Multiple sclerosis: Myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model

Benjamin Pulli, Lionel Bure, Gregory R. Wojtkiewicz, Yoshiko Iwamoto, Muhammad Ali, Dan Li, Stefan Schob, Kevin Li Chun Hsieh, Andreas H. Jacobs, John W. Chen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 MPOGd- 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 DTPAGd, 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 MPOsecreting 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.

Original languageEnglish
Pages (from-to)480-489
Number of pages10
JournalRadiology
Volume275
Issue number2
DOIs
Publication statusPublished - May 1 2015

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Acute Disease
Peroxidase
Multiple Sclerosis
Chronic Disease
Theoretical Models
Acids
Autoimmune Experimental Encephalomyelitis
Brain
Blood-Brain Barrier
Monocytes
Neutrophils
Animal Care Committees
Magnetic Resonance Imaging
Recurrence
Gadolinium
Immunohistochemistry
Enzymes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Pulli, B., Bure, L., Wojtkiewicz, G. R., Iwamoto, Y., Ali, M., Li, D., ... Chen, J. W. (2015). Multiple sclerosis: Myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model. Radiology, 275(2), 480-489. https://doi.org/10.1148/radiol.14141495

Multiple sclerosis : Myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model. / Pulli, Benjamin; Bure, Lionel; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Ali, Muhammad; Li, Dan; Schob, Stefan; Hsieh, Kevin Li Chun; Jacobs, Andreas H.; Chen, John W.

In: Radiology, Vol. 275, No. 2, 01.05.2015, p. 480-489.

Research output: Contribution to journalArticle

Pulli, B, Bure, L, Wojtkiewicz, GR, Iwamoto, Y, Ali, M, Li, D, Schob, S, Hsieh, KLC, Jacobs, AH & Chen, JW 2015, 'Multiple sclerosis: Myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model', Radiology, vol. 275, no. 2, pp. 480-489. https://doi.org/10.1148/radiol.14141495
Pulli, Benjamin ; Bure, Lionel ; Wojtkiewicz, Gregory R. ; Iwamoto, Yoshiko ; Ali, Muhammad ; Li, Dan ; Schob, Stefan ; Hsieh, Kevin Li Chun ; Jacobs, Andreas H. ; Chen, John W. / Multiple sclerosis : Myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model. In: Radiology. 2015 ; Vol. 275, No. 2. pp. 480-489.
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AU - Ali, Muhammad

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