Estimating NAA in cortical gray matter with applications for measuring changes due to aging

N-acetylaspartic acid (NAA), a prominent peak in the proton spectrum, is an amino acid thought to be present almost exclusively in neurons and their dendritic and axonal extensions. While 1H MRS studies are showing promise in identifying NAA deficits in different patient groups, unwanted lipid signal from subcutaneous fat surrounding the skull, and necessarily large voxels have limited investigators' ability to assess NAA in cortical gray matter. Here we report a technique developed to derive estimates of NAA signal from cortical gray matter. This approach uses an inversion recovery imaging pulse sequence with a long TE to suppress lipid signal from the scalp and information from concurrently obtained structural MR images to determine the CSF, white and gray matter composition of each spectroscopic voxel. A regression analysis is then used to estimate what NAA levels would be in "pure" white and gray matter voxels. This technique has been applied to demonstrate reduced NAA gray/white levels in the brains of five healthy older compared with five healthy younger women.     

Automatic identification of gray matter structures from MRI to improve the segmentation of white matter lesions

The segmentation of MRI scans of patients with white matter lesions (WML) is difficult because the MRI characteristics of WML are similar to those of gray matter. Intensity-based statistical classification techniques misclassify some WML as gray matter and some gray matter as WML. We developed a fast elastic matching algorithm that warps a reference data set containing information about the location of the gray matter into the approximate shape of the patient's brain. The region of white matter was segmented after segmenting the cortex and deep gray matter structures. The cortex was identified by using a three-dimensional, region-growing algorithm that was constrained by anatomical, intensity gradient, and tissue class parameters. White matter and WML were then segmented without interference from gray matter by using a two-class minimum-distance classifier. Analysis of double-echo spin-echo MRI scans of 16 patients with clinically determined multiple sclerosis (MS) was carried out. The segmentation of the cortex and deep gray matter structures provided anatomical context. This was found to improve the segmentation of MS lesions by allowing correct classification of the white matter region despite the overlapping tissue class distributions of gray matter and MS lesion.     

Preoperative cortical localization with functional MRI for use in stereotactic radiosurgery

Accurate localization of the lesion with respect to functionally significant brain is essential to safe stereotactic radiosurgical dose planning. We report the use of functional MR imaging in 3 patients to identify critical areas of surrounding brain and to provide assistance with dose planning, especially with regard to shaping the peripheral isodose around the lesion. We used a functional MRI system employing a conventional 1.5-tesla MRI unit that can detect decreases in deoxyhemoglobin concentration occurring with performance of specific tasks. Two of the patients had supratentorial arteriovenous malformations and 1 patient had a recurrent parasagittal meningioma. Functional MRI provided information on the location of speech, motor, and sensory cortex in these patients. Radiosurgical dose plans were constructed that kept these cortical areas outside of the 30% isodose curves. We believe that the safety of supratentorial parenchymal radiosurgery will be enhanced by the localization of critical brain regions around the target.     

The prevalence of cortical gray matter atrophy may be overestimated in the healthy aging brain.

Prevailing opinion holds that normal brain aging is characterized by substantial atrophy of cortical gray matter. However, this conclusion is based on earlier studies whose findings may be influenced by the inclusion of subjects with subclinical cognitive disorders like preclinical dementia. The present magnetic resonance imaging study tested this hypothesis. Cognitively healthy subjects (mean age 72 years, range 52–82) who remained cognitively stable over a 3-year period were compared to subjects with significant cognitive decline. Subjects who developed dementia within 6 years after the scan session were excluded. The gray matter volumes of seven cortical regions were delineated on T1-weighted magnetic resonance imaging scans. Participants without cognitive decline did not exhibit an age effect on the gray matter volume. Conversely, participants with cognitive decline exhibited a significant age effect in all the seven areas. These results suggest that cortical gray matter atrophy may have been overestimated in studies on healthy aging, since most studies were unable to exclude participants with a substantial atypical cognitive decline or preclinical dementia. Our results underscore the importance of establishing stringent inclusion criteria for future studies on normal aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

MRI visualization of multiple sclerosis lesions

Magnetic resonance imaging represents voxels (volume elements) of the body placed in a magnet, by their magnetization determined under various acquisition conditions weighting the contrast of the image by the density of free water protons and their relaxation times T1 and T2. Thus, the sensitivity in depicting lesions is high but pathological specificity is poor. Efforts are made to increase the diagnosis powerfulness of M.R.I. in multiple sclerosis: a careful correlation with the clinical presentation and the use of better M.R.I. criteria increase the specificity of the conventional T2 sequences. New sequences such as fast spin echo (F.S.E.), turbo spin echo (T.S.E.) or derived from inversion recovery (F.L.A.I.R.: fluid attenuated inversion recovery) improve the detection of lesions. Under specific conditions M.R.I. can be used to monitor the evolution of M.S. Acute phase monitoring focuses on changes in disease activity, new, recurring, enlarging, gadolinium (Gd) enhancing lesions, and chronic phase monitoring appreciate the burden of the disease. However M.R.I. is always considered as a secondary outcome in the phase III trials because insufficient correlations with the clinical disability. In the neurological daily practice conventional M.R.I. is of poor interest in the follow up of individual M.S. patients considering the weakness of prognosis value and the problems in the measurement of the lesions load which is emphasized in the methodology of the clinical trials. Nevertheless, there is a continuing search for techniques which correlate better with clinical measures of the disease such as the quantification of "black holes" on T1 w images or the cerebral and spinal atrophy. New techniques allow to weight the signal by the movement (diffusion imaging), by the complexity of the molecular architecture (magnetization transfer imaging), by the chemical shift (chemical shift imaging) or by the local status of oxygenation (functional M.R.I.). The basic aspects of the pathological lesions in M.S., edema, membrane disruption, demyelination, gliosis, cellular infiltration and axonal loss can be studied more precisely by these new M.R. techniques which should better describe the actual clinical impact of the destructive process. In the last year the importance of axonal loss has simultaneously been confirmed by M. R. spectroscopy and pathological findings. However, magnetization transfer imaging, M.R. diffusion imaging and functional M.R.I. are intensively under investigation for a better analysis of these different factors conditioning the reversibility of the patient disability.     

MRI of focal cortical dysplasia

We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain.     

Selective measurement of white matter and gray matter diffusion trace values in normal human brain

The trace of the diffusion tensor (or simply the trace) is diagnostically valuable for detecting acute ischemic lesions. A number of studies indicate that the trace of human gray matter (GM) and white matter (WM) are quite similar. This is somewhat surprising considering the different cellular environments of GM and WM. It is possible that partial volume averaging (PVA) effects between GM and WM, inherent in many of the ultrafast imaging sequences used for diffusion measurements, are responsible for this observation. In order to minimize PVA effects, the trace values of GM and WM have been selectively measured by implementing double inversion recovery (DIR) echo planar imaging (EPI) pulse sequences. Results on six normal volunteers indicate that the trace values of WM and GM are not statistically different.     

A comparison of spatial prediction techniques for an exploratory analysis of human cortical motor representations

We compare the use of two-dimensional Laplacian smoothing splines and median polish kriging for an exploratory analysis of spatial data sets. Splines were developed originally for modelling a process with determinstic mean structure, while median polish kriging was developed for predicting a spatial random process. We review the fundamentals of both methods, including smoothing parameter selection for splines and variogram estimation and solving the kriging equations for median polish kriging. We demonstrate application of the methods on maps of muscle representations on the human motor cortex (cortical maps). After applying both methods to 20 cortical maps (left and right hemispheres on each of 10 subjects), we compare the fitted surfaces on the basis of predictive ability, aesthetic appeal, and ease of computation.     

Quantification of white matter and gray matter volumes from T1 parametric images using fuzzy classifiers

Implementation of clinical practice guidelines in a large setting is a complex process. This article describes the many issues encountered in trying to implement Agency for Health Care Policy and Research acute pain and cancer pain guidelines in an academic medical center. Issues addressed include the membership of the task forces involved, incorporation of the guidelines into the institution-specific standards of care, selection and implementation of self-reporting tools for assessment of pain throughout the institution, issues involved in standardizing documentation of pain throughout the institution, measurement of the current status of pain control and integration into the existing quality assessment and improvement program, various analgesic interventions addressed throughout the hospital, educational strategies used and planned, and how multidisciplinary involvement was obtained.     

Differentiation of gray matter and white matter perfusion in patients with unilateral internal carotid artery occlusion

In this study, we investigated differences between gray matter and white matter perfusion in patients with a unilateral occlusion of the internal carotid artery (ICA) with dynamic susceptibility contrast. Seventeen patients and 17 control subjects were studied, using T2*-weighted gradient echo acquisition. Gray and white matter regions were obtained by segmentation of inversion recovery MRI. Lesions were excluded by segmentation of T2-weighted MRI. In the symptomatic hemisphere, cerebral blood volume was increased in white matter (P < .05) but not in gray matter. No cerebral blood flow changes were found. All timing parameters (mean transit time [MTT], time of appearance, and time to peak) showed a significant delay for both white and gray matter (P < .05), but the MTT increase of white matter was significantly larger than for gray matter (P < .05). These findings indicate that differentiation between gray and white matter is essential to determine the hemodynamic effects of an ICA occlusion.     

MRI of fibrous cortical defect of the femur

Concurrent with the new technologies in oral disease prevention, diagnosis, and treatment are the changing global perspectives on health which impact significantly on who will actually receive the new technologies and services. Issues of access to care, the rapidly changing social, political, and economic environments and the growing recognition of the disparities and barriers to oral health are stimulating new strategies for positive change and enhancement. Governments, in partnership with professional associations, private sector concerns and consumer interests in Canada and the United States, have recently reviewed current oral health status and identified needs and inequities. A few bold new multisectoral initiatives have evolved but not enough to address all the trends. The challenges not adequately addressed by current policies and practices have been identified. Goals for oral health have been established both nationally and internationally to address the trends and the challenges. Critical areas for taking action have been also been identified and include research in epidemiology, behavioural and social sciences, health services, and evaluation. This type of research considers the social and environmental context of where and how oral services are provided. Ultimately this is the kind of research that can radically change the role of the dental hygienist in the delivery of oral health care.     

Modeling hemodynamic response for analysis of functional MRI time-series

The standard Gaussian function is proposed for the hemodynamic modulation function (HDMF) of functional magnetic resonance imaging (fMRI) time-series. Unlike previously proposed parametric models, the Gaussian model accounts independently for the delay and dispersion of the hemodynamic responses and provides a more flexible and mathematically convenient model. A suboptimal noniterative scheme to estimate the hemodynamic parameters is presented. The ability of the Gaussian function to represent the HDMF of brain activation is compared with Poisson and Gamma models. The proposed model seems valid because the lag and dispersion values of hemodynamic responses rendered by the Gaussian model are in the ranges of their previously reported values in recent optical and fMR imaging studies. An extension of multiple regression analysis to incorporate the HDMF is presented. The detected activity patterns exhibit improvements with hemodynamic correction. The proposed model and efficient parameter estimation scheme facilitated the investigation of variability of hemodynamic parameters of human brain activation. The hemodynamic parameters estimated over different brain regions and across different stimuli showed significant differences. Measurement of hemodynamic parameters over the brain during sensory or cognitive stimulation may reveal vital information on physiological events accompanying neuronal activation and functional variability of the human brain, and should lead to the investigation of more accurate and complex models.     

MRI visualization of focal induced neocortical malformations of the rat

In an attempt to determine whether small focal malformations of the neocortex can be visualized in vivo, focal microgyria were induced in the neocortex of otherwise normal rats by freezing injury to the developing cortical plate, and in adulthood the malformation was visualized using MRI. Induced microgyria of varying size were successfully visualized with MRI, and the location and extent of the malformation was confirmed on subsequent histology. This work has potential implications for the field of experimental neuropathology by enhancing the ability to study the behavioral and connectional consequences of these malformations in animals. In addition, this work points toward future research for the in vivo visualization of these small, focal malformations in humans.     

Finding parametric representations of the cortical sulci using an active contour model

The cortical sulci are brain structures resembling thin convoluted ribbons embedded in three dimensions. The importance of the sulci lies primarily in their relation to the cytoarchitectonic and functional organization of the underlying cortex and in their utilization as features in non-rigid registration methods. This paper presents a methodology for extracting parametric representations of the cerebral sulcus from magnetic resonance images. The proposed methodology is based on deformable models utilizing characteristics of the cortical shape. Specifically, a parametric representation of a sulcus is determined by the motion of an active contour along the medial surface of the corresponding cortical fold. The active contour is initialized along the outer boundary of the brain and deforms toward the deep root of a sulcus under the influence of an external force field, restricting it to lie along the medial surface of the particular cortical fold. A parametric representation of the medial surface of the sulcus is obtained as the active contour traverses the sulcus. Based on the first fundamental form of this representation, the location and degree of an interruption of a sulcus can be readily quantified; based on its second fundamental form, shape properties of the sulcus can be determined. This methodology is tested on magnetic resonance images and it is applied to three medical imaging problems: quantitative morphological analysis of the central sulcus; mapping of functional activation along the primary motor cortex and non-rigid registration of brain images.     

Event-related functional MRI: Implications for cognitive psychology.

Functional magnetic resonance imaging (fMRI) has rapidly emerged as a powerful technique in cognitive neuroscience. We describe and critique a new class of imaging experimental designs called event-related fMRI that exploit the temporal resolution of fMRI by modeling fMRI signal changes associated with behavioral trials as opposed to blocks of behavioral trials. Advantages of this method over block designs include the ability to (a) randomize trial presentations, (b) test for functional correlates of behavioral measures with greater power, (c) directly examine the neural correlates of temporally dissociable components of behavioral trials (e.g., the delay period of a working memory task), and (d) test for differences in the onset time of neural activity evoked by different trial types. Consequently, event-related fMRI has the potential to address a number of cognitive psychology questions with a degree of inferential and statistical power not previously available. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia

We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic resonance image data into spatially normalized images of gray (or white) matter density, effected by segmenting the images and smoothing, and then (ii) to use Statistical Parametric Mapping to make inferences about the relationship between gray (or white) matter density and symptoms (or other pathophysiological measures) in a regionally specific fashion. Because the whole brain sum of gray (or white) matter indices is treated as a confound, the analysis reduces to a characterization of relative gray (or white) matter density on a voxel by voxel basis. We suggest that this is a powerful approach to voxel-based statistical anatomy. Using the technique, we constructed maps of the regional cerebral gray and white matter density correlates of syndrome scores (distinct psychotic symptoms) in a group of 15 schizophrenic patients. There was a negative correlation between the score for the reality distortion syndrome and regional gray matter density in the left superior temporal lobe (P = 0.01) and regional white matter density in the corpus callosum (P < 0.001). These abnormalities may be associated with functional changes predisposing to auditory hallucinations and delusions. This method permits the detection of structural differences within the entire brain (as opposed to selected regions of interest) and may be of value in the investigation of structural gray and white matter abnormalities in a variety of brain diseases.     

A model of cortical associative memory based on a horizontal network of connected columns

An attractor network model of cortical associative memory functions has been constructed and simulated. By replacing the single cell as the functional unit by multiple cells in cortical columns connected by long-range fibers, the model is improved in terms of correspondence with cortical connectivity. The connectivity is improved, since the original dense and symmetric connectivity of a standard recurrent network becomes sparse and asymmetric at the cell-to-cell level. Our simulations show that this kind of network, with model neurons of the Hodgkin-Huxley type arranged in columns, can operate as an associative memory in much the same way as previous models having simpler connectivity. The network shows attractor-like behaviour and performs the standard assembly operations despite differences in the dynamics introduced by the more detailed cell model and network structure. Furthermore, the model has become sufficiently detailed to allow evaluation against electrophysiological and anatomical observations. For instance, cell activities comply with experimental findings and reaction times are within biological and psychological ranges. By introducing a scaling model we demonstrate that a network approaching experimentally reported neuron numbers and synaptic distributions also could work like the model studied here.     

Clinical applications of functional MRI in neuropsychiatry

Clinical neuroimaging is due for yet another sea change as functional neuroimaging becomes increasingly powerful and available. Functional magnetic resonance imaging (fMRI) is perhaps the most promising of the emerging techniques. The following review helps us understand the physics, strengths, limitations, and promise of fMRI. The authors are all affiliated with the Brain Imaging Center at McLean Hospital and with the Departments of Neurology (Dr. Levin) and Psychiatry (Dr. Renshaw) at Harvard Medical School.     

Conjunctive representations in learning and memory: Principles of cortical and hippocampal function.

The authors present a theoretical framework for understanding the roles of the hippocampus and neocortex in learning and memory. This framework incorporates a theme found in many theories of hippocampal function: that the hippocampus is responsible for developing conjunctive representations binding together stimulus elements into a unitary representation that can later be recalled from partial input cues. This idea is contradicted by the fact that hippocampally lesioned rats can learn nonlinear discrimination problems that require conjunctive representations. The authors' framework accommodates this finding by establishing a principled division of labor, where the cortex is responsible for slow learning that integrates over multiple experiences to extract generalities whereas the hippocampus performs rapid learning of the arbitrary contents of individual experiences. This framework suggests that tasks involving rapid, incidental conjunctive learning are better tests of hippocampal function. The authors implement this framework in a computational neural network model and show that it can account for a wide range of data in animal learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)