Contributions
Abstract: P1068
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Objective: In-vivo imaging of the cortical demyelination, thought to be extensive in chronic MS, has been challenging. Prior ex-vivo MRI studies have detected signal changes in cortical lesions (CL) and attributed them to loss of myelin and the presence of iron-laden microglia. If so, MR microscopy could be used to image individual iron-laden cells within the lesions, and shed light on possible ways to image CL in-vivo.
Method: Two blocks of formalin-fixed tissue, approximately 250 mm3 in size one including a CL and other with normal appearing cortex (CN), were removed postmortem from 77 y.o. male MS patient with 50-year disease duration. The blocks were imaged on a 11.7T MRI with custom build coil using a T2*-weighted 3D GRE sequence (TR/TE=100/10 ms, FA=30 deg, isotropic resolution of 18 microns, scan time=50 hours). Blocks were then embedded in paraffin, and histochemical and immunostaining done for iron (3,3´-Diaminobenzidine Turnbull), myelin (Luxol fast blue- Periodic acid schiff), oligodendrocytes
(olg using Aspartoacylase), neurons (neuronal nuclear antigen or NeuN), macrophages and microglia
(CD68 and IBA-1), and astrocytes (glial fibrillary acidic protein). MR images were aligned with histology to identify source of MR signal.
Results and discussion: MRI of CN revealed regions of punctate and linear hypo-intensities in the cortex that were identified as iron-laden olg and iron in myelinated axons respectively using histological correlation. In addition, patchy regions of hypointensities were observed in the white matter near the grey-white junction, which corresponded histologically to iron laden olg near blood vessels. Region corresponding to the cortical lesion was clearly identified as hyperintense on the MRI primarily due to the lack of hypo-intensities. Histological evaluation of the tissue confirmed the loss of iron within olg, without a commensurate loss of olg. or neurons in the affected region. Some iron-laden macrophages could also be seen in the white matter using MRI.
Conclusion: MR microscopy could identify individual iron-laden olg and myelinated axons with high sensitivity and specificity. Loss of iron in olg and myelin seemed to cause the increased MRI signal within the cortical lesion. These results suggest that a high-resolution T2* sequence, probably with motion compensation, should be able to detect cortical lesions in-vivo. Comparative studies are underway on a postmortem brain of 13-y.o. female with HHV6 encephalitis.
Disclosure: None.
Abstract: P1068
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Objective: In-vivo imaging of the cortical demyelination, thought to be extensive in chronic MS, has been challenging. Prior ex-vivo MRI studies have detected signal changes in cortical lesions (CL) and attributed them to loss of myelin and the presence of iron-laden microglia. If so, MR microscopy could be used to image individual iron-laden cells within the lesions, and shed light on possible ways to image CL in-vivo.
Method: Two blocks of formalin-fixed tissue, approximately 250 mm3 in size one including a CL and other with normal appearing cortex (CN), were removed postmortem from 77 y.o. male MS patient with 50-year disease duration. The blocks were imaged on a 11.7T MRI with custom build coil using a T2*-weighted 3D GRE sequence (TR/TE=100/10 ms, FA=30 deg, isotropic resolution of 18 microns, scan time=50 hours). Blocks were then embedded in paraffin, and histochemical and immunostaining done for iron (3,3´-Diaminobenzidine Turnbull), myelin (Luxol fast blue- Periodic acid schiff), oligodendrocytes
(olg using Aspartoacylase), neurons (neuronal nuclear antigen or NeuN), macrophages and microglia
(CD68 and IBA-1), and astrocytes (glial fibrillary acidic protein). MR images were aligned with histology to identify source of MR signal.
Results and discussion: MRI of CN revealed regions of punctate and linear hypo-intensities in the cortex that were identified as iron-laden olg and iron in myelinated axons respectively using histological correlation. In addition, patchy regions of hypointensities were observed in the white matter near the grey-white junction, which corresponded histologically to iron laden olg near blood vessels. Region corresponding to the cortical lesion was clearly identified as hyperintense on the MRI primarily due to the lack of hypo-intensities. Histological evaluation of the tissue confirmed the loss of iron within olg, without a commensurate loss of olg. or neurons in the affected region. Some iron-laden macrophages could also be seen in the white matter using MRI.
Conclusion: MR microscopy could identify individual iron-laden olg and myelinated axons with high sensitivity and specificity. Loss of iron in olg and myelin seemed to cause the increased MRI signal within the cortical lesion. These results suggest that a high-resolution T2* sequence, probably with motion compensation, should be able to detect cortical lesions in-vivo. Comparative studies are underway on a postmortem brain of 13-y.o. female with HHV6 encephalitis.
Disclosure: None.