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Optimization of brain conformal mapping with landmarks.

To compare and integrate brain data, data from multiple subjects are typically mapped into a canonical space. One method to do this is to conformally map cortical surfaces to the sphere. It is well known that any genus zero Riemann surface can be conformally mapped to a sphere. Therefore, conformal mapping offers a convenient method to parameterize cortical surfaces without angular distortion, generating an orthogonal grid on the cortex that locally preserves the metric. To compare cortical surfaces more effectively, it is advantageous to adjust the conformal parameterizations to match consistent anatomical features across subjects. This matching of cortical patterns improves the alignment of data across subjects, although it is more challenging to create a consistent conformal (orthogonal) parameterization of anatomy across subjects when landmarks are constrained to lie at specific locations in the spherical parameter space. Here we propose a new method, based on a new energy functional, to optimize the conformal parameterization of cortical surfaces by using landmarks. Experimental results on a dataset of 40 brain hemispheres showed that the landmark mismatch energy can be greatly reduced while effectively preserving conformality. The key advantage of this conformal parameterization approach is that any local adjustments of the mapping to match landmarks do not affect the conformality of the mapping significantly. We also examined how the parameterization changes with different weighting factors. As expected, the landmark matching error can be reduced if it is more heavily penalized, but conformality is progressively reduced.

Adult↗

Conduction aphasia as a function of the dominant posterior perisylvian cortex. Report of two cases.

Assessment of eloquent functions during brain mapping usually relies on testing reading, speech, and comprehension to uncover transient deficits during electrical stimulation. These tests stem from findings predicted by the Geschwind-Wernicke hypothesis of receptive and expressive cortices connected by white matter tracts. Later work, however, has emphasized cortical mechanisms of language function. The authors report two cases that demonstrate that conduction aphasia is cortically mediated and can be inadequately assessed if not specifically evaluated during brain mapping. To determine the distribution of language on the dominant cortex, electrical cortical stimulation was performed in two cases by using implanted subdural electrodes during brain mapping before epilepsy surgery. A transient isolated deficit in repetition of language was reported during stimulation of the posterior portion of the dominant superior temporal gyrus in one patient and during stimulation of the supramarginal gyrus in the other patient. These cases demonstrate a localization of language repetition to the posterior perisylvian cortex. Brain mapping of this region should include assessment of verbal repetition to avoid potential deficits resembling conduction aphasia.

Adult↗

Clinical magnetic susceptibility mapping of the brain.

A field mapping technique was used to detect changes in the local magnetic field in 14 tumors, five hematomas, one lacunar infarct, and two cases of multiple sclerosis. These changes were attributed to variations in the tissue susceptibility. A partial or complete rim of changed susceptibility was detected at the margin of five of the tumors and localized changes were seen within two of the tumors. All five hematomas displayed susceptibility effects. These were seen at the rim of the hematoma in all cases but central effects were also seen in four cases. One area of probable lacunar infarction also displayed susceptibility effects. The effects described may be due to the paramagnetic contribution of species such as deoxyhemoglobin, methemoglobin, free ferric iron, hemosiderin, and other breakdown products of blood. Local field inhomogeneities due to changes in tissue susceptibility have implications for magnetic resonance (MR) image interpretation and the performance of MR spectroscopy.

Brain Diseases↗

Optics-free spatial genomics for mapping mammalian brain aging by IRISeq.

Spatial transcriptomics has emerged as a transformative approach for in situ mapping of cellular heterogeneity and interactions, yet existing methods often compromise throughput, cost and tissue coverage. Here we introduce Imaging Reconstruction using Indexed Sequencing (IRISeq): an optics-free, cost-effective platform that leverages spatial interaction mapping by indexed sequencing to profile tissues at adjustable sizes and resolutions (5-50 µm). We applied IRISeq to map gene expression across more than 70 coronal sections from both adult and aged mouse brains, including wild-type and two lymphocyte-deficient models (Rag1 and Prkdc mutants) and generated more than 460,000 spatial transcriptome profiles. Our integrated analysis with 783,264 single-cell transcriptomes revealed region-specific aging signatures that are lymphocyte dependent, notably a downregulation of interferon signaling and inflammation in ventricular regions upon lymphocyte depletion, alongside mutant-specific upregulation of senescence pathways. Furthermore, lymphocyte deficiency was linked to preserved abundance of ependymal cells that line the brain's ventricles and to distinct microglial state dynamics, highlighting a key role for lymphocytes in driving inflammatory processes during brain aging. Overall, IRISeq provides a high-throughput and cost-effective solution for spatially resolved transcriptomic profiling, opening new avenues for elucidating region-specific cellular mechanisms underlying aging and identifying potential therapeutic targets to preserve brain homeostasis.

Animals↗

Semi-automated extraction of brain contours from MRI.

We compared brain volumes computed by trained operators using the BRAIN-MAP algorithm, which automatically extracts the contours of the brain from gradient-echo magnetic resonance images. The images of 19 subjects randomly selected from a group of normals and a group of patients with dementia were included. BRAIN-MAP found brain perimeters that were on the average ca. 3% tighter than those obtained by two experienced operators. Between-operator and within-operator reproducibility of the analyses were also estimated and found to be (-0.13 +/- 0.51)% and (-0.63 +/- 0.08)%, respectively. Replicate volume measurement by the computer alone provided a reproducibility of (0.44 +/- 0.46)%.

Adult↗

Effect of stimulus intensity on visually-evoked electrical brain activity maps in rabbit.

Stimulation by means of flashes is a commonly-used method in basic research into evoked potentials. Nevertheless, the different responses obtained at different luminous intensities, to which the inter-individual and intra-individual differences are added, determine the need to control this stimulus parameter for each experimental model. Maps of visually-evoked activity in the rabbit brain, obtained after monocular stimulation with flashes at different intensities of luminosity, are presented. Variation in the intensity of the luminous stimulus does not substantially affect the distribution of the electrical potential on the surface of rabbit brain described in previous articles.

Animals↗

A comparative evaluation of wavelet-based methods for hypothesis testing of brain activation maps.

Wavelet-based methods for hypothesis testing are described and their potential for activation mapping of human functional magnetic resonance imaging (fMRI) data is investigated. In this approach, we emphasise convergence between methods of wavelet thresholding or shrinkage and the problem of hypothesis testing in both classical and Bayesian contexts. Specifically, our interest will be focused on the trade-off between type I probability error control and power dissipation, estimated by the area under the ROC curve. We describe a technique for controlling the false discovery rate at an arbitrary level of error in testing multiple wavelet coefficients generated by a 2D discrete wavelet transform (DWT) of spatial maps of fMRI time series statistics. We also describe and apply change-point detection with recursive hypothesis testing methods that can be used to define a threshold unique to each level and orientation of the 2D-DWT, and Bayesian methods, incorporating a formal model for the anticipated sparseness of wavelet coefficients representing the signal or true image. The sensitivity and type I error control of these algorithms are comparatively evaluated by analysis of "null" images (acquired with the subject at rest) and an experimental data set acquired from five normal volunteers during an event-related finger movement task. We show that all three wavelet-based algorithms have good type I error control (the FDR method being most conservative) and generate plausible brain activation maps (the Bayesian method being most powerful). We also generalise the formal connection between wavelet-based methods for simultaneous multiresolution denoising/hypothesis testing and methods based on monoresolution Gaussian smoothing followed by statistical testing of brain activation maps.

Algorithms↗

Functional mapping of human medial frontal motor areas. The combined use of functional magnetic resonance imaging and cortical stimulation.

Two functional brain-mapping techniques, functional magnetic resonance imaging (fMRI) and cortical stimulation by chronically implanted subdural electrodes, were used in combination for presurgical evaluation of three patients with intractable, partial motor seizures. Brain mapping was focused on characterizing motor-related areas in the medial frontal cortex, where all patients had organic lesions. Behavioral tasks for fMRI involved simple finger and foot movements in all patients and mental calculations in one of them. These tasks allowed us to discriminate several medial frontal motor areas: the presupplementary motor areas (pre-SMA), the somatotopically organized SMA proper, and the foot representation of the primary motor cortex. All patients subsequently underwent cortical stimulation through subdural electrodes placed onto the medial hemispheric wall. In each patient, the cortical stimulation map was mostly consistent with that patient's brain map by fMRI. By integrating different lines of information, the combined fMRI and cortical stimulation map will contribute not only to safe and effective surgery but also to further understanding of human functional neuroanatomy.

Adult↗

Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.

Adult↗

An intensity consistent filtering approach to the analysis of deformation tensor derived maps of brain shape.

Deformation tensor morphometry makes use of the derivatives of spatial transformations between anatomies, to provide highly localized volumetric maps of relative anatomical size. The analysis of such maps, however, has the challenge of describing the data in a way that allows the spatial scale and extent of the local shape properties to match those induced by the disease process being studied. This study examines an approach to the spatial filtering of transformation Jacobian maps created in multisubject studies of brain anatomy, which constrains the filter neighborhood within common structural boundaries present in the spatially normalized image data. The filtering incorporates information derived from the spatial normalization process, using a statistical framework to introduce a measure of uncertainty in local regional intensity correspondence following spatial normalisation. The proposed filtering approach is compared to the use of spatially invariant Gaussian filtering in the analysis of Jacobian determinant maps of brain shape and shape change in Alzheimer's disease and normal aging. Results show significantly improved delineation of fine scale patterns of shape difference (in cross-sectional studies) and shape change (from multiple serial magnetic resonance imaging studies).

Age Factors↗

Investigation of different transcript quantitation tools for high-throughput mapping of brain gene expression using voxelation.

Voxelation is a new approach for genome scale acquisition of brain gene expression patterns. The method employs high-throughput analysis of spatially registered voxels (cubes) to create multiple volumetric images of brain gene expression, similar to those obtained from biomedical imaging systems. The spatial resolution of voxelation depends on voxel size, with smaller voxels giving higher resolution. An important question is the applicability of different transcript profiling tools for the various levels of resolution that can be employed. Here, we describe the use of three methods to analyze voxel transcript abundance: real-time PCR, microarray analysis and linear amplification coupled with microarrays. We show statistically significant concordance between real-time PCR and microarray analysis for the myelin basic protein gene in human brain specimens at differing levels of spatial resolution. In addition, we also demonstrate the feasibility of using linear amplification coupled with microarray analysis to create voxelation maps from the mouse brain at high resolution, 1 microl. These data indicate the suitability of a number of transcript profiling tools for various levels of spatial resolution in voxelation.

Brain↗

Functional magnetic resonance imaging - basics and applications in oncology.

Functional MR imaging (F-MRI) permits to visualize active processes evolving in the human brain. The shifts in blood oxygenation following local neuronal activation are used for generating an MR signal. Specific procedural problems have to be solved when using F-MRI in patients with brain neoplasms. The relationship between perirolandic tumors and the adjacent motor areas has been studied most intensively. When the resection of tumors in the motor area is considered, functional imaging can help the surgeon to avoid or at least to minimize postoperative functional deficits. Overall, F-MRI study results are useful in at least one crucial preoperative decision step for about 90% of brain tumor patients. Experience with functional imaging in radiotherapy of brain neoplasms is still limited. Presently, F-MRI cannot yet replace intraoperative brain mapping.

Brain↗

Transcranial magnetic stimulation--a new tool for functional imaging of the brain.

Recent progress in the theory and technology of transcranial magnetic stimulation (TMS) is leading to novel approaches in brain mapping. TMS becomes a powerful functional brain mapping tool when other imaging methods are used to record TMS-evoked activity or when peripheral effects are observed as a function of stimulus location. TMS-evoked activity currently can be recorded by EEG, PET, and fMRI. In addition to providing indices of cortical excitability, these methods allow one to study brain connectivity directly, without the need for behavioral activations. When the coordinate systems in the different imaging modalities are combined, anatomical structures seen in MRI and activation sites determined by PET, fMRI, or MEG/EEG can be used for the selection of target areas in the brain. PET and fMRI can be used to map the spatial distribution of TMS-evoked activity. On the other hand, the combination of TMS and high-resolution EEG may often be the method of choice for basic neuroscience and for clinical diagnosis, for example, in the assessment of brain connectivity in patients suffering from neurodegenerative diseases or head injuries.

Brain↗

Cortical mapping by functional magnetic resonance imaging in patients with brain tumors.

The aim of our study was to establish the effectiveness of the functional MRI (fMRI) technique in comparison with intraoperative cortical stimulation (ICS) in planning cortex-saving neurosurgical interventions. The combination of sensory and motor stimulation during fMRI experiments was used to improve the exactness of central sulcus localization. The study subjects were 30 volunteers and 33 patients with brain tumors in the rolandic area. Detailed topographical relations of activated areas in fMRI and intraoperative techniques were compared. The agreement in the location defined by the two methods for motor centers was found to be 84%; for sensory centers it was 83%. When both kinds of activation are taken into account this agreement increases to 98%. A significant relation was found between fMRI and ICS for the agreement of the distance both for motor and sensory centers (p=0.0021-0.0024). Also a strong dependence was found between the agreement of the location and the agreement of the distance for both kinds of stimulation. The spatial correlation between fMRI and ICS methods for the sensorimotor cortex is very high. fMRI combining functional and structural information is very helpful for preoperative neurosurgical planning. The sensitivity of the fMRI technique in brain mapping increases when using both motor and sensory paradigms in the same patient.

Adult↗

Mapping individual brains to guide restorative therapy after stroke: rationale and pilot studies.

Some treatments under development to improve motor outcome after stroke require information about organization of individual subject's brain. The current study aimed to characterize normal inter-subject differences in localization of motor functions, and to consider these findings in relation to a potential treatment of motor deficits after stroke. Functional MRI (fMRI) scanning in 14 subjects examined right index finger tapping, shoulder rotation, or facial movement. The largest activation cluster in left sensorimotor cortex was identified for each task, and its center expressed in Talairach stereotaxic coordinates. Across subjects, each task showed considerable variability in activation site coordinates. For example, during finger tapping, the range for center of activation was 7 mm in the x-axis, 19 mm in the y-axis, and 11 mm in the z-axis. The mean value for center of activation was significantly different for all three coordinates for all pairwise task comparisons. However, the distribution of activation site centers for the finger task overlapped with the other two tasks in the x- and y-axes, and with the shoulder task in the z-axis. On average, the center of activation for the three motor tasks were spatially separated and somatotopically distributed. However, across the population, there was considerable overlap in the center of activation site, especially for finger and shoulder movements. Restorative therapies that aim to target specific body segments, such as the hand, in the post-stroke motor system may need to map the individual brain rather than rely on population averages. Initial details are presented of a study using this approach to evaluate such a therapy.

Aged↗

Functional MRI in the brain tumor patient.

Functional magnetic resonance imaging (fMRI) has been adopted almost universally by disciplines that endeavor to understand how the brain works. As basic scientists tune the technique, clinicians are increasingly able to apply brain mapping with fMRI to their clinical practice. We present here a guide to using fMRI in a clinical setting. We discuss the basic considerations of functional brain mapping in patients with brain tumors including: patient screening and training, paradigm design, data analysis and interpretation of the fMRI scans.

Brain Mapping↗

Mixture model mapping of the brain activation in functional magnetic resonance images.

We report on a novel method of identifying brain regions activated by periodic experimental design in functional magnetic resonance imaging data. This involves fitting a mixture distribution with two components to a test statistic estimated at each voxel in an image. The two parameters of this distribution, the proportion of nonactivated voxels, and the effect size can be estimated using maximum likelihood methods. Standard errors of the parameters can also be estimated. The fitted distribution can be used to derive brain activation maps and two examples are described, one involving a visual stimulation task, the other an auditory stimulation task. The method appears to have some advantages over direct use of the P-values corresponding to each voxel's value of the test statistic.

Acoustic Stimulation↗

High-dimensional mapping of the hippocampus in depression.

OBJECTIVE: Abnormalities of the hippocampus may play a role in the pathophysiology of depression, but efforts to identify a structural abnormality in this brain structure among depressed patients have produced mixed results. Previous research may have been limited by exclusive reliance on measures of hippocampal volume. High-dimensional brain mapping is a new analytic method that quantitatively characterizes the shape as well as volume of a brain structure. In this study, high-dimensional brain mapping was used to evaluate hippocampal shape and volume in patients with major depressive disorder and healthy comparison subjects. METHOD: By using magnetic resonance imaging, brain scans were obtained from 27 patients with major depressive disorder and 42 healthy comparison subjects. High-dimensional brain mapping generated a series of 10 variables (components) that represented hippocampal shape, and hippocampal volumes were also computed. Analysis of variance techniques were used to compare depressed patients and comparison subjects on hippocampal shape and volume. RESULTS: While the depressed patients and comparison subjects did not differ in hippocampal volume, there were highly significant group differences in hippocampal shape. The two groups did not overlap on a discriminant function computed from a model comprising the 10 components. The pattern of hippocampal surface deformation in the depressed patients suggested specific involvement of the subiculum. CONCLUSIONS: Patients with major depression may have structural abnormalities of the hippocampus that can be detected by analysis of hippocampal shape but not volume. A specific defect in the subiculum could have widespread effects throughout neurocircuits that appear to be abnormal in depression.

Adult↗