Measuring the Thickness of the Human Cerebral Cortex
Accurate and automated methods for measuring the
thickness of human cerebral cortex could provide powerful tools for
diagnosing and studying a variety of neurodegenerative and psychiatric
disorders. Manual methods for estimating cortical thickness from
neuroimaging data are labor intensive, requiring several days of
effort by a trained anatomist. Furthermore, the highly folded nature
of the cortex is problematic for manual techniques, frequently
resulting in measurement errors in regions in which the cortical
surface is not perpendicular to any of the cardinal axes. As a
consequence, it has been impractical to obtain accurate thickness
estimates for the entire cortex in individual subjects, or group
statistics for patient or control populations. Here, we present an
automated method for accurately measuring the thickness of the
cerebral cortex across the entire brain, and for generating
cross-subject statistics in a coordinate system based on cortical
anatomy. The inter-subject variability in the thickness measures is
shown to be less then 1/2 mm, implying the ability to detect focal
atrophy in small populations or even individual subjects. The
reliability and accuracy of this new method are assessed via
within-subject test-retest studies, as well as comparison of
cross-subject regional thickness measures with published values, as
shown below.
The difficulty of properly measuring the thickness of the cortex
without explicit representations of both the gray/white and pial
surfaces is illustrated in the above figure, which shows coronal
and axial slices through a T1-weighted MRI volume. Measuring the
thickness from the coronal slice at the point indicated by the green
cross would result in an estimate in excess of 1 cm. Examining the
other view reveals that this is a dramatic overestimation, resulting
from the fact that the surface is locally parallel to the coronal
slice. The use of multiple orthogonal views in this fashion can reduce
the degree of inaccuracy, as one can choose the slice plane that is
closest to being perpendicular to the surface
In order to validate the thickness measurements, we computed the
thickness of the cortical gray matter for the left hemisphere of 30
subjects (17 male, 13 female, ages 20-37). The individual thickness
estimates were then combined across the 30 subjects using a
high-resolution surface-based averaging technique that aligns cortical
folding patterns [4].
The results of this procedure, shown bovee,
reveals that, consistent with published findings [1],
the crowns of
gyri are thicker than the fundi of sulci, and that sensory areas are
among the thinnest in cortex. More specifically, we find that gyral
regions have an average thickness of 2.7+-0.3 mm, versus 2.2+-0.3 mm for
sulcal regions.
An illustration of the variability of these results across the cortex
is given in this figure, which shows the spatial distribution of the
cross-subject standard deviations of the thickness measurements. As
can be seen, the measurements are quite consistent across subjects,
with a standard deviation of less than = mm over much of cortex, with
a mean of 0.54 mm. Applying a small surface-based Gaussian blurring
kernel (s=7 mm) reduced the standard deviation to 0.32 mm, indicating
the auto-correlation of the noise falls off quite sharply with
distance. One further point to note is that the majority of the
variance is localized in association areas: anterior ventral temporal
and prefrontal cortices, which are among the thickest of cortical regions.
In order to assess the portion of this variability attributable to
measurement noise as opposed to true inter-subject differences, we
performed two test-retest experiments. In the first, we scanned the
same subject in two different sessions and reconstructed surface
models for each, aligning them with the group average. The mean
inter-session standard deviation of these thickness measures was found
to be 0.25 mm. Applying the surface-based blurring kernel reduced the
variability to 0.1 mm. Next, in order to assess the robustness of the
technique to the varying contrast properties of different pulse
sequences, we scanned the same subject on two different scanner types
and MR protocols (GE 3D-SPGR and Siemens MP-RAGE). Reconstructing and
aligning as before, we found the mean cross-scanner standard deviation
in the thickness measures increased slightly over the within-platform
case to 0.31 mm (0.23 mm with the same blurring kernel as before),
suggesting that the measurements are relatively robust to differences
in MR protocols and scanners. These results indicate that much of the
variability in the cross-subject thickness measurements reflects true
inter-subject differences, and that even focal abnormalities in
cortical thickness may be detectable with these techniques.
Further validation was obtained by comparing the automated thickness
measurements with manual measurements of cortical thickness from MRI
data. A recent study, in which a trained anatomist used a jeweler's
eyepiece to estimate the thickness in 0.1 mm gradations from slices
oriented perpendicular to the central sulcus, found that the thickness
of the anterior and posterior banks of the sulcus differed
substantially [3], in agreement with earlier postmortem results
[1]. Specifically, the average thickness of the anterior bank of the
central sulcus was found to be 2.69 mm, while the average thickness of
the posterior bank was substantially less, averaging 1.81 mm, allowing
the banks to be distinguished based solely on thickness. Figure 6
illustrates these manually measured findings, and compares them with
the average thickness measured with our technique across the left
hemispheres of the same 30 subjects. As can be seen, our measurements
are in close agreement with the MR results, as well as earlier
postmortem work that found the mean thickness of the anterior and
posterior banks to be 2.7 mm and 1.7 mm respectively [5], It is
important to note here that these results validate both the accuracy
of the thickness measurements and the precision of the inter-subject
alignment in this region. That is, if the alignment procedure did not
map anterior banks to anterior banks and posterior banks to posterior
banks, the thick cortex on the anterior bank would be averaged with
the thin cortex on the posterior bank, yielding no distinction between
the two banks in the average.
Finally, a more quantitative and regionally specific comparison with
postmortem findings was performed, the results of which are summarized
in Table 1 . Note the excellent agreement between the overall average
measured using the current procedure and the postmortem
results. Further, the agreement in the regional measurements generated
using the two techniques is quite good, with a maximum discrepancy of
slightly more than 1/4 mm. These differences may be accounted for by a
number of factors such as individual variability, fixation effects,
the precise location of the measurements, as well as MR artifacts.
| Lateral cortex | 3.5 mm [1] | 2.9 ± 0.3 mm |
| Medial cortex | 2.7 mm [1] | 2.4 ± 0.3 mm |
| Inferior cortex | 3.0 mm [1] | 2.7 ± 0.3 mm |
| Area 4 | 3.0 - 4.5 mm [2] | 2.6 ± 0.3 mm |
| Area 17 | 2.3 - 2.6 mm [2] | 2.3 ± 0.3 mm |
| Overall average | 2.5 mm [1] | 2.5 ± 0.7 mm |
Table 1.
Comparison of reported postmortem thickness (column 2) with the automated methods outlined in this paper, averaged across 30 subjects (column 3). All ranges are standard deviations.
REFERENCES
[1] von Economo, C., The cytoarchitectonics of the human cerebral
cortex. 1929, London: Oxford University Press.
[2] Brodmann, K., Vergleichende Lokalisationslehre der
Gro_hirnrinde in ihren Prinzipien dargestellt auf Grund des
Zellenbaues. 1909, Leipzig: Barth.
[3] Meyer, J.R., S. Roychowdhury, E.J. Russell, C. Callahan,
D. Gitelman, and M.M. Mesulam, Location of the central sulcus via
cortical thickness of the precentral and postcentral gyri on
MR. American Journal of Neuroradiology, 1996. 17(9): p. 1699-1706.
[4]Fischl, B., M.I. Sereno, R.B.H. Tootell, and A.M. Dale,
High-resolution inter-subject averaging and a coordinate system for
the cortical surface. Human Brain Mapping, 1999. 8(4): p. 272-284.
[5] Sholl, D.A., The Organization of the Cerebral Cortex. 1956,
New York: John Wiley & Sons, Inc.