Validating Cortical Surface Analysis of Medial Prefrontal Cortex J. T. Ratnanather,* ,1 K. N. Botteron,† T. Nishino,† A. B. Massie,* R. M. Lal,* S. G. Patel,* S. Peddi,* R. D. Todd,† and M. I. Miller* *Center for Imaging Science, The Johns Hopkins University, Baltimore, Maryland 21218-2686; and †Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110 Received January 30, 2001 This paper describes cortical analysis of 19 high res- olution MRI subvolumes of medial prefrontal cortex (MPFC), a region that has been implicated in major depressive disorder. An automated Bayesian segmen- tation is used to delineate the MRI subvolumes into cerebrospinal fluid (CSF), gray matter (GM), white matter (WM), and partial volumes of either CSF/GM or GM/WM. The intensity value at which there is equal probability of GM and GM/WM partial volume is used to reconstruct MPFC cortical surfaces based on a 3-D isocontouring algorithm. The segmented data and the generated surfaces are validated by comparison with hand segmented data and semiautomated contours, respectively. The L 1 distances between Bayesian and hand segmented data are 0.05– 0.10 (n  5). Fifty per- cent of the voxels of the reconstructed surface lie within 0.12– 0.28 mm (n  14) from the semiautomated contours. Cortical thickness metrics are generated in the form of frequency of occurrence histograms for GM and WM labelled voxels as a function of their po- sition from the cortical surface. An algorithm to com- pute the surface area of the GM/WM interface of the MPFC subvolume is described. These methods repre- sent a novel approach to morphometric chacterization of regional cortex features which may be important in the study of psychiatric disorders such as major depression. © 2001 Academic Press INTRODUCTION Major depressive disorder is recognized to be a com- mon, impairing, and frequently recurrent illness with significant public health impact. As detailed in the Global Burden of Disease study, major depressive dis- order ranked second in disease incidence and third in disability adjusted life years, where one disability ad- justed life year is defined as the loss of 1 year of healthy life to disease (Murray and Lopez, 1996). A variety of recent functional and structural neuroimaging studies of both normal affect regulation and differences asso- ciated with affective disorders such as major depres- sive disorder or bipolar affective disorder, implicate specific limbic circuits involving the ventral and medial prefrontal cortex, along with subcortical limbic struc- tures such as the amygdala and related parts of the striatum and thalamus in the pathophysiology of de- pression (reviewed in Swerdlow and Koob, 1987; Dre- vets et al., 1992; Drevets and Todd, 1997; Botteron and Figiel, 1997; Drevets, 1999). For example, in clinically ascertained depressed adults cerebral blood flow and metabolism are increased in the ventral prefrontal cor- tex, the amygdala and the medial thalamus while flow is reduced in the medial caudate and subgenual pre- frontal cortex (Drevets, 1999). Several studies have reported that structures in these specific limbic circuits may be reduced or increased in volume in adults with a history of major depressive disorder or bipolar affec- tive disorder. Although there are some conflicting re- sults reported for structural brain changes in affective disorders, recent critical reviews (Botteron and Figiel, 1997; Drevets and Botteron, 1996; Drevets and Todd, 1997; Soares and Mann, 1997) support that major de- pression is associated with specific neuromorphometric differences and suggest that some conflict in reported studies is probably related to limitations in image ac- quisition or image analysis in earlier studies. Although recent advances in MRI technology and image analysis have allowed for the more precise volumetric definition of smaller and more anatomically relevant regions than was possible even 5 years ago, the majority of the studies involving the structure of specific prefrontal or limbic regions in major depression have been reported for small subject numbers over limited anatomical re- gions. These limitations are largely related to the dif- ficulty and labor intensity required by skilled raters for regionally specific or anatomically relevant measures. Medial and ventral or orbital prefrontal regions have not been rigorously studied with robust automated methods which are sensitive to detailed regional neu- roanatomy. Given the public health burden of depres- sion and the increased resolution in neuroimaging, 1 To whom correspondence and reprint requests should be ad- dressed. Fax: (410) 516-4594. E-mail: tilak@cis.jhu.edu. NeuroImage 14, 1058 –1069 (2001) doi:10.1006/nimg.2001.0906, available online at http://www.idealibrary.com on 1058 1053-8119/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.