Myeloperoxidase-Sensitive Magnetic Resonance Imaging Assesses Inflammatory Activation State in Experimental Mouse Acute Gout.

ABSTRACT

BACKGROUND: A novel myeloperoxidase-activatable manganese-based (MPO-Mn) MRI probe may enable the activation state of inflammatory foci to be detected and monitored noninvasively. PURPOSE: To evaluate the inflammatory response in a mouse model of acute gout using MPO as an imaging biomarker and a potential therapeutic target. STUDY TYPE Prospective. ANIMAL MODEL A total of 40 male Swiss mice with monosodium urate crystals induced acute gout. FIELD STRENGTH/SEQUENCE A 3.0 T/T1-weighted imaging with 2D fast spoiled gradient recalled echo and T2-weighted imaging with fast recovery fast spin-echo sequences. ASSESSMENT The difference in contrast-to-noise ratio between left hind limb (lesion) and right hind limb (internal reference) (ΔCNR), and normalized signal-to-noise ratio (nSNR) on the right hind limb were calculated and compared. The expression level and activity of myeloperoxidase (MPO) were analyzed using western blotting and spectrophotometric quantitation activity assay. MPO-positive cell infiltration and lesion volume were evaluated using immunofluorescence staining and T2-weighted images, respectively. STATISTICAL TESTS Student's t test. A P-value less than 0.05 was considered to be statistically significant. RESULTS: MPO-Mn resulted in a significantly higher ΔCNR than Gd-DTPA (22.54 ± 1.86 vs. 13.90 ± 2.22) but lower nSNR on the reference right hind limb (1.08 ± 0.07 vs. 1.21 ± 0.08). Compared to the nontreatment group, MPO-inhibition resulted in a significantly reduced contrast enhancement at the lesion (17.81 ± 1.58 vs. 22.96 ± 3.12), which was consistent with a remission of the inflammatory response, as evidenced by a substantial reduction of lesion volume (0.55 ± 0.16 mm3 /g vs. 1.14 ± 0.15 mm3 /g), myeloperoxidase expression level (0.98 ± 0.09 vs. 1.48 ± 0.19) and activity (0.75 ± 0.12 vs. 1.12 ± 0.07), and inflammatory cell recruitment. DATA CONCLUSION: MPO-Mn MRI has potential to evaluate the activation state of inflammatory foci in the experimental model of acute gout. EVIDENCE LEVEL 1. TECHNICAL EFFICACY Stage 1.