesion volumes and diffusion-weighted MRI to measure ADC.
Results:
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.
Conclusions:
The increase in pHe during the reduction in lesion volume indicates a role for lactic acid in the proposed feed-forward loop of IPF.
Insights
Idiopathic pulmonary fibrosis (IPF) may involve a lactic acid feed-forward loop. AcidoCEST MRI revealed increased extracellular pH during lesion reduction, supporting lactic acid
Area of Science:
- Biomedical Imaging
- Pulmonary Medicine
- Biochemistry
Background:
- Idiopathic pulmonary fibrosis (IPF) pathogenesis is not fully understood.
- A potential feed-forward loop involving lactic acid production has been hypothesized in IPF development.
Purpose of the Study:
- To investigate the role of lactic acid in IPF by measuring extracellular pH (pHe) using acidoCEST MRI.
- To correlate pHe with contrast agent uptake, lesion size, and apparent diffusion coefficient (ADC) in IPF lesions.
Main Methods:
- Developed a respiration-gated acidoCEST MRI technique for precise pHe and contrast uptake measurements.
- Utilized T2-weighted MRI for lesion volume quantification and diffusion-weighted MRI for ADC assessment.
Main Results:
- Longitudinal measurements showed an inverse relationship between pHe/contrast uptake and lung lesion volume reduction.
- No significant changes in the average apparent diffusion coefficient (ADC) were observed over the study period.
Conclusions:
- An increase in extracellular pH during decreasing lesion volume suggests lactic acid contributes to the proposed IPF feed-forward loop.
- These findings provide MRI-based evidence for the involvement of lactic acid metabolism in IPF progression.
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