Voxel-based morphometry (VBM) is a powerful tool for analyzing changes in g
ray or white matter density of the brain. By using an automated segmentatio
n procedure and standardized parametric statistics it avoids biases inheren
t in operator-dependent morphological operations (J. Ashburner and K. J. Fr
iston, 2000, NeuroImage 11, 805-821), Since its introduction in 1995, VERI
has been used to examine anatomical changes in a variety of diseases associ
ated with neurologic and psychiatric dysfunction. Given the power of this t
echnique for discerning subtle anatomical changes, we wanted to assess its
performance on brains with gross structural abnormalities. Such results cou
ld have implications regarding the difficulties to be faced when examining
other types of distorted brains (e.g., brains with changes due to degenerat
ive disease). This report describes the use of VBM for examining individual
and group changes in gray matter concentration in five patients who had re
covered from herpes simplex encephalitis (HSE) compared with age- and sex-m
atched controls. Because HSE tends to affect a specific set of brain region
s we thought that this would (1) provide an opportunity to assess the anato
mical face validity of VBM, (2) allow us to assess the problems of this tec
hnique when used on distorted brains, and (3) provide an in vivo demonstrat
ion of the gray matter changes due to HSE. We found that, despite problems
in normalizing and segmenting these severely distorted brains, VBM was able
to identify correctly a number of the regional gray matter abnormalities i
n HSE. The results, while consistent with the well-known histopathology of
the disease, also demonstrate potential difficulties with this method. (C)
2001 Academic Press.