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PubMed2001

Perfusion imaging using dynamic arterial spin labeling (DASL).

Recently, a technique based on arterial spin labeling, called dynamic arterial spin labeling (DASL (Magn Reson Med 1999;41:299-308)), has been introduced to measure simultaneously the transit time of the labeled blood from the labeling plane to the exchange site, the longitudinal relaxation time of the tissue, and the perfusion of the tissue. This technique relies on the measurement of the tissue magnetization response to a time varying labeling function. The analysis of the characteristics of the tissue magnetization response (transit time, filling time constant, and perfusion) allows for quantification of the tissue perfusion and for transit time map computations. In the present work, the DASL scheme is used in conjunction with echo planar imaging at 4.7 T to produce brain maps of perfusion and transit time in the anesthetized rat, under graded hypercapnia. The data obtained show the variation of perfusion and transit time as a function of arterial pCO2. Based on the data, CO2 reactivity maps are computed. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed1994

Estimation of changes in side chain configurational entropy in binding and folding: general methods and application to helix formation.

Theoretical estimations of changes in side chain configurational entropy are essential for understanding the different contributions to the overall thermodynamic behavior of important biological processes like folding and binding. The configurational entropy of any given side chain in any particular protein can be evaluated from the complete energy profile of the side chain. Calculations of the energy profiles can be performed using the side chain single bond dihedrals as the only independent variables as long as the structures at each value of the dihedrals are allowed to relax through small changes in the valence bond angles. The probabilities of different side chain conformers obtained from these energy profiles are very similar to the conformer populations obtained by analysis of side chain preferences in the proteins of the Protein Data Bank. Also, side chain conformational entropies obtained from the energy profiles agree extremely well with those obtained from the Protein Data Bank conformer populations. Changes in side chain configurational entropy in binding and folding can be computed as differences in conformational entropy because, in most cases, the frequency of the rotational oscillation around the energy minimum of any given conformer does not appear to change significantly in the reactions. Changes of side chain conformational entropy calculated in this way were compared with experimental values. The only available experimental data--the effect of side chain substitution on the stability of alpha-helices--were used for this comparison. The experimental values were corrected to subtract the solvent contributions. This comparison yields an excellent agreement between calculated and experimental values, validating not only the theoretical estimates but also the separability of the entropic contributions into configurational terms and solvation related terms.

Amino Acids↗
PubMed1993

Crystallographic studies on a family of cellular lipophilic transport proteins. Refinement of P2 myelin protein and the structure determination and refinement of cellular retinol-binding protein in complex with all-trans-retinol.

P2 myelin protein (P2) and cellular retinol binding protein (CRBP) are members of a family of cellular lipophilic transport proteins. P2 has been refined at a resolution of 2.7 A, and CRBP has been solved by molecular replacement and refined to a resolution of 2.1 A. The members of this family form a compact three-dimensional structure built up from ten antiparallel strands that fold to form an orthogonal barrel containing the ligand. In P2, the carboxylate group of an oleic acid ligand interacts with the side-chains of two arginine (106 and 126), and one tyrosine (128) residues. The ligand adopts a U-shaped conformation. In CRBP, the all-trans-retinol has a planar conformation with its alcohol group hydrogen bonding to the side-chain of glutamine 108 (equivalent to residue 106 in P2). The local interactions of glutamine 108 explain CRBP's preference for binding retinol rather than retinal. The side-chain of lysine 40 makes a close contact with the isoprene tail of the retinol.

Amino Acid Sequence↗
PubMed1995

Interference and facilitation effects during selective attention: an H215O PET study of Stroop task performance.

To investigate the functional anatomy of interference and facilitation during selective attention, we studied 15 normal subjects using the H215O positron emission tomography technique and a computer presented single-trial Stroop task for cognitive activation. Increases in regional cerebral blood flow (rCBF) were observed in a network of structures that have been previously associated with selective attention, including the anterior cingulate gyrus, the frontal polar cortex, the inferior parietal lobule, and the thalamus, as well as the lingual gyrus. Furthermore rCBF decreases (compared to control states) were observed in lateral extra-striate cortex. rCBF changes in prefrontal and extra-striate regions varied with differences in the need to modulate the influence of word and color information while subjects responded to either incongruent or congruent Stroop stimuli. These results indicate the utility of Stroop procedures for investigating the functional anatomy of selective attention. Given recent interest regarding the role of the anterior cingulate gyrus in the pathophysiology of neuropsychiatric disorders, our results also suggest that the Stroop task can serve as a reliable neurobehavioral probe for this region. The significance of these results for understanding processing mechanisms underlying selective attention is discussed within the framework of a parallel distributed processing model of Stroop task performance.

Adult↗
PubMed1997

Incorporating prior knowledge into image registration.

The first step in the spatial normalization of brain images is usually to determine the affine transformation that best maps the image to a template image in a standard space. We have developed a rapid and automatic method for performing this registration, which uses a Bayesian scheme to incorporate prior knowledge of the variability in the shape and size of heads. We compared affine registrations with and without incorporating the prior knowledge. We found that the affine transformations derived using the Bayesian scheme are much more robust and that the rate of convergence is greater.

Adolescent↗
PubMed1998

Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping.

The aging process is thought to result in changes in synaptic activity reflecting both functional and structural cell derangement. However, previous PET reports on age-related changes in resting brain glucose utilization (CMRglc) have been discrepant, presumably because of methodological as well as subject screening differences. In contrast to other studies, which used a region of interest approach, the objective of the present work was to determine, by means of the SPM software, the changes in regional CMRglc as a function of age in 24 optimally healthy, unmedicated volunteers of ages from 20 to 67 years. Global CMRglc showed a significant decline with age (approximately 6% per decade, P < 0.05), which concerned all the voxels studied save for most of the occipital cortex and part of the cerebellum. The most significant effects (P < 0.001) concerned the association neocortex in perisylvian temporoparietal and anterior temporal areas, the insula, the inferior and posterior-lateral frontal regions, the anterior cingulate cortex, the head of caudate nucleus, and the anterior thalamus, in a bilateral and essentially symmetrical fashion. The high posterior parietal cortex was not sampled in this study. This distribution of changes in CMRglc with age may differ from that seen in Alzheimer' disease, where the earliest metabolic reduction has been shown to affect the posterior cingulate cortex.

Adult↗
PubMed2001

Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients.

Apathy is the most frequent behavioral symptom in Alzheimer's disease and is also frequently reported in other brain organic disorders occurring in the elderly. Based on the literature, we hypothesized that apathy was related to an anterior cingulate hypofunction. Forty-one subjects were studied. According to ICD 10 diagnostic criteria, 28 patients had Alzheimer dementia (demented: diagnostic group 1), and 13 had organic personality disorders or mild cognitive impairment not attributable to dementia (nondemented: diagnostic group 2). Apathy was evaluated by the Neuro-Psychiatric Inventory. As a result each diagnostic group was divided into two symptomatic subgroups: apathetic or nonapathetic. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) brain SPECT and the images were compared using Statistical Parametric Mapping (SPM96). We began by comparing apathetic vs nonapathetic patients, whatever their diagnostic group (whole population), then analyzed them within each group. Twenty-one subjects were apathetic (14 in group 1 and 7 in group 2) and 20 were not (14 in group 1 and 6 in group 2). For the whole population, the Z map showed a significant decrease in ECD uptake for the apathetic patients in the anterior cingulate (P < 0.002) bilaterally. This area was also identified as hypoactive by SPM analysis in the demented (P < 0.035) and in the nondemented (P < 0.02) apathetic patient groups. Finally, conjunction analysis indicated that the anterior cingulate was the common hypoactive structure of the two apathetic subgroups (Z = 4.35, P < 0.0009). These results point to a close relationship between apathy and the anterior cingulate region.

Aged↗
PubMed2001

Estimation of the number of "true" null hypotheses in multivariate analysis of neuroimaging data.

The repeated testing of a null univariate hypothesis in each of many sites (either regions of interest or voxels) is a common approach to the statistical analysis of brain functional images. Procedures, such as the Bonferroni, are available to maintain the Type I error of the set of tests at a specified level. An initial assumption of these methods is a "global null hypothesis," i.e., the statistics computed on each site are assumed to be generated by null distributions. This framework may be too conservative when a significant proportion of the sites is affected by the experimental manipulation. This report presents the development of a rigorous statistical procedure for use with a previously reported graphical method, the P plot, for estimation of the number of "true" null hypotheses in the set. This estimate can then be used to sharpen existing multiple comparison procedures. Performance of the P plot method in the multiple comparison problem is investigated in simulation studies and in the analysis of autoradiographic data.

Anesthesia, General↗
PubMed2002

Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake.

BACKGROUND: For a quantitative comparison of images obtained during (99m)Tc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i.e., global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization. METHODS: Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs. RESULTS: The reduction of cerebral blood flow in the group of ATD patients appeared 1.7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone. CONCLUSION: An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.

Aged↗
PubMed1995

Computer-assisted multidimensional atlas for functional stereotaxy.

Functional stereotactic operations are currently performed primarily for medically uncontrollable Parkinson's disease and pain. In contrast to the targets in neuro-oncology, those in functional stereotaxy cannot be represented directly by modern imaging methods. The target co-ordinates must therefore be calculated with the aid of special stereotactic atlases. These are publications in which a model brain has been constructed from autopsy examinations on a number of brains, or the data obtained have been compiled in the form of tables and histograms on which the calculation is then based. The target can then be determined based on the classic stereotactic landmarks and reference lines, such as the anterior commissure (AC), the foramen of Monro (FM), the posterior commissure (PC) or the base line FM-PC or AC-PC and the height of thalamus, taking into account the interindividually different anatomical proportions. Since the computational procedures involve repetitious algorithms, it was obvious that such procedures should be run by a computer program. For the most common stereotactic targets, we have developed a computer program for data storage on the one hand and computation and graphic output on the other. The output can be displayed on the monitor and can also be plotted out on paper or overhead transparency. Calibrating between the program and printer renders a 1:1 reproduction, i.e. the graph can be superimposed directly onto original x-rays or images from computed tomography or nuclear magnetic imaging. The graph can be plotted in the three dimensions of the Cartesian co-ordinate system. An additional dimension can be attained by simultaneously including and plotting the data from different atlases and thus from different authors, including one's own data. In addition to the information capacity which this system offers, it also makes possible a considerable reduction in the time for computing the target while at the same time increasing the reliability.

Algorithms↗
PubMed2003

The comparison of reliabilities in dental imaging methods.

OBJECTIVES: Common practice in the statistical comparison of imaging instruments with limited reproducibility consists in the separate estimation of the instrument's reliabilities. However, as soon as one of the imaging methods is subject to item-specific bias (which has to be expected in many dentomaxillofacial imaging procedures), this approach will end in severe errors in reliability computation and in corresponding erroneous clinical conclusions. This paper seeks to point out these effects and to illustrate a more appropriate model for the comparison of instrumental reliabilities. METHODS: A standard reliability model was adjusted for item-specific bias and illustrated by the comparison of twice repeated planimetric cephalometry versus twice repeated noninvasive orthodontic video imaging (based on the Digigraph 100 device) in 50 children; the anterior cranial base length was used for illustration. RESULTS: The proposed model revealed pronounced inferiority of the video-based imaging system concerning its reliability compared with the X-ray based standard. Analysis using separate estimation of the two reliabilities would result in the reverse conclusion and thus falsely establish video imaging, which is in fact less reliable, as a superior diagnostic method. CONCLUSION: The reliabilities of dentomaxillofacial imaging methods have to be adjusted for potential item-specific bias to avoid the erroneous conclusion of the superiority of a diagnostic innovation.

Adolescent↗
PubMed2002

Stratification of mammographic computerized analysis by BI-RADS categories.

The Breast Imaging Reporting and Data System (BI-RADS) was implemented to standardize characterization of mammographic findings. The purpose of the present study was to evaluate in which BI-RADS categories the changes recommended by computerized mammographic analysis are most beneficial. Archival cases including, 170 masses (101 malignant, 69 benign) and 63 clusters of microcalcifications (MCs; 36 malignant, 27 benign), were evaluated retrospectively, using the BI-RADS categories, by several radiologists, blinded to the pathology results. A computerized system then automatically extracted from the digitized mammogram features characterizing mammographic lesions, which were used to classify the lesions. The results of the computerized classification scheme were compared, by receiver operating characteristics (ROC) analysis, to the conventional interpretation. In the "low probability of malignancy group" (excluding BI-RADS categories 4 and 5), computerized analysis improved the A(z )of the ROC curve significantly, from 0.57 to 0.89. In the "high probability of malignancy group" (mostly category 5) the computerized analysis yielded an ROC curve with an A(z )of 0.99. In the "intermediate probability of malignancy group" computerized analysis improved the A(z )significantly, from 0.66 for to 0.83. Pair-wise analysis showed that in the latter group the modifications resulting from computerized analysis were correct in 83% of cases. Computerized analysis has the ability to improve the performance of the radiologists exactly in the BI-RADS categories with the greatest difficulties in arriving at a correct diagnosis. It increased the performance significantly in the problematic group of "intermediate probability of malignancy" and pinpointed all the cases with missed cancers in the "low probability" group.

Biopsy↗
PubMed2003

Multidetector-row cardiac CT: diagnostic value of calcium scoring and CT coronary angiography in patients with symptomatic, but atypical, chest pain.

The aim of this study was to investigate the accuracy of multidetector-row cardiac CT (MDCT), calcium scoring (Ca-Sc), and MDCT coronary angiography (MD CTA) in the assessment of coronary atherosclerosis. Thirty-eight patients underwent invasive coronary angiography (CA) and MDCT (collimation 4x1 mm, pitch 1.5 mm, TI 500 ms, 120 kV, 300 mAs, and retrospective ECG-gating). Calcium scoring was calculated for the total coronary artery territory and for RCA, LCA, and LCX separately. The MD CTA served to assess the degree and the localization of stenoses. All findings were compared to invasive coronary angiography. Approximately 68.4% (390 of 570) of all coronary segments could be visualized by MDCT. Correlation coefficient for MD CTA and CA amounted to r=0.58, showing distinct differences for the individual segments. Proximal segments generally showed better correlation (range 0.81-0.77) than medial segments (range 0.91-0.20), distal segments (range 0.55-0.04), or side branches (range 0.76-0.00). Patients with hemodynamically relevant (>75%) stenoses were detected by MD CTA with 72.2% sensitivity (13 of 18) and 100% specificity (20 of 20). For Ca-Sc sensitivity ranged between 94.7% (17 of 18) and 66.7% (12 of 18), specificity between 20% (4 of 20) and 80% (16 of 20) respectively, depending on the prevailing cutoff value. Combination of both methods led to 83.3% sensitivity (15 of 18) and 100% specificity (20 of 20), reaching no level of significance as compared with Ca-Sc (p=0.73) or MD CTA (p=0.23) alone. Calcium scoring as a single method showed highest sensitivity in the detection of coronary atherosclerosis but at the expense of low specificity. In patients with no or moderate calcifications, combination with MD CTA helped to distinctly increase specificity and NPV.

Adult↗
PubMed2005

Evaluation of the cavotricuspid isthmus and right atrium by multidetector-row computed tomography in patients with common atrial flutter.

The sizes of the right atrium (RA), cavotricuspid isthmus, and Eustachian valve are predictors of success of radiofrequency catheter ablation for atrial flutter (AFL). We examined the relationship between the sizes of cavotricuspid isthmus as measured by multidetector-row computed tomography (MDCT) and fluoroscopy. We used eight-detector MDCT to measure the tricuspid isthmus of 23 patients prior to linear ablation for common AFL. One patient with a deep pouch in the RA was excluded. Parameters measured were (1) the length of the trace of isthmus (Ti), which was equivalent to the blocking line; (2) the size of the tricuspid isthmus (DTi); and (3) the distance from the tricuspid valve and inferior vena cava (IVC) (LDTi). DTi and LDTi indicate the size of the RA, reflecting the appropriately sized steerable ablation catheter, respectively. Of the 22 patients, 21 were ablated successfully without recurrence of AFL, and clinical success was achieved in one additional patient despite failure to obtain a bidirectional block. Ti, DTi, and LDTi were correlated with fluoroscopy time (r = 0.84, r = 0.88, and r = 0.88, respectively; P < 0.0001), total delivered energy (r = 0.81, r = 0.80, and r = 0.83, respectively; P < 0.0001), and application time (r = 0.84, r = 0.80, and r = 0.87, respectively; P < 0.0001). Measurement of the tricuspid isthmus by MDCT may noninvasively provide important information for successful linear ablation.

Atrial Fibrillation↗
PubMed2003

Left atrial appendage morphology: comparison of transesophageal images and postmortem casts.

BACKGROUND: Aim of the study was to compare 1) transesophageal echocardiographic (TEE) measurements of the left atrial appendage (LAA) with postmortem casts and 2) the TEE with the postmortem diagnosis of LAA thrombi. METHODS: From the TEE images and LAA casts length, orifice, diameter and number of branches were assessed. LAA area was measured by TEE and LAA volume from the cast. RESULTS: In 12 patients who underwent TEE and autopsy, measurements of LAA length and area correlated well with the cast volume ( r=0.6 to r=0.93). The agreement between TEE and LAA casts, concerning the number of branches, was only moderate. In one patient, a false positive diagnosis of a LAA thrombus occurred. CONCLUSIONS: LAA size and orifice diameter can be assessed reliably by TEE. The complex LAA morphology hampers measurements of LAA length, branches, course and diagnosis of thrombi.

Acrylic Resins↗
PubMed1991

Sample size and dimensionality in multivariate classification: implications for body surface potential mapping.

This paper presents empirically determined guidelines for specifying the number of features appropriate for multivariate classification studies for given sample sizes. Sample size was considered adequate if the mean distance between two sample sets, taken from the same continuous multivariate distribution and projected onto the best separating direction, remained below a prescribed level. To quantitate the sample size requirement, homogeneity of sample set pairs of equal size. N, taken from the same continuous multivariate distribution was studied as a function of dimensionality. M. Homogeneity was characterized by the maximum absolute distances (Dmax) between the corresponding pairs of empirical cumulative probability distributions on the best separating projection. Computer generated data sets were used to estimate the cumulative probability distribution, P(D)M.N, for sample sizes, N, ranging from 5 to 100 and the dimensionality, M, ranging from 1 to 4. An empirical relationship between the estimated step-polygons and the Kolmogorov type one dimensional limiting distribution L(z) has been established. Based on the sample size data of 34 key papers on clinical body surface potential mapping (BSPM) it is noted that in 30% of the cases only one, and in 6% of the cases only two parameters could be used for statistical group representation to ensure a reasonable reliability (Dmax less than 0.2). In 56% of the published cases the sample sizes could not guarantee this reliability even for one feature or parameter.

Computer Simulation↗
PubMed1987

Limiting efficiencies of the non-parametric median method for A exp(-kt) data.

Weighted least squares analysis and the median method are used to extract A and k from simulated single exponential decays. The standard deviations of these parameters (sigma p) depend upon the method of analysis. The sigma p are compared as efficiencies (= sigma 2p[least squares]/sigma 2p[median]). These efficiencies depend upon the range of the decay and the underlying error structure. These include errors independent of the data, approximately equal to the data and approximately equal to the square root of the data. Some efficiencies fall well below 25% for the median method. Such instances reflect the large cost of not knowing or not using the weights; they amount to ignoring greater than 75% of the data we strive to collect.

Computer Simulation↗
PubMed1988

Computer simulation of neuronal circuit models of rhythmic behavior in the electroencephalogram.

A computer program for modeling some features of the electroencephalogram (EEG) recorded by scalp electrodes in terms of the time- and space-dependent interactions of populations of neurons in different hypothetical brain configurations was developed. The input of the model consists of: (1) geometric and anatomic data characterizing the brain configuration; (2) physiologic features characterizing neurons; and (3) functions describing the time-dependent afferent impulses to the brain configuration under study. The output of the model consists of plots of selected intracellular and extracellular potentials as a function of time. In application of the model to various brain configurations, some configurations were sufficiently compact spatially that propagation times of action potentials between elements were either taken to be constant or were nearly independent of distance within the accuracy of the calculations. Other configurations represented cerebral cortex alone or a combined thalamocortical system in which many elements interacted via global interconnections. The basic requirement for rhythmic behavior is the existence of circuits containing inhibitory neurons. The characteristic frequencies of rhythmic oscillations are primarily determined by the local circuit parameters and are relatively independent of global circuit parameters.

Action Potentials↗