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The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Occupational exposure to hypobaria (low atmospheric pressure) is a risk factor for reduced white matter integrity, increased white matter hyperintensive burden, and decline in cognitive function. We tested the hypothesis that a discrete hypobaric exposure will have a transient impact on cerebral physiology. Cerebral blood flow, fractional anisotropy of water diffusion in cerebral white matter, white matter hyperintensity volume, and concentrations of neurochemicals were measured at baseline and 24 hr and 72 hr postexposure in N = 64 healthy aircrew undergoing standard US Air Force altitude chamber training and compared to N = 60 controls not exposed to hypobaria. We observed that hypobaric exposure led to a significant rise in white matter cerebral blood flow (CBF) 24 hr postexposure that remained elevated, albeit not significantly, at 72 hr. No significant changes were observed in structural measurements or gray matter CBF. Subjects with higher baseline concentrations of neurochemicals associated with neuroprotection and maintenance of normal white matter physiology (glutathione, N-acetylaspartate, glutamate/glutamine) showed proportionally less white matter CBF changes. Our findings suggest that discrete hypobaric exposure may provide a model to study white matter injury associated with occupational hypobaric exposure., (© 2019 Wiley Periodicals, Inc.)

Introduction: Quantitative longitudinal magnetic resonance imaging and spectroscopy (MRI/S) is used to assess progress of brain disorders and treatment effects. Understanding the significance of MRI/S changes requires knowledge of the inherent technical and physiological consistency of these measurements. This longitudinal study examined the variance and reproducibility of commonly used quantitative MRI/S measurements in healthy subjects while controlling physiological and technical parameters., Methods: Twenty-five subjects were imaged three times over 5 days on a Siemens 3T Verio scanner equipped with a 32-channel phase array coil. Structural (T1, T2-weighted, and diffusion-weighted imaging) and physiological (pseudocontinuous arterial spin labeling, proton magnetic resonance spectroscopy) data were collected. Consistency of repeated images was evaluated with mean relative difference, mean coefficient of variation, and intraclass correlation (ICC). Finally, a "reproducibility rating" was calculated based on the number of subjects needed for a 3% and 10% difference., Results: Structural measurements generally demonstrated excellent reproducibility (ICCs 0.872-0.998) with a few exceptions. Moderate-to-low reproducibility was observed for fractional anisotropy measurements in fornix and corticospinal tracts, for cortical gray matter thickness in the entorhinal, insula, and medial orbitofrontal regions, and for the count of the periependymal hyperintensive white matter regions. The reproducibility of physiological measurements ranged from excellent for most of the magnetic resonance spectroscopy measurements to moderate for permeability-diffusivity coefficients in cingulate gray matter to low for regional blood flow in gray and white matter., Discussion: This study demonstrates a high degree of longitudinal consistency across structural and physiological measurements in healthy subjects, defining the inherent variability in these commonly used sequences. Additionally, this study identifies those areas where caution should be exercised in interpretation. Understanding this variability can serve as the basis for interpretation of MRI/S data in the assessment of neurological disorders and treatment effects.

Background: Repetitive hypobaric exposure in humans induces subcortical white matter change, observable on magnetic resonance imaging (MRI) and associated with cognitive impairment. Similar findings occur in traumatic brain injury (TBI). We are developing a swine MRI-driven model to understand the pathophysiology and to develop treatment interventions., Methods: Five miniature pigs (Sus scrofa domestica) were repetitively exposed to nonhypoxic hypobaria (30,000 feet/FIO 2 100%/transcutaneous PO 2 >90%) while under general anesthesia. Three pigs served as controls. Pre-exposure and postexposure MRIs were obtained that included structural sequences, dynamic contrast perfusion, and diffusion tensor quantification. Statistical comparison of individual subject and group change was performed utilizing a two-tailed t test., Findings: No structural imaging change was noted on T2-weighted or three-dimensional fluid-attenuated inversion recovery imaging between MRI 1 and MRI 2. No absolute difference in dynamic contrast perfusion was observed. A trend (p = 0.084) toward increase in interstitial extra-axonal fluid was noted. When individual subjects were examined, this trend toward increased extra-axonal fluid paralleled a decrease in contrast perfusion rate., Discussion/impact/recommendations: This study demonstrates high reproducibility of quantitative noninvasive MRI, suggesting MRI is an appropriate assessment tool for TBI and hypobaric-induced injury research in swine. The lack of fluid-attenuated inversion recovery change may be multifactorial and requires further investigation. A trend toward increased extra-axonal water content that negatively correlates with dynamic contrast perfusion implies generalized axonal injury was induced. This study suggests this is a potential model for hypobaric-induced injury as well as potentially other axonal injuries such as TBI in which similar subcortical white matter change occurs. Further development of this model is necessary., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Introduction: Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability., Methods: There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values., Results: Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots., Discussion: Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.McGuire SA, Boone GRE, Sherman PM, Tate DF, Wood JD, Patel B, Eskandar G, Wijtenburg SA, Rowland LM, Clarke GD, Grogan PM, Sladky JH, Kochunov PV. White matter integrity in high-altitude pilots exposed to hypobaria. Aerosp Med Hum Perform. 2016; 87(12):983-988.

We present a multi-cohort shape heritability study, extending the fast spherical demons registration to subcortical shapes via medial modeling. A multi-channel demons registration based on vector spherical harmonics is applied to medial and curvature features, while controlling for metric distortion. We registered and compared seven subcortical structures of 1480 twins and siblings from the Queensland Twin Imaging Study and Human Connectome Project: Thalamus, Caudate, Putamen, Pallidum, Hippocampus, Amygdala, and Nucleus Accumbens . Radial distance and tensor-based morphometry (TBM) features were found to be highly heritable throughout the entire basal ganglia and limbic system. Surface maps reveal subtle variation in heritability across functionally distinct parts of each structure. Medial Demons reveals more significantly heritable regions than two previously described surface registration methods. This approach may help to prioritize features and measures for genome-wide association studies.

Objective: Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery magnetic resonance imaging (MRI)., Methods: Eighty-three altitude chamber personnel (PHY), 105 U-2 pilots (U2P), and 148 age- controlled and health-matched doctorate degree controls (DOC) underwent high-resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas-based stereotactic frame., Results: Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p < 0.001/count p < 0.001) when compared to DOC, whereas PHY were not significantly different than U2P., Interpretation: This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. Ann Neurol 2014;76:719-726., (© 2014 American Neurological Association.)

Objective: Determine whether United States Air Force (USAF) U-2 pilots (U2Ps) with occupational exposure to repeated hypobaria had lower neurocognitive performance compared to pilots without repeated hypobaric exposure and whether U2P neurocognitive performance correlated with white matter hyperintensity (WMH) burden., Methods: We collected Multidimensional Aptitude Battery-II (MAB-II) and MicroCog: Assessment of Cognitive Functioning (MicroCog) neurocognitive data on USAF U2Ps with a history of repeated occupational exposure to hypobaria and compared these with control data collected from USAF pilots (AFPs) without repeated hypobaric exposure (U2Ps/AFPs MAB-II 87/83; MicroCog 93/80). Additional comparisons were performed between U2Ps with high vs low WMH burden., Results: U2Ps with repeated hypobaric exposure had significantly lower scores than control pilots on reasoning/calculation (U2Ps/AFPs 99.4/106.5), memory (105.5/110.9), information processing accuracy (102.1/105.8), and general cognitive functioning (103.5/108.5). In addition, U2Ps with high whole-brain WMH count showed significantly lower scores on reasoning/calculation (high/low 96.8/104.1), memory (102.9/110.2), general cognitive functioning (101.5/107.2), and general cognitive proficiency (103.6/108.8) than U2Ps with low WMH burden (high/low WMH mean volume 0.213/0.003 cm(3) and mean count 14.2/0.4)., Conclusion: In these otherwise healthy, highly functioning individuals, pilots with occupational exposure to repeated hypobaria demonstrated lower neurocognitive performance, albeit demonstrable on only some tests, than pilots without repeated exposure. Furthermore, within the U2P population, higher WMH burden was associated with lower neurocognitive test performance. Hypobaric exposure may be a risk factor for subtle changes in neurocognition., (© 2014 American Academy of Neurology.)

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/)., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation., Methods: We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups., Results: The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant., Conclusion: A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions.

Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain structures. Two types of mean preserving scaling methods were investigated, "shape preserving" and "shape standardizing". aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to ρ (2), the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages.

Studies of the central sulcus (CS) often use observer-dependent procedures to assess CS morphology and sulcal landmarks. Here, we applied a novel method combining automated sulcus reconstruction, surface parameterization, and an observer-independent depth measurement to study the CS. This facilitated the quantitative assessment of the spatial position and intersubject variability of several sulcal landmarks. Sulcal depth profiles also allowed us to develop an algorithm for the clear identification of several landmarks, including the pli de passage fronto-pariétal moyen (PPFM), first described by Broca. Using this algorithm, the PPFM was identified in the majority of sulci, but exhibited limited spatial variability. This appears to support Cunningham's theory that this landmark may be a developmental remnant, and may argue against its role as a guide to the more variable somatotopic hand area. Sulcal depth profiles were also utilized to assess the influence of sex, handedness, and age on CS morphology. These profiles revealed leftward depth asymmetry in the superior extent of the CS of male subjects and near the midpoint of the CS in female subjects. Age correlations were performed for these asymmetries, and a significant correlation was seen only in the male subgroup.

Previous investigations of cerebral anatomy in persistent developmental stutterers have reported bilateral anomalies in the perisylvian region and atypical patterns of cerebral asymmetry. In this study, perisylvian sulcal patterns were analyzed to compare subjects with persistent developmental stuttering (PDS) and an age-, hand-, and gender-matched control group. This analysis was accomplished using software designed for 3-dimensional sulcal identification and extraction. Patterns of cerebral asymmetry were also investigated with standard planimetric measurements. PDS subjects showed a small but significant increase in both the number of sulci connecting with the second segment of the right Sylvian fissure and in the number of suprasylvian gyral banks (of sulci) along this segment. No differences were seen in the left perisylvian region for either sulcal number or gyral bank number. Measurements of asymmetry revealed typical patterns of cerebral asymmetry in both groups with no significant differences in frontal and occipital width asymmetry, frontal and occipital pole asymmetry, or planum temporale and Sylvian fissure asymmetries. The subtle difference in cortical folding of the right perisylvian region observed in PDS subjects may correlate with functional imaging studies that have reported increased right-hemisphere activity during stuttered speech.

Purpose: The baboon (Papio hamadryas spp) offers a natural primate animal model of photosensitive generalized epilepsy. This study compared changes in cerebral blood flow (CBF) during intermittent light stimulation (ILS) between photosensitive and asymptomatic baboons., Methods: Six photosensitive, epileptic (PS) and four nonphotosensitive, asymptomatic (CTL) baboons, matched for age, gender, and weight, were selected based on previous scalp EEG evaluation. Continuous intravenous ketamine (5-13 mg/kg) was used for sedation. Subjects underwent five sequential blood-flow PET studies within 60 min with 20 mCi (15)O-labeled water. Images were acquired in 3D mode (CTI/Siemens HR+ scanner, 63 contiguous slices, 2.4-mm thickness). Three resting scans were alternated with two activation scans during ILS. ILS was performed at 25 Hz for 60 s before to 60 s after the start of an activation scan. PET images were coregistered with MRI (3T Siemens Trio, T(1)-weighted 3D Turboflash sequence; TE/TR/TI, 3.04/2,100/785 ms; flip angle, 13 degrees). PET scans were reviewed and corrected for motion artifact. Resting scans were contrasted with activation scans and averaged independently for both groups. Quantitative CBF analyses were performed for the occipital and motor cortices., Results: The CTL baboons showed greatest ILS-induced activation in the left middle frontal and inferior temporal gyri, left brainstem structures and right postcentral gyrus, bilateral occipital lobes, and in the posterior cingulate gyrus and cerebellum. In contrast, the PS animals showed strongest ILS activation in the right anterior cingulate and medial orbital gyri, amygdala, globus pallidum, and left inferior and superior temporal gyri. A striking finding was the absence of occipital and variable motor cortex activation in the PS animals. Deactivations were noted in the right orbitofrontal and anterior cingulate cortices in the CTL baboons and in the posterior cingulate gyrus, brainstem and cerebellum of the PS animals., Conclusions: The patterns of ILS-induced CBF changes differed between CTL and PS groups. These differences of activations and inhibitions suggest involvement of specific cortical-subcortical or networks in photosensitivity.

The detection of asymmetry of exposed brain surfaces is examined, and a new method, deformation-based asymmetry (DBA), is introduced. DBA is based on analysis of two high-resolution magnetic resonance brain images, each with features representative of the subject group from which they were derived. Warping of individual brain images to their group representative image using octree spatial normalization provides sets of displacement vectors that are used in estimating deformation variance. For DBA group-representative left and right hemisphere images are compared. Representative hemisphere images are warped to each other and asymmetry analyzed using standardized d-values calculated as the ratio of displacement vector magnitude to the estimated component of variance in the direction of the displacement vector for each surface voxel. D-values were calculated within hemispheres by dividing subjects into two equal groups and comparing left-to-left and right-to-right. D-values from this ipsilateral hemisphere grouping were pooled. D-values from contralateral hemispheres were compared with the pooled ipsilateral hemisphere data. The proportion of d-values above a fixed level was used to test for difference between the two groups. High-resolution magnetic resonance (MR) images from 20 young, right-handed males were studied using DBA. No significant differences were seen between sub-grouped ipsilateral d-values (P > 0.10). Highly significant asymmetries (P < 0.0001) were found between hemispheres, and in each lobe. Common right frontal and left occipital petalias were seen. The DBA method can theoretically be applied to any two groups of globally similar structures where analysis of dissimilarity of regional features is sought., (Copyright 2003 Wiley-Liss, Inc.)

Shifting of echoplanar images (EPI) in the phase-encoding direction during functional magnetic resonance imaging (fMRI) experiments can be observed due to B(0) drift. These shifts can cause artifacts in functional activation maps that can be corrected using a navigator echo (NE) technique, but the NE correction requires pulse sequence modifications not available on many clinical systems. A fast, postprocessing correction method based on edge root-mean-square error reduction (ERMSR) is introduced and shown to provide an equivalent correction. J. Magn. Reson. Imaging 2000;12:956-959., (Copyright 2000 Wiley-Liss, Inc.)

An automated coordinate-based system to retrieve brain labels from the 1988 Talairach Atlas, called the Talairach Daemon (TD), was previously introduced [Lancaster et al., 1997]. In the present study, the TD system and its 3-D database of labels for the 1988 Talairach atlas were tested for labeling of functional activation foci. TD system labels were compared with author-designated labels of activation coordinates from over 250 published functional brain-mapping studies and with manual atlas-derived labels from an expert group using a subset of these activation coordinates. Automated labeling by the TD system compared well with authors' labels, with a 70% or greater label match averaged over all locations. Author-label matching improved to greater than 90% within a search range of +/-5 mm for most sites. An adaptive grey matter (GM) range-search utility was evaluated using individual activations from the M1 mouth region (30 subjects, 52 sites). It provided an 87% label match to Brodmann area labels (BA 4 & BA 6) within a search range of +/-5 mm. Using the adaptive GM range search, the TD system's overall match with authors' labels (90%) was better than that of the expert group (80%). When used in concert with authors' deeper knowledge of an experiment, the TD system provides consistent and comprehensive labels for brain activation foci. Additional suggested applications of the TD system include interactive labeling, anatomical grouping of activation foci, lesion-deficit analysis, and neuroanatomy education.

The goal of regional spatial normalization is to remove anatomical differences between individual three-dimensional (3-D) brain images by warping them to match features of a standard brain atlas. Full-resolution volumetric spatial normalization methods use a high-degree-of-freedom coordinate transform, called a deformation field, for this task. Processing to fit features at the limiting resolution of a 3-D MR image volume is computationally intensive, limiting broad use of full-resolution regional spatial normalization. A highly efficient method, designed using an octree decomposition and analysis scheme, is presented to resolve the speed problem while targeting accuracy comparable to current volumetric methods. Translation and scaling capabilities of octree spatial normalization (OSN) were tested using computer models of solid objects (cubes and spheres). Boundary mismatch between transformed and target objects was zero for cubes and less than 1% for spheres. Regional independence of warping was tested using brain models consisting of a homogenous brain volume with one internal homogenous region (lateral ventricle). Boundary mismatch improved with successively smaller octant-level processing and approached levels of less than 1% for the brain and 5% for the lateral ventricle. Five 3-D MR brain images were transformed to a target 3-D brain image to assess boundary matching. Residual boundary mismatch was approximately 4% for the brain and 8% for the lateral ventricle, not as good as with homogeneous brain models, but similar to other results. Total processing time for OSN with a 256(3) brain image (1-mm voxel spacing) was less than 10 min., (Copyright 1999 Academic Press.)

Unlabelled: Global spatial normalization transforms a brain image so that its principal global spatial features (position, orientation and dimensions) match those of a standard or atlas brain, supporting consistent analysis and referencing of brain locations. The convex hull (CH), derived from the brain's surface, was selected as the basis for automating and standardizing global spatial normalization. The accuracy and precision of CH global spatial normalization of PET and MR brain images were evaluated in normal human subjects., Methods: Software was developed to extract CHs of brain surfaces from tomographic brain images. Pelizzari's hat-to-head least-square-error surface-fitting method was modified to fit individual CHs (hats) to a template CH (head) and calculate a nine-parameter coordinate transformation to perform spatial normalization. A template CH was refined using MR images from 12 subjects to optimize global spatial feature conformance to the 1988 Talairach Atlas brain. The template was tested in 12 additional subjects. Three major performance characteristics were evaluated: (a) quality of spatial normalization with anatomical MR images, (b) optimal threshold for PET and (c) quality of spatial normalization for functional PET images., Results: As a surface model of the human brain, the CH was shown to be highly consistent across subjects and imaging modalities. In MR images (n = 24), mean errors for anterior and posterior commissures generally were <1 mm, with SDs < 1.5 mm. Mean brain-dimension errors generally were <1.3 mm, and bounding limits were within 1-2 mm of the Talairach Atlas values. The optimal threshold for defining brain boundaries in both 18F-fluorodeoxyglucose (n = 8) and 15O-water (n = 12) PET images was 40% of the brain maximum value. The accuracy of global spatial normalization of PET images was shown to be similar to that of MR images., Conclusion: The global features of CH-spatially normalized brain images (position, orientation and size) were consistently transformed to match the Talairach Atlas in both MR and PET images. The CH method supports intermodality and intersubject global spatial normalization of tomographic brain images.

The general approach to spatial normalization using a deformation field is presented. Current high degree-of-freedom deformation methods are extremely time-consuming (10-40 hr), and a k-tree method is proposed to greatly reduce this time. A general k-tree method for analysis of source and target images and synthesis of deformation fields is described. The k-tree method simplifies scale control and feature extraction and matching, making it highly efficient. A two-dimensional (2-D), or quadtree, application program was developed for preliminary testing. The k-tree method was evaluated with 2-D images to test rotating ability, nonhomologous region matching, inner and outer brain-structure independence, and feasibility with human brain images. The results of these tests indicate that a three-dimensional (3-D), or octree, method is feasible. Preliminary work with an octree application program indicates that a processing time of under 10 min for 256(3) image arrays is attainable on a Sun Ultra30 workstation.