The attribute of signal sparsity is widely used to sparse representaion. The existing nuclear norm minimization and weighted nuclear norm minimization may achieve a suboptimal in real application with the inaccurate approximation of rank function. This paper presents a novel denoising method that preserves fine structures in the image by imposing L1norm constraints on the wavelet transform coefficients and low rank on high-frequency components of group similar patches. An efficient proximal operator of Truncated Weighted Nuclear Norm (TWNN) is proposed to accurately recover the underlying high-frequency components of low rank patches. By combining a wavelet domain sparse preservation prior with TWNN, the proposed method significantly improves the reconstruction accuracy, leading to a higher PSNR/SSIM and visual quality than state of the art approaches.

The Canadian Open Neuroscience Platform (CONP) takes a multifaceted approach to enabling open neuroscience, aiming to make research, data, and tools accessible to everyone, with the ultimate objective of accelerating discovery. Its core infrastructure is the CONP Portal, a repository with a decentralized design, where datasets and analysis tools across disparate platforms can be browsed, searched, accessed, and shared in accordance with FAIR principles. Another key piece of CONP infrastructure is NeuroLibre, a preprint server capable of creating and hosting executable and fully reproducible scientific publications that embed text, figures, and code. As part of its holistic approach, the CONP has also constructed frameworks and guidance for ethics and data governance, provided support and developed resources to help train the next generation of neuroscientists, and has fostered and grown an engaged community through outreach and communications. In this manuscript, we provide a high-level overview of this multipronged platform and its vision of lowering the barriers to the practice of open neuroscience and yielding the associated benefits for both individual researchers and the wider community.

The cerebral cortex is connected to sub-cortical structures through multiple hierarchically organized descending and ascending pathways. Cortical representations of subcortical neural activity reflect embedded complex spatiotemporal dynamics. Past studies extensively examined the molecular, cellular and circuit properties of intracortical and cortico-subcortical pathways. It remains poorly understood how the spiking activity of a cortical or subcortical neuron is associated with cortex-wide network dynamics. In this study, we use simultaneously recorded mesoscale calcium imaging and behavior video as multi-modality for predicting neuron spiking on awake mice. A novel group patch wise classification and asymptotic model is proposed to address the ultra imbalanced spikes prediction problem. Experiments demonstrate the efficacy of the proposed classification and asymptotic predicting strategies. Our empirical results reveal that the spike activities of neurons were associated with distinct cortical calcium signals and behavior information,which was observed that ongoing neural cortical activity encodes a high-dimensional latent signal of behavior and sensory.

Science gateways often rely on workflow engines to execute applications on distributed infrastructures. We investigate six software architectures commonly used to integrate workflow engines into science gateways. In tight integration, the workflow engine shares software components with the science gateway. In service invocation, the engine is isolated and invoked through a specific software interface. In task encapsulation, the engine is wrapped as a computing task executed on the infrastructure. In the pool model, the engine is bundled in an agent that connects to a central pool to fetch and execute workflows. In nested workflows, the engine is integrated as a child process of another engine. In workflow conversion, the engine is integrated through workflow language conversion. We describe and evaluate these architectures with metrics for assessment of integration complexity, robustness, extensibility, scalability and functionality. Tight integration and task encapsulation are the easiest to integrate and the most robust. Extensibility is equivalent in most architectures. The pool model is the most scalable one and meta-workflows are only available in nested workflows and workflow conversion. These results provide insights for science gateway architects and developers.

Programs may generate different results depending on the computing system where they are executed. Consequently, distributed applications are restricted to a few computing sites to avoid being flawed by numerical variations. We propose algorithms to increase the use of infrastructures while controlling the risk created by numerical variations. Our algorithms rely on a classification of the computing sites updated regularly depending on (i) the amount of observed numerical differences, and (ii) the number of tasks to execute. We simulate our algorithms on a 40-site infrastructure using SimGrid, in 3 different configurations. Results show that for one of the configurations, our algorithm speeds up the execution by a factor of about 4 in 10% of the cases. For the remaining cases and the other 2 configurations, we show that sites cannot be aggregated unless a high risk of numerical variations is tolerated. We conclude that site classifications are a promising approach to handle numerical variability among computing sites. Results could be further improved by integrating more a-priori information in the classifications.

The emergence of hardware virtualization, notably exploited by cloud infrastructures, led to a paradigm shift in distributed computing by enabling complete software customization and elastic scaling of resources. However, new software architectures and deployment algorithms are still required to fully exploit virtualization in web platforms used for scientific computing, commonly called science gateways. We propose a software architecture and an algorithm to enable and optimize the deployment of virtual machines on clusters and clouds in science gateways. Our architecture is based on 3 design principles: (i) separation between resource provisioning and task scheduling (ii) encapsulation of VMs in regular computing tasks (iii) association of a virtual computing site to each disk image. Our algorithm submits and removes VMs on clusters and clouds based on the current system workload, the number of available job slots in active VMs, the cost and current performance of clouds clusters, and a parameter quantifying the performance-cost trade-off. To cope with variable queuing and booting times, it replicates VMs on independent computing sites selected from a minimization of a make span-cost linear combination in the Pareto set of non-dominated solutions. Make span and cost are estimated from the last measured queuing, booting, and task execution times, using an exponential model of the gain yielded by VM replication. We implement this algorithm in CBRAIN, a science gateway widely used for neuroimaging, and we evaluate it on an infrastructure of 2 clusters and 1 cloud. Results show that it is able to reach some points of the performance-cost trade-off associated to VM deployment.

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

Many automatic algorithms have been proposed for analyzing magnetic resonance imaging (MRI) data sets. With the increasingly large data sets being used in brain mapping, there has been a significant rise in the need for accelerating these algorithms. Partial volume estimation (PVE), a brain tissue classification algorithm for MRI, was implemented on a field-programmable gate array (FPGA)-based high performance reconfigurable computer using the Mitrion-C high-level language (HLL). This work develops on prior work in which we conducted initial studies on accelerating the prior information estimation algorithm. In this paper, we extend the work to include probability density estimation and present new results and additional analysis. We used several simulated and real human brain MR images to evaluate the accuracy and performance improvement of the proposed algorithm. The FPGA-based probability density estimation and prior information estimation implementation achieved an average speedup over an Itanium 2 CPU of 2.5 x and 9.4 x , respectively. The overall performance improvement of the FPGA-based PVE algorithm was 5.1 x with four FPGAs.

Many automatic algorithms have been proposed for analyzing magnetic resonance imaging (MRI) data sets. These algorithms allow clinical researchers to generate quantitative data analyses with consistently accurate results. With the increasingly large data sets being used in brain mapping, there has been a significant rise in the need for methods to accelerate these algorithms, as their computation time can consume many hours. This paper presents the results from a recent study on implementing such quantitative analysis algorithms on High-Performance Reconfigurable Computers (HPRCs). A brain tissue classification algorithm for MRI, the Partial Volume Estimation (PVE), is implemented on an SGI RASC RC100 system using the Mitrion-C High-Level Language (HLL). The CPU-based PVE algorithm is profiled and computationally intensive floating-point functions are implemented on FPGA-accelerators. The images resulting from the FPGA-based algorithm are compared to those generated by the CPU-based algorithm for verification. The Similarity Indexes (SI) for pure tissues are calculated to measure the accuracy of the images resulting from the FPGA-based implementation. The portion of the PVE algorithm thatwas implemented on hardware achieved a 11× performance improvement over the CPU-based implementation. The overall performance improvement of the FPGA-accelerated PVE algorithm was 3.5× with four FPGAs.

This paper presents a novel directional morphometry method for surfaces using first order derivatives. Non-directional surface morphometry has been previously used to detect regions of cortical atrophy using brain MRI data. However, evaluating directional changes on surfaces requires computing gradients to obtain a full metric tensor. Non-directionality reduces the sensitivity of deformationbased morphometry to area-preserving deformations. By proposing a method to compute directional derivatives, this paper enables analysis of directional deformations on surfaces. Moreover, the proposed method exhibits improved numerical accuracy when evaluating mean curvature, compared to the so-called cotangent formula. The directional deformation of folding patterns was measured in two groups of surfaces and the proposed methodology allowed to detect morphological differences that were not detected using previous non-directional morphometry. The methodology uses a closed-form analytic formalism rather than numerical approximation and is readily generalizable to any application involving surface deformation.

We present a novel weighted Fourier series (WFS) representation for cortical surfaces. The WFS representation is a data smoothing technique that provides the explicit smooth functional estimation of unknown cortical boundary as a linear combination of basis functions. The basic properties of the representation are investigated in connection with a self-adjoint partial differential equation and the traditional spherical harmonic (SPHARM) representation. To reduce steep computational requirements, a new iterative residual fitting (IRF) algorithm is developed. Its computational and numerical implementation issues are discussed in detail. The computer codes are also available at http://www.stat.wisc.edu/-mchung/softwares/weighted.SPHARM/weighted-SPHARM.html. As an illustration, the WFS is applied i n quantifying the amount ofgray matter in a group of high functioning autistic subjects. Within the WFS framework, cortical thickness and gray matter density are computed and compared.

This paper describes the construction of simulated SPECT and MRI databases that account for realistic anatomical and functional variability. The data is used as a gold-standard to evaluate four SPECT/MRI similarity-based registration methods. Simulation realism was accounted for using accurate physical models of data generation and acquisition. MRI and SPECT simulations were generated from three subjects to take into account inter-subject anatomical variability. Functional SPECT data were computed from six functional models of brain perfusion. Previous models of normal perfusion and ictal perfusion observed in Mesial Temporal Lobe Epilepsy (MTLE) were considered to generate functional variability. We studied the impact noise and intensity non-uniformity in MRI simulations and SPECT scatter correction may have on registration accuracy. We quantified the amount of registration error caused by anatomical and functional variability. Registration involving ictal data was less accurate than registration involving normal data. MR intensity nonuniformity was the main factor decreasing registration accuracy. The proposed simulated database is promising to evaluate many functional neuroimaging methods, involving MRI and SPECT data.

Simulations provide a way of generating data where ground truth is known, enabling quantitative testing of image processing methods. In this paper, we present the construction of 20 realistic digital brain phantoms that can be used to simulate medical imaging data. The phantoms are made from 20 normal adults to take into account intersubject anatomical variabilities. Each digital brain phantom was created by registering and averaging four T1, T2, and proton density (PD)-weighted magnetic resonance imaging (MRI) scans from each subject. A fuzzy minimum distance classification was used to classify voxel intensities from T1, T2, and PD average volumes into grey-matter, white matter, cerebro-spinal fluid, and fat. Automatically generated mask volumes were required to separate brain from nonbrain structures and ten fuzzy tissue volumes were created: grey matter, white matter, cerebro-spinal fluid, skull, marrow within the bone, dura, fat, tissue around the fat, muscles, and skin/muscles. A fuzzy vessel class was also obtained from the segmentation of the magnetic resonance angiography scan of the subject. These eleven fuzzy volumes that describe the spatial distribution of anatomical tissues define the digital phantom, where voxel intensity is proportional to the fraction of tissue within the voxel. These fuzzy volumes can be used to drive simulators for different modalities including MRI, PET, or SPECT. These phantoms were used to construct 20 simulated T1-weighted MR scans. To evaluate the realism of these simulations, we propose two approaches to compare them to real data acquired with the same acquisition parameters. The first approach consists of comparing the intensities within the segmented classes in both real and simulated data. In the second approach, a whole brain voxel-wise comparison between simulations and real T1-weighted data is performed. The first comparison underlines that segmented classes appear to properly represent the anatomy on average, and that inside these classes, the simulated and real intensity values are quite similar. The second comparison enables the study of the regional variations with no a priori class. The experiments demonstrate that these variations are small when real data are corrected for intensity nonuniformity.

During the process of validation of a new tracer, estimation of performance and validation of processing algorithms have to be investigated with data sets representative of the ground truth. Because this ground truth is hardly accessible in positron emission tomography (PET), validations of processing algorithms often rely on the use of simulated data sets. Considering that Monte Carlo simulators are very time consuming and are not very easy to use, the building of publicly available databases of simulated PET volumes are becoming highly desirable. We present here the methodology employed for the creation of a database of simulated dynamic [18F]MPPF-PET data, including inter-individual anatomical and biological variability which meets the criteria of a gold standard database as defined by Lehmann: reliance, equivalence, independence, relevance, significance. The assessment of the realism of the built database against actual MPPF PET data is also presented here. Whereas the database was specifically created for the investigations of quantification of activity and binding of ligand-receptor with the [18F]MPPF PET tracer, it may serve the community with countless purposes. The full strength of this database, does not only stem from the knowledge of important information such as the true activity map and underlying anatomical data, but also from the possibility to fully control the biological difference between sets of simulated PET data. Indeed, time activity curves included in the simulated data sets are controlled by a multicompartmental model of ligand-receptor exchanges. This latter feature is of a great interest in the context of the improvement of the detectability of biological variation in PET.

We are all familiar with the correlation coefficient between two sets of numbers. Now suppose we replace the numbers by vector-valued images in any number of dimensions. The correlation random field is the 'image' of correlations at all possible pairs of points in the two images. We use random field theory to set a threshold on the correlations so that those above the threshold are statistically significant, corrected for searching over all pairs of points. We apply this idea to resting state networks of fMRI images of brain activity, and networks of connectivity in cortical thickness.

Most of the approaches dedicated to automatic morphometry rely on a point-by-point strategy based on warping each brain toward a reference coordinate system. In this paper, we describe an alternative object-based strategy dedicated to the cortex. This strategy relies on an artificial neuroanatomist performing automatic recognition of the main cortical sulci and parcellation of the cortical surface into gyral patches. A set of shape descriptors, which can be compared across subjects, is then attached to the sulcus and gyrus related objects segmented by this process. The framework is used to perform a study of 142 brains of the International Consortium for Brain Mapping (ICBM) database. This study reveals some correlates of handedness on the size of the sulci located in motor areas, which was not detected previously using standard voxel based morphometry.

We present a unified computational approach to tensor-based morphometry in detecting the brain surface shape difference between two clinical groups based on magnetic resonance images. Our approach is novel in a sense that we combined surface modeling, surface data smoothing and statistical analysis in a coherent unified mathematical framework. The cerebral cortex has the topology of a 2D highly convoluted sheet. Between two different clinical groups, the local surface area and curvature of the cortex may differ. It is highly likely that such surface shape differences are not uniform over the whole cortex. By computing how such surface metrics differ, the regions of the most rapid structural differences can be localized. To increase the signal to noise ratio, diffusion smoothing based on the explicit estimation of Laplace-Beltrami operator has been developed and applied to the surface metrics. As an illustration, we demonstrate how this new tensor-based surface morphometry can be applied in localizing the cortical regions of the gray matter tissue growth and loss in the brain images longitudinally collected in the group of children.

Although numerous methods to register brains of different individuals have been proposed, no work has been done, as far as we know, to evaluate and objectively compare the performances of different nonrigid (or elastic) registration methods on the same database of subjects. In this paper, we propose an evaluation framework, based on global and local measures of the relevance of the registration. We have chosen to focus more particularly on the matching of cortical areas, since intersubject registration methods are dedicated to anatomical and functional normalization, and also because other groups have shown the relevance of such registration methods for deep brain structures. Experiments were conducted using 6 methods on a database of 18 subjects. The global measures used show that the quality of the registration is directly related to the transformation's degrees of freedom. More surprisingly, local measures based on the matching of cortical sulci did not show significant differences between rigid and non rigid methods.

The quantitative analysis of magnetic resonance imaging (MRI) data has become increasingly important in both research and clinical studies aiming at human brain development, function, and pathology. Inevitably, the role of quantitative image analysis in the evaluation of drug therapy will increase, driven in part by requirements imposed by regulatory agencies. However, the prohibitive length of time involved and the significant intraand inter-rater variability of the measurements obtained from manual analysis of large MRI databases represent major obstacles to the wider application of quantitative MRI analysis. We have developed a fully automatic "pipeline" image analysis framework and have successfully applied it to a number of large-scale, multicenter studies (more than 1,000 MRI scans). This pipeline system is based on robust image processing algorithms, executed in a parallel, distributed fashion. This paper describes the application of this system to the automatic quantification of multiple sclerosis lesion load in MRI, in the context of a phase III clinical trial. The pipeline results were evaluated through an extensive validation study, revealing that the obtained lesion measurements are statistically indistinguishable from those obtained by trained human observers. Given that intra- and inter-rater measurement variability is eliminated by automatic analysis, this system enhances the ability to detect small treatment effects not readily detectable through conventional analysis techniques. While useful for clinical trial analysis in multiple sclerosis, this system holds widespread potential for applications in other neurological disorders, as well as for the study of neurobiology in general.

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype- phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

Systematic mapping of the variability in cortical sulcal anatomy is an area of increasing interest which presents numerous methodological challenges. To address these issues, we have implemented sulcal extraction and assisted labeling (SEAL) to automatically extract the two-dimensional (2-D) surface ribbons that represent the median axis of cerebral sulci and to neuroanatomically label these entities. To encode the extracted three-dimensional (3-D) cortical sulcal schematic topography (CSST) we define a relational graph structure composed of two main features: vertices (representing sulci) and arcs (representing the relationships between sulci). Vertices contain a parametric representation of the surface ribbon buried within the sulcus. Points on this surface are expressed in stereotaxic coordinates (i.e., with respect to a standardized brain coordinate system). For each of these vertices, we store length, depth, and orientation as well as anatomical attributes (e.g., hemisphere, lobe, sulcus type, etc.). Each arc stores the 3-D location of the junction between sulci as well as a list of its connecting sulci. Sulcal labeling is performed semiautomatically by selecting a sulcal entity in the CSST and selecting from a menu of candidate sulcus names. In order to help the user in the labeling task, the menu is restricted to the most likely candidates by using priors for the expected sulcal spatial distribution. These priors, i.e., sulcal probabilistic maps, were created from the spatial distribution of 34 sulci traced manually on 36 different subjects. Given these spatial probability maps, the user is provided with the likelihood that the selected entity belongs to a particular sulcus. The cortical structure representation obtained by SEAL is suitable to extract statistical information about both the spatial and the structural composition of the cerebral cortical topography. This methodology allows for the iterative construction of a successively more complete statistical models of the cerebral topography containing spatial distributions of the most important structures, their morphometrics, and their structural components.

With the increased interest in computer-aided image analysis methods, there is a greater need for objective methods of algorithm evaluation. Validation of in vivo MRI studies is complicated by a lack of reference data and the difficulty of constructing anatomically realistic physical phantoms. We present here an extensible MRI simulator that efficiently generates realistic three-dimensional (3-D) brain images using a hybrid Bloch equation and tissue template simulation that accounts for image contrast, partial volume, and noise. This allows image analysis methods to be evaluated with controlled degradations of image data.

After conception and implementation of any new medical image processing algorithm, validation is an important step to ensure that the procedure fulfills all requirements set forth at the initial design stage. Although the algorithm must be evaluated on real data, a comprehensive validation requires the additional use of simulated data since it is impossible to establish ground truth with in vivo data. Experiments with simulated data permit controlled evaluation over a wide range of conditions (e.g., different levels of noise, contrast, intensity artefacts, or geometric distortion). Such considerations have become increasingly important with the rapid growth of neuroimaging, i.e., computational analysis of brain structure and function using brain scanning methods such as positron emission tomography and magnetic resonance imaging. Since simple objects such as ellipsoids or parallelepipedes do not reflect the complexity of natural brain anatomy, we present the design and creation of a realistic, high-resolution, digital, volumetric phantom of the human brain. This three-dimensional digital brain phantom is made up of ten volumetric data sets that define the spatial distribution for different tissues (e.g., grey matter, white matter, muscle, skin, etc.), where voxel intensity is proportional to the fraction of tissue within the voxel. The digital brain phantom can be used to simulate tomographic images of the head. Since the contribution of each tissue type to each voxel in the brain phantom is known, it can be used as the gold standard to test analysis algorithms such as classification procedures which seek to identify the tissue "type" of each image voxel. Furthermore, since the same anatomical phantom may be used to drive simulators for different modalities, it is the ideal tool to test intermodality registration algorithms. The brain phantom and simulated MR images have been made publicly available on the Internet (http://www.bic.mni.mcgill.ca/brainweb).

Many critical functionally distinct subcortical structures are not distinguishable on anatomical magnetic resonance imaging (MRI) scans. In order to provide the neurosurgeon with this missing information, a deformable volumetric atlas of the basal ganglia and thalamus has been created from the Schaltenbrand and Wahren atlas of cryogenic slices. The volumetric atlas can be automatically deformed to an individual patient's MRI. To facilitate the clinical use of the atlas, a visualization platform has been developed for preoperative and intraoperative use which permits manipulation of the merged atlas and MRI data sets in two- and three-dimensional views. The platform includes graphical tools which allow the visualization of projections of a leukotome and other surgical tools with respect to the atlas data, as well as preregistered images from any other imaging modality. In addition, a graphical interface has been designed to create custom virtual lesions using computer models of neurosurgical tools for intraoperative planning. To date this system has been employed as an adjunct to over 30 functional neurosurgical cases including surgery for movement disorders.

A novel approach to correcting for intensity nonuniformity in magnetic resonance (MR) data is described that achieves high performance without requiring a model of the tissue classes present. The method has the advantage that it can be applied at an early stage in an automated data analysis, before a tissue model is available. Described as nonparametric nonuniform intensity normalization (N3), the method is independent of pulse sequence and insensitive to pathological data that might otherwise violate model assumptions. To eliminate the dependence of the field estimate on anatomy, an iterative approach is employed to estimate both the multiplicative bias field and the distribution of the true tissue intensities. The performance of this method is evaluated using both real and simulated MR data.

Magnetic resonance imaging (MRI) has become the modality of choice for neuro-anatomical imaging. Quantitative analysis requires the accurate and reproducible labeling of all voxels in any given structure within the brain. Since manual labeling is prohibitively time-consuming and error-prone we have designed an automated procedure called ANIMAL (Automatic Nonlinear Image Matching and Anatomical Labeling) to objectively segment gross anatomical structures from 3D MRIs of normal brains. The procedure is based on nonlinear registration with a previously labeled target brain, followed by numerical inverse transformation of the labels to the native MRI space. Besides segmentation, ANIMAL has been applied to non-rigid registration and to the analysis of morphometric variability. In this paper, the nonlinear registration approach is validated on five test volumes, produced with simulated deformations. Experiments show that the ANIMAL recovers 64% of the nonlinear residual variability remaining after linear registration. Segmentations of the same test data are presented as well. The paper concludes with two applications of ANIMAL using real data. In the first, one MRI volume is nonlinearly matched to a second and is automatically segmented using labels, predefined on the second MRI volume. The automatic segmentation compares well with manual labeling of the same structures. In the second application, ANIMAL is applied to seventeen MRI data sets, and a 3D map of anatomical variability estimates is produced. The automatic variability estimates correlate well (r =0.867, p = 0.01) with manual estimates of inter-subject variability.

The authors developed a method for mapping the change in cerebral glucose utilization at two different physiological states using [(18 )F]fluorodeoxyglucose (FDC) double infection and the constrained weighted-integration method. The authors studied young normal subjects without (baseline-baseline group, n=5) and with (baseline-stimulation group, n=5) vibrotactile stimulation of the fingertips of the right hand. Dynamic scans were performed using positron emission tomography (PET) following an initial dose (the first session, 0-30 min) and an additional dose (the second session, 30-60 min). The parametric images of the net clearance of FDG from blood to brain (K*), unidirectional blood-to-brain clearance (K(1)*), and cerebral metabolic rate of glucose (CMR(glc)) of the two sessions were generated. The averaged subtraction (second minus first session) and t-statistic images were generated, which were rendered into Talairach's stereotaxic coordinates and merged with the averaged magnetic resonance imaging (MRI) image. In the baseline-baseline group, regional K*, K(1)* and CMR(glc) in the first and second sessions were strongly correlated (r(2)=0.953, 0.935, and 0.951, respectively, n=330). In the baseline-stimulation group, significant increases in these estimates were obtained in the contralateral primary somatosensory cortex (SI) (from 3.43+/-0.78 to 4.02+/-1.01 ml/100 g/min for K*, 7.85+/-1.88 to 9.09+/-1.71 ml/100 g/min for K(1)*, and 280+/-5.9 to 32.3+/-5.5 mumol/100 g/min for CMR(glc)), while there were no significant changes in the ipsilateral SI (from 3.45+/-0.83 to 359+/-0.72 ml/100 g/min for K*, 8.17+/-2.33 to 837+/-1.75 ml/100 g/min for K(1 )* and 29.5+/-8.1 to 29.1+/-8.2 mumol/100 g/mln for CMR (glc)), Significant increases in K* and CMR(glc) in the contralateral SI were clearly demonstrated in the t-statistic image. In conclusion, the proposed method allows mapping of changes in cerebral glucose utilization during physiological stimulation of the brain, and will be useful for studying the relationship between neural activity and regional cerebral glucose metabolism.

The authors address the use of multimodality imaging as an aid to the planning and guidance of neurosurgical procedures, and discuss the integration of anatomical (CT and MRI), vascular (DSA), and functional (PET) data for presentation to the surgeon during surgery. The authors' workstation is an enhancement of a commercially available system, and in addition to the guidance offered via a hand-held probe, it incorporates the use of multimodality imaging and adds enhanced realism to the surgeon through the use of a stereoscopic three-dimensional (3-D) image display. The probe may be visualized stereoscopically in single or multimodality images. The integration of multimodality data in this manner provides the surgeon with a complete overview of brain structures on which he is performing surgery, or through which he is passing probes or cannulas, enabling him to avoid critical vessels and/or structures of functional significance.

Human investigators instinctively segment medical images into their anatomical components, drawing upon prior knowledge of anatomy to overcome image artifacts, noise, and lack of tissue contrast. The authors describe: 1) the development and use of a brain tissue probability model for the segmentation of multiple sclerosis (MS) lesions in magnetic resonance (MR) brain images, and 2) an empirical comparison of the performance of statistical and decision tree classifiers, applied to MS lesion segmentation. Based on MR image data obtained from healthy volunteers, the model provides prior probabilities of brain tissue distribution per unit voxel in a standardized 3-D "brain space". In comparison to purely data-driven segmentation, the use of the model to guide the segmentation of MS lesions reduced the volume of false positive lesions by 50-80%