Multiple sclerosis: myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model.
Multiple sclerosis: myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model.
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DOI：
10.1148/radiol.14141495
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发表时间：
2015-05
期刊：
影响因子：
19.7
通讯作者：
B. Pulli;Lionel Buré;G. Wojtkiewicz;Y. Iwamoto;Muhammad Ali;Dan Li;S. Schob;K. Hsieh;A. Jacobs;John W. Chen
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文献类型：
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作者：
B. Pulli;Lionel Buré;G. Wojtkiewicz;Y. Iwamoto;Muhammad Ali;Dan Li;S. Schob;K. Hsieh;A. Jacobs;John W. Chen
目的 测试 MPO-Gd（一种基于钆的磁共振 (MR) 成像探针，对某些炎症细胞分泌的促炎和氧化酶髓过氧化物酶 (MPO) 敏感且特异）在揭示实验性自身免疫性脑脊髓炎 (EAE) 小鼠模型中是否比二乙烯三胺五乙酸 (DTPA)-Gd 更敏感，以揭示大脑中的早期亚临床和慢性疾病活动。硬化。材料和方法动物实验方案得到机构动物护理委员会的批准。总共 61 只雌性 SJL 小鼠接受 EAE 诱导。小鼠在诱导后第 6 天、第 8 天和第 10 天、临床疾病发生之前以及慢性疾病缓解和第一次复发期间接受了 MPO-Gd 或 DTPA-Gd 增强 MR 成像。在这些时间点收获大脑用于免疫细胞亚型和免疫组织化学的流式细胞术评估。进行统计分析，P<0.05被认为表明存在显着差异。结果 与 DTPA-Gd 相比，MPO-Gd 有助于更早（症状出现前 5.2 天与 2.3 天，P = .004）和更多（3.1 vs 0.3，P = .008）检测亚临床炎症病变，包括在 DTPA-Gd 增强没有检测到明显血脑屏障 (BBB) 破坏证据的情况下。 MPO-Gd 增强病变的数量与分泌 MPO 的单核细胞和中性粒细胞早期浸润大脑相关（r = 0.91）。与 DTPA-Gd 相比，MPO-Gd 还有助于在亚临床疾病缓解时（5.5 vs 1.3，P = .006）和首次复发时（9.0 vs 2.7，P = .03）检测到更多病变，这也与大脑中分泌 MPO 的炎症细胞的存在和积累密切相关（r = 0.93）。结论 MPO-Gd 特异性地揭示了炎症单核细胞和中性粒细胞的病变，这些细胞积极分泌 MPO。这些结果证明了体内检测亚临床炎症性疾病活动的可行性，这与明显的血脑屏障破坏不同。
PURPOSE To test if MPO-Gd, a gadolinium-based magnetic resonance (MR) imaging probe that is sensitive and specific for the proinflammatory and oxidative enzyme myeloperoxidase (MPO), which is secreted by certain inflammatory cells, is more sensitive than diethylenetriaminepentaacetic acid (DTPA)-Gd in revealing early subclinical and chronic disease activity in the brain in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. MATERIALS AND METHODS The protocol for animal experiments was approved by the institutional animal care committee. A total of 61 female SJL mice were induced with EAE. Mice underwent MPO-Gd- or DTPA-Gd-enhanced MR imaging on days 6, 8, and 10 after induction, before clinical disease develops, and during chronic disease at remission and the first relapse. Brains were harvested at these time points for flow cytometric evaluation of immune cell subtypes and immunohistochemistry. Statistical analysis was performed, and P < .05 was considered to indicate a significant difference. RESULTS MPO-Gd helps detect earlier (5.2 vs 2.3 days before symptom onset, P = .004) and more (3.1 vs 0.3, P = .008) subclinical inflammatory lesions compared with DTPA-Gd, including in cases in which there was no evidence of overt blood-brain barrier (BBB) breakdown detected with DTPA-Gd enhancement. The number of MPO-Gd-enhancing lesions correlated with early infiltration of MPO-secreting monocytes and neutrophils into the brain (r = 0.91). MPO-Gd also helped detect more lesions during subclinical disease at remission (5.5 vs 1.3, P = .006) and at the first relapse (9.0 vs 2.7, P = .03) than DTPA-Gd, which also correlated well with the presence and accumulation of MPO-secreting inflammatory cells in the brain (r = 0.93). CONCLUSION MPO-Gd specifically reveals lesions with inflammatory monocytes and neutrophils, which actively secrete MPO. These results demonstrate the feasibility of detection of subclinical inflammatory disease activity in vivo, which is different from overt BBB breakdown.