Transoral laser resection versus lip-split mandibulotomy in the management of oropharyngeal squamous cell carcinoma (OPSCC): a case match study.

The objective of this study was to compare transoral laser microsurgery (TLM) with lip-split mandibulotomy (LSM) and radial forearm free-flap reconstruction, for the resection of squamous cell carcinoma of the oropharynx (SCCOP). This study is designed as a case-control study matching 24 patients treated with TLM for SCCOP with those treated with LSM. Patients were matched by age (in 5-year epochs), sex, TNM stage, tumour sub site and type of neck dissection. Each group comprised 20 males and 4 females (mean age 56 years). Seven patients treated with TLM had an elective tracheostomy compared with all patients undergoing LSM. Moreover, the time for decanulation was reduced in patients undergoing tracheostomy for TLM. Although similar rates of patients were able to swallow to some degree on discharge, 29% of patients having LSM were discharged requiring enterostomy feeding compared with 4% of patients treated using TLM. Of those able to swallow on discharge, patients who had TLM resumed swallowing in half the time taken for those having LSM. Moreover, those treated with TLM remained in hospital for half the length of time than those treated with LSM. Due to these factors, overall cost for TLM is reduced in comparison with LSM. In comparison with LSM, TLM for the treatment of SCCOP results in fewer tracheostomies and shorter time to decanulation; a quicker recovery of swallowing function and a reduced length of hospital stay. As a result of this, treatment with TLM is on average cheaper. These factors should be considered when deciding on the surgical treatment of a patient with SCCOP.

Relationship between fractional anisotropy of cerebral white matter and metabolite concentrations measured using (1)H magnetic resonance spectroscopy in healthy adults.

Fractional anisotropy (FA) of water diffusion in cerebral white matter (WM), derived from diffusion tensor imaging (DTI), is a sensitive index of microscopic WM integrity. Physiological and metabolic factors that explain intersubject variability in FA values were evaluated in two cohorts of healthy adults of different age spans (N=65, range: 28-50years; and N=25, age=66.6±6.2, range: 57-80years). Single voxel magnetic resonance spectroscopy (MRS) was used to measure N-acetylaspartate (NAA), total choline-containing compounds, and total creatine, bilaterally in an associative WM tract: anterior corona radiata (ACR). FA values were calculated for the underlying, proximal and two distal WM regions. Two-stage regression analysis was used to calculate the proportion of variability in FA values explained by spectroscopy measurements, at the first stage, and subject's age, at the second stage. WM NAA concentration explained 23% and 66% of intersubject variability (p<0.001) in the FA of the underlying WM in the younger and older cohorts, respectively. WM NAA concentration also explained a significant proportion of variability in FA of the genu of corpus callosum (CC), a proximal WM tract where some of the fibers contained within the spectroscopic voxel decussate. NAA concentrations also explained a significant proportion of variability in the FA values in the splenium of CC, a distal WM tract that also carries associative fibers, in both cohorts. These results suggest that MRS measurements explained a significant proportion of variability in FA values in both proximal and distal WM tracts that carry similar fiber-types.

Genetics of primary cerebral gyrification: Heritability of length, depth and area of primary sulci in an extended pedigree of Papio baboons.

Genetic control over morphological variability of primary sulci and gyri is of great interest in the evolutionary, developmental and clinical neurosciences. Primary structures emerge early in development and their morphology is thought to be related to neuronal differentiation, development of functional connections and cortical lateralization. We measured the proportional contributions of genetics and environment to regional variability, testing two theories regarding regional modulation of genetic influences by ontogenic and phenotypic factors. Our measures were surface area, and average length and depth of eleven primary cortical sulci from high-resolution MR images in 180 pedigreed baboons. Average heritability values for sulcal area, depth and length (h(2)(Area)=.38+/-.22; h(2)(Depth)=.42+/-.23; h(2)(Length)=.34+/-.22) indicated that regional cortical anatomy is under genetic control. The regional pattern of genetic contributions was complex and, contrary to previously proposed theories, did not depend upon sulcal depth, or upon the sequence in which structures appear during development. Our results imply that heritability of sulcal phenotypes may be regionally modulated by arcuate U-fiber systems. However, further research is necessary to unravel the complexity of genetic contributions to cortical morphology.

Genetics of microstructure of cerebral white matter using diffusion tensor imaging.

We analyzed the degree of genetic control over intersubject variability in the microstructure of cerebral white matter (WM) using diffusion tensor imaging (DTI). We performed heritability, genetic correlation and quantitative trait loci (QTL) analyses for the whole-brain and 10 major cerebral WM tracts. Average measurements for fractional anisotropy (FA), radial (L( perpendicular)) and axial (L( vertical line)) diffusivities served as quantitative traits. These analyses were done in 467 healthy individuals (182 males/285 females; average age 47.9+/-13.5 years; age range: 19-85 years), recruited from randomly-ascertained pedigrees of extended families. Significant heritability was observed for FA (h(2)=0.52+/-0.11; p=10(-7)) and L( perpendicular) (h(2)=0.37+/-0.14; p=0.001), while L( vertical line) measurements were not significantly heritable (h(2)=0.09+/-0.12; p=0.20). Genetic correlation analysis indicated that the FA and L( perpendicular) shared 46% of the genetic variance. Tract-wise analysis revealed a regionally diverse pattern of genetic control, which was unrelated to ontogenic factors, such as tract-wise age-of-peak FA values and rates of age-related change in FA. QTL analysis indicated linkages for whole-brain average FA (LOD=2.36) at the marker D15S816 on chromosome 15q25, and for L( perpendicular) (LOD=2.24) near the marker D3S1754 on the chromosome 3q27. These sites have been reported to have significant co-inheritance with two psychiatric disorders (major depression and obsessive-compulsive disorder) in which patients show characteristic alterations in cerebral WM. Our findings suggest that the microstructure of cerebral white matter is under a strong genetic control and further studies in healthy as well as patients with brain-related illnesses are imperative to identify the genes that may influence cerebral white matter.

Loss of cerebral white matter structural integrity tracks the gray matter metabolic decline in normal aging.

Relationships between structural MRI-based markers of declining cerebral integrity, and regional PET measurements of (18)FDG uptake have not been studied well in normal aging. In this manuscript we relate changes in cerebral morphology to regional cerebral glucose uptake for 14 major cortical areas in 19 healthy older individuals (age 59-92 years). Measurements of cerebral integrity included gray matter (GM) thickness, sulcal and intergyral spans, fractional anisotropy (FA) of water diffusion and volume of hyperintense WM (HWM) lesions. (18)FDG-PET measurements were converted to standard uptake values and corrected for partial volume artifact. Following this, cortical FDG uptake was significantly correlated with several indices of WM integrity that we previously observed to be sensitive to cognitive decline in executive function, including intergyral span and HWM volumes. Our findings suggest that the age-related decline in white matter integrity, observed as increases in HWM lesions, intergyral spans and reduction in FA, correlated with a decline in the global and regional cerebral glucose uptake. Our findings support the emerging consensus that WM integrity indices are sensitive predictors of declining cerebral health in normal aging. Specifically, age-related WM degradation in the thinly myelinated association tracts appears to track the decreases in global and regional rates of glucose uptake.

3D modeling of the total electric field induced by transcranial magnetic stimulation using the boundary element method.

Transcranial magnetic stimulation (TMS) delivers highly localized brain stimulations via non-invasive externally applied magnetic fields. This non-invasive, painless technique provides researchers and clinicians with a unique tool capable of stimulating both the central and peripheral nervous systems. However, a complete analysis of the macroscopic electric fields produced by TMS has not yet been performed. In this paper, we addressed the importance of the secondary E-field created by surface charge accumulation during TMS using the boundary element method (BEM). 3D models were developed using simple head geometries in order to test the model and compare it with measured values. The effects of tissue geometry, size and conductivity were also investigated. Finally, a realistically shaped head model was used to assess the effect of multiple surfaces on the total E-field. Secondary E-fields have the greatest impact at areas in close proximity to each tissue layer. Throughout the head, the secondary E-field magnitudes typically range from 20% to 35% of the primary E-field's magnitude. The direction of the secondary E-field was generally in opposition to the primary E-field; however, for some locations, this was not the case (i.e. going from high to low conductivity tissues). These findings show that realistically shaped head geometries are important for accurate modeling of the total E-field.

High prevalence of pineal cysts in healthy adults demonstrated by high-resolution, noncontrast brain MR imaging.

BACKGROUND AND PURPOSE: Although the prevalence of pineal cysts in autopsy series has been reported as being between 25% and 40%, MR studies have documented their frequency to range between 1.5% and 10.8%. The purpose of this high-resolution brain MR imaging study at 1.9T was to determine the prevalence of pineal cysts in healthy adults. MATERIALS AND METHODS: Brain MR images of 100 healthy young volunteers were randomly selected from our International Consortium for Brain Mapping project data base. Cysts were detected as circular areas of isointensity relative to CSF on both 3D gradient-echo T1-weighted and 2D fast spin-echo T2-weighted images. The inner diameters of all visualized pineal cysts were measured, and a criterion of 2.0 mm of the largest inner cross-sectional diameter was used to categorize cysts as being either small cystic changes (<2.0-mm diameter) or pineal cysts (>2.0-mm diameter). RESULTS: Twenty-three percent (23/100) of the volunteers had pineal cysts with a mean largest inner cross-sectional diameter of 4.3 mm (range, 2-14 mm); 13% (13/100) demonstrated cystic changes involving the pineal gland with the largest inner cross-sectional diameter of less than 2.0 mm. There was a slight female predominance. Two subjects with long-term follow-up scans showed no symptoms or changes in the size of their pineal cysts. CONCLUSION: On high-resolution MR imaging, the prevalence of pineal cysts was 23% in our healthy group of adults, which is consistent with previous autopsy studies. Long-term follow-up studies of 2 cases demonstrated the stability of the cysts.

Detailed 3D models of the induced electric field of transcranial magnetic stimulation coils.

Previous models neglected contributions from current elements spanning the full geometric extent of wires in transcranial magnetic stimulation (TMS) coils. A detailed account of TMS coil wiring geometry is shown to provide significant improvements in the accuracy of electric field (E-field) models. Modeling E-field dependence based on the TMS coil's wire width, height, shape and number of turns clearly improved the fit of calculated-to-measured E-fields near the coil body. Detailed E-field models were accurate up to the surface of the coil body (within 0.5% of measured) where simple models were often inadequate (up to 32% different from measured).

Beyond the single study: function/location metanalysis in cognitive neuroimaging.

Cognitive neuroimaging maps the brain locations of mental operations. This process is iterative, as no single study can fully characterize a mental operation or its brain location. This iterative discovery process, in combination with the location-reporting standard (i.e. spatial coordinates) of the cognitive neuroimaging community, has engendered a new form of metanalysis. Response locations from multiple studies have been analyzed collectively so as to better describe the spatial distribution of brain activations, with promising results. New hypotheses regarding elementary mental operations and their respective brain locations are being generated and refined via metanalysis. These hypotheses are being tested and confirmed by subsequent, prospective experiments. Function/location metanalysis is an important new tool for hypothesis generation in cognitive neuroimaging. This form of metanalysis is fundamentally different from the effect-size metanalyses prevalent in other literatures, with unique advantages and challenges.

MR imaging volumetry of subcortical structures and cerebellar hemispheres in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: There is mounting evidence of extratemporal volume changes associated with medically refractory temporal lobe epilepsy (TLE). This MR imaging study aimed to characterize volume changes in subcortical structures and cerebellar hemispheres with respect to lateralization of the seizure focus, onset and duration of epilepsy, and frequency of generalized tonic-clonic seizures (GTCS). METHODS: Amygdalar, hippocampal, thalamic, caudate head, and cerebellar volume measurements were obtained in the preoperative MR images of 40 patients with TLE (20 right, 20 left), who underwent temporal lobe resection with good outcome, and in 20 right-handed control participants. All 3D MR images were spatially aligned and normalized before measurements were obtained. Standardized volumes and right-to-left volume ratios (VRs) were compared between control participants and right and left TLE groups. Multiple regression analyses were performed to study the effects of epilepsy onset and duration and GTCS frequency on ipsilateral-to-contralateral VRs with respect to the resected seizure focus. RESULTS: Thalamic volumes were smaller bilaterally in patients with TLE. Hippocampal volumes were smaller ipsilateral to the seizure focus, but there was no significant volume loss involving the amygdala, caudate, or cerebellum. Hippocampal and amygdalar right-to-left VRs differed significantly between right and left TLE groups and controls, whereas thalamic right-to-left VRs differed only between the TLE groups. Thalamic ipsilateral-to-contralateral VRs were correlated positively with epilepsy onset and negatively with epilepsy duration. Caudate ipsilateral-to-contralateral VRs were positively, whereas amygdalar and cerebellar VRs were negatively, correlated with GTCS frequency. CONCLUSIONS: Unilateral amygdalar and bilateral thalamic volume loss, in the absence of caudate head atrophy, is likely to reflect seizure-induced injury due to TLE. Correlations of VRs affecting the amygdala, caudate, and cerebellum with GTCS frequency may also reflect injury or a prediposition for secondary generalization. Potential effects of complex partial seizures, febrile seizures, or antiepileptic medications on subcortical structures need to be evaluated in future studies.

Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women.

In this study, total body fat content and fat topography were related to glucose metabolism in the basal and insulin-stimulated states in 18 nonobese and 18 obese premenopausal nondiabetic women. All subjects received a euglycemic insulin (20 mU.min-1.m2) clamp study in combination with [3-3H]-D-glucose infusion and indirect calorimetry to quantitate total body glucose uptake, glucose oxidation, and nonoxidative glucose disposal. Total body fat content was determined with tritiated water, whereas body fat distribution was estimated from the WHR, the STR, and the VSR (measured by magnetic resonance imaging). In the postabsorptive state, total body glucose utilization, glucose oxidation, and nonoxidative glucose disposal rates were similar in nonobese and obese women, whereas during the insulin clamp all three metabolic parameters were reduced significantly in the obese group. In nonobese women, total body fat content was related inversely to both total and nonoxidative glucose disposal during the insulin clamp, whereas no relationship was found between glucose metabolism (total, oxidative, and nonoxidative) and WHR, STR, or VSR. In contrast, in obese women, no relationship was observed between total body fat content and any measure of insulin-mediated glucose metabolism. However, both WHR and VSR were related inversely to total, oxidative, and nonoxidative glucose disposal rates during the insulin clamp. These results suggest that total body fat content and body fat topography are associated differently with insulin-mediated glucose metabolism in nonobese and obese women. In the nonobese women, total body fat mass appears to be a primary determinant of tissue sensitivity to insulin, whereas in obese women, body fat topography exerts a more dominant effect.

Conservative management of epistaxis: are we putting patients at risk of developing venous thromboembolic complications?

A retrospective study of 1585 patients, admitted with epistaxis to a busy District General Hospital in the United Kingdom between 1990 and 2000, was undertaken in order to identify the relationship between hospital admission for epistaxis and the development of a venous thromboembolic event. Only one person (0.06%) developed pulmonary embolus (PE) within 6 weeks of hospital admission. No one developed a deep vein thrombosis (DVT). This compares with the incidence of DVT and fatal PE in the general population. In our study population, the incidence of both PE and DVT was found to be no greater than that seen within the community and certainly less than the incidence seen within a group of high risk hospitalised patients. We conclude that hospital admission for epistaxis does not place the patient at increased risk of thromboembolic disease.

Bromocriptine: a novel approach to the treatment of type 2 diabetes.

OBJECTIVE: In vertebrates, body fat stores and insulin action are controlled by the temporal interaction of circadian neuroendocrine oscillations. Bromocriptine modulates neurotransmitter action in the brain and has been shown to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes. We studied the effect of a quick-release bromocriptine formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: There were 22 obese subjects with type 2 diabetes randomized to receive a quick-release formulation of bromocriptine (n = 15) or placebo (n = 7) in a 16-week double-blind study. Subjects were prescribed a weight-maintaining diet to exclude any effect of changes in body weight on the primary outcome measurements. Fasting plasma glucose concentration and HbA(1c) were measured at 2- to 4-week intervals during treatment. Body composition (underwater weighing), body fat distribution (magnetic resonance imaging), oral glucose tolerance (oral glucose tolerance test [OGTT]), insulin-mediated glucose disposal, and endogenous glucose production (2-step euglycemic insulin clamp, 40 and 160 mU x min(-1) x m(-2)) were measured before and after treatment. RESULTS: No changes in body weight or body composition occurred during the study in either placebo- or bromocriptine-treated subjects. Bromocriptine significantly reduced HbA(1c) (from 8.7 to 8.1%, P = 0.009) and fasting plasma glucose (from 190 to 172 mg/dl, P = 0.02) levels, whereas these variables increased during placebo treatment (from 8.5 to 9.1%, NS, and from 187 to 223 mg/dl, P = 0.02, respectively). The differences in HbA(1c) (delta = 1.2%, P = 0.01) and fasting glucose (delta = 54 mg/dl, P < 0.001) levels between the bromocriptine and placebo group at 16 weeks were highly significant. The mean plasma glucose concentration during OGTT was significantly reduced by bromocriptine (from 294 to 272 mg/dl, P = 0.005), whereas it increased in the placebo group. No change in glucose disposal occurred during the first step of the insulin clamp in either the bromocriptine- or placebo-treated group. During the second insulin clamp step, bromocriptine improved total glucose disposal from 6.8 to 8.4 mg x min(-1) kg(-1) fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg min(-1) x kg(-1) FFM (P < 0.05), whereas both of these variables deteriorated significantly (P < or = 0.02) in the placebo group. CONCLUSIONS: Bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients. Both reductions in fasting and postprandial plasma glucose levels appear to contribute to the improvement in glucose tolerance. The bromocriptine-induced improvement in glycemic control is associated with enhanced maximally stimulated insulin-mediated glucose disposal.

Strategies for 3-D visualization of ocular structures.

The ability to visualize noninvasively the internal structure of the body has been widely utilized in clinical and research applications. Current tomographic structural imaging modalities, i.e., x-ray computed tomography (CT) and magnetic resonance imaging, produce image data which can be processed to reveal the three-dimensional surface of an internal object using surface rendering, or alternatively, the surface and internal details of the object using volume rendering. To take full advantage of these techniques, the acquisition and preparation of the tomographic data must be optimized for the imaging modality, for the target tissue, and for the specific visualization needs of the structure of interest. Strategies for optimizing each of these parameters are presented using, as an example, an x-ray CT study of a bony orbital fracture.

Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness.

OBJECTIVE: Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. METHOD: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively. RESULTS: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. CONCLUSIONS: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.

Technical anc clinical characteristics of a surgical biopsy probe.

A probe intended for intraoperative biopsy was designed. It is small, collimated, and separated from the photomultiplier tube and high-voltage source by a flexible fiberoptic light guide. Its use in four patients undergoing bone or soft-tissue biopsies is described.

Practical gamma camera quality control with a four-point phantom.

A gamma camera QC phantom for practical assessment of resolution (average FWHM), spatial calibration (pixels/mm), nonhomogeneity of spatial calibration, and average point-source sensitivity (cpm/muCi) was developed and evaluated. The phantom consists of four 57Co-point sources mounted on a Plexiglas base at corners of a square 10 cm on each side. Computer acquisition and processing are fully automated and require less than 1 min for point sources totaling 100 muCi (3.7 MBq) activity. The normal range of variability of measured QC parameters from a 12 wk evaluation period with four different gamma cameras (assumed to be operating normally) yielded coefficients of variation ranging from 0.3% for spatial calibration (pixels/mm) to 2.3% for sensitivity (cpm/muCi) assessments. From the normal range of variability a minimum detectable difference (MDD) was determined for each measured parameter and each gamma camera. The range of acceptable operation of a gamma camera system was set as the measured value +/- MDD for each QC parameter. The ability to detect and track small changes in the measured QC parameters was evaluated.

Effect of errors in reangulation on planar and tomographic thallium-201 washout profile curves.

Cardiac phantom studies were performed with and without a defect present to test the hypothesis that myocardial 201TI quantitative circumferential washout profile curves calculated from planar and rotating slant hole (RSH) collimator tomographic images are equally affected by errors in axial repositioning. Simulated stress images were acquired with the long axis of the phantom perpendicular to the camera surface and redistribution images were acquired to represent 50% 201TI washout with axial repositioning errors relative to the stress position ranging from 0 to 20 degrees in 5 degrees increments. There was a decrease in the 201TI washout profile curves compared to that expected (50%) in the wall tilted away from the camera surface, and a reciprocal increase in the 201TI washout profile curves in the wall tilted towards the camera surface for both imaging techniques whether a lesion was present or not. This effect became more pronounced as the error in axial repositioning was increased for both the planar (p less than 0.001) and the RSH tomographic (p less than 0.001) techniques. However, the deviation of the 201TI washout profile curves from that expected (50%) was greater for the planar imaging technique with or without a lesion (p less than 0.05 to 0.001). Thus, we conclude that 201TI quantitative circumferential washout profile curves calculated using this tomographic imaging technique are less affected by errors in axial repositioning than those calculated using an equivalent projection by standard planar imaging methods. These data emphasize the importance which must be placed on the repositioning of patients to obtain valid 201TI washout profile curves for the detection and localization of coronary artery disease.

Quantification of left-ventricular regional dyssynergy by radionuclide angiography.

To determine whether variables obtained from Fourier analysis of gated equilibrium radionuclide angiographic (RNA) images can detect and quantify changes in left-ventricular (LV) regional wall motion induced by transient ischemia, 11 chronically instrumented dogs were simultaneously studied with hemodynamic measurements and RNA during control, left circumflex (LCx) coronary artery occlusion, and postocclusion conditions. The dogs were preinstrumented with aortic and LV catheters, electromagnetic aortic and LCx coronary artery flow probes, high-fidelity LV micromanometers, LCx coronary artery occluders, and 4-mm ultrasonic transverse LV diameter and 2-mm regional LV segment crystal pairs. Radionuclide LV regional phase and amplitude variables were calculated for each condition. The absolute changes in LCx region RNA mean, median, and standard deviation of mean phase correlated with the percent changes in LCx segment crystal fractional shortening (r = -0.71, -0.64, and -0.51, respectively; all p less than or equal to 0.01). Similarly, the absolute changes and percent changes in LCx region RNA mean amplitude per pixel correlated with the percent changes in LCx segment crystal fractional shortening (r = 0.89 and 0.94, respectively; both p less than 0.001). When these LCx region RNA phase variables were subgrouped according to mild or severe depression or augmentation in LCx segment crystal fractional shortening, progressive differences were observed between the average values for these subgroups (p less than 0.05 to p less than 0.001). These data, therefore, suggest that these regional RNA phase variables may be able to detect and quantify alterations in LV contraction patterns due to transient ischemia.

Global spatial normalization of human brain using convex hulls.

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.