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Focused ultrasound (FUS) combined with a circulating microbubble agent is a promising strategy to non-invasively disrupt the blood-brain barrier (BBB) and could enable targeted delivery of therapeutics that normally do not leave the brain vasculature. This study investigated the kinetics of the BBB permeability using dynamic contrast-enhanced MRI (DCE-MRI) and the resulting payload of the chemotherapy agent, doxorubicin (DOX). We also investigated how the disruption and drug delivery were affected by a double sonication (DS) with two different time intervals (10 or 120 min). Two locations were sonicated transcranially in one hemisphere of the brain in 20 rats using a 690 kHz FUS transducer; the other hemisphere served as a control. For BBB disruption, 10 ms bursts were applied at 1 Hz for 60s and combined with IV injection of a microbubble ultrasound contrast agent (Definity; 10 μl/kg). DOX was injected immediately after the second location was sonicated. The transfer coefficient (K(trans)) for an MRI contrast agent (Gd-DTPA) was estimated serially at 4-5 time points ranging from 30 min to 7.5 hrs after sonication using DCE-MRI. After a single sonication (SS), the mean K(trans) was 0.0142 ± 0.006 min(-1) at 30 min and was two or more orders of magnitude higher than the non-sonicated targets. It decreased exponentially as a function of time with an estimated half-life of 2.22 hrs (95% confidence intervals (CI): 1.06-3.39 hrs). Adding a second sonication increased K(trans), and with a 120 min interval between sonications, prolonged the duration of the BBB disruption. Mean K(trans) estimates of 0.0205 (CI: 0.016-0.025) and 0.0216 (CI: 0.013-0.030) min(-1) were achieved after DS with 10 and 120 min delays, respectively. The half-life of the K(trans) decay that occurred as the barrier was restored was 1.8 hrs (CI: 1.20-2.41 hrs) for a 10 min interval between sonications and increased to 3.34 hrs (CI: 0.84-5.84 hrs) for a 120 min interval. DOX concentrations were significantly greater than in the non-sonicated brain for all experimental groups (p<0.0001), and 1.5-fold higher for DS with a 10 min interval between sonications. A linear correlation was found between the DOX concentration achieved and the K(trans) measured at 30 min after sonication (R: 0.7). These data suggest that one may be able to use Gd-DTPA as a surrogate tracer to estimate DOX delivery to the brain after FUS-induced BBB disruption. The results of this study provide information needed to take into account the dynamics BBB disruption over time after FUS., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To investigate the utility of a proposed clinical diffusion imaging scheme for rapidly generating multiple b-value diffusion contrast in brain magnetic resonance imaging (MRI) with high signal-to-noise ratio (SNR)., Materials and Methods: Our strategy for efficient image acquisition relies on the invariance property of the diffusion tensor eigenvectors to b-value. A simple addition to the conventional diffusion tensor MR imaging (DTI) data acquisition scheme used for tractography yields diffusion-weighted images at twice and three times the conventional b-value. An example from a neurosurgical brain tumor is shown. Apparent diffusion-weighted (ADW) images were calculated for b-values 800, 1600, and 2400 s/mm(2), and a map of excess diffusive kurtosis was computed from the three ADWs., Results: High b-value ADW images demonstrated decreased contrast between normal gray and white matter, while the heterogeneity and contrast of the lesion was emphasized relative to conventional b-value data. Kurtosis maps indicated the deviation from Gaussian diffusive behavior., Conclusion: DTI data with multiple b-values and good SNR can be acquired in clinically reasonable times. High b-value ADW images show increased contrast and add information to conventional DWI. Ambiguity in conventional b-value images over whether hyperintense signal results from abnormally low diffusion, or abnormally long T(2), is better resolved in high b-value images., ((c) 2009 Wiley-Liss, Inc.)

Automated interpretation and classification of functional MRI (fMRI) data is an emerging research field that enables the characterization of underlying cognitive processes with minimal human intervention. In this work, we present a method for the automated classification of human thoughts reflected on a trial-based paradigm using fMRI with a significantly shortened data acquisition time (less than one minute). Based on our preliminary experience with various cognitive imagery tasks, six characteristic thoughts were chosen as target tasks for the present work: right-hand motor imagery, left-hand motor imagery, right foot motor imagery, mental calculation, internal speech/word generation, and visual imagery. These six tasks were performed by five healthy volunteers and functional images were obtained using a T(*)(2)-weighted echo planar imaging (EPI) sequence. Feature vectors from activation maps, necessary for the classification of neural activity, were automatically extracted from the regions that were consistently and exclusively activated for a given task during the training process. Extracted feature vectors were classified using the support vector machine (SVM) algorithm. Parameter optimization, using a k-fold cross validation scheme, allowed the successful recognition of the six different categories of administered thought tasks with an accuracy of 74.5% (mean)+/-14.3% (standard deviation) across all five subjects. Our proposed study for the automated classification of fMRI data may be utilized in further investigations to monitor/identify human thought processes and their potential link to hardware/computer control.

We report an automated method to simultaneously monitor blood-oxygenation-level-dependent (BOLD) MR signals from multiple cortical areas in real-time. Individual brain anatomy was normalized and registered to a pre-segmented atlas in standardized anatomical space. Subsequently, using real-time fMRI (rtfMRI) data acquisition, localized BOLD signals were measured and displayed from user-selected areas labeled with anatomical and Brodmann's Area (BA) nomenclature. The method was tested on healthy volunteers during the performance of hand motor and internal speech generation tasks employing a trial-based design. Our data normalization and registration algorithm, along with image reconstruction, movement correction and a data display routine were executed with enough processing and communication bandwidth necessary for real-time operation. Task-specific BOLD signals were observed from the hand motor and language areas. One of the study participants was allowed to freely engage in hand clenching tasks, and associated brain activities were detected from the motor-related neural substrates without prior knowledge of the task onset time. The proposed method may be applied to various applications such as neurofeedback, brain-computer-interface, and functional mapping for surgical planning where real-time monitoring of region-specific brain activity is needed.

Both post-mortem and neuroimaging studies have contributed significantly to what we know about the brain and schizophrenia. MRI studies of volumetric reduction in several brain regions in schizophrenia have confirmed early speculations that the brain is disordered in schizophrenia. There is also a growing body of evidence suggesting that a disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, are responsible for the clinical symptoms and cognitive dysfunctions observed in this disorder. Thus an interest in white matter fiber tracts, subserving anatomical connections between distant, as well as proximal, brain regions, is emerging. This interest coincides with the recent advent of diffusion tensor imaging (DTI), which makes it possible to evaluate the organization and coherence of white matter fiber tracts. This is an important advance as conventional MRI techniques are insensitive to fiber tract direction and organization, and have not consistently demonstrated white matter abnormalities. DTI may, therefore, provide important new information about neural circuitry, and it is increasingly being used in neuroimaging studies of psychopathological disorders. Of note, in the past five years 18 DTI studies in schizophrenia have been published, most describing white matter abnormalities. Questions still remain, however, regarding what we are measuring that is abnormal in this disease, and how measures obtained using one method correspond to those obtained using other methods? Below we review the basic principles involved in MR-DTI, followed by a review of the different methods used to evaluate diffusion. Finally, we review MR-DTI findings in schizophrenia.

MRI-guided and monitored focused ultrasound thermal surgery of brain through intact skull was tested in three rhesus monkeys. The aim of this study was to determine the amount of skull heating in an animal model with a head shape similar to that of a human. The ultrasound beam was generated by a 512 channel phased array system (Exablate 3000, InSightec, Haifa, Israel) that was integrated within a 1.5-T MR-scanner. The skin was pre-cooled by degassed temperature controlled water circulating between the array surface and the skin. Skull surface temperature was measured with invasive thermocouple probes. The results showed that by applying surface cooling the skin and skull surface can be protected, and that the brain surface temperature becomes the limiting factor. The MRI thermometry was shown to be useful in detecting the tissue temperature distribution next to the bone, and it should be used to monitor the brain surface temperature. The acoustic intensity values during the 20 s sonications were adequate for thermal ablation in the human brain provided that surface cooling is used.

Antibody-based anticancer agents are promising chemotherapeutic agents. Among these agents, Herceptin (trastuzumab), a humanized anti-human epidermal growth factor receptor 2 (HER2/c-erbB2) monoclonal antibody, has been used successfully in patients with breast cancer. However, in patients with brain metastasis, the blood-brain barrier limits its use, and a different delivery method is needed to treat these patients. Here, we report that Herceptin can be delivered locally and noninvasively into the mouse central nervous system through the blood-brain barrier under image guidance by using an MRI-guided focused ultrasound blood-brain barrier disruption technique. The amount of Herceptin delivered to the target tissue was correlated with the extent of the MRI-monitored barrier opening, making it possible to estimate indirectly the amount of Herceptin delivered. Histological changes attributable to this procedure were minimal. This method may represent a powerful technique for the delivery of macromolecular agents such as antibodies to treat patients with diseases of the central nervous system.

Hemisphere asymmetry was explored in normal healthy subjects and in patients with schizophrenia using a novel voxel-based tensor analysis applied to fractional anisotropy (FA) of the diffusion tensor. Our voxel-based approach, which requires precise spatial normalization to remove the misalignment of fiber tracts, includes generating a symmetrical group average template of the diffusion tensor by applying nonlinear elastic warping of the demons algorithm. We then normalized all 32 diffusion tensor MRIs from healthy subjects and 23 from schizophrenic subjects to the symmetrical average template. For each brain, six channels of tensor component images and one T2-weighted image were used for registration to match tensor orientation and shape between images. A statistical evaluation of white matter asymmetry was then conducted on the normalized FA images and their flipped images. In controls, we found left-higher-than-right anisotropic asymmetry in the anterior part of the corpus callosum, cingulum bundle, the optic radiation, and the superior cerebellar peduncle, and right-higher-than-left anisotropic asymmetry in the anterior limb of the internal capsule and the anterior limb's prefrontal regions, in the uncinate fasciculus, and in the superior longitudinal fasciculus. In patients, the asymmetry was lower, although still present, in the cingulum bundle and the anterior corpus callosum, and not found in the anterior limb of the internal capsule, the uncinate fasciculus, and the superior cerebellar peduncle compared to healthy subjects. These findings of anisotropic asymmetry pattern differences between healthy controls and patients with schizophrenia are likely related to neurodevelopmental abnormalities in schizophrenia.

A brain-computer interface (BCI) is a way of conveying an individual's thoughts to control computer or electromechanical hardware. Capitalizing on the ability to characterize brain activity in a reproducible manner, we explored the possibility of using real-time fMRI to interpret the spatial distribution of brain function as BCI commands. Using a high-field (3T) MRI scanner, brain activities associated with four distinct covert functional tasks were detected and subsequently translated into predetermined computer commands for moving four directional cursors. The proposed fMRI-BCI method allowed volunteer subjects to navigate through a simple 2D maze solely through their thought processes.

We created a spatial probability atlas of schizophrenia to provide information about the neuroanatomic variability of brain regions of patients with the disorder. Probability maps of 16 regions of interest (ROIs) were constructed by taking manually parcellated ROIs from subjects' magnetic resonance images (MRIs) and linearly transforming them into Talairach space using the Montreal Neurological Institute (MNI) template. ROIs included temporal, parietal, and prefrontal cortex subregions, with a principal focus on temporal lobe structures. Subject Ns ranged from 11 to 28 for the different ROIs. Our global measure of the spatial distribution of the transformed ROI was the sum of voxels with 50% overlap among subjects. The superior temporal gyrus (STG) and fusiform gyrus (FG) had lower values for schizophrenic subjects than for normal controls, suggestive of greater spatial variability for these ROIs in schizophrenic subjects. For the computation of statistical significance of group differences in portions of the ROI, we used voxel-wise comparisons and Fisher's exact test. First-episode schizophrenic patients compared with controls showed lower probability (P < 0.05) at dorso-posterior areas of planum temporale and Heschl's gyrus, lateral and anterior regions in the left hippocampus (HIPP), and dorsolateral regions of fusiform gyrus. Importantly, most ROIs of schizophrenic subjects showed a significantly lower spatial overlap than controls, even after nonlinear spatial normalization, suggesting a greater heterogeneity in the spatial distribution of ROIs. There is consequently a need for caution in neuroimaging studies where data from schizophrenic subjects are normalized to a particular stereotaxic coordinate system based on healthy controls. Apparent group differences in activation may simply reflect a greater heterogeneity of spatial distribution in schizophrenia., (Copyright 2004 Elsevier Inc.)

Several studies have shown that in tissues over an extended range of b-factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b-factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b-factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast-diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow-diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas., (Copyright 2004 Wiley-Liss, Inc.)

Diffusion Tensor MRI (DT-MRI) can provide important in vivo information for the detection of brain abnormalities in diseases characterized by compromised neural connectivity. To quantify diffusion tensor abnormalities based on voxel-based statistical analysis, spatial normalization is required to minimize the anatomical variability between studied brain structures. In this article, we used a multiple input channel registration algorithm based on a demons algorithm and evaluated the spatial normalization of diffusion tensor image in terms of the input information used for registration. Registration was performed on 16 DT-MRI data sets using different combinations of the channels, including a channel of T2-weighted intensity, a channel of the fractional anisotropy, a channel of the difference of the first and second eigenvalues, two channels of the fractional anisotropy and the trace of tensor, three channels of the eigenvalues of the tensor, and the six channel tensor components. To evaluate the registration of tensor data, we defined two similarity measures, i.e., the endpoint divergence and the mean square error, which we applied to the fiber bundles of target images and registered images at the same seed points in white matter segmentation. We also evaluated the tensor registration by examining the voxel-by-voxel alignment of tensors in a sample of 15 normalized DT-MRIs. In all evaluations, nonlinear warping using six independent tensor components as input channels showed the best performance in effectively normalizing the tract morphology and tensor orientation. We also present a nonlinear method for creating a group diffusion tensor atlas using the average tensor field and the average deformation field, which we believe is a better approach than a strict linear one for representing both tensor distribution and morphological distribution of the population.

MRI-guided focused ultrasound was tested in the brains of rhesus monkeys. Locations up to 4.8 cm deep were targeted. Focal heating was observed in all cases with MRI-derived temperature imaging. Subthreshold heating was observed at the focus when the ultrasound beam was targeted with low power sonications, and in the ultrasound beam path during high-power exposures. Lethal temperature values and histologically confirmed tissue damage were confined to the focal zone (e.g., not in the ultrasound beam path), except when the focus was close to the bone. In that case, damage to the neighboring brain tissue was observed. Focal lesions were observed on histological examination and, in some cases, in MR images acquired immediately after the ultrasound exposures. The capabilities demonstrated in this study will be of benefit for clinical ultrasound therapies in the brain., (Copyright 2003 Wiley-Liss, Inc.)

The feasibility of using a metabolite signal as an internal reference for self-referenced temperature distribution measurement was examined. Line scan echo-planar spectroscopic imaging (LSEPSI) was applied to obtain quick multi-voxel spectroscopic measurements and to avoid possible spectral degradation from motion. Temperature distribution in a rabbit brain in vivo was successfully visualized by means of the chemical shift of water, which was measured by using naturally abundant (up to 10 mM) N-acetyl-aspartate (NAA) as the reference signal. Unlike the phase-mapping approach, this technique does not require a pixel-by-pixel subtraction. Therefore, in theory, it is more resistant to inter-scan motion or changes in susceptibility. The spatial and temporal resolutions of this technique are 1.5 cm3 and 4.5 min. A higher signal-to-noise ratio and optimization of the water and outer-volume suppression capabilities will be required to further enhance the temperature-mapping capabilities.

fMRI investigation on the neural substrates involved in tactile imagery is reported. Healthy subjects performed mental imagery of tactile stimulation on the dorsal aspect of the right hand. The results were compared with the regions of activation during the actual tactile stimulation. During imagery, contralateral primary and secondary somatosensory areas were activated along with activation in the left parietal lobe. Activations in left inferior frontal gyri (Brodmann's area 44), left dorsolateral prefrontal area, left precentral gyrus, left insula, and medial frontal gyrus were also observed. In the basal ganglia, activation in the left thalamus (ventral posteromedial nucleus) and putamen was found. Our results suggest that the primary and secondary somatosensory areas are recruited during tactile imagery, and have partially overlapping neural substrates for the perception of tactile stimulation.

The increased use of image-guided surgery systems during neurosurgery has brought to prominence the inaccuracies of conventional intraoperative navigation systems caused by shape changes such as those due to brain shift. We propose a method to track the deformation of the brain and update preoperative images using intraoperative MR images acquired at different crucial time points during surgery. We use a deformable surface matching algorithm to capture the deformation of boundaries of key structures (cortical surface, ventricles and tumor) throughout the neurosurgical procedure, and a linear finite element elastic model to infer a volumetric deformation. The boundary data are extracted from intraoperative MR images using a real-time intraoperative segmentation algorithm. The algorithm has been applied to a sequence of intraoperative MR images of the brain exhibiting brain shift and tumor resection. Our results characterize the brain shift after opening of the dura and at the different stages of tumor resection, and brain swelling afterwards. Analysis of the average deformation capture was assessed by comparing landmarks identified manually and the results indicate an accuracy of 0.7+/-0.6 mm (mean+/-S.D.) for boundary surface landmarks, of 0.9+/-0.6 mm for landmarks inside the boundary surfaces, and 1.6+/-0.9 mm for landmarks in the vicinity of the tumor., (Copyright 2002 Published by Elsevier Science B.V.)

In this study, we investigated the use of MRI-derived thermal imaging for determining the exposure parameters for focused ultrasound (FUS) surgery. Since the temperature rise induced by a FUS beam scales linearly with power, the temperature maps acquired during subthreshold sonications can be used to determine the power necessary to produce thermal tissue damage with a desired size. Thermal images acquired during multiple sonications delivered at different locations in rabbit thigh muscle and brain tissue in vivo were analyzed to test this hypothesis. First, the linearity of the induced temperature rise with the acoustic power was tested. Next, the temperature maps acquired during preliminary low power sonications were scaled up until the estimated size of the tissue damage was equal to the tissue damage size of subsequent high power sonications. A threshold thermal dose was used to estimate the onset of thermal damage. The predicted power (based on amount of scaling required to reach the target size) was then compared to the true high power value. Overall, the temperature rise varied linearly with power (slope of deltaThigh/deltaTlow vs Power(high)/Power(low) = 0.97, 0.93 for pairs of sonications at each location in brain, muscle). The predicted power matched the true high power in the brain sonications (slope = 1.04). The predicted power underestimated the true high power in the muscle sonications (slope = 0.87). This under-prediction was due to a deviation from linearity in those cases where tissue damage was detected in subsequent MR images (slope of deltaThigh/deltaTlow vs Power(high)/Power(low) = 1.02, 0.84 for no tissue damage, tissue damage). The source of this deviation was not clear from these experiments. Even with this underestimation of the power, this method will be useful because it will allow an estimate of the proper power to use during FUS surgery without exact knowledge of the tissue parameters.

Background and Purpose: MR diffusion tensor imaging permits detailed visualization of white matter fiber tracts. This technique, unlike T2-weighted imaging, also provides information about fiber direction. We present findings of normal white matter fiber tract anatomy at high resolution obtained by using line scan diffusion tensor imaging., Methods: Diffusion tensor images in axial, coronal, and sagittal sections covering the entire brain volume were obtained with line scan diffusion imaging in six healthy volunteers. Images were acquired for b factors 5 and 1000 s/mm(2) at an imaging resolution of 1.7 x 1.7 x 4 mm. For selected regions, images were obtained at a reduced field of view with a spatial resolution of 0.9 x 0.9 x 3 mm. For each pixel, the direction of maximum diffusivity was computed and used to display the course of white matter fibers., Results: Fiber directions derived from diffusion tensor imaging were consistent with known white matter fiber anatomy. The principal fiber tracts were well observed in all cases. The tracts that were visualized included the following: the arcuate fasciculus; superior and inferior longitudinal fasciculus; uncinate fasciculus; cingulum; external and extreme capsule; internal capsule; corona radiata; auditory and optic radiation; anterior commissure; corpus callosum; pyramidal tract; gracile and cuneatus fasciculus; medial longitudinal fasciculus; rubrospinal, tectospinal, central tegmental, and dorsal trigeminothalamic tract; superior, inferior, and middle cerebellar peduncle; pallidonigral and strionigral fibers; and root fibers of the oculomotor and trigeminal nerve., Conclusion: We obtained a complete set of detailed white matter fiber anatomy maps of the normal brain by means of line scan diffusion tensor imaging at high resolution. Near large bone structures, line scan produces images with minimal susceptibility artifacts.

This is an application of new longitudinal structural equation modeling techniques to time-dependent associations of memory and brain structure measurements. There were 225 participants aged 30-80 years at baseline who were measured again after a 7-year interval on both the lateral ventricular size and Wechsler memory score. Multiple regression analyses show nonlinear associations with age but no relationships among longitudinal changes. Mixed-effects latent growth curve analyses and analyses based on latent difference scores indicate that longitudinal changes in both variables are reasonably well described by an exponential or dual change model. Bivariate dynamic structural equation modeling analyses indicate age-lagged changes operate in a coupled-over-time fashion, with the brain measure (lateral ventricular size) as a leading indicator in time of memory (Wechsler memory score) declines.

We present a new algorithm for the nonrigid registration of three-dimensional magnetic resonance (MR) intraoperative image sequences showing brain shift. The algorithm tracks key surfaces of objects (cortical surface and the lateral ventricles) in the image sequence using a deformable surface matching algorithm. The volumetric deformation field of the objects is then inferred from the displacements at the boundary surfaces using a linear elastic biomechanical finite-element model. Two experiments on synthetic image sequences are presented, as well as an initial experiment on intraoperative MR images showing brain shift. The results of the registration algorithm show a good correlation of the internal brain structures after deformation, and a good capability of measuring surface as well as subsurface shift. We measured distances between landmarks in the deformed initial image and the corresponding landmarks in the target scan. Cortical surface shifts of up to 10 mm and subsurface shifts of up to 6 mm were recovered with an accuracy of 1 mm or less and 3 mm or less respectively. Index Terms--Brain modeling, finite element method, intraoperative image registration, tetrahedral mesh generation.

We report the long-term effect of real-time functional MRI (rtfMRI) training on voluntary regulation of the level of activation from a hand motor area. During the performance of a motor imagery task of a right hand, blood-oxygenation-level-dependent (BOLD) signal originating from a primary motor area was presented back to the subject in real-time. Demographically-matched individuals also received the same procedure without valid feedback information. Followed by the initial rtfMRI sessions, both groups underwent 2-week long, daily-practice of the task. Off-line data analysis revealed that the individuals in the experimental group were able to increase the level of BOLD signal from the regulatory target to a greater degree compared with the control group. Furthermore, the learned level of activation was maintained after the 2-week period, with the recruitment of additional neural circuitries such as the hippocampus and the limbo-thalamo-cortical pathway. The activation obtained from the control group, in the absence of proper feedback, was indifferent across the training conditions. The level of BOLD activity from the target regulatory region was positively correlated with a self evaluative score within the experimental group, while the majority of control subjects had difficulty adopting a strategy to attain the desired level of functional regulation. Our results suggest that rtfMRI helped individuals learn how to increase region-specific cortical activity associated with a motor imagery task, and the level of increased activation in motor areas was consolidated after the 2-week self-practice period, with the involvement of neural circuitries implicated in motor skill learning. © 2008 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 18, 69–78, 2008 [ABSTRACT FROM AUTHOR]

During functional MRI (fMRI) studies, blood oxygenation-level dependent (BOLD) signal associated with neuronal activity acquired from multiple individuals are subject to the derivation of group-averaged brain activation patterns. Unlike other cortical areas, subcortical areas such as the thalamus and basal ganglia often manifest smaller, biphasic BOLD signal that are aberrant from signals originating from cortices. Independent component analysis (ICA) can offer session/individual specific brain activation maps without a priori assumptions regarding the timing or pattern of the signal responses. The small activation loci within the subcortical areas are sparsely distributed among the subjects, and a conventional group processing method based on the general linear model (GLM) or ICA may fail to characterize the activation loci. In this article, we present an independent vector analysis (IVA) to overcome these limitations by offering an analysis of additional dependent components (compared to the ICA-based method) that are assigned for use in the automated grouping of dependent (i.e., similar) activation patterns across subjects. The proposed IVA algorithm was applied to simulated data, and its utility was confirmed from real fMRI data employing a trial-based hand motor task. A GLM and the group ICA of the fMRI toolbox (GIFT) were also applied for comparison. From the analysis of activation patterns within subcortical areas, in which the hemodynamic responses (HRs) often deviate from a canonical, model-driven HR, IVA detected task-related activation loci that were not detected through GLM and GIFT. IVA may offer a unique advantage for inferring group activation originating from subcortical areas. © 2008 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 18, 29–41, 2008 [ABSTRACT FROM AUTHOR]

The investigation of the reproducibility in functional MRI (fMRI) is an important step in the quantification and analysis of paradigm-related brain activation. This article reports on reproducibility of cortical activation characterized by repeated fMRI runs (10 times) during the performance of a motor imagery and a passive auditory stimulation as a control task. Two parameters, the size of activation and BOLD signal contrast, were measured from regions-of-interest for 10 subjects across different threshold conditions. The variability of these parameters was normalized with respect to the mean obtained from 10 runs, and represented as the intrasession variability. It was found that the variability was significantly lower in the measurement of BOLD signal contrast as compared to the measurement of the size of activation. The variability of the activation volume measurement was greater in the motor imagery task than in the auditory tasks across all thresholds. This task-dependent difference was not apparent from the measurement of the BOLD signal contrast. The presence of threshold dependence in the variability measurement was also examined, but no such dependency was found. The results suggest that a measurement of BOLD signal itself is a more reliable indicator of paradigm-related brain activation during repeated fMRI scans. [ABSTRACT FROM AUTHOR]

Abstract: Previously, activation of vesicular transport in the brain microvasculature was shown to be one of the mechanisms of focused ultrasound-induced blood-brain barrier (BBB) opening. In the present study, we aimed to estimate the rate of the transendothelial vesicular traffic after focused ultrasound sonication in the rabbit brain, using ultrastructural morphometry and horseradish peroxidase (HRP) as a tracer. In the capillaries, the mean endothelial pinocytotic densities (the number of HRP-containing vesicles per μm2 of the cell cytoplasm) were 0.9 and 1.05 vesicles/μm2 1 h after sonication with ultrasound frequencies of 0.69 and 0.26 MHz, respectively. In the arterioles, these densities were 1.63 and 2.43 vesicles/μm2, values 1.8 and 2.3 times higher. In control locations, the densities were 0.7 and 0.14 vesicles/μm2 for capillaries and arterioles, respectively. A small number of HRP-positive vesicles were observed in the venules. Focal delivery of HRP tracer was also observed in light microscopy. The results indicate that the precapillary microvessels play an important role in macromolecular transcytoplasmic traffic through the ultrasound-induced BBB modulation, which should be considered in the future development of trans-BBB drug delivery strategies. (E-mail: nsheikov@bwh.harvard.edu) [Copyright &y& Elsevier]

Abstract: Objective: The usefulness of neurosurgical navigation with current visualizations is seriously compromised by brain shift, which inevitably occurs during the course of the operation, significantly degrading the precise alignment between the pre-operative MR data and the intra-operative shape of the brain. Our objectives were (i) to evaluate the feasibility of non-rigid registration that compensates for the brain deformations within the time constraints imposed by neurosurgery, and (ii) to create augmented reality visualizations of critical structural and functional brain regions during neurosurgery using pre-operatively acquired fMRI and DT-MRI. Materials and methods: Eleven consecutive patients with supratentorial gliomas were included in our study. All underwent surgery at our intra-operative MR imaging-guided therapy facility and have tumors in eloquent brain areas (e.g. precentral gyrus and cortico-spinal tract). Functional MRI and DT-MRI, together with MPRAGE and T2w structural MRI were acquired at 3 T prior to surgery. SPGR and T2w images were acquired with a 0.5 T magnet during each procedure. Quantitative assessment of the alignment accuracy was carried out and compared with current state-of-the-art systems based only on rigid registration. Results: Alignment between pre-operative and intra-operative datasets was successfully carried out during surgery for all patients. Overall, the mean residual displacement remaining after non-rigid registration was 1.82 mm. There is a statistically significant improvement in alignment accuracy utilizing our non-rigid registration in comparison to the currently used technology (p <0.001). Conclusions: We were able to achieve intra-operative rigid and non-rigid registration of (1) pre-operative structural MRI with intra-operative T1w MRI; (2) pre-operative fMRI with intra-operative T1w MRI, and (3) pre-operative DT-MRI with intra-operative T1w MRI. The registration algorithms as implemented were sufficiently robust and rapid to meet the hard real-time constraints of intra-operative surgical decision making. The validation experiments demonstrate that we can accurately compensate for the deformation of the brain and thus can construct an augmented reality visualization to aid the surgeon. [Copyright &y& Elsevier]

: BackgroundEvidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI).: MethodsWe used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB.: ResultsResults showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test.: ConclusionsThese data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities. [Copyright &y& Elsevier]

The purpose of this study was to test the hypothesis that burst ultrasound (US) in the presence of a US contrast agent using parameters similar to those used in brain blood flow measurements causes tissue damage. The brains of 10 rabbits were sonicated in 3–8 locations with 1.5-MHz, 10-μs bursts repeated at a frequency of 1 kHz at temporal peak acoustic pressure amplitudes ranging from 2 to 12.7 MPa. The total sonication time for each location was 20 s. Before each sonication, a bolus of US contrast agent was injected IV. Contrast-enhanced magnetic resonance (MR) images were obtained after the sonications to detect local enhancement in the brain. Whole brain histological evaluation was performed, and the sections were stained with hematoxylin and eosin (H and E), TUNEL, and vanadium acid fuchsin (VAF) staining to evaluate tissue effects, including apoptosis and ischemia. Both the magnetic resonance imaging (MRI) contrast enhancement and histology findings indicated that brain tissue damage was induced at a pressure amplitude level of 6.3 MPa. The damage included vascular wall damage, hemorrhage and, eventually, necrosis. Mild vascular damage was observed localized in a few microscopic tissue volumes in about half of the sonicated locations at all pressure values tested (down to 2 MPa). However, these sonications did not induce any detectable tissue effects, including ischemia or apoptosis. As a conclusion, the study showed that the US exposure levels currently used for blood flow measurements in brain are below the threshold of blood-brain barrier opening or brain tissue damage. However, one should be aware that brain damage can be induced if the exposure level is increased. [Copyright &y& Elsevier]