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In vivo MRI and its histological correlates in acute adoptive transfer experimental allergic encephalomyelitis.
S P Morrissey1, H Stodal, U Zettl
1Department of Neurology, Julius- Maximilians-University, Würzburg, Germany.
Abstract:
In vivo proton MRI was carried out on a 7 Tesla system at 2-3 day intervals over 10 days in rats with adoptive transfer experimental allergic encephalomyelitis (AT-EAE), an animal model of some aspects of multiple sclerosis. In order to assess the integrity of the blood-brain barrier (BBB), MRI was performed by acquiring quantitative MR-relaxation time T1 images of the AT-EAE rat brain before and after i.v. injection gadolinium-diethylene triaminepentaacetic acid (Gd-DTPA) using an ultrafast MRI technique. The MRI findings were compared with the immunohistochemical stain of T cells, macrophages and albumin and, in addition, apoptosis of T cells was assessed using in situ nick translation (ISNT). Prior to injection of Gd-DTPA, an increase of T1 times in the brain of the AT-EAE rats was observed, which paralleled the time course of albumin in histological sections. These were MRI findings observed well before the onset of major cellular infiltration and before the onset of clinical signs. After i.v. injection of Gd-DTPA the observed decrease of T1 times paralleled macrophage activation, and less closely T-cell infiltration. Our results provide evidence that using MRI, it is possible to assess quantitatively the breach of the BBB and to distinguish in vivo between two components of the early phase of the lesion, inflammatory infiltrates and vasogenic oedema.
Insights
This study used MRI to detect early blood-brain barrier (BBB) changes in a multiple sclerosis rat model. MRI can identify early BBB damage and differentiate between inflammation and edema before clinical signs appear.
Area of Science:
- Neuroimaging
- Immunology
- Pathology
Background:
- Experimental allergic encephalomyelitis (AT-EAE) is a model for multiple sclerosis.
- Assessing blood-brain barrier (BBB) integrity is crucial for understanding neuroinflammatory diseases.
Purpose of the Study:
- To evaluate the utility of in vivo proton MRI for assessing BBB integrity in AT-EAE rats.
- To correlate MRI findings with histological markers of inflammation and BBB breakdown.
Main Methods:
- Proton MRI (7 Tesla) was performed on AT-EAE rats over 10 days.
- Quantitative T1-weighted images were acquired before and after Gd-DTPA injection.
- MRI data were compared with immunohistochemistry for T cells, macrophages, albumin, and in situ nick translation (ISNT) for apoptosis.
Main Results:
- Increased T1 times were observed in the AT-EAE rat brain before Gd-DTPA injection, correlating with albumin levels.
- These MRI changes preceded major cellular infiltration and clinical symptoms.
- Post-Gd-DTPA, decreased T1 times correlated with macrophage activation and T-cell infiltration.
Conclusions:
- In vivo MRI can quantitatively assess BBB breaches in experimental allergic encephalomyelitis.
- MRI can distinguish between inflammatory infiltrates and vasogenic edema in early lesion phases.
- This technique offers potential for early diagnosis and monitoring of neuroinflammatory conditions.