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Laterality in functional brain imaging studies of schizophrenia.

Brain laterality in schizophrenia has been examined through the application of functional neuroimaging methods. These methods have included the 133Xenon technique for measuring cerebral blood flow (CBF); positron emission tomography for assessing rates of glucose metabolism, CBF, and neuroreceptor functioning; single photon emission computerized tomography for studying CBF and neuroreceptors; and functional magnetic resonance imaging for measuring changes attributable to CBF. This article highlights the application of this technology in schizophrenia research, emphasizing more recent studies that have evaluated hemispheric differences. There is evidence for lateralized abnormalities in some studies that have examined this dimension. In general, the results implicate abnormalities in left hemispheric activity. Recent advances in basic and clinical neuroscience provide an opportunity for focused application of functional imaging in neurobiological studies of schizophrenia.

Brain↗

Registration of MR/MR and MR/SPECT brain images by fast stochastic optimization of robust voxel similarity measures.

This paper describes a robust, fully automated algorithm to register intrasubject 3D single and multimodal images of the human brain. The proposed technique accounts for the major limitations of the existing voxel similarity-based methods: sensitivity of the registration to local minima of the similarity function and inability to cope with gross dissimilarities in the two images to be registered. Local minima are avoided by the implementation of a stochastic iterative optimization technique (fast simulated annealing). In addition, robust estimation is applied to reject outliers in case the images show significant differences (due to lesion evolution, incomplete acquisition, non-Gaussian noise, etc.). In order to evaluate the performance of this technique, 2D and 3D MR and SPECT human brain images were artificially rotated, translated, and corrupted by noise. A test object was acquired under different angles and positions for evaluating the accuracy of the registration. The approach has also been validated on real multiple sclerosis MR images of the same patient taken at different times. Furthermore, robust MR/SPECT image registration has permitted the representation of functional features for patients with partially complex seizures. The fast simulated annealing algorithm combined with robust estimation yields registration errors that are less than 1 degree in rotation and less than 1 voxel in translation (image dimensions of 128(3)). It compares favorably with other standard voxel similarity-based approaches.

Algorithms↗

Autoregulation of blood pressure and thought: preliminary results of an application of brain imaging to psychosomatic medicine.

OBJECTIVE: This presentation seeks to demonstrate the use of brain imaging techniques for understanding the interaction between hypertension and psychosocial function. METHODS: The historical background for the study of brain function among hypertensive patients is reviewed. An initial and a current project examining rCBF with 15O water radiotracer and PET in unmedicated hypertensives and normotensives are described. The rCBF response is assessed during the performance of spatial and verbal working memory tasks of increasing memory load. The assessment also addresses the influence on rCBF and performance of white matter hyperintensities and the presence of carotid artery thickening. RESULTS: Initial results suggest that hypertensives relative to normotensives show less CBF and less posterior parietal rCBF in response to increases in memory load. Hypertensives, however, increase lateral prefrontal (Broca's area)/insula and amygdala/hippocampal rCBF more than normotensives. CONCLUSION: Initial results are sufficient to show that hypertension induces changes in rCBF. A tentative hypothesis is that a relatively general decrease in rCBF responsivity induces specific compensatory cognitive strategies as well as subcortical activation. The rCBF changes appear to have implications for information processing and, as such, hold promise for understanding prior reports relating hypertension to affective regulation and cardiovascular reactivity. Imaging techniques provide a powerful tool for psychosomatic research.

Adult↗

A robust method for extraction and automatic segmentation of brain images.

A new protocol is introduced for brain extraction and automatic tissue segmentation of MR images. For the brain extraction algorithm, proton density and T2-weighted images are used to generate a brain mask encompassing the full intracranial cavity. Segmentation of brain tissues into gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) is accomplished on a T1-weighted image after applying the brain mask. The fully automatic segmentation algorithm is histogram-based and uses the Expectation Maximization algorithm to model a four-Gaussian mixture for both global and local histograms. The means of the local Gaussians for GM, WM, and CSF are used to set local thresholds for tissue classification. Reproducibility of the extraction procedure was excellent, with average variation in intracranial capacity (TIC) of 0.13 and 0.66% TIC in 12 healthy normal and 33 Alzheimer brains, respectively. Repeatability of the segmentation algorithm, tested on healthy normal images, indicated scan-rescan differences in global tissue volumes of less than 0.30% TIC. Reproducibility at the regional level was established by comparing segmentation results within the 12 major Talairach subdivisions. Accuracy of the algorithm was tested on a digital brain phantom, and errors were less than 1% of the phantom volume. Maximal Type I and Type II classification errors were low, ranging between 2.2 and 4.3% of phantom volume. The algorithm was also insensitive to variation in parameter initialization values. The protocol is robust, fast, and its success in segmenting normal as well as diseased brains makes it an attractive clinical application.

Adult↗

Functional brain imaging at 1.5 T using conventional gradient echo MR imaging techniques.

There is considerable interest in the use of MR imaging to study brain function. Recently, it has been demonstrated that small changes in signal intensity occur in the visual cortex in T2*-weighted imaging in response to appropriate visual stimuli. Similar responses to activation have also been recorded in motor cortex as well as frontal lobes. To date most of these studies have been carried out at very high field strength or they have used echo planar imaging. We report our preliminary results showing that the effects of activation of visual and motor areas of the brains of normal volunteers can be recorded using conventional MR imaging methods on a standard 1.5 T clinical scanner. Using gradient-echo imaging sequences, we have been able to map activated visual and motor cortex with high spatial resolution in multiple planes, and are using this technique to examine the relationship between physiological response and stimulus parameters. Signal changes of the order of 2-12% in images with TE = 45 msec, TR = 120 msec, and alpha = 40 degrees, permit excellent depiction of the regions affected.

Brain↗

Neural modeling and functional brain imaging: an overview.

This article gives an overview of the different functional brain imaging methods, the kinds of questions these methods try to address and some of the questions associated with functional neuroimaging data for which neural modeling must be employed to provide reasonable answers.

Brain↗

Functionally activated brain imaging (O-15 PET and fMRI) in the study of learning and memory after traumatic brain injury.

Advances in functional imaging technology and cognitive neuropsychology have resulted in paradigms in which participants can perform cognitive tasks during functional image acquisition. We will discuss the application of two approaches (oxygen-15 positron emission tomography and functional magnetic resonance imaging) that have recently been used to examine components of learning and memory following traumatic brain injury (TBI). Activated functional brain imaging findings that we will discuss may suggest possible functional reallocation and reorganization of brain substrates involved in verbal learning and memory following brain injury. The findings also are clearly in line with other research that indicates a prominent role for the frontal lobes in learning and memory functioning, and support the concept of distributed neural networks for memory-related functions, cognitive load, and the potential for examining brain re-organization after injury.

Brain Injuries↗

Functional brain imaging of a catatonic type of schizophrenia: PET and SPECT studies.

A brain imaging study was conducted in the case of a catatonic type of schizophrenia (DSM-IIIR) by applying (i) positron emission tomography (PET) and (ii) single photon emission computed tomography (SPECT). A PET study using [18F]-2-fluoro-2-deoxy-D-glucose revealed a lower glucose utilization in the dorsal frontal and parietal lobes of both cerebral hemispheres. Correlative SPECT studies using [123I]-iodoamphetamine showed a diminished regional cerebral blood flow in similar regions of the cerebral hemisphere. A three-dimensional volume rendering method of the SPECT images (TITAN) identified the dorsal region of the fronto-parietal lobe as the most severely affected region. These patterns of deficits implicated the role of the dorsal frontal and parietal lobes in the pathogenesis of catatonic syndromes.

Activities of Daily Living↗

Learning-based deformable registration of MR brain images.

This paper presents a learning-based method for deformable registration of magnetic resonance (MR) brain images. There are two novelties in the proposed registration method. First, a set of best-scale geometric features are selected for each point in the brain, in order to facilitate correspondence detection during the registration procedure. This is achieved by optimizing an energy function that requires each point to have its best-scale geometric features consistent over the corresponding points in the training samples, and at the same time distinctive from those of nearby points in the neighborhood. Second, the active points used to drive the brain registration are hierarchically selected during the registration procedure, based on their saliency and consistency measures. That is, the image points with salient and consistent features (across different individuals) are considered for the initial registration of two images, while other less salient and consistent points join the registration procedure later. By incorporating these two novel strategies into the framework of the HAMMER registration algorithm, the registration accuracy has been improved according to the results on simulated brain data, and also visible improvement is observed particularly in the cortical regions of real brain data.

Algorithms↗

Supercomputer algorithms for efficient linear octree encoding of three-dimensional brain images.

We designed and implemented algorithms for three-dimensional (3-D) reconstruction of brain images from serial sections using two important supercomputer architectures, vector and parallel. These architectures were represented by the Cray YMP and Connection Machine CM-2, respectively. The programs operated on linear octree representations of the brain data sets, and achieved 500-800 times acceleration when compared with a conventional laboratory workstation. As the need for higher resolution data sets increases, supercomputer algorithms may offer a means of performing 3-D reconstruction well above current experimental limits.

Algorithms↗

Current and future radiopharmaceuticals for brain imaging with single photon emission computed tomography.

Development of radiopharmaceuticals for functional brain imaging has progressed rapidly in recent years. Measurement of regional cerebral blood flow in humans can be achieved by using [123I]-iodoamphetamine or [99mTc]-HMPAO. Several other lipid-soluble [99mTc]-technetium complexes are currently undergoing clinical trials. New 123I-labeled agents designed to measure central nervous system receptors, including D1 and D2 dopamine, serotonin, muscarinic, and benzodiazepine receptors, have been developed. In conjunction with single photon emission computed tomography, they may provide useful tools to evaluate brain function related to changes in receptor concentration.

Brain↗

Phenylpiperazine-based radiopharmaceuticals for brain imaging. 3. Synthesis and evaluation of radioiodinated 1-alkyl-4-phenylpiperazines.

As part of our program in radiopharmaceutical chemistry we have prepared and evaluated a series of radioiodinated 1-alkyl-4-phenylpiperazines as potential brain-imaging agents. The compounds were chosen on the basis of their synthetic versatility, activation toward electrophilic substitution, and ease of purification. The intermediates 1-6 were readily obtained and converted to the corresponding radioiodinated products 7-12 in 76-91% isolated radiochemical yields. The tissue distribution in rats indicated that the 1-N-butyl derivative 9 possesses the best combination of brain uptake (0.28-0.35% ID X kg/g), retention, and selectivity (brain/blood greater than 20) over the 4-h evaluation period. A subsequent imaging and tissue distribution study in the dog using 131I-labeled 9 supported the results observed in the rat and suggested the potential of this agent as a brain-imaging agent.

Animals↗

Functional brain imaging of human sleep.

This paper presents an overview of the contribution of functional brain mapping to the study of human sleep. Early studies were essentially successful in describing the variations of the global level of cerebral metabolism. More recently, regional distribution of cerebral blood flow was reported. The results suggest that the permissive and executive processes of slow wave sleep and REM sleep are similar in humans and in animals. They also show cortical blood flow distributions specific to each sleep stage. The cellular mechanisms underlying the involvement of these cortical areas in sleep are not yet precisely known. They should be looked for by further investigations in animals. Future research in functional neuroimaging will attempt to explore functional and, hopefully, effective connectivity between cerebral areas involved in sleep processes. This final goal will probably require the co-registration of two or more brain imaging techniques to precisely describe the spatio-temporal course of neuronal interactions occurring during sleep.

Brain↗

201Tl-diethyldithiocarbamate: a possible radiopharmaceutical for brain imaging.

For estimating regional brain perfusion with a gamma camera lipophilic radiopharmaceuticals are required. This paper describes the development of 201Tl-diethyldithiocarbamate (201TlDDC). First the compound NaDDC was tested for stability and an assay was developed. Next the 201TlDDC complex was prepared and checked for lipophilicity and stability by paper chromatography. A scintigraphic pilot study using this agent in a rabbit showed considerable brain uptake, compared to 201TlCl. Finally we performed a study in rats on the distribution of 201TlDDC in different organs. The results confirmed the lipophilicity of the agent. Within the first hour the percentage of injected dose per gram tissue was 2.73% in the cerebrum and 1.35% in the cerebellum. These data are in good agreement with some other agents used for assessment of brain blood flow.

Animals↗

Optimal number of pinholes in multi-pinhole SPECT for mouse brain imaging--a simulation study.

This study simulates a multi-pinhole single-photon emission computed tomography (SPECT) system using the Monte Carlo method, and investigates different multi-pinhole designs for quantitative mouse brain imaging. Prior approaches investigating multi-pinhole SPECT were not often optimal, as the number and geometrical arrangement of pinholes were usually chosen empirically. The present study seeks to optimize the number of pinholes for a given pinhole arrangement, and also for the specific application of quantitative neuroreceptor binding in the mouse brain. An analytical Monte Carlo simulation based method was used to generate the projection data for various count levels. A three-dimensional ordered-subsets expectation-maximization algorithm was developed and used to reconstruct the images, incorporating a realistic pinhole model for resolution recovery and noise reduction. Although artefacts arising from overlapping projections could be a major problem in multi-pinhole reconstruction, the cold-rod phantom study showed minimal loss of spatial resolution in multi-pinhole systems, compared to a single-pinhole system with the same pinhole diameter. A quantitative study of neuroreceptor binding sites using a mouse brain phantom and low activity (37 MBq) showed that the multi-pinhole system outperformed the single-pinhole system by maintaining the mean and lowering the variance in the measured uptake ratio. Multi-pinhole collimation can be used to reduce the injected dose and thereby reduce the radiation exposure to the animal. Results also suggest that the nine-pinhole configuration shown in this paper is a good choice for mouse brain imaging.

Algorithms↗

The statistical interaction of cerebral specialization and integration in the interpretation of dynamic brain images.

Two constructs of brain function, namely cerebral specialization and integration, have been examined in the analysis of blood flow and metabolic function resulting from dynamic imaging procedures. The purpose of the current paper is to illustrate the interaction of these two constructs at the statistical level. Because of the statistical interaction, it is argued that the currently accepted statistical evidence for cerebral specialization is, in fact, partially a function of the degree of regional cerebral integration. Therefore, found asymmetries of flow or rate may be solely a function of cerebral integration. These points are discussed with respect to developing a better understanding of stimulus/brain/behavior relations.

Blood Glucose↗

Biological parametric mapping: A statistical toolbox for multimodality brain image analysis.

In recent years, multiple brain MR imaging modalities have emerged; however, analysis methodologies have mainly remained modality-specific. In addition, when comparing across imaging modalities, most researchers have been forced to rely on simple region-of-interest type analyses, which do not allow the voxel-by-voxel comparisons necessary to answer more sophisticated neuroscience questions. To overcome these limitations, we developed a toolbox for multimodal image analysis called biological parametric mapping (BPM), based on a voxel-wise use of the general linear model. The BPM toolbox incorporates information obtained from other modalities as regressors in a voxel-wise analysis, thereby permitting investigation of more sophisticated hypotheses. The BPM toolbox has been developed in Matlab with a user-friendly interface for performing analyses, including voxel-wise multimodal correlation, ANCOVA, and multiple regression. It has a high degree of integration with the SPM (statistical parametric mapping) software relying on it for visualization and statistical inference. Furthermore, statistical inference for a correlation field, rather than a widely used T-field, has been implemented in the correlation analysis for more accurate results. An example with in vivo data is presented, demonstrating the potential of the BPM methodology as a tool for multimodal image analysis.

Brain↗

Discriminant analysis of brain imaging data identifies subjects with early Alzheimer's disease.

In vivo functional brain imaging provides an opportunity to quantify and localize functional deficits associated with Alzheimer's disease (AD), in relation to dementia severity and heterogeneous cognitive profiles. Such imaging also provides a basis for distinguishing AD from other causes of dementia and for making an early diagnosis of disease. One imaging modality that can elucidate AD is positron emission tomography (PET), which is used to measure regional cerebral metabolic rates for glucose (rCMRglc) and regional cerebral blood flow (rCBF). Resting-state measurements with PET, when related to cognitive profiles in longitudinal studies, indicate that specific cognitive defects are preceded and predicted by reductions in rCMRglc in regions subserving the cognitive functions tested. Metabolic reductions and right/left metabolic asymmetries can be used to convert a "possible" to a "probable" diagnosis of AD by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. Furthermore, discriminant analyses of PET metabolic patterns can identify patients at risk for AD with mild memory deficits as having probable AD. In the future, stimulation PET studies should augment the power of this discriminant analysis.

Aged↗