Biomedical subjects

S C Strother

Publications and source records attributed to S C Strother.

At least 19 recordsLinked to original sources

PubMed2001

Effects of changes in experimental design on PET studies of isometric force.

Based on single-cell recordings in primates, the relationship between neuronal activity and force magnitude is thought to be monotonic, at least for a subset of pyramidal cells in the motor cortex. Functional neuroimaging studies have also suggested a monotonic relationship between cerebral activation and force magnitude. In order to more precisely define this relationship and to characterize the activation pattern(s) associated with the modulation of static force, we studied 40 normal subjects using [(15)O]water PET and a simple visuomotor task-application of static force on a micro force sensor with the thumb and index finger of the right hand. When our experimental design did not produce the expected result (evidence of a relationship between cerebral activation and force magnitude in ten subjects), we made serial changes in the experimental protocol, including the addition of control (baseline) trials, and increased the number of subjects in an effort to increase our sensitivity to variations in force magnitude. We compared univariate and multivariate data-analytic strategies, but we relied on our multivariate results to elucidate the interaction of attentional and motor networks. We found that increasing the number of subjects from 10 to 20 resulted in an increase in statistical power and a more stable (i.e., more replicable) but qualitatively similar result, and that the inclusion of control trials in a 10-subject group did not enhance our ability to discern significant brain-behavior relationships. Our results suggest that sample sizes greater than 20 may be required to detect parametric variation in some instances and that failure to detect such variation may result from unanticipated neurobehavioral effects.

Adult↗

PubMed2001

Consensus inference in neuroimaging.

We introduce model averaging in neuroimaging. We show that model summary images can be directly compared and averaged after histogram equalization. We demonstrate that averaging enhances the ROC curve in a simulation study. The averaging procedure is applied to a fMRI study of motor cortex.

Brain Mapping↗

PubMed2000

Multivariate predictive relationship between kinematic and functional activation patterns in a PET study of visuomotor learning.

Imaging studies of visuomotor learning have reported practice-related activation in brain regions mediating sensorimotor functions. However, development and testing of functional motor learning models, based on the relationship between imaging and behavioral measures, is complicated by the multidimensional nature of motoric control. In the present study, multivariate techniques were used to analyze [15O]water PET and kinematic correlates of learning in a visuomotor tracing task. Fourteen subjects traced a geometric form over a series of eight tracing trials, preceded and followed by baseline trials in which they passively viewed the geometric form. Simultaneous evaluation of multiple behavioral measures indicated that performance improvement was most strongly associated with a global performance measure and least strongly associated with measures of fine motor control. Results of three independent analytic techniques (i.e., intertrial correlation matrices, power function modeling, iterative canonical variate analysis) indicated that imaging and behavioral measures were most closely related on early learning trials. Performance improvement was associated with covarying increases in normalized activity among superior parietal, postcentral gyrus, and premotor regions and covarying decreases in normalized activity among cerebellar, inferior parietal, pallidal, and medial occipital regions. These findings suggest that performance improvement may be associated with increased activation in neural systems previously implicated in visually guided reaching and decreased activation in neural systems previously implicated in attentive visuospatial processing.

Adult↗

PubMed2000

Comparison of voxel- and volume-of-interest-based analyses in FDG PET scans of HIV positive and healthy individuals.

UNLABELLED: Abnormal glucose metabolic patterns in the brain have been reported for HIV-1 seropositive (HIV+) patients when compared with seronegative healthy individuals. The metabolic covariance pattern obtained from voxel- or volume-of-interest (VOI)-based multivariate data analysis techniques can be used to characterize disease and potentially to detect and monitor disease progression in the early stage of AIDS dementia complex. However, the arbitrary smoothing typically applied to PET data during reconstruction and processing to reduce noise has an unknown effect on the data, especially for the voxel-based analysis. METHODS: To investigate the impact of smoothing on a discrimination task, we applied principal component analysis with scaled subprofile-model preprocessing (SSM/PCA) followed by Fisher discriminant analysis to FDG PET data that were reconstructed and processed with different degrees of smoothing. Receiver operating characteristic curves were used to compare the ability of derived metabolic covariance patterns to discriminate HIV+ patients from healthy volunteers. RESULTS: For the voxel-based analysis, we found that the spatial distribution of voxel weights from the SSM/PCA analysis suggested edge effects along major tissue and cerebrospinal fluid boundaries, indicative of a disease-specific pattern of cerebral atrophy for the HIV+ patients. In terms of its discrimination performance, this metabolic covariance pattern is stable and insensitive to a wide range of smoothing kernels, except for ramp reconstruction and Hanning reconstruction with 7 x 7 x 7 block smoothing. In these reconstructions, the discrimination performance decreased as a result of high image noise and excessive smoothing, respectively. Our results also indicated that if sufficient variance from the VOI measurements is included, the overall performance of a conventional VOI-based analysis can be similar to that of the voxel-based analysis for the same discrimination task. However, the VOI-based analysis performed poorly at low false-positive fraction and is less tolerant to noise in the metabolic covariance pattern than the voxel-based analysis. CONCLUSION: We have obtained a unique covariance pattern of brain glucose metabolism for HIV+ patients compared with healthy volunteers. Discrimination based on this covariance pattern was found to be insensitive to a wide range of image smoothness.

AIDS Dementia Complex↗

PubMed1999

Reproducibility of BOLD-based functional MRI obtained at 4 T.

The reproducibility of activation patterns in the whole brain obtained by functional magnetic resonance imaging (fMRI) experiments at 4 Tesla was studied with a simple finger-opposition task. Six subjects performed three runs in one session, and each run was analyzed separately with the t-test as a univariate method and Fisher's linear discriminant analysis as a multivariate method. Detrending with a first- and third-order polynomial as well as logarithmic transformation as preprocessing steps for the t-test were tested for their impact on reproducibility. Reproducibility across the whole brain was studied by using scatter plots of statistical values and calculating the correlation coefficient between pairs of activation maps. In order to compare reproducibility of "activated" voxels across runs, subjects and models, 2% of all voxels in the brain with the highest statistical values were classified as activated. The analysis of reproducible activated voxels was performed for the whole brain and within regions of interest. We found considerable variability in reproducibility across subjects, regions of interest, and analysis methods. The t-test on the linear detrended data yielded better reproducibility than Fisher's linear discriminant analysis, and therefore seems to be a robust although conservative method. Preliminary data indicate that these modeling results may be reversed by preprocessing to reduce respiratory and cardiac physiological noise effects. The reproducibility of both the position and number of activated voxels in the sensorimotor cortex was highest, while that of the supplementary motor area was much lower, with reproducibility of the cerebellum falling in between the other two areas.

Adult↗

PubMed1999

Generalizable patterns in neuroimaging: how many principal components?

Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets.

Algorithms↗

PubMed1999

Are brain functions really additive?

Although Positron Emission Tomography (PET) and functional magnetic resonance imaging (fMRI) studies commonly subtract data obtained during two or more experimental conditions to decompose a complex task, there have been few opportunities to evaluate this approach directly. In the present study, PET was used to study three motor speech tasks selected such that two were constituent components of the third, making possible a direct examination of decomposition by subtraction. In Experiment 1, a group of 13 right-handed normal volunteers participated in three activation studies: syllable repetition; phonation; and repetitive lip closure. A scanning session was devoted to a single task, repeated four times. In Experiment 2, six of the original subjects performed the same three activation studies during a single scanning session. Whether tasks were studied in separate scanning sessions or combined within a single session, the results of decomposition by compound subtraction differed significantly from the results obtained when individual tasks were compared to a simple baseline condition. These data failed to demonstrate task additivity, a necessary property if decomposition by subtraction is to provide an accurate characterization of the brain activity accompanying complex behavior.

Adult↗

PubMed1999

Plurality and resemblance in fMRI data analysis.

We apply nine analytic methods employed currently in imaging neuroscience to simulated and actual BOLD fMRI signals and compare their performances under each signal type. Starting with baseline time series generated by a resting subject during a null hypothesis study, we compare method performance with embedded focal activity in these series of three different types whose magnitudes and time courses are simple, convolved with spatially varying hemodynamic responses, and highly spatially interactive. We then apply these same nine methods to BOLD fMRI time series from contralateral primary motor cortex and ipsilateral cerebellum collected during a sequential finger opposition study. Paired comparisons of results across methods include a voxel-specific concordance correlation coefficient for reproducibility and a resemblance measure that accommodates spatial autocorrelation of differences in activity surfaces. Receiver-operating characteristic curves show considerable model differences in ranges less than 10% significance level (false positives) and greater than 80% power (true positives). Concordance and resemblance measures reveal significant differences between activity surfaces in both data sets. These measures can assist researchers by identifying groups of models producing similar and dissimilar results, and thereby help to validate, consolidate, and simplify reports of statistical findings. A pluralistic strategy for fMRI data analysis can uncover invariant and highly interactive relationships between local activity foci and serve as a basis for further discovery of organizational principles of the brain. Results also suggest that a pluralistic empirical strategy coupled formally with substantive prior knowledge can help to uncover new brain-behavior relationships that may remain hidden if only a single method is employed.

Brain↗

PubMed1999

Enhancing the multivariate signal of [15O] water PET studies with a new nonlinear neuroanatomical registration algorithm.

This paper addresses the problem of neuro-anatomical registration across individuals for functional [15O] water PET activation studies. A new algorithm for three-dimensional (3-D) nonlinear structural registration (warping) of MR scans is presented. The method performs a hierarchically scaled search for a displacement field, maximizing one of several voxel similarity measures derived from the two-dimensional (2-D) histogram of matched image intensities, subject to a regularizer that ensures smoothness of the displacement field. The effect of the nonlinear structural registration is studied when it is computed on anatomical MR scans and applied to coregistered [15O] water PET scans from the same subjects: in this experiment, a study of visually guided saccadic eye movements. The performance of the nonlinear warp is evaluated using multivariate functional signal and noise measures. These measures prove to be useful for comparing different intersubject registration approaches, e.g., affine versus nonlinear. A comparison of 12-parameter affine registration versus non-linear registration demonstrates that the proposed nonlinear method increases the number of voxels retained in the cross-subject mask. We demonstrate that improved structural registration may result in an improved multivariate functional signal-to-noise ratio (SNR). Furthermore, registration of PET scans using the 12-parameter affine transformations that align the coregistered MR images does not improve registration, compared to 12-parameter affine alignment of the PET images directly.

Algorithms↗

PubMed1999

Comparison of matched BOLD and FAIR 4.0T-fMRI with [15O]water PET brain volumes.

Valid comparisons of functional activation volumes from fMRI and PET require accurate registration, matched spatial resolution, and if possible matched noise. We coregistered 4.0T-fMRI and PET volumes, using a series of linear and nonlinear transformations applied to the PET volumes. Because of the limited number of fMRI slices that were available, PET volumes were transformed to the fMRI space. Since 4.0T-fMRI and 4.0T-MRI volumes have significant spatial distortion due to magnet inhomogeneities, high resolution 1.5T-MRI volumes were nonlinearly transformed to 4.0T-MRI volumes as part of the transformation chain. The smoothing effects of these registration transformations were measured, in order to match the spatial resolution of the coregistered fMRI and PET volumes. Spatial resolution of the transformed PET volumes in the fMRI space was degraded by up to 60% due to the transformation process. Due to both the image acquisition characteristics and the coregistration process, the transformed PET volumes had a spatial resolution that was lower than that of tMRI. Therefore, significant smoothing of fMRI volumes was necessary to match their spatial resolution with that of the transformed PET volumes. Matching the spatial resolution of the fMRI volumes to those of the transformed PET volumes was achieved by matching the shape of their point spread functions. In order to do this, Gaussian kernels were employed to smooth the fMRI volumes. We were unable to simultaneously match the resolution and noise of fMRI and PET signals in the motor cortex. Activation maps derived from transformed PET and smoothed fMRI volumes were compared. Contralateral motor cortex was active in all modalities but there were large variations in the size of the activated region and its signal to noise ratio across BOLD, FAIR, and PET images within each subject. Nevertheless, the relative CBF changes measured by FAIR were consistent with those determined by PET.

Biophysical Phenomena↗

PubMed1998

A symbolic environment for visualizing activated foci in functional neuroimaging datasets.

This paper presents a symbolic visualization environment known as the Corner Cube environment, which was developed to facilitate rapid examination and comparison of activated foci defined by analyses of functional neuroimaging datasets. We have performed a comparative evaluation of this environment against maximum-intensity projection and 'gallery of slices' displays, and the results suggest that the Corner Cube environment has definite advantages over both conventional display techniques. We conclude that the Corner Cube is an effective tool for summarizing the spatial characteristics of activated foci within an easily understood visual context and is especially useful for displaying the similarities and differences in functional neuroimaging datasets.

Brain↗

PubMed1997

Improved resolution for PET volume imaging through three-dimensional iterative reconstruction.

UNLABELLED: It has been demonstrated that in two-dimensional iterative reconstruction, a resolution model can improve image resolution while controlling noise. With the lower noise levels of three-dimensional PET volume imaging, these iterative reconstruction advantages may be extended to three dimensions to further improve the reconstructed image resolution. METHODS: We have implemented three-dimensional versions of iterative filtered backprojection (IFBP) and the maximum likelihood by expectation maximization (ML-EM) reconstruction algorithms and applied them to three-dimensional PET volume datasets. The results were compared to images obtained using the standard three-dimensional reprojection reconstruction (3DRP) algorithm. RESULTS: For IFBP with 15 iterations and no regularization compared to 3DRP, both using a ramp filter, the transaxial resolution improved 52%, and the axial resolution improved 39%. With a strong regularization, the transaxial and axial resolution improvements were reduced to 6% and 5%, respectively. If a Hanning roll-off is applied to the ramp filter in the transaxial direction, the transaxial resolution for IFBP without regularization improved 35% compared to 3DRP; with regularization the improvement dropped to 19%. The axial resolution for IFBP and 3DRP was unaffected by this transaxial smoothing in the reconstruction filter. With the same Hanning roll-off, the noise for IFBP without regularization increased by a factor of 6 compared to 3DRP; with regularization the noise was increased only by a factor of 3. Compared to IFBP, the three-dimensional ML-EM reconstruction produced similar resolution improvements with a much smaller increase in noise and slower convergence. Resolution improvements from both IFBP and ML-EM reconstructions are visually apparent in three-dimensional FDG brain images and result in increased activation signals in a three-dimensional [15O]water functional activation study. CONCLUSION: Our results demonstrate that resolution improvement is possible for IFBP and ML-EM compared to 3DRP with or without noise increase.

Algorithms↗

PubMed1996

Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia.

UNLABELLED: This study was undertaken in order to extend our previous finding of relative basal ganglia hypermetabolism in AIDS dementia complex (ADC) and to develop clinically useful metabolic indices of CNS involvement in HIV-seropositive (HIV+) subjects. METHODS: Twenty-one HIV+ subjects (11 with AIDS) underwent FDG-PET scanning; 12 had a follow-up scan at 6 mo and 4 had a third scan at 12 mo. Forty-three age-matched heterosexual volunteers served as controls. FDG-PET scanning was performed with arterial blood sampling, and scan data were analyzed using the Scaled Subprofile Model (SSM) with principal component analysis. RESULTS: SSM/principal component analysis of the combined (HIV+ and controls) FDG-PET dataset extracted two major disease-related metabolic components: (a) a nonspecific indicator of cerebral dysfunction, which was significantly correlated with age, cerebral atrophy and ADC stage and (b) the striatum, which was heavily weighted (relatively hypermetabolic) and appeared to provide a disease-specific measure of early CNS involvement. CONCLUSION: FDG-PET scans provide quantitative measures of abnormal functional connectivity in HIV-seropositives-with or without AIDS or ADC. These measures, which are robust across centers with respect to instrumentation, scanning technique and disease severity, appear to track the progression of CNS involvement in patients with subclinical neurologic or neuropsychologic dysfunction.

AIDS Dementia Complex↗

PubMed1995

Commentary and opinion: I. Principal component analysis, variance partitioning, and "functional connectivity".

We briefly review the need for careful study of "variance partitioning" and "optimal model selection" in functional positron emission tomography (PET) data analysis, emphasizing the use of principal component analysis (PCA) and the importance of data analytic techniques that allow for heterogeneous spatial covariance structures. Using an [15O]water dataset, we demonstrate that--even after data processing--the intrasubject signal component of primary interest in baseline activation studies constitutes a very small fraction of the intersubject variance. This small intrasubject variance component is subtly but significantly changed by using analysis of covariance instead of scaled subprofile model processing before applying PCA. Finally, we argue that the concept of "functional connectivity" should be interpreted very generally until the relative roles of inter- and intrasubject variability in both disease and normal PET datasets are better understood.

Analysis of Variance↗

PubMed1995

Principal component analysis and the scaled subprofile model compared to intersubject averaging and statistical parametric mapping: I. "Functional connectivity" of the human motor system studied with [15O]water PET.

Using [15O]water PET and a previously well studied motor activation task, repetitive finger-to-thumb opposition, we compared the spatial activation patterns produced by (1) global normalization and intersubject averaging of paired-image subtractions, (2) the mean differences of ANCOVA-adjusted voxels in Statistical Parametric Mapping, (3) ANCOVA-adjusted voxels followed by principal component analysis (PCA), (4) ANCOVA-adjustment of mean image volumes (mean over subjects at each time point) followed by F-masking and PCA, and (5) PCA with Scaled Subprofile Model pre- and postprocessing. All data analysis techniques identified large positive focal activations in the contralateral sensorimotor cortex and ipsilateral cerebellar cortex, with varying levels of activation in other parts of the motor system, e.g., supplementary motor area, thalamus, putamen; techniques 1-4 also produced extensive negative areas. The activation signal of interest constitutes a very small fraction of the total nonrandom signal in the original dataset, and the exact choice of data preprocessing steps together with a particular analysis procedure have a significant impact on the identification and relative levels of activated regions. The challenge for the future is to identify those preprocessing algorithms and data analysis models that reproducibly optimize the identification and quantification of higher-order sensorimotor and cognitive responses.

Adult↗

PubMed1994

Display of merged multimodality brain images using interleaved pixels with independent color scales.

UNLABELLED: This article reviews common methods for two-dimensional display of registered multimodality brain images and describes a software package for presentation of merged MRI and PET images that runs on a workstation with an eight-bit color display. The software package displays merged brain images from multiple modalities in a way that is readily manipulated, visually pleasing and easy to interpret. The display method used, i.e., interleaving of alternate pixels with independent color scales, is effective in producing merged images with high contrast-detail for each volume. Interleaving images from different volumes creates unusual perceptual effects, one of which is the apparent camouflage of low-contrast signals by high values in the paired volume. METHODS: The camouflage effect was thought to arise from perceptual merging of adjacent pixels. An observer experiment was conducted to investigate this tendency of high-activity PET data to obscure low-contrast detail in interleaved MRI data in spite of the digital independence of neighboring pixels. Four observers were presented with 20 combinations of signal plus background targets with uniform mask images, using a two-alternative forced-choice experimental design with 50 trials per combination. RESULTS: The psychophysical evaluation of the ability of human observers to detect the simple test objects in an interleaved image presentation indicated a statistically significant camouflage effect of one volume on the other for some combinations of target and mask. The concept of perceptual merging of adjacent pixels was able to predict which combinations caused the greatest degradations in performance. CONCLUSIONS: The image interleaving approach to the display of two-dimensional slices from registered image volumes makes efficient use of an eight-bit color display. Contrast resolution of both individual volumes is high compared with that in other techniques and the volumes are presented in familiar color scales. However, the method yields an unexpected camouflage effect that tends to obscure low-contrast signals. The practical effect of such camouflage on the interpretation of clinical images remains to be investigated.

Brain↗

PubMed1993

The convergence of object dependent resolution in maximum likelihood based tomographic image reconstruction.

Study of the maximum likelihood by EM algorithm (ML) with a reconstruction kernel equal to the intrinsic detector resolution and sieve regularization has demonstrated that any image improvements over filtered backprojection (FBP) are a function of image resolution. Comparing different reconstruction algorithms potentially requires measuring and matching the image resolution. Since there are no standard methods for describing the resolution of images from a nonlinear algorithm such as ML, we have defined measures of effective local Gaussian resolution (ELGR) and effective global Gaussian resolution (EGGR) and examined their behaviour in FBP images and in ML images using two different measurement techniques. For FBP these two resolution measures are equal and exhibit the standard convolution behaviour of linear systems. For ML, the FWHM of the ELGR monotonically increased with decreasing Gaussian object size due to slower convergence rates for smaller objects. For the simple simulated phantom used, this resolution dependence is independent of object position. With increasing object size, number of iterations and sieve size the object size dependence of the ELGR decreased. The FWHM of the EGGR converged after approximately 200 iterations, masking the fact that the ELGR for small objects was far from convergence. When FBP is compared to a nonlinear algorithm such as ML, it is recommended that at least the EGGR be matched; for ML this requires more than the number of iterations (e.g., < 100) that are typically run to minimize the mean square error or to satisfy a feasibility or similar stopping criterion. For many tasks, matching the EGGR of ML to FBP images may be insufficient and >> 200 iterations may be needed, particularly for small objects in the ML image because their ELGR has not yet converged.

Algorithms↗

PubMed1991

Abnormal cerebral glucose metabolism in long-term survivors of childhood acute lymphocytic leukemia.

Chemotherapy and radiation treatment of the central nervous system may cause delayed neurotoxicity in children with acute lymphocytic leukemia. We evaluated 12 long-term survivors of childhood leukemia using [18F]fluorodeoxyglucose positron emission tomography, computed tomography scans, clinical neurological examinations, and neuropsychological tests. Regional cerebral metabolic rate for glucose (rCMRGlc) values for white matter were lower in the older long-term survivors (greater than 18 years old) treated with cranial radiation and intrathecal chemotherapy than in normal control subjects or survivors who had been treated with intrathecal chemotherapy alone. The ratio of white matter: cortex rCMRGlc values was lower than control values in the long-term survivors treated with cranial radiation and intrathecal chemotherapy, regardless of age, but not in those treated with intrathecal chemotherapy alone. By contrast, thalamic rCMRGlc values were lower than control values in older survivors regardless of treatment, and the ratio for thalamus:cortex rCMRGlc values was lower in all the treatment groups than in the control subjects. The highest rCMRGlc values were found in the youngest children, indicating an important effect of age on cerebral glucose metabolism. No neuropsychological deficits were identified in patients treated only with intrathecal chemotherapy; however, lower IQ scores were found in the long-term survivors who had been treated with cranial radiation and intrathecal chemotherapy. Treatment of the central nervous system with cranial radiation and intrathecal chemotherapy may cause prolonged alterations in white-matter and thalamic rCMRGlc, which may permit the identification and assessment of neurotoxicity in long-term survivors of acute lymphocytic leukemia by [18F]fluorodeoxyglucose positron emission tomography.

Adolescent↗