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PubMed2004

Evaluation of anatomy based reconstruction for partial volume correction in brain FDG-PET.

UNLABELLED: FDG-PET contributes to the diagnosis and management of neurological diseases. In some of these diseases, pathological gray matter (GM) areas may have a reduced FDG uptake. Detection of these regions can be difficult and some remain undiscovered using visual assessment. The main reason for this detection problem is the relatively small thickness of GM compared to the spatial resolution of PET, known as the partial volume effect. We have developed an anatomy-based maximum-a-posteriori reconstruction algorithm (A-MAP) which corrects for this effect during the reconstruction using segmented magnetic resonance (MR) data. Monte-Carlo based 3-D brain software phantom simulations were used to investigate the influence of the strength of anatomy-based smoothing in GM, the influence of misaligned MR data, and the effect of local segmentation errors. A human observer study was designed to assess the detection performance of A-MAP versus post-smoothed maximum-likelihood (ML) reconstruction. We demonstrated the applicability of A-MAP using real patient data. The results for A-MAP showed improved recovery values and robustness for local segmentation errors. Misaligned MR data reduced the recovery values towards those obtained by post-smoothed ML, for small registration errors. In the human observer study, detection accuracy of hypometabolic regions was significantly improved using A-MAP, compared to post-smoothed ML (P < 0.004). The patient study confirmed the applicability of A-MAP in clinical practice. CONCLUSION: A-MAP is a promising technique for voxel-based partial volume correction of FDG-PET of the human brain.

Adult↗
PubMed2004

Statistical mapping of functional olfactory connections of the rat brain in vivo.

The olfactory pathway is a unique route into the brain. To better characterize this system in vivo, rat olfactory functional connections were mapped using magnetic resonance (MR) imaging and manganese ion (Mn2+) as a transport-mediated tracer combined with newly developed statistical brain image analysis. Six rats underwent imaging on a 1.5-T MR scanner at pre-administration, and 6, 12, 24, 36, 48, and 72 h and 5.5, 7.5, 10.5, and 13.5 days post-administration of manganese chloride (MnCl2) into the right nasal cavity. Images were coregistered, pixel-intensity normalized, and stereotactically transformed to the Paxinos and Watson rat brain atlas, then averaged across subjects using automated image analysis software (NEUROSTAT). Images at each time point were compared to pre-administration using a one-sample t statistic on a pixel-by-pixel basis in 3-D and converted to Z statistic maps. Statistical mapping and group averaging improved signal to noise ratios and signal detection sensitivity. Significant transport of Mn2+ was observed in olfactory structures ipsilateral to site of Mn2+ administration including the bulb, lateral olfactory tract (lo) by 12 h and in the tubercle, piriform cortex, ventral pallidum, amygdala, and in smaller structures such as the anterior commissure after 24 h post-administration. MR imaging with group-wise statistical analysis clearly demonstrated bilateral transsynaptic Mn2+ transport to secondary and tertiary neurons of the olfactory system. The method permits in vivo investigations of functional neuronal connections within the brain.

Amygdala↗
PubMed2005

Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study.

Chromosome 22q11.2 deletion syndrome is a highly prevalent genetic disorder whose manifestations include developmental disability and sometimes mental retardation. The few studies that have examined brain morphology in different samples from this population have found similar general patterns, mostly using region of interest measures. We employed voxel-based techniques to concurrently examine specific morphologic changes in multiple brain tissue measures. Results were similar to previous findings of volumetric reductions in the posterior brain. They also extended them in two ways. First, our methods provided greater specificity in the localization of changes detected. Second, the combination of our measures of gray and white matter along with cerebrospinal fluid volume and fractional anisotropy, which indicates the structure of white matter, showed a posterior displacement of and morphologic changes to the corpus callosum in affected children.

Adolescent↗
PubMed2005

Voxel-based morphometry of the thalamus in patients with refractory medial temporal lobe epilepsy.

Previous research has suggested that patients with refractory medial temporal lobe epilepsy (MTLE) show gray matter atrophy both within the temporal lobes as well as in the thalamus. However, these studies have not distinguished between different nuclei within the thalamus. We examined whether thalamic atrophy correlates with the nuclei's connections to other regions in the limbic system. T1-weighted MRI scans were obtained from 49 neurologically healthy control subjects and 43 patients diagnosed with chronic refractory MTLE that was unilateral in origin (as measured by ictal EEG and hippocampal atrophy observed on MRI). Measurements of gray matter concentration (GMC) were made using automated segmentation algorithms. GMC was analyzed both voxel-by-voxel (preserving spatial precision) as well as using predefined regions of interest. Voxel-based morphometry revealed intense GMC reduction in the anterior portion relative to posterior thalami. Furthermore, thalamic atrophy was greater ipsilateral to the MTLE origin than on the contralateral side. Here we demonstrate that the thalamic atrophy is most intense in the thalamic nuclei that have strong connections with the limbic hippocampus. This finding suggests that thalamic atrophy reflects this region's anatomical and functional association with the limbic system rather than a general vulnerability to damage.

Adolescent↗
PubMed2006

Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs.

A major attraction of voxel-based morphometry (VBM) is that it allows researchers to explore large datasets with minimal human intervention. However, the validity and sensitivity of the Statistical Parametric Mapping (SPM2) approach to VBM are the subject of considerable debate. We visually inspected the SPM2 gray matter segmentations for 101 research participants and found a gross inclusion of non-brain tissue surrounding the entire brain as gray matter in five subjects and focal areas bordering the brain in which non-brain tissue was classified as gray matter in many other subjects. We also found many areas in which the cortical gray matter was incorrectly excluded from the segmentation of the brain. The major source of these errors was the misregistration of individual brain images with the reference T1-weighted brain template. These errors could be eliminated if SPM2 operated on images from which non-brain tissues (scalp, skull, and meninges) are removed (brain-extracted images). We developed a modified SPM2 processing pipeline that used brain-extracted images as inputs to test this hypothesis. We describe the modifications to the SPM2 pipeline that allow analysis of brain-extracted inputs. Using brain-extracted inputs eliminated the non-brain matter inclusions and the cortical gray matter exclusions noted above, reducing the residual mean square errors (RMSEs, the error term of the SPM2 statistical analyses) by over 30%. We show how this reduction in the RMSEs profoundly affects power analyses. SPM2 analyses of brain-extracted images may require sample sizes only half as great as analyses of non-brain-extracted images.

Adult↗
PubMed2006

Fibertract segmentation in position orientation space from high angular resolution diffusion MRI.

In diffusion MRI, standard approaches for fibertract identification are based on algorithms that generate lines of coherent diffusion, currently known as tractography. A tract is then identified as a set of such lines selected on some criteria. In the present study, we investigate whether fibertract identification can be formulated as a segmentation task that recognizes a fibertract as a region where diffusion is intense and coherent. Indeed, we show that it is possible to segment efficiently well-known fibertracts with classical image processing methods provided that the problem is formulated in a five-dimensional space of position and orientation. As an example, we choose to adapt to this newly defined high-dimensional non-Euclidean space, called position orientation space, an algorithm based on the hidden Markov random field framework. Structures such as the cerebellar peduncles, corticospinal tract, association bundles can be identified and represented in three dimensions by a back projection technique similar to maximum intensity projection. Potential advantages and drawbacks as compared to classical tractography are discussed; for example, it appears that our formulation handles naturally crossing tracts and is not biased by human intervention.

Algorithms↗
PubMed2006

Reproducibility and reliability of MR measurements in white matter: clinical implications.

The purpose of this study was to determine the reproducibility and reliability of five MRI-derived measurements, namely, total water content (WC), myelin water content (MWC), mean T2 relaxation time (GMT2), T1 relaxation time (T1) and magnetization transfer ratio (MTR). Five controls were scanned 5 times over 1 year. The five MR measurements were made for 5 white matter regions. All measurements were found to be highly reproducible. MTR had a low reliability coefficient because all individual values were similar. Therefore, MTR would be most sensitive in detecting changes from normal. WC had a high reliability coefficient in all regions. For MWC, GMT2 and T1, the overall reliability coefficients were high but for some individual regions were low. The high coefficients suggest that these measurements, although different between normal subjects, are consistent over time. They could be used to explore natural differences in the normal population, but due to the large spread in normal values, larger sample sizes are needed to detect pathological changes.

Adult↗
PubMed2002

Equilibrium expert: an add-in to Microsoft Excel for multiple binding equilibrium simulations and parameter estimations.

An add-in to Microsoft Excel was developed to simulate multiple binding equilibriums. A partition function, readily written even when the equilibrium is complex, describes the experimental system. It involves the concentrations of the different free molecular species and of the different complexes present in the experiment. As a result, the software is not restricted to a series of predefined experimental setups but can handle a large variety of problems involving up to nine independent molecular species. Binding parameters are estimated by nonlinear least-square fitting of experimental measurements as supplied by the user. The fitting process allows user-defined weighting of the experimental data. The flexibility of the software and the way it may be used to describe common experimental situations and to deal with usual problems such as tracer reactivity or nonspecific binding is demonstrated by a few examples. The software is available free of charge upon request.

Algorithms↗
PubMed1995

PC program for assessing the effect of a treatment when subjects are growing: comparative studies.

We describe, illustrate, and make available a menu-driven PC program which can be used to assess the effect of a treatment on growth when random allocation of subjects to the treatment and control groups is not feasible. Three different estimators of, and confidence intervals for, this effect are computed, namely, the simple gains, standardized gains, and covariance adjusted estimators. It is shown by means of several examples that these estimators can differ substantially, and some guidelines for choosing between them in specific circumstances are provided.

Analysis of Variance↗
PubMed2003

Pre-operative planning and gait analysis of total hip replacement following hip fusion.

A computer-based pre- and post-operative analysis of total hip replacement (THR) is presented. The analysis was performed by using and innovative combination of X-ray measurements and gait analysis. The several important biomechanical factors that affect effective THR are analysed in a test clinical case of conversion of hip fusion into THR. Geometrical positioning of the artificial joint should restore correct motion and adequate leverage of the surrounding muscles in order to exert the appropriate functional joint moments. Hip joint centre positioning pre- and post-operation was evaluated using a computer-based X-ray measurement tool. This enabled the calculation of the medio-lateral and proximal-distal off-set of the joint centre, the lever arms of the abductor muscles and the limb length discrepancy. Pre- and post-operative function was also evaluated using gait analysis, including joint kinematics, kinetics and electromyography. The whole analysis suggests that a good restoration of joint motion, a regression of pelvic compensation and a phasic activity of gluteus medius occur only when a good positioning of the prosthetic hip joint is obtained. This study proved a fundamental role played by these two computer-based tools in the support of the clinical decision making process.

Arthroplasty, Replacement, Hip↗
PubMed2003

New method for simultaneous anatomical and functional studies of articular joints and its application to the human knee.

In this paper a new methodology is described for the acquisition and computer elaboration of joint anatomy and motion data and the study of their correlation. The method uses a particular commercial electrogoniometer never used before for biomechanic investigations and software developed by the author for numerical interpolations and interactive display of the anatomical structures during joint motion. The original data acquisition protocol and computer elaboration software are described in detail, the theoretical and experimental accuracy of the method is reported and the original features and potential benefits of this approach in the field of joint biomechanics are discussed. Finally an experimental application for geometrical and functional analysis of the knee is presented as a practical example.

Biomechanical Phenomena↗
PubMed1998

Modeling and forecasting monthly patient volume at a primary health care clinic using univariate time-series analysis.

Two univariate time-series analysis methods have been used to model and forecast the monthly patient volume at the family and community medicine primary health care clinic of King Faisal University, Al-Khobar, Saudi Arabia. Models were based on nine years of data and forecasts made for 2 years. The optimum ARIMA model selected is an autoregressive model of the fourth order operating on the data after differencing twice at the nonseasonal level and once at the seasonal level. It gives mean and maximum absolute percentage errors of 1.86 and 4.23%, respectively, over the forecasting interval. A much simpler method based on extrapolating the growth curve of the annual means of the patient volume using a polynomial fit gives the better figures of 0.55 and 1.17%, respectively. This is due to the fairly regular nature of the data and the lack of strong random components that require ARIMA processes for modeling.

Ambulatory Care↗
PubMed2003

Caudate and putamen volumes in good and poor outcome patients with schizophrenia.

Magnetic resonance images of 37 patients with schizophrenia and 37 age- and sex-matched volunteers were acquired. The caudate nucleus and putamen were traced on axial slices from the most superior extent of the caudate to the most inferior point where the caudate and putamen merge. Two subtypes of schizophrenia were compared, the Kraepelinian subtype (n=13), characterized by an unremitting and severe course, and the non-Kraepelinian subtype (n=24), characterized by a remitting course and some periods of self-care. Patients with good outcome schizophrenia had larger relative mean putamen size (0.0129) than poor outcome patients (0.0123) or normal controls (0.0121), but not caudate size. This enlargement was most marked for the dorsal putamen and right hemisphere. Striatal size was not related to whether patients were currently being treated with atypical or typical neuroleptics or whether they had been predominantly treated with typical or atypical neuroleptics over the past 3 years. This suggests the possibility that the expansion of putamen size may be a physiological correlate of neuroleptic responsiveness or that small putamen size at disease onset may be a predictor of outcome.

Adult↗
PubMed2003

Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study.

Gray matter brain volume decreases have been found in patients with schizophrenia as compared to healthy control subjects measured by using Magnetic Resonance Imaging (MRI). An association has been suggested between decreased gray matter volume and poor outcome in chronically ill patients with schizophrenia. The present longitudinal multi-center study investigated whether gray matter volume at illness onset can predict poor outcome in recent-onset schizophrenia after a follow-up of approximately 2 years. An MRI calibration study was performed since scans of patients with recent-onset psychosis were conducted at three sites with 1.5 T MR scanners from two different manufacturers. Applying a linear scaling procedure on the histogram improved comparability between volume measurements acquired from images from the different scanners. Brain scans were obtained from 109 patients with recent-onset schizophrenia. Volumes of intracranium, total brain, cerebral gray and white matter, third and lateral ventricles, and cerebellum were measured. After a mean follow-up period of approximately 2 years, measurements of symptoms, functioning, need for care, and illness history variables were assessed. No significant correlations were found between the brain volume measures and any of these measures. Gray matter volume at illness onset does not predict outcome after 2 years in recent-onset schizophrenia.

Adolescent↗
PubMed2003

A new point-based warping method for enhanced and simplified analysis of functional brain image data.

Comparison of brain imaging data requires the exact matching of data sets from different individuals. Warping methods, used to optimize matching of data sets, can exploit either local gray value distribution or identifiable reference points within the images to be compared. Gray value-based warping, which is more comfortable, cannot be used if gray values include functional information that should be compared between images. A major drawback in the use of point-based warping methods is the lack of methods for efficient and precise definition of reference points (landmarks) within comparable data sets. Here, we present a novel approach to automatically detect sufficient numbers of landmarks, which is based on 3D differential operators. In addition, we have developed a new distance-weighted warping method, which optimizes individual local weighting factors of displacement vectors. The quality of the methods was evaluated using a set of autoradiographs documenting the metabolic activity of gerbil brains after acoustic stimulation. The new warping method was compared with known methods of landmark-based warping, i.e., warping with radial basis functions and with distance-weighted methods. For the data sets presented in this study our new optimized warping method produced an increase in linear cross correlation of 4.44%, an increase in volume overlap index of 1.55%, and a decrease in the registration error of 36.2%. In addition, the detection of functional differences was improved after warping. Therefore, the new method is a powerful tool, which enhances the comparison of complex biological structures and the quantitative evaluation of functional imaging data.

Algorithms↗
PubMed2006

White matter and subcortical gray matter lesion volume changes and late-life depression outcome: a 4-year magnetic resonance imaging study.

BACKGROUND: Cross-sectional studies have shown that late-onset depression is associated with larger deep white matter lesions (WMLs) and subcortical gray matter lesions (GMLs). In a longitudinal analysis, we examined changes in deep WMLs and subcortical GMLs in older depressed and nondepressed subjects over a 4-year period. METHODS: Brain magnetic resonance imaging (MRI) scans were obtained on 164 depressed and 126 healthy subjects aged 60 years or older at baseline, and 2 and 4 years after recruitment. WMLs and GMLs were measured using a semiautomated technique. We used repeated-measures analysis of covariance to determine cross-sectional lesion volume differences, whether lesion volume changes differed between patients and controls, and the effect of lesion volume changes on outcome in late-life depression. RESULTS: Mean volumes of lesions for the depressive group were 6.51, 8.18 and 7.75 cm2 for WMLs and 0.23, 0.30 and 0.34 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Mean volumes of lesions for the control group were 4.83, 6.22 and 6.45 cm2 for WMLs and 0.17, 0.25 and 0.23 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Cross-sectional between-group mean lesion volumes were significantly different for each measure. However, the pattern of WML and GML volume changes over time was not significantly different between groups. Treatment outcome was associated with changes in total and white matter lesion volume over time. CONCLUSIONS: Lesion volume progression is associated with aging and the pathological condition of late-life depression. The mechanisms that produce these progressive lesion changes remain unclear. Treatments aimed at arresting lesion progression may play a role in the management of late-life depression.

Aged↗
PubMed1998

Transient-state kinetic analysis of Synechococcus glutamate 1-semialdehyde aminotransferase.

We report a transient-state kinetic analysis relating to the mechanism of glutamate 1-semialdehyde aminotransferase (GSAT). Multiple-wavelength spectral kinetic data were collected by micro-stopped-flow spectrophotometry. Time resolved spectral sketches resulting from reactions with glutamate 1-semialdehyde (GSA), 4,5-diaminovalerate (DAVA), and 5-aminolevulinate (ALA) indicated various transient chromophoric intermediates. On the basis of the generally accepted mechanism of other aminotransferases and absorbance characteristics of associated intermediates, these transient chromophores are likely associated with Schiff base formation, ketimine/aldimine tautomerization, and transimidation etc. Spectral kinetic changes associated with these putative intermediates were, in general, concentration dependent. Various experimental evidence, including reactions with the GSAT lys272ile mutant, suggested rapid equilibrium of isomeric aldimines and geminal diamines. With this and related simplifying assumptions, a minimal mechanism was derived which provided a means for transient-state spectral kinetic analysis of reactions with GSA, DAVA, and ALA, all of which lead to the formation of the same putative central enzyme complex. Resulting kinetic constants were internally consistent, in general agreement with steady-state and equilibrium data (KM, kcat, and Keq), and provided the basis for a reasonable computer simulation of the original data set (variance approximately 4 x 10(-5)). Reequilibration of enzyme intermediates following an apparent pseudoequilibrium indicated thermodynamically driven dissociation of the central aldiminic enzyme complex. This is consistent with previous observations and the minimal mechanism used in this kinetic analysis and suggests a plausible regulatory mechanism of GSAT.

Amino Acids, Diamino↗
PubMed1998

Calculation of the dimensions of drug-polymer devices based on diffusion parameters.

The release kinetics of a polymeric-controlled release device are determined by its geometry and dimensions. A method to calculate the required size and shape of diffusion-controlled dosage forms to achieve a particular release profile is presented. The diffusion parameters are determined for various drugs (theophylline, diltiazem hydrochloride and caffeine) with thin ethyl cellulose (EC) films, containing different plasticizers [dibutyl sebacate (DBS) and acetyl tributyl citrate (ATBC)]. Computer simulations are then used to predict the drug release kinetics from various dosage forms (e.g. microparticles and cylinders). The practical benefit of these simulations is to optimize the geometry and dimensions of a controlled release device without the need of experimental studies. To verify the theoretical predictions, the release kinetics of theophylline from EC/ATBC microparticles of different size have also been determined experimentally. Good agreement is found between theory and experiment, proving the validity of the presented method.

Chemistry, Pharmaceutical↗