Trying to spot Grey matter lesions

Popescu V, Klaver R, Versteeg A, Voorn P, Twisk JW, Barkhof F, Geurts JJ, Vrenken H. Post-mortem validation of MRI cortical volume measurements in MS. Hum Brain Mapp. 2016 . doi: 10.1002/hbm.23168. [Epub ahead of print]

Grey matter (GM) atrophy is a prominent aspect of multiple sclerosis pathology and an important outcome in studies. GM atrophy measurement requires accurate GM segmentation. Several methods are used in vivo for measuring GM volumes in MS, but assessing their validity in vivo remains challenging. In this post-mortem study, we evaluated the correlation between post-mortem MRI cortical volume or thickness and the cortical thickness measured on histological sections. Sixteen MS brains were scanned in situ using 3DT1-weighted MRI and these images were used to measure regional cortical volume using FSL-SIENAX, FreeSurfer, and SPM, and regional cortical thickness using FreeSurfer. Subsequently, cortical thickness was measured histologically in 5 systematically sampled cortical areas. Linear regression analyses were used to evaluate the relation between MRI regional cortical volume or thickness and histological cortical thickness to determine which post-processing technique was most valid. After correction for multiple comparisons, we observed a significant correlation with the histological cortical thickness for FSL-SIENAX cortical volume with manual editing (std. β = 0.345, adjusted R2  = 0.105, P = 0.005), and FreeSurfer cortical volume with manual editing (std. β = 0.379, adjusted R2  = 0.129, P = 0.003). In addition, there was a significant correlation between FreeSurfer cortical thickness with manual editing and histological cortical thickness (std. β = 0.381, adjusted R2  = 0.130, P = 0.003). The results support the use of FSL-SIENAX and FreeSurfer in cases of severe MS pathology. Interestingly none of the methods were significant in automated mode, which supports the use of manual editing to improve the automated segmentation.

Grey matter lesions were missed for years by MRI at 1-3T and in this study they attempted to correlate different types of MRI analysis with grey matter lesion load. Using automated analysis didn’t find anything, but if you have the human  touch you can find some corrleation and whilst it is statistical is as long as your arm, with an R2 of ~0.1 it maybe explains why grey matter lesions were missed.

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  • Could be due to the small slices made by 1.5T MRIs (3-5mm/slice).
    Are grey matter lesions smaller than average white matter lesions?

  • Yes in terms of orthogonal expanse (outer > inner layers of the cortex, then white matter), however no when looking at the total area/volume affected by demyelination. Pathologically, ~25% of the grey, but only about 7% of the white matter is demyelinated.

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