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Updated: Apr 19, 2026
Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis
Published on: February 28, 2021
Multiple sclerosis: myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental
Benjamin Pulli1, Lionel Bure, Gregory R Wojtkiewicz
1From the Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge St, Boston, MA 02114 (B.P., L.B., G.R.W., Y.I., M.A., D.L., S.S., K.L.C.H., J.W.C.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (B.P., J.W.C.); and European Institute for Molecular Imaging, University of Münster, Münster, Germany (A.H.J.).
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.
Insights
MPO-Gd MRI contrast agent detects early, subclinical inflammation in experimental autoimmune encephalomyelitis (EAE) mouse models. This probe reveals inflammatory lesions missed by standard DTPA-Gd, indicating its potential for early multiple sclerosis detection.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Early detection of subclinical disease activity is crucial for effective MS management.
- Current imaging techniques may not reliably detect early inflammatory changes.
Purpose of the Study:
- To evaluate MPO-Gd, a novel MR imaging contrast agent, for its sensitivity in detecting early and chronic disease activity in a mouse model of MS.
- To compare the efficacy of MPO-Gd with standard DTPA-Gd in revealing subclinical brain inflammation.
Main Methods:
- Experimental autoimmune encephalomyelitis (EAE) was induced in 61 female SJL mice.
- Mice underwent MR imaging with MPO-Gd or DTPA-Gd at various disease stages, including pre-symptomatic, remission, and relapse.
- Brain tissue was analyzed using flow cytometry and immunohistochemistry to assess immune cell infiltration.
Main Results:
- MPO-Gd detected significantly more subclinical inflammatory lesions earlier than DTPA-Gd (5.2 vs 2.3 days before symptom onset).
- MPO-Gd identified lesions even without apparent blood-brain barrier (BBB) breakdown detected by DTPA-Gd.
- MPO-Gd enhancement correlated strongly with the infiltration of MPO-secreting monocytes and neutrophils.
Conclusions:
- MPO-Gd specifically targets and visualizes lesions associated with MPO-secreting inflammatory cells (monocytes and neutrophils).
- This study demonstrates the feasibility of in vivo detection of subclinical inflammatory disease activity distinct from BBB breakdown.
- MPO-Gd shows promise as a sensitive tool for early MS diagnosis and monitoring.
