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Voxel processing techniques for the antemortem study of neuroanatomy and neuropathology using magnetic resonance imaging. J Neuropsychiatry Clin Neurosci abstract pdf (3.5M) 1993
Automatic atlas-based volume estimation of human brain regions from MR images. J Comput Assist Tomogr abstract pdf (2.9M) 1996
Human frontal cortex: an MRI-based parcellation method. Neuroimage abstract pdf (6.3M) 1999
Improving tissue classification in MRI: a three-dimensional multispectral discriminant analysis method with automated training class selection. J Comput Assist Tomogr abstract pdf (3.4M) 1999
Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging. Cereb Cortex abstract pdf (3.5M) 1999
Measurement of brain structures with artificial neural networks: two- and three-dimensional applications. Radiology abstract pdf (3.3M) 1999
An MRI-based parcellation method for the temporal lobe. Neuroimage abstract pdf (6.0M) 2000
Visualization of subthalamic nuclei with cortex attenuated inversion recovery MR imaging. Neuroimage abstract pdf (1.8M) 2000
A new method for the in vivo volumetric measurement of the human hippocampus with high neuroanatomical accuracy. Hippocampus abstract pdf (2.4M) 2000
Color enhancement of multispectral MR images: improving the visualization of subcortical structures. J Comput Assist Tomogr abstract pdf (2.5M) 2001
Subcortical, cerebellar, and magnetic resonance based
consistent brain image registration
Neuroimage abstract pdf (0.5M) 2003

 





Andreasen, N. C., T. Cizadlo, et al. (1993). ?Voxel processing techniques for the antemortem study of neuroanatomy and neuropathology using magnetic resonance imaging. ? J Neuropsychiatry Clin Neurosci 5(2): 121-30. BRAINBLAST, a program that uses voxel processing, was developed in order to produce high-fidelity three-dimensional reconstructions of the brain. Four steps were used to produce images: washing away cerebrospinal fluid (via histogramming), dissecting away the blood vessels (via a connectivity heuristic), highlighting the sulci and gyri (via a lighting model), and resampling the interior contents of the brain. After reconstruction, the images can be resampled, rotated, written on, measured, or redissected. The technique has a variety of applications: study of individual variation in sulcal and gyral patterns, evaluation of structure/function relationships, measurement of volumes or subregions using anatomically defined landmarks, and teaching of neuroanatomy.
pdf (3.5M)




Andreasen, N. C., R. Rajarethinam, et al. (1996). ?Automatic atlas-based volume estimation of human brain regions from MR images. ? J Comput Assist Tomogr 20(1): 98-106.OBJECTIVE: MRI offers many opportunities for noninvasive in vivo measurement of structure-function relationships in the human brain. Although automated methods are now available for whole-brain measurements, an efficient and valid automatic method for volume estimation of subregions such as the frontal or temporal lobes is still needed. MATERIALS AND METHODS: We adapted the Talairach atlas to the study of brain subregions. We supplemented the atlas with additional boxes to include the cerebellum. We assigned all the boxes to 1 of 12 regions of interest (ROIs) (frontal, parietal, temporal, and occipital lobes, cerebellum, and subcortical regions on right and left sides of the brain). Using T1-weighted MR scans collected with an SPGR sequence (slice thickness = 1.5 mm), we manually traced these ROIs and produced volume estimates. We then transformed the scans into Talairach space and compared the volumes produced by the two methods ("traced" versus "automatic"). The traced measurements were considered to be the "gold standard" against which the automatic measurements were compared. RESULTS: The automatic method was found to produce measurements that were nearly identical to the traced method. We compared absolute measurements of volume produced by the two methods, as well as the sensitivity and specificity of the automatic method. We also compared the measurements of cerebral blood flow obtained through [15O]H2O PET studies in a sample of nine subjects. Absolute measurements of volume produced by the two methods were very similar, and the sensitivity and specificity of the automatic method were found to be high for all regions. The flow values were also found to be very similar by both methods. CONCLUSION: The automatic atlas-based method for measuring the volume of brain subregions produces results that are similar to manual techniques. The method is rapid, efficient, unbiased, and not subject to the problems of rater drift or potentially poor interrater reliability that plague manual methods. Consequently, this method may be very useful for the study of structure-function relationships in the human brain.
pdf (2.9M)




Crespo-Facorro, B., J. J. Kim, et al. (1999). ?Human frontal cortex: an MRI-based parcellation method. ? Neuroimage 10(5): 500-19.The frontal lobe is not a single anatomical and functional brain region. Several lines of research have demonstrated that particular subregions within the frontal lobe are associated with specific motor and cognitive functions in the human being. Our main purpose is to develop a magnetic resonance image (MRI)-based parcellation method of the frontal lobe that permits us to explore plausible abnormalities in functionally relevant frontal subregions in brain illnesses. We describe a procedure using MRI for subdividing the entire frontal cortex into 11 subregions: supplementary motor area (SMA), rostral anterior cingulate gyrus (r-ACiG), caudal anterior cingulate gyrus (c- ACiG), superior cingulate gyrus (SCiG), medial frontal cortex (MFC), straight gyrus (SG), orbitofrontal cortex (OFC), precentral gyrus (PCG), superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and middle frontal gyrus (MFG). Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the three-dimensional (3D) rendered brain and the three orthogonal planes simultaneously. The reliability study for gray matter volume and surface area of each subregion was performed on a set of 10 MR scans by two raters. The intraclass R coefficients for gray matter volume of each subregion ranged between 0.86 and 0.99. We describe here a reproducible and reliable topography-based parcellation method of the frontal lobe that will allow us to use new approaches to understand the role of particular frontal cortical subregions in schizophrenia and other brain illnesses.
pdf (6.3M)




Harris, G., N. C. Andreasen, et al. (1999). ?Improving tissue classification in MRI: a three-dimensional multispectral discriminant analysis method with automated training class selection. ? J Comput Assist Tomogr 23(1): 144-54.PURPOSE: To improve the reliability, accuracy, and computational efficiency of tissue classification with multispectral sequences [T1, T2, and proton density (PD)], we developed an automated method for identifying training classes to be used in a discriminant function analysis. We compared it with a supervised operator-dependent method, evaluating its reliability and validity. We also developed a fuzzy (continuous) classification to correct for partial voluming. METHOD: Images were obtained on a 1.5 T GE Signa MR scanner using three pulse sequences that were co-registered. Training classes for the discriminant analysis were obtained in two ways. The operator-dependent method involved defining circular ROIs containing 5-15 voxels that represented "pure" samples of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), using a total of 150-300 voxels for each tissue type. The automated method involved selecting a large number of samples of brain tissue with sufficiently low variance and randomly placed throughout the brain ("plugs"), partitioning these samples into GM, WM, and CSF, and minimizing the amount of variance within each partition of samples to optimize its "purity." The purity of the plug was estimated by calculating the variance of 8 voxels in all modalities (T1, T2, and PD). We also compared "sharp" (discrete) measurements (which classified tissue only as GM, WM, or CSF) and "fuzzy" (continuous) measurements (which corrected for partial voluming by weighting the classification based on the mixture of tissue types in each voxel). RESULTS: Reliability was compared for the operator- dependent and automated methods as well as for the fuzzy versus sharp classification. The automated sharp classifications consistently had the highest interrater and intrarater reliability. Validity was assessed in three ways: reproducibility of measurements when the same individuals were scanned on multiple occasions, sensitivity of the method to detecting changes associated with aging, and agreement between the automated segmentation values and those produced through expert manual segmentation. The sharp automated classification emerged as slightly superior to the other three methods according to each of these validators. Its reproducibility index (intraclass r) was 0.97, 0.98, and 0.98 for total CSF, total GM, and total WM, respectively. Its correlations with age were 0.54, -0.61, and -0.53, respectively. Its percent agreement with the expert manually segmented tissue for the three tissue types was 93, 90, and 94%, respectively. CONCLUSION: Automated identification of training classes for discriminant analysis was clearly superior to a method that required operator intervention. A sharp (discrete) classification into three tissue types was also slightly superior to one that used "fuzzy" classification to produce continuous measurements to correct for partial voluming. This multispectral automated discriminant analysis method produces a computationally efficient, reliable, and valid method for classifying brain tissue into GM, WM, and CSF. It corrects some of the problems with reliability and computational inefficiency previously observed for operator-dependent approaches to segmentation.
pdf (3.4M)




Magnotta, V. A., N. C. Andreasen, et al. (1999). ?Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging. ? Cereb Cortex 9(2): 151-60.Clinical observation suggests that the aging process affects gyrification, with the brain appearing more 'atrophic' with increasing age. Empirical studies of tissue type indicate that gray matter volume decreases with age while cerebrospinal fluid increases. Quantitative changes in cortical surface characteristics such as sulcal and gyral shape have not been measured, however, due to difficulties in developing a method that separates abutting gyral crowns and opens up the sulci -- the 'problem of buried cortex'. We describe a quantitative method for measuring brain surface characteristics that is reliable and valid. This method is used to define the gyral and sulcal characteristics of atrophic and non-atrophic brains and to examine changes that occur with aging in a sample of 148 normal individuals from a broad age range. The shape of gyri and sulci change significantly over time, with the gyri becoming more sharply and steeply curved, while the sulci become more flattened and less curved. Cortical thickness also decreases over time. Cortical thinning progresses more rapidly in males than in females. The progression of these changes appears to be relatively stable during midlife and to begin to progress some time during the fourth decade. Measurements of sulcal and gyral shape may be useful in studying the mechanisms of both neurodevelopmental and neurodegenerative changes that occur during brain maturation and aging.
pdf (3.5M)




Magnotta, V. A., D. Heckel, et al. (1999). ?Measurement of brain structures with artificial neural networks: two- and three-dimensional applications. ? Radiology 211(3): 781-90.PURPOSE: To evaluate the ability of an artificial neural network (ANN) to identify brain structures. This ANN was applied to postprocessed magnetic resonance (MR) images to segment various brain structures in both two- and three-dimensional applications. MATERIALS AND METHODS: An ANN was designed that learned from experience to define the corpus callosum, whole brain, caudate, and putamen. Manual segmentation was used as a training set for the ANN. The ANN was trained on two-thirds of the manually segmented images and was tested on the remaining one- third. The reliability of the ANN was compared against manual segmentations by two technicians. RESULTS: The ANN was able to identify the brain structures as readily and as well as did the two technicians. Reliability of the ANN compared with the technicians was 0.96 for the corpus callosum, 0.95 for the whole brain, 0.86 (right) and 0.93 (left) for the caudate, and 0.71 (right) and 0.88 (left) for the putamen. CONCLUSION: The ANN was able to identify the structures used in this study as well as did the two technicians. The ANN could do this much more rapidly and without rater drift. Several other cortical and subcortical structures could also be readily identified with this method.
pdf (3.3M)


 

Kim, J. J., B. Crespo-Facorro, et al. (2000). ?An MRI-based parcellation method for the temporal lobe. ? Neuroimage 11(4): 271-88.The temporal lobe has long been a focus of attention with regard to the underlying pathology of several major psychiatric illnesses. Previous postmortem and imaging studies describing regional volume reductions or perfusion defects in temporal subregions have shown inconsistent findings, which are in part due to differences in the definition of the subregions and the methodology of measurement. The development of precise reproducible parcellation systems on magnetic resonance images may help improve uniformity of results in volumetric MR studies and unravel the complex activation patterns seen in functional neuroimaging studies. The present study describes detailed guidelines for the parcellation of the temporal neocortex. It parcels the entire temporal neocortex into 16 subregions: temporal pole, heschl's gyrus, planum temporale, planum polare, superior temporal gyrus (rostral and caudal), middle temporal gyrus (rostral, intermediate, and caudal), inferior temporal gyrus (rostral, intermediate, and caudal), occipitotemporal gyrus (rostral and caudal), and parahippocampal gyrus (rostral and caudal). Based upon topographic landmarks of individual sulci, every subregion was consecutively traced on a set of serial coronal slices. In spite of the huge variability of sulcal topography, the sulcal landmarks could be identified reliably due to the simultaneous display of three orthogonal (transaxial, coronal, and sagittal) planes, triangulated gray matter isosurface, and a 3-D-rendered image. The reliability study showed that the temporal neocortex could be parceled successfully and reliably; intraclass correlation coefficient for each subregion ranged from 0.62 to 0.99. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in the temporal subregions that might reflect underlying neuropathological processes in psychiatric illnesses such as schizophrenia.

pdf (6.0M)




Magnotta, V. A., S. Gold, et al. (2000). ?Visualization of subthalamic nuclei with cortex attenuated inversion recovery MR imaging. ? Neuroimage 11(4): 341-6.There is a significant amount of interest in studying the thalamus because of its central location in the brain and its role as a gatekeeper to higher centers of cognition. Imaging and measuring of the individual subnuclei of the thalamus has proven extremely difficult in MR because of the contrast-to-noise (CNR) of the MR sequences used. This report describes a novel MR pulse sequence known as cortex attenuated inversion recovery (CAIR), which increases the CNR in images and allows the individual subnuclei of the thalamus to be visualized by selectively nulling the gray matter in the brain using an inversion recovery sequence with an inversion time of 700 ms at 1.5 T.
pdf (1.8M)




Pantel, J., D. S. O'Leary, et al. (2000). ?A new method for the in vivo volumetric measurement of the human hippocampus with high neuroanatomical accuracy. ? Hippocampus 10(6): 752-8.Accurate and reproducible in vivo measurement of hippocampal volumes using magnetic resonance (MR) imaging is complicated by the morphological complexity of the structure. Additionally, separation of certain parts of the hippocampus from the adjacent brain structures on MR images is sometimes very difficult. These difficulties have led most investigators to either use arbitrary landmarks or to exclude certain parts of the structure from their measurements. Based on three- dimensional MR data, we have developed a reliable in vivo volumetric measurement of the human hippocampus. In contrast to most of the previously described volumetric MR-based methods, we aimed to sample the entire hippocampal formation using its true anatomical definition. This was accomplished by relying on the capacity of the BRAINS software to simultaneously visualize in multiple planes, to "telegraph" tracings or cursor position from one plane to another, and to simultaneously rely on multispectral data from three different image sets (T1, T2, and tissue classified). The methods for identifying boundaries and measuring the hippocampal volume are described. The method has excellent reliability, sensitivity, and specificity. The method may be of use in studies of structure-function relationships in neuropsychiatric disorders such as schizophrenia, temporal lobe epilepsy, and Alzheimer's disease. Future work will use these measurements as training data for a neural net-based technique to identify the anatomical boundaries automatically.
pdf (2.4M)




Ward, J., V. Magnotta, et al. (2001). ?Color enhancement of multispectral MR images: improving the visualization of subcortical structures. ? J Comput Assist Tomogr 25(6): 942-9.PURPOSE: The current investigation was undertaken to evaluate a new method for creating MR multispectral color images, which we call "Superimages." They were developed to improve the delineation of small brain structures composed of mixed tissue types, such as the basal ganglia. METHOD: To qualitatively validate the method, visual comparisons were made of six unimodal and multispectral images, including the Superimage. Quantitative validation was undertaken by comparing the reliability values for parcellation of the globus pallidus (GP) using either a gray scale (T1-weighted) image or the Superimage. RESULTS: Qualitative assessment of the Superimage revealed enhanced visualization of the GP, caudate, and putamen. Quantitative assessment resulted in good reliability for Superimage traces. CONCLUSION: The Superimage significantly improves both the visualization and the parcellation of structures visualized by MRI.
pdf (2.5M)


Magnotta, V. A., H. J. Bockholt, et al. (2003). ?Subcortical, cerebellar, and magnetic resonance based consistent brain image registration.? Neuroimage 19(): 233-45.A new landmark-initialized segmentation and intensity-based (LI-SI) inverse-consistent linear elastic image registration algorithm is presented. This method uses manually identified landmarks, segmented volumetric (anatomical) structures, and normalized image signal intensity information to co-register datasets. The features used for image registration and evaluation include: 35 cortical, cerebellar, and commissure landmarks manually identified by experts, sub-cortical and cerebellar regions defined semi-automatically by an artificial neural network and manually trimmed for validity by experts, and tissue classified images that were generated using a discriminant analysis of three magnetic resonance image sets representing T1, T2, and PD modalities. Four groups of results were computed for co-registering 16 datasets with the following registration techniques: rigid registration, extended Talairach registration, intensity-only inverse-consistent linear elastic registration, and the new LI-SI registration. Results are presented showing that relative overlap measurements increased as the dimensionality of the registration algorithm and amount of anatomical information increased. The average relative overlap improved from $ 0.53$ for the rigid registration to $ 0.55$ for the Talairach registration to $ 0.74$ for the intensity-only and to $ 0.85$ for the LI-SI algorithm. We showed a statistically significant improvement for all but one structure using the intensity-only algorithm as compared to the Talairach registration. Furthermore, statistically significant improvements for all structures were achieved using the LI-SI algorithm compared to the intensity-only algorithm.

pdf (0.5M)



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