In vivo Myeloarchitectonic Analysis of Human Striate and Extrastriate Cortex Using Magnetic Resonance Imaging
Vincent P. Clark,1 Eric Courchesne,1-2 and Marjorie Grafe3
A primary goal of investigations into the organization of human cerebral cortex is to determine the functional specificity of architectonic regions. This includes the correlation of neurobehavioral deficits with neuropathological data for clinical diagnosis and treatment, and the identification of active brain regions using functional neural imaging techniques, such as positron emission tomography, electroencephalographic and magnetoencephalographic (EEG and MEG) source localization algorithms, and direct cortical stimulation. Currently, the architectonic classification of a cortical region identified by these methods is inferred from the comparison of its cerebral topographic position to cytoarchitectonic brain atlases. However, substantial intersubject variability in the position of cytoarchitectonic regions with respect to cerebral topographic landmarks may lead to errors in this procedure. An alternative method is presented here, which uses magnetic resonance (MR) imaging to identify myeloarchitectonic regions of isocortex directly by estimating the relative concentration of myelin within cortical laminae. This high-resolution MR protocol is used to identify striate cortex (Brodmann's area 17) and extrastriate cortex in vivo. Correspondence of MR signal intensity with myeloarchitectonic data from a postmortem brain confirms this identification. As MR imaging technology improves, this noninvasive method has the potential to identify and discriminate among at least 50 cortical regions in the living human brain.
Recent improvements in noninvasive functional imaging techniques that monitor cerebral glucose utilization and blood flow (Fox et al., 1987; Mintun et al., 1989; Mora et al., 1989; Petersen et al., 1990; Belliveau et al., 1991; Corbetta et al., 1991) and that indicate the locations of cortical electromagnetic field sources (Nunez, 1981; Hari and Lounasmaa, 1989; Aine et al., 1990; Cohen et al., 1990; Kaufman and Williamson, 1990; Simpson etal., 1990; McCarthy and Scabini, 1991; A. Dale and M. Sereno, unpublished observations) allow the localization of functional brain regions with a spatial resolution of 1 cm or less. This should be adequate to differentiate the activity of individual architectonic regions. However, to determine the identity of these functionally defined cortical regions, the topographic location of architectonic regions must be known with an equivalent spatial resolution. The use of brain atlases to infer this identification (Talairach et al., 1967; Talairach and Tournoux, 1988; Damasio and Damasio, 1989) is greatly limited by the substantial intersubject variability observed in the size and location of some cytoarchitectonic regions. In the case of human primary visual cortex, significant variability has been observed between subjects in its topography (Filiminoff, 1932; Polyak, 1957; Brindley, 1972), exhibiting approximately 2.5 cm of variance in the position of its borders relative to the lips of the calcarine sulcus (Stensaas et al., 1974). Also, its area and volume have been found to vary by factors of 3 and 3.4, respectively (Stensaas et al., 1974; Murphy, 1985). A high degree of topographic, areal, and volumetric variability has also been observed for other cortical regions in humans (Sarkisov, 1966; Galaburda and Sanides, 1980), and in primary visual cortex and other cortical regions in lower primates (Merzenich et al., 1978; Sur et al., 1980; Sur et al., 1982; Van Essen et al., 1984). Thus, the architectonic identity of a neural population cannot be known with absolute certainty based solely on its cortical topographic location. Cortical architectonic regions are identified by the thickness and composition of their laminae. Adjacent architectonic regions are distinguished on the basis of observed differences in these measures. This is frequently done by examining cytoarchitectonic structure (which describes the type and distribution of cell bodies) using a Nissl stain. Although this method is the best known and is widely used, a number of other methods are also available for architectonic
1
Department of Neurosciences, University of California at San Diego, La Jolla, California, 920930608, 2 Neuropsychology Research Laboratory', Children's Hospital Research Center, San Diego, California 92123, and i Departments of Pathology and Anesthesiology, University of California at San Diego, School of Medicine, San Diego, California 92103
Downloaded from http://cercor.oxfordjournals.org/ at Cornell University Library on June 24, 2015
Cerebral Cortex Sep/Oci 1992,2:417-424; 1047-3211/92/14.00
Materials and Methods
MR Scans of Living Volunteers The feasibility of identifying specific myeloarchitectonic regions in vivo was ascertained by performing MR studies of the living human brain in four neurologically normal volunteers (two female). A 1.5 tesla superconductive scanner (Signa, General Electric, Milwaukee, WI) was used with a 5 inch surface coil. The surface coil was positioned directly beneath the subject's head, separated by a foam pad, and was centered approximately 2 cm above the inion. Subjects were requested to lie completely still during the scan. Foam pads and surgical tape were used to help stabilize the head of the subject. Tl-weighted spin echo (SE) sequences in the sagittal and axial planes were performed to determine sulcal morphology. The imaging plane was oriented orthogonal to the surface of the region in question, and high-resolution oblique proton density (PD)-weighted inversion recovery [IR; repetition time (TR) = 2500 msec, echo time (TE) = 27 msec, inversion time (TI) = 160 msec, 2 excitations (NEX), field of view (FOV) = 10 cm, thickness = 3 mm] and spin echo (SE; TR = 3000 msec, TE = 23 and 80 msec, 4 NEX, FOV = 10 cm, matrix = 256 x 256, thickness = 3.0 mm) images were obtained (Fig. 1£>), providing 391 Mm in-plane resolution, which allowed a minimum offivesampling points through the width of gray matter in this region (Economo, 1929). MR Scans of a Postmortem Brain High-resolution MR images were obtained from a formalin-fixed postmortem brain to verify the findings of the in vivo images (Fig. 2a,b). The brain had been 418 Imaging Cortical Myeloarchitecture with MR1 • Clark et al.
Figure 1 . High-resolution MR images of a living volunteer, a shows plane of sectioning [ps] for b: T1-weighted parasagittal image using a head coil (TR = 600 msec, TE = 12 msec, 2 NEX, FOV = 20 cm, matrix = 256 x 256, thickness = 3.0 mm]. It is possible to identify the calcarine sulcus [CS\ anterior to the occipital pole [OP], the parieto-occipital sulcus [P0S\. and the marginal ramus of the cingulate sulcus [CngSmr). The corpus callosum [CC] and anterior vermis of the cerebellum \AV) can also be identified, b shows the stria of Gennari in vivo: PD-weighted oblique SE image (TR = 3000 msec, TE = 23 msec, 4 NEX, FOV = 10 cm, matrix = 256 x 256, thickness = 3.0 mm] of the left hemisphere [L) using a 5" surface coil. The collateral sulcus [ColS] is situated anterior to the calcarine sulcus. Arrows point to the stria of Gennari, which is seen as a layer of low signal intensity within middle cortical lamina in this region. Region of cortex between arrows marked 1 and 2 was used for statistical analysis and laminar intensity curves
Vincent P. Clark,1 Eric Courchesne,1-2 and Marjorie Grafe3
A primary goal of investigations into the organization of human cerebral cortex is to determine the functional specificity of architectonic regions. This includes the correlation of neurobehavioral deficits with neuropathological data for clinical diagnosis and treatment, and the identification of active brain regions using functional neural imaging techniques, such as positron emission tomography, electroencephalographic and magnetoencephalographic (EEG and MEG) source localization algorithms, and direct cortical stimulation. Currently, the architectonic classification of a cortical region identified by these methods is inferred from the comparison of its cerebral topographic position to cytoarchitectonic brain atlases. However, substantial intersubject variability in the position of cytoarchitectonic regions with respect to cerebral topographic landmarks may lead to errors in this procedure. An alternative method is presented here, which uses magnetic resonance (MR) imaging to identify myeloarchitectonic regions of isocortex directly by estimating the relative concentration of myelin within cortical laminae. This high-resolution MR protocol is used to identify striate cortex (Brodmann's area 17) and extrastriate cortex in vivo. Correspondence of MR signal intensity with myeloarchitectonic data from a postmortem brain confirms this identification. As MR imaging technology improves, this noninvasive method has the potential to identify and discriminate among at least 50 cortical regions in the living human brain.
Recent improvements in noninvasive functional imaging techniques that monitor cerebral glucose utilization and blood flow (Fox et al., 1987; Mintun et al., 1989; Mora et al., 1989; Petersen et al., 1990; Belliveau et al., 1991; Corbetta et al., 1991) and that indicate the locations of cortical electromagnetic field sources (Nunez, 1981; Hari and Lounasmaa, 1989; Aine et al., 1990; Cohen et al., 1990; Kaufman and Williamson, 1990; Simpson etal., 1990; McCarthy and Scabini, 1991; A. Dale and M. Sereno, unpublished observations) allow the localization of functional brain regions with a spatial resolution of 1 cm or less. This should be adequate to differentiate the activity of individual architectonic regions. However, to determine the identity of these functionally defined cortical regions, the topographic location of architectonic regions must be known with an equivalent spatial resolution. The use of brain atlases to infer this identification (Talairach et al., 1967; Talairach and Tournoux, 1988; Damasio and Damasio, 1989) is greatly limited by the substantial intersubject variability observed in the size and location of some cytoarchitectonic regions. In the case of human primary visual cortex, significant variability has been observed between subjects in its topography (Filiminoff, 1932; Polyak, 1957; Brindley, 1972), exhibiting approximately 2.5 cm of variance in the position of its borders relative to the lips of the calcarine sulcus (Stensaas et al., 1974). Also, its area and volume have been found to vary by factors of 3 and 3.4, respectively (Stensaas et al., 1974; Murphy, 1985). A high degree of topographic, areal, and volumetric variability has also been observed for other cortical regions in humans (Sarkisov, 1966; Galaburda and Sanides, 1980), and in primary visual cortex and other cortical regions in lower primates (Merzenich et al., 1978; Sur et al., 1980; Sur et al., 1982; Van Essen et al., 1984). Thus, the architectonic identity of a neural population cannot be known with absolute certainty based solely on its cortical topographic location. Cortical architectonic regions are identified by the thickness and composition of their laminae. Adjacent architectonic regions are distinguished on the basis of observed differences in these measures. This is frequently done by examining cytoarchitectonic structure (which describes the type and distribution of cell bodies) using a Nissl stain. Although this method is the best known and is widely used, a number of other methods are also available for architectonic
1
Department of Neurosciences, University of California at San Diego, La Jolla, California, 920930608, 2 Neuropsychology Research Laboratory', Children's Hospital Research Center, San Diego, California 92123, and i Departments of Pathology and Anesthesiology, University of California at San Diego, School of Medicine, San Diego, California 92103
Downloaded from http://cercor.oxfordjournals.org/ at Cornell University Library on June 24, 2015
Cerebral Cortex Sep/Oci 1992,2:417-424; 1047-3211/92/14.00
Materials and Methods
MR Scans of Living Volunteers The feasibility of identifying specific myeloarchitectonic regions in vivo was ascertained by performing MR studies of the living human brain in four neurologically normal volunteers (two female). A 1.5 tesla superconductive scanner (Signa, General Electric, Milwaukee, WI) was used with a 5 inch surface coil. The surface coil was positioned directly beneath the subject's head, separated by a foam pad, and was centered approximately 2 cm above the inion. Subjects were requested to lie completely still during the scan. Foam pads and surgical tape were used to help stabilize the head of the subject. Tl-weighted spin echo (SE) sequences in the sagittal and axial planes were performed to determine sulcal morphology. The imaging plane was oriented orthogonal to the surface of the region in question, and high-resolution oblique proton density (PD)-weighted inversion recovery [IR; repetition time (TR) = 2500 msec, echo time (TE) = 27 msec, inversion time (TI) = 160 msec, 2 excitations (NEX), field of view (FOV) = 10 cm, thickness = 3 mm] and spin echo (SE; TR = 3000 msec, TE = 23 and 80 msec, 4 NEX, FOV = 10 cm, matrix = 256 x 256, thickness = 3.0 mm) images were obtained (Fig. 1£>), providing 391 Mm in-plane resolution, which allowed a minimum offivesampling points through the width of gray matter in this region (Economo, 1929). MR Scans of a Postmortem Brain High-resolution MR images were obtained from a formalin-fixed postmortem brain to verify the findings of the in vivo images (Fig. 2a,b). The brain had been 418 Imaging Cortical Myeloarchitecture with MR1 • Clark et al.
Figure 1 . High-resolution MR images of a living volunteer, a shows plane of sectioning [ps] for b: T1-weighted parasagittal image using a head coil (TR = 600 msec, TE = 12 msec, 2 NEX, FOV = 20 cm, matrix = 256 x 256, thickness = 3.0 mm]. It is possible to identify the calcarine sulcus [CS\ anterior to the occipital pole [OP], the parieto-occipital sulcus [P0S\. and the marginal ramus of the cingulate sulcus [CngSmr). The corpus callosum [CC] and anterior vermis of the cerebellum \AV) can also be identified, b shows the stria of Gennari in vivo: PD-weighted oblique SE image (TR = 3000 msec, TE = 23 msec, 4 NEX, FOV = 10 cm, matrix = 256 x 256, thickness = 3.0 mm] of the left hemisphere [L) using a 5" surface coil. The collateral sulcus [ColS] is situated anterior to the calcarine sulcus. Arrows point to the stria of Gennari, which is seen as a layer of low signal intensity within middle cortical lamina in this region. Region of cortex between arrows marked 1 and 2 was used for statistical analysis and laminar intensity curves
