髓过氧化物酶敏感磁共振成像评估实验性小鼠急性痛风的炎症激活状态。

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

机构信息

Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan, China.

Department of Oncology Ward 2, Chengdu Third People's Hospital, Chengdu, Sichuan, China.

出版信息

J Magn Reson Imaging. 2023 Dec;58(6):1714-1722. doi: 10.1002/jmri.28752. Epub 2023 Apr 20.

DOI:10.1002/jmri.28752

PMID:37078554

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 mm /g vs. 1.14 ± 0.15 mm /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

TECHNICAL EFFICACY

Stage 1.

摘要

背景

一种新型的髓过氧化物酶激活的锰基（MPO-Mn）MRI 探针可以实现对炎症病灶激活状态的无创检测和监测。

目的

以髓过氧化物酶（MPO）为成像生物标志物和潜在的治疗靶点，评估急性痛风小鼠模型中的炎症反应。

研究类型

前瞻性。

动物模型

共 40 只雄性瑞士小鼠，尿酸单钠晶体诱导急性痛风。

磁场强度/序列：3.0T/T1 加权成像，二维快速扰相梯度回波和 T2 加权成像，快速恢复快速自旋回波序列。

评估

左后肢（病变）和右后肢（内参）之间的对比噪声比差异（ΔCNR），以及右后肢的归一化信噪比（nSNR）进行计算和比较。采用 Western blot 和分光光度定量活性测定分析髓过氧化物酶（MPO）的表达水平和活性。通过免疫荧光染色和 T2 加权图像分别评估 MPO 阳性细胞浸润和病变体积。

统计学检验

Student's t 检验。P 值小于 0.05 被认为具有统计学意义。

结果

MPO-Mn 引起的 ΔCNR 明显高于 Gd-DTPA（22.54±1.86 比 13.90±2.22），但右后肢参考侧的 nSNR 较低（1.08±0.07 比 1.21±0.08）。与未治疗组相比，MPO 抑制导致病变处的对比增强明显降低（17.81±1.58 比 22.96±3.12），这与炎症反应的缓解一致，表现为病变体积明显缩小（0.55±0.16 mm/g 比 1.14±0.15 mm/g），髓过氧化物酶表达水平（0.98±0.09 比 1.48±0.19）和活性（0.75±0.12 比 1.12±0.07）以及炎症细胞募集减少。