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. 2022 Apr 18;23(8):4466.
doi: 10.3390/ijms23084466.

AcidoCEST-UTE MRI Reveals an Acidic Microenvironment in Knee Osteoarthritis

Alecio F Lombardi  1   2 , Yajun Ma  2 , Hyungseok Jang  2 , Saeed Jerban  2 , Qingbo Tang  1   2 , Adam C Searleman  2 , Robert Scott Meyer  3 , Jiang Du  2 , Eric Y Chang  1   2
Affiliations

AcidoCEST-UTE MRI Reveals an Acidic Microenvironment in Knee Osteoarthritis

Alecio F Lombardi et al. Int J Mol Sci. .

Erratum in

Abstract

A relationship between an acidic pH in the joints, osteoarthritis (OA), and pain has been previously demonstrated. Acidosis Chemical Exchange Saturation Transfer (acidoCEST) indirectly measures the extracellular pH through the assessment of the exchange of protons between amide groups on iodinated contrast agents and bulk water. It is possible to estimate the extracellular pH in the osteoarthritic joint using acidoCEST MRI. However, conventional MR sequences cannot image deep layers of cartilage, meniscus, ligaments, and other musculoskeletal tissues that present with short echo time and fast signal decay. Ultrashort echo time (UTE) MRI, on the other hand, has been used successfully to image those joint tissues. Here, our goal is to compare the pH measured in the knee joints of volunteers without OA and patients with severe OA using acidoCEST-UTE MRI. Patients without knee OA and patients with severe OA were examined using acidoCEST-UTE MRI and the mean pH of cartilage, meniscus, and fluid was calculated. Additionally, the relationship between the pH measurements and the Knee Injury and Osteoarthritis Outcome Score (KOOS) was investigated. AcidoCEST-UTE MRI can detect significant differences in the pH of knee cartilage, meniscus, and fluid between joints without and with OA, with OA showing lower pH values. In addition, symptoms and knee-joint function become worse at lower pH measurements.

Keywords: CEST; MRI; OA; UTE; cartilage; chemical exchange saturation transfer; meniscus; osteoarthritis; pH; ultrashort echo time.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative image examples from patients without OA (A) and with OA (B). Sagittal PD-weighted (first row), low-power acido-CEST UTE (second row), high-power acido-CEST UTE (third row), and pH pixel maps (fourth row) of cartilage, meniscus, and fluid. The pH is directly correlated with the radiofrequency power mismatch (RPM) measurements, as described in Equations (3) and (4). Note the higher pH values (yellow and red colors) in patients without OA compared with patients with OA (blue colors).
Figure 2
Figure 2
Boxplots of mean pH measurements versus groups for all ROIs. Significant differences are observed between the two groups. ***: p values lower than 0.001.
Figure 3
Figure 3
Boxplots of mean pH measurements versus each group of participants (No OA and OA) for ROIs drew in cartilage (A), meniscus (B), and fluid (C). Significant differences in pH measurements are observed between groups with lower pH in patients with OA compared with patients without OA. “***”: p values lower than 0.001; “**”: p values lower than 0.01; “*”: p values lower than 0.05.
Figure 4
Figure 4
Boxplots of mean pH measurements versus ROIs in patients without OA (A) and with advanced OA (B). No significant differences were found, except for the pH of cartilage and meniscus in the OA group (p = 0.024). “*”: p values lower than 0.05; “•”: outliers.
Figure 5
Figure 5
Scatterplots of pH versus KOOS scores and the visual analog pain score. Strong direct correlations were observed for all KOOS subscale scores (A–F). There was a strong inverse correlation between pH measurements and the visual analog pain score (G). KOOS: Knee Injury and Osteoarthritis Outcome Score; ADL: activities of daily living; Sports/Rec: sports and recreation activities; QOL: quality of life; PF: patellofemoral.
See this image and copyright information in PMC

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