Imaging correlates of axonal swelling in chronic multiple sclerosis brains.
OBJECTIVE
T2-weighted magnetic resonance imaging is a sensitive tool for monitoring progression of multiple sclerosis, but it does not provide information on the severity of the underlying tissue damage. Measurement of T1 hypointensities and magnetization transfer ratio (MTR) can potentially distinguish lesions with more severe tissue damage. The objective of this study was to use image-guided pathology to determine histological differences between lesions that are abnormal only on T2-weighted images versus lesions that are abnormal on T2-weighted, T1-weighted, and MTR images.


METHODS
A total of 110 regions were selected from postmortem magnetic resonance images of 10 multiple sclerosis patients. Regions were classified into three magnetic resonance imaging-defined categories: normal-appearing white matter; abnormal on T2-weighted image only (T2-only); and abnormal on T2-weighted, T1-weighted, and MTR images (T2T1MTR). Myelin status, lesion activity, astrocytosis, serum protein distribution, axonal area, and axonal loss were evaluated histopathologically.


RESULTS
Comparisons between groups showed that T2T1MTR regions were more likely to be demyelinated (83% compared with 55% of T2-only regions) and more likely to be chronic inactive lesions (68% compared with 0% of demyelinated T2-only regions). There was no difference between T2-only and T2T1MTR regions in axonal area, but there was a significant difference in axonal count, indicating that axons in the T2T1MTR regions were enlarged relative to those in T2-only regions.


CONCLUSIONS
Axonal swelling and axonal loss were major pathological features that distinguish T2T1MTR regions from T2-only regions.
Fisher
Elizabeth
E
Department of Biomedical Engineering, Lerner Research Institute, Cleveland, OH 44195, USA. fishere@ccf.org
Chang
Ansi
A
Fox
Robert J
RJ
Tkach
Jean A
JA
Svarovsky
Therese
T
Nakamura
Kunio
K
Rudick
Richard A
RA
Trapp
Bruce D
BD
D001369:Axons / Q000473:pathology*; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D002908:Chronic Disease; D003627:Data Interpretation, Statistical; D005260:Female; D005911:Gliosis / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology
D001798:Blood Proteins