We present a method for coregistration and warping of magnetic resonance im
ages (MRI) to histological sections for comparison purposes. This methodolo
gy consists of a modified head and hat surface-based registration algorithm
followed by a new automated warping approach using nonlinear thin plate sp
lines to compensate for distortions between the data sets. To test the meth
odology, 15 male Wistar rats were subjected to focal cerebral ischemia via
permanent occlusion of the middle cerebral artery. The MRI images were acqu
ired in separate groups of animals at 16-24 h (n=9) and 48-168 h (n=6) post
occlusion, After imaging, animals were immediately sacrificed and hematoxyl
in- and eosin-stained brain sections were obtained for histological analysi
s. The MRI was coregistered and warped to histological sections. The MRI le
sion areas were defined using the Eigenimage (EI) filter technique. The EI
is a linear filter that maximizes the projection of a desired tissue (ische
mic tissue) while it minimizes the projection of undesired tissues (nonisch
emic tissue) onto a composite image called an EI. When using coregistration
without warping the MRI lesion area demonstrated poor correlation (r=0.55,
p>0.01) with a percent difference between the two lesion areas of 22.5%+/-
10.8%. After warping, the MRI and histology had significant correlation (r=
0.97, p<0.01) and a decreased percent difference of 5.56%+/-4.31%. This met
hodology is simple and robust for coregistration and warping of MRI to hist
ological sections and can be utilized in many applications for comparison o
f MRI to histological data. (C) 1999 American Association of Physicists in
Medicine. [S0094-2405(99)00908-6].