Biomedical subjects

R Somorjai

Publications and source records attributed to R Somorjai.

18 recordsLinked to original sources

PubMed2004

Classification of signatures of Bovine Spongiform Encephalopathy in serum using infrared spectroscopy.

Signatures of Bovine Spongiform Encephalopathy (BSE) have been identified in serum by means of "Diagnostic Pattern Recognition (DPR)". For DPR-analysis, mid-infrared spectroscopy of dried films of 641 serum samples was performed using disposable silicon sample carriers and a semi-automated DPR research system operating at room temperature. The combination of four mathematical classification approaches (principal component analysis plus linear discriminant analysis, robust linear discriminant analysis, artificial neural network, support vector machine) allowed for a reliable assignment of spectra to the class "BSE-positive" or "BSE-negative". An independent, blinded validation study was carried out on a second DPR research system at the Veterinary Laboratory Agency, Weybridge, UK. Out of 84 serum samples originating from terminally-ill, BSE-positive cattle, 78 were classified correctly. Similarly, 73 out of 76 BSE-negative samples were correctly identified by DPR such that, numerically, an accuracy of 94.4 % can be calculated. At a confidence level of 0.95 (alpha = 0.05) these results correspond to a sensitivity > 85% and a specificity > 90%. Identical class assignment by all four classifiers occurred in 75% of the cases while ambiguous results were obtained in only 8 of the 160 cases. With an area under the ROC (receiver operating charateristics) curve of 0.991, DPR may potentially supply a valuable surrogate marker for BSE even in cases in which a deliberate bias towards improved sensitivity or specificity is desired. To the best of our knowledge, DPR is the first and--up to now--only method which has demonstrated its capability of detecting BSE-related signatures in serum.

Animals↗

PubMed2004

Unsupervised feature dimension reduction for classification of MR spectra.

We present an unsupervised feature dimension reduction method for the classification of magnetic resonance spectra. The technique preserves spectral information, important for disease profiling. We propose to use this technique as a preprocessing step for computationally demanding wrapper-based feature subset selection. We show that the classification accuracy on an independent test set can be sustained while achieving considerable feature reduction. Our method is applicable to other classification techniques, such as neural networks, support vector machines, etc.

Candida↗

PubMed2001

Ranking fMRI time courses by minimum spanning trees: assessing coactivation in fMRI.

In fMRI, time courses with similar temporal "activation" patterns may belong to different brain regions (i.e., these regions are functionally connected, coactivated). A group of time courses (TCs) corresponding to a particular type of temporal activation pattern should be maximally self-consistent (homogeneous). We demonstrate that ordering a group of multidimensional fMRI time courses by a minimum spanning tree (MST) may be used to investigate the temporal homogeneity of a group of TCs. We show the utility of MST ranking for data-driven analysis methods in investigating coactivation in fMRI. MST ranking is equally useful for hypothesis-led methods. Furthermore, MST ranking enables pairwise comparisons of groups/clusters (i.e., any collection of TCs, no matter how derived) of fMRI time courses.

Brain↗

PubMed2001

Disease pattern recognition testing for rheumatoid arthritis using infrared spectra of human serum.

BACKGROUND: In view of the importance of the diagnosis of rheumatoid arthritis, a novel diagnostic method based on spectroscopic pattern recognition in combination with laboratory parameters such as the rheumatoid factor is described in the paper. Results of a diagnostic study of rheumatoid arthritis employing this method are presented. METHOD: The method uses classification of infrared (IR) spectra of serum samples by means of discriminant analysis. The spectroscopic pattern yielding the highest discriminatory power is found through a complex optimization procedure. In the study, IR spectra of 384 serum samples have been analyzed in this fashion with the objective of differentiating between rheumatoid arthritis and healthy subjects. In addition, the method integrates results from the classification with levels of the rheumatoid factor in the sample by optimized classifier weighting, in order to enhance classification accuracy, i.e. sensitivity and specificity. RESULTS: In independent validation, sensitivity and specificity of 84% and 88%, respectively, have been obtained purely on the basis of spectra classification employing a classifier designed specifically to provide robustness. Sensitivity and specificity are improved by 1% and 6%, respectively, upon inclusion of rheumatoid factor levels. Results for less robust methods are also presented and compared to the above numbers. CONCLUSION: The discrimination between RA and healthy by means of the pattern recognition approach presented here is feasible for IR spectra of serum samples. The method is sufficiently robust to be used in a clinical setting. A particular advantage of the method is its potential use in RA diagnosis at early stages of the disease.

Adolescent↗

PubMed2001

Graphical display of fMRI data: visualizing multidimensional space.

Visualization of multidimensional data is an integral part of computational statistics and exploratory data analysis (EDA). We show how visualization of fMRI time-courses may be used to reveal the fMRI data structure. We consider fMRI time-courses (TCs) as points in multidimensional space. In simulated and in vivo data, we show that minimum spanning tree (MST)-based sequencing of multivariate time-courses, in combination with a homogeneity map visualization, allows for effective and useful graphical display of the groups of coactivated time-courses obtained by temporal clustering. This display may serve as a tool for investigation of brain connectivity. We also suggest a simple overall display of the entire fMRI data set.

Artifacts↗

PubMed2000

Resampling as a cluster validation technique in fMRI.

Exploratory, data-driven analysis approaches such as cluster analysis, principal component analysis, independent component analysis, or neural network-based techniques are complementary to hypothesis-led methods. They may be considered as hypothesis generating methods. The representative time courses they produce may be viewed as alternative hypotheses to the null hypothesis, i.e., "no activation." We present here a resampling technique to validate the results of exploratory fuzzy clustering analysis. In this case an alternative hypothesis is represented by a cluster centroid. For both simulated and in vivo functional magnetic resonance imaging data, we show that by permutation-based resampling, statistical significance may be computed for each voxel belonging to a cluster of interest without parametric distributional assumptions.

Brain↗

PubMed2000

Correlator beware: correlation has limited selectivity for fMRI data analysis.

Groups of time-courses created from fMRI data by the frequently used correlation analysis are often highly heterogeneous. This heterogeneity is due to the limited selectivity of correlation when trying to match brain time-courses to an externally imposed activation paradigm. Thus, this process unnecessarily generates many type I errors (false positives). Furthermore, as a consequence of the heterogeneity, time-courses identified and grouped by correlation may in fact describe different activations. After demonstrating this inadequacy, we give one particular approach to partition such a heterogeneous group into internally more homogeneous subgroups, using Kendall's coefficient of concordance W, and show its applicability and application to both simulated and in vivo data. Such group partition and "purification" will help subsequent inferential methods to deal more efficiently with false positives.

Algorithms↗

PubMed2000

Functional magnetic resonance imaging in rats subjected to intense electrical and noxious chemical stimulation of the forepaw.

We examined whether cerebral activation to two different intense and painful stimuli could be detected using functional magnetic resonance imaging (fMRI) in alpha-chloralose anesthetized rats. Experiments were performed using a 9.4 T magnet and a surface coil centered over the forebrain. A set of gradient echo images were acquired and analyzed using our software based on fuzzy cluster analysis (EvIdent). Following the injection of 50 microl of formalin (5%) into the forepaw we observed a regional increase in signal intensity in the MR images in all animals. Anterior cingulate cortex, frontal cortex and sensory-motor cortex were some of the regions that activated frequently and often bilaterally. Surprisingly, activation appeared sequentially, often occurring first in either the right or the left hemisphere with a separation of seconds to minutes between peak activations. Morphine pre-treatment (1 mg/kg, i. v.) delayed and/or reduced the intensity of the activation resulting in a decrease in the overall response. Following episodes of intense electrical stimulation, produced by two brief stimulations (15 V, 0. 3 ms, 3 Hz) of the forepaw, activation was observed consistently in the sensory-motor cortex contralateral to the stimulation. Activation also occurred frequently in the anterior cingulate cortex, ipsilateral sensory-motor cortex and frontal cortical regions. All these regions of activation were markedly reduced during nitrous oxide inhalation. Treatment with morphine resulted in an inhibition of the activation response to electrical stimulation in most regions except for sensory-motor cortex. Thus, electrical and chemical noxious stimuli activated regions that are known to be involved in the central processing of pain and morphine modified the activation observed. fMRI combined with appropriate exploratory data analysis tools could provide an effective new tool with which to study novel analgesics and their effects on the CNS processing of pain in animal models.

Animals↗

PubMed2000

Novelty indices: identifiers of potentially interesting time-courses in functional MRI data.

In a systematic study of hybrid MR time-series with simulated "activation" (contrast-to-noise range 1-10) we investigated the power and compared the ability of the "novelty indices" (NI) kurtosis, negentropy, and 1-lag autocorrelation, to discriminate between potentially interesting ("structured") and uninteresting ("noisy") time-courses (TCs). NIs may be employed as preprocessing tools to focus only on the interesting TCs prior to any further exploratory or confirmatory approach.

Humans↗

PubMed2000

Comparison of two exploratory data analysis methods for fMRI: fuzzy clustering vs. principal component analysis.

Exploratory data-driven methods such as Fuzzy clustering analysis (FCA) and Principal component analysis (PCA) may be considered as hypothesis-generating procedures that are complementary to the hypothesis-led statistical inferential methods in functional magnetic resonance imaging (fMRI). Here, a comparison between FCA and PCA is presented in a systematic fMRI study, with MR data acquired under the null condition, i.e., no activation, with different noise contributions and simulated, varying "activation." The contrast-to-noise (CNR) ratio ranged between 1-10. We found that if fMRI data are corrupted by scanner noise only, FCA and PCA show comparable performance. In the presence of other sources of signal variation (e.g., physiological noise), FCA outperforms PCA in the entire CNR range of interest in fMRI, particularly for low CNR values. The comparison method that we introduced may be used to assess other exploratory approaches such as independent component analysis or neural network-based techniques.

Brain↗

PubMed2000

Motor area activity during mental rotation studied by time-resolved single-trial fMRI.

The functional equivalence of overt movements and dynamic imagery is of fundamental importance in neuroscience. Here, we investigated the participation of the neocortical motor areas in a classic task of dynamic imagery, Shepard and Metzler's mental rotation task, by time-resolved single-trial functional Magnetic Resonance Imaging (fMRI). The subjects performed the mental-rotation task 16 times, each time with different object pairs. Functional images were acquired for each pair separately, and the onset times and widths of the activation peaks in each area of interest were compared to the response times. We found a bilateral involvement of the superior parietal lobule, lateral premotor area, and supplementary motor area in all subjects; we found, furthermore, that those areas likely participate in the very act of mental rotation. We also found an activation in the left primary motor cortex, which seemed to be associated with the right-hand button press at the end of the task period.

Brain↗

PubMed2000

Subclinical rejection--a potential surrogate marker for chronic rejection--may be diagnosed by protocol biopsy or urine spectroscopy.

Our studies of protocol biopsy studies have shown that normal allograft histology can not be assumed by crude tests of renal function such as the serum creatinine concentration, and that there is a high prevalence of subclinical rejection in the first 6 months post-transplant (7, 13-17). The apparent ability of urine MR and IR spectra to reliably identify patients with normal allograft histology, if confirmed in a larger database, will preclude the need for a protocol biopsy in approximately 20-50% of patients. Conversely, finding urine MR or IR spectra characteristic of subclinical rejection would provide the opportunity for early treatment. The clear separation between patients with normal histology from those with subclinical rejection can be attributed to the use of the whole urine spectrum to develop the classifiers. Additional advantages of using MR or IR spectra of urine as a diagnostic tool compared to the biopsy include simplicity (i.e. no processing is required), low cost, rapid turnaround (i.e. < 15 minutes/sample), and, particularly, low risk, thus allowing for repetitive sampling. The ability to non-invasively diagnose acute inflammation in the kidney would be of great assistance in the post-transplant monitoring of renal transplant patients. Indeed, by following subclinical inflammation as detected in the MR/IR spectra it will be possible to tailor the intensity of the immunosuppression to the inflammatory status of the graft, thus minimising the risks of both insufficient and excessive immunosuppression. Furthermore, by following subclinical inflammation, as detected in the MR/IR spectra, it will be possible to test the hypothesis that subclinical rejection (i.e. persistence of its MR/IR spectral classifier) is a surrogate marker for the development of chronic rejection.

Acute Disease↗

PubMed1999

Assessment of cluster homogeneity in fMRI data using Kendall's coefficient of concordance.

In fMRI both model-led and exploratory data-driven methods are used to identify groups of voxels according to their correlation either with an external reference or with some similarity measure. Here we present a technique to assess intragroup homogeneity using Kendall's coefficient of concordance W once groups have been identified. We show that the time-courses belonging to the group may be ranked according to their contribution to the overall concordance and describe an algorithm for group purification. We suggest the use of W as a cluster validation index in exploratory data analysis approaches, such as fuzzy or hard clustering, principal component analysis, independent component analysis and Kohonen maps.

Algorithms↗

PubMed1999

An interleaved T1-T2* imaging sequence for assessing myocardial injury.

We developed a sequence by which T1- and T2*-weighted images can be acquired simultaneously and demonstrated its validity for assessing myocardial injury. The interleaved T1-T2* imaging sequence consisted of one preparatory pulse (a 90 degrees pulse) and a gradient-echo imaging sequence with a dynamically variable echo time varying between 4.2 msec for T1-weighted imaging and 15 msec for T2*-weighted imaging. The sequence was tested and validated on isolated blood-perfused pig hearts (n = 4). We found that contrast agent-induced T1 and T2* effects were clearly delineated during the first-pass and steady-state periods of a contrast agent (gadolinium diethylenetriaminopentaacetic acid). With a bolus injection of contrast agent, the maximum changes in T2* signal intensity occur significantly earlier than the changes in T1 signal. We also found that the maximum change in T1 signal intensity during the first pass of contrast agent was significantly greater in a reperfused-infarcted region than in normal regions. The suppression of T2* signal was similar in both regions. At steady state of contrast agent, T2* signal intensities gradually recovered to a significantly higher level in the reperfused-infarcted region than in normal regions. This suggests that the contrast agent diffused into the intracellular space, indicating the loss of cell membrane integrity. As a result, T1 signal intensity was also higher in the reperfused-infarcted myocardium than in normal myocardium. T1- and T2*-weighted images can be acquired simultaneously. The interleaved T1-T2* sequence is useful in assessing myocardial injury.

Animals↗

PubMed1998

Impact of unified procedures as implemented in the Canadian Quality Assurance Program for T lymphocyte subset enumeration. Participating Flow Cytometry Laboratories of the Canadian Clinical Trials Network for HIV/AIDS Therapies.

The objective of the Canadian Quality Assurance Program (CQAP) is to provide the most reproducible and accurate T-cell subset enumeration for individuals living with HIV who are enrolled in the Canadian Clinical Trial Network for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) Therapies (abbreviated as CTN). The Canadian National Laboratory for Analytical Cytology, within the Laboratory Centre for Disease Control, is part of the Health Protection Branch of Health Canada. For the past eight years, the Laboratory for Analytical Cytology has been responsible for delivering a bilingual quality assurance program for CD4 T-cell enumeration. This federal program, which integrates biotechnology transfer with quality assessment, was achieved through the organization of workshops focused on technology transfer and essential skill-building techniques. Two training sessions were conducted for the CTN flow cytometer operators. The first introduced the concept of window of analysis, to demonstrate the practical benefits of unified quantitative fluorescent measurement. As a follow-up to the first workshop, participants performed a series of quantitative assays that monitored the expression of CD69, an early activation marker. This quantitative fluorescence protocol was performed with acceptable inter-laboratory variation using modified commercial kits. The second workshop focused on a absolute count method based on a single platform. Four preserved whole-blood preparations were tested with this approach. The combined effort reduced inter-laboratory variation. The direct impact was monitored as related to the frequency of participation. Over the years, the standard deviation of average accumulated variation decreased dramatically with increased frequency of participation, from 10% to <4%.

Canada↗

PubMed1998

Does simultaneous antegrade/retrograde cardioplegia improve myocardial perfusion in the areas at risk? A magnetic resonance perfusion imaging study in isolated pig hearts.

OBJECTIVE: This study was designed to determine whether simultaneous antegrade/retrograde cardioplegia improves myocardial perfusion in areas supplied by occluded vessels. METHODS: Isolated pig hearts placed in a Langendorff preparation were divided into two groups. The left anterior descending coronary artery was occluded at its origin. In group 1 (n = 7), simultaneous antegrade/retrograde cardioplegia was conducted with use of a single perfusion unit with tubing in a Y-shaped configuration at the end, joined to the aorta and the coronary sinus. In group 2 (n = 8) simultaneous antegrade/retrograde cardioplegia was performed with two separate units, one for antegrade delivery of cardioplegic solution and the other for retrograde cardioplegic solution delivery. Myocardial perfusion in the region supplied by the left anterior descending artery and the region not supplied by this artery was assessed by magnetic resonance imaging, with use of a magnetic resonance contrast agent. The contrast agent was introduced into the common perfusion line in group 1 and into the aortic line only in group 2. RESULTS: Magnetic resonance images showed that the myocardium in the region supported by the left anterior descending artery could not be perfused with antegrade cardioplegic solution because of occlusion of the artery. During simultaneous antegrade/retrograde cardioplegia, however, the myocardium in the left anterior descending region was perfused by approximately 40% to 50% (group 1) or 20% to 30% (group 2) of the degree of perfusion in the region not perfused by the left anterior descending artery (100%). Almost no cardioplegic solution was delivered to the heart through the coronary sinus route during simultaneous antegrade/retrograde cardioplegia in both groups of hearts. Myocardial perfusion in the region supported by the left anterior descending artery was heterogeneous during simultaneous antegrade/retrograde cardioplegia. CONCLUSIONS: Simultaneous antegrade/retrograde cardioplegia significantly improved myocardial perfusion in jeopardized areas of the myocardium. The jeopardized myocardium was mainly perfused by the solution drained from the adjacent normal tissue. Elevated pressure at the coronary sinus during simultaneous antegrade/retrograde cardioplegia is responsible for the redistribution of antegradely delivered cardioplegic solution.

Animals↗

PubMed1993

A Monte Carlo method for conformational analysis of saccharides.

A Metropolis Monte Carlo (MMC) algorithm was applied to explore conformational spaces spanned by the exocyclic dihedral angles of four disaccharides alpha-D-Man(1-->3)-alpha-D-Man(1-->O)Me (1), alpha-D-Man(1-->2)-alpha-D-Man(1-->O)Me (2), methyl beta-cellobioside (3), and methyl beta-maltoside (4). The simulation method uses the HSEA force field and randomly samples the conformational space with an automatic preference for low-energy states. In comparison to a systematic grid search, MMC offers a much more convenient and efficient protocol for the computation of ensemble average values of experimentally accessible NMR parameters such as NOE effects or 3J coupling constants. Energy barriers of a few kcal/mol were found to be surmounted easily when running the simulations with the temperature parameter set at room temperature, whereas passing significantly higher barriers required elevated temperature parameters. Ensemble average NOE values were calculated using the MMC technique and a conventional systematic grid search showing that the MMC method adequately samples the conformational spaces of 1-4. Theoretical NOEs derived for global or local minimum conformations are different from ensemble average values, and it is shown that averaged NOEs agree significantly better with experimental data. Ensemble average NOEs for 1 derived from MMC/HSEA, and previously reported MM2CARB and AMBER calculations all showed good agreement with experimental data, with MMC/HSEA giving the closest fit.

Algorithms↗

PubMedDate not supplied

Fuzzy clustering of gradient-echo functional MRI in the human visual cortex. Part I: reproducibility.

Reproducibility of human functional MRI (fMRI) studies is essential for clinical and neuroresearch applications of this new human brain mapping method. Based on a recently presented study on reproducibility of gradient-echo fMRI in the human visual cortex (Moser et al. Magn Reson Imaging 1996; 14:567-579), comparing the performance of three different threshold strategies for correlation analysis, we demonstrate that (a) fuzzy clustering is a robust, model-independent method to extract functional information in time and space; (b) intertrial reproducibility of cortical activation is significantly improved by the capability of fuzzy clustering to separate signal contributions from larger vessels, running perpendicular to the slice orientation, from activation apparently close to the primary visual cortex; and (c) for repeated single subject studies, SDs of <20% for signal enhancement in approximately 80% of the studies and SDs of <30% for activated area size in approximately 65% of the studies are obtained. This, however, depends also on signal-to-noise ratio, (motion) artifacts, and subject cooperation.

Adult↗