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Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and
C J De Groot1, E Bergers, W Kamphorst
1Department of Pathology, MS Centre for Research and Care (MSCRC), Vrije Universiteit Medical Centre and Netherlands Brain Bank, Amsterdam, The Netherlands. cja.degroot@vumc.nl
Abstract:
Macroscopic sampling of multiple sclerosis lesions in the brain tends to find chronic lesions. For a better understanding of the dynamics of the multiple sclerosis disease process, research into new and developing lesions is of great interest. As MRI in vivo effectively demonstrates lesions in multiple sclerosis patients, we have applied it to unfixed post-mortem brain slices to identify abnormalities, in order to obtain a higher yield of active lesions. The Netherlands Brain Bank organized the rapid autopsy of 29 multiple sclerosis patients. The brain was cut in 1 cm coronal slices. One or two slices were subjected to T(1)- and T(2)-weighted MRI, and then cut at the plane of the MRI scan into 5 mm thick opposing sections. Areas of interest were identified based on the MRI findings and excised. One half was fixed in 10% formalin and paraffin-embedded, and the corresponding area in the adjacent half was snap-frozen in liquid nitrogen. In total, 136 out of 174 brain tissue samples could be matched with the abnormalities seen on T(2)-weighted MRIs. The stage of lesional development was determined (immuno) histochemically. For 54 MRI-detectable samples, it was recorded whether they were macroscopically detectable, i.e. visible and/or palpable. Histopathological analysis revealed that 48% of the hyperintense areas seen on T(2)-weighted images represented active lesions, including lesions localized in the normal appearing white matter, without apparent loss of myelin but nevertheless showing a variable degree of oedema, small clusters of microglial cells with enhanced major histocompatibility complex class II antigen, CD45 and CD68 antigen expression and a variable number of perivascular lymphocytes around small blood vessels [designated as (p)reactive lesions]. From the macroscopically not-visible/not-palpable MRI-detected abnormalities, 58% were (p)reactive lesions and 21% contained active demyelinating lesions. In contrast, visible and/or palpable brain tissue samples mainly contained chronic inactive lesions. We conclude that MRI-guided sampling of brain tissue increases the yield of active multiple sclerosis lesions, including active demyelinating and (p)reactive lesions.
Insights
Magnetic Resonance Imaging (MRI) of post-mortem brain slices helps identify active multiple sclerosis (MS) lesions. This MRI-guided sampling technique significantly increases the yield of early-stage MS lesions, crucial for understanding disease dynamics.
Area of Science:
- Neuroscience
- Pathology
- Medical Imaging
Background:
- Macroscopic sampling of multiple sclerosis (MS) brain lesions primarily identifies chronic, inactive disease stages.
- Understanding the dynamics of early and active MS lesions is critical for comprehending disease progression.
Purpose of the Study:
- To apply in vivo Magnetic Resonance Imaging (MRI) techniques to unfixed post-mortem human brain slices to enhance the identification and yield of active multiple sclerosis lesions.
- To compare MRI-detected abnormalities with histopathological findings to characterize lesion activity and stage.
Main Methods:
- Post-mortem brain slices from 29 multiple sclerosis patients were analyzed using T(1)- and T(2)-weighted MRI.
- MRI-identified areas of interest were excised, with one half processed for histopathology and the other snap-frozen.
- Lesion activity and stage were determined using (immuno)histochemical analysis.
Main Results:
- 136 out of 174 MRI-detectable abnormalities were successfully matched with tissue samples.
- Histopathological analysis revealed 48% of T(2)-weighted hyperintense areas were active lesions, including those in normal-appearing white matter.
- Macroscopically undetectable MRI-detected lesions showed a higher proportion of active (58% (p)reactive, 21% active demyelinating) compared to visible/palpable lesions.
Conclusions:
- MRI-guided sampling of post-mortem brain tissue significantly increases the yield of active multiple sclerosis lesions.
- This method allows for the identification of active demyelinating and (p)reactive lesions, often missed by macroscopic examination.
- The findings highlight the utility of MRI in characterizing the full spectrum of MS lesion activity in post-mortem tissue.