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Biomedical subjects

M Elizabeth Meyerand

Publications and source records attributed to M Elizabeth Meyerand.

At least 19 recordsLinked to original sources

Investigation of anomalous estimates of tensor-derived quantities in diffusion tensor imaging.

The diffusion tensor is typically assumed to be positive definite. However, noise in the measurements may cause the eigenvalues of the tensor estimate to be negative, thereby violating this assumption. Negative eigenvalues in diffusion tensor imaging (DTI) data occur predominately in regions of high anisotropy and may cause the fractional anisotropy (FA) to exceed unity. Two constrained least squares methods for eliminating negative eigenvalues are explored. These methods, the constrained linear least squares method (CLLS) and the constrained nonlinear least squares method (CNLS), are compared with other commonly used algebraic constrained methods. The CLLS tensor estimator can be shown to be equivalent to the linear least squares (LLS) tensor estimator when the LLS tensor estimate is positive definite. Similarly, the CNLS tensor estimator can be shown to be equivalent to the nonlinear least squares (NLS) tensor estimator when the NLS tensor estimate is positive definite. The constrained least squares methods for eliminating negative eigenvalues are evaluated with both simulations and in vivo human brain DTI data. Simulation results show that the CNLS method is, in terms of mean squared error for estimating trace and FA, the most effective method for correcting negative eigenvalues.

Anisotropy↗

Physiologic characterisation of glioblastoma multiforme using MRI-based hypoxia mapping, chemical shift imaging, perfusion and diffusion maps.

PURPOSE: A multiparametric, physiologic MRI approach was considered to more completely characterise biopsy-confirmed glioblastoma multiforme (GBM). Chemical shift imaging (CSI) supplied biochemical information in metabolite ratios, while perfusion images provided data on presumed vascularity from regional cerebral blood volume (rCBV) and permeability maps. Diffusion-weighted images were reduced to apparent diffusion coefficient (ADC) maps to evaluate cellularity, and blood oxygen level-dependent imaging was used to create maps of putative hypoxic regions. METHODS: Six post-treatment GBM patients were scanned at 3-month intervals until recurrence was suggested by conventional MRI parameters, yielding 20 scans for consideration. The percentage of extreme values in each technique that overlapped with other parameters was measured and compared across hemispheres to assess utility. RESULTS: We found significantly better performance in selecting the diseased hemisphere for overall percent overlap when compared to voxel counts from individual thresholded parameter maps. Parameters were selected on the basis of highest overlap, and corresponding composite overlap maps show increased specificity to likely recurrent regions by reducing the number of falsely positive voxels, and offer insight into relationships between various parameters. CONCLUSION: In a pilot group of patients, percent overlap appears to be sensitive to recurrent disease. When used to combine multiple parameters, voxels containing overlap can specifically target probable recurrent areas.

Brain Mapping↗

Axial rotation of the lumbar spinal motion segments correlated with concordant pain on discography: a preliminary study.

OBJECTIVE: One possible cause of back pain in patients with intervertebral disk degeneration is decreased stability of the motion segment. Axial rotations between lumbar spinal vertebrae can be measured noninvasively with CT. We tested the hypothesis that larger axial rotations are found in motion segments with disks that test positive for concordant pain, which is considered by some investigators to be a reasonable, accurate predictor of spinal instability. SUBJECTS AND METHODS: Between October 2002 and March 2004, all patients undergoing discography were evaluated for inclusion in the study, with the approval of the institutional review board. All patients in whom concordant pain was detected at discography were enrolled in the study. The patients were placed supine in the CT scanner on a table that rotated the pelvis 8 degrees clockwise and then counterclockwise with respect to the thorax. CT images were obtained with the patient in the two positions of rotation. An automated program calculated the amount of rotation between each lumbar vertebra as a result of the table rotations. Rotations were stratified by disk level and by disk classification (concordant pain, nonconcordant pain, no significant pain). RESULTS: We recorded the axial rotations of 94 disks in 16 consecutive patients (10 women, six men; age range, 26-53 years) after two disks were excluded because of a previous fusion. There were 68 normal disks by MRI and discography, six disks with nonconcordant pain, and 20 disks with concordant pain. Rotation averaged 0.6 degrees for the normal disks, 1.4 degrees for disks with nonconcordant pain, and 1.8 degrees for disks with concordant pain. The differences were significant (analysis of variance, p < 0.001). Disks at L3-L4 with concordant pain rotated on average 1.2 degrees , whereas disks classified as normal or nonconcordant pain rotated on average 0.7 degrees (significant at p = 0.005). Disks at L4-L5 with concordant pain rotated on average 1.9 degrees , and those without concordant pain rotated on average 1.4 degrees (significant at p = 0.05). Disks with concordant pain at L5-S1 had an average rotation of 2.2 degrees , whereas disks without concordant pain had an average rotation of 1.5 degrees (marginally significant difference at p = 0.07). CONCLUSION: Concordant pain at discography predicts increased axial rotation at a lumbar disk level.

Adult↗

Independent component analysis applied to self-paced functional MR imaging paradigms.

Self-paced functional MR imaging (fMRI) paradigms, in which the task timing is determined by the subject's performance, can offer several advantages over commonly applied paradigms with predetermined stimulus timing. Independent component analysis (ICA) does not require specification of a timed response function, and could be an advantageous method of deriving results from fMRI data sets with varying response timings and durations. In this study normal volunteers (N = 10) each performed two self-paced fMRI motor and arithmetic paradigms. Individual data sets were analyzed with the Infomax spatial ICA algorithm. Conventional regression analysis was performed for comparison purposes. Spatial ICA effectively produced task-related components from each of the self-paced data sets, even in a few cases where regression analysis yielded non-specific functional maps. For the motor paradigm, these components consistently mapped to primary motor areas. ICA of the arithmetic paradigm yielded multiple task-related components that variably mapped to regions of parietal and frontal lobes. Regression analysis generally yielded similar spatial maps. The multiple task-related ICA components that were sometimes produced from each self-paced data set can be challenging to identify and evaluate for significance. These preliminary results indicate that ICA is useful as an exploratory and complementary method to conventional regression analysis for fMRI of self-paced paradigms.

Adult↗

Comparison of Fourier and wavelet resampling methods.

Resampling can be used to compute the null distribution of any test statistic for the purpose of measuring the significance of the measured value. This study investigated how well the spatial and temporal correlations of simulated and experimentally observed fMRI time series were preserved under Fourier and wavelet resampling methods. The null distributions of a test statistic estimated by each resampling method were compared. In addition, both resampling methods were applied to locate activated voxels in an fMRI dataset and ROC analysis showed that wavelet resampling performed more accurately than Fourier resampling.

Brain Mapping↗

Hemispheric asymmetry in supplementary motor area connectivity during unilateral finger movements.

Studies of unilateral finger movement in right-handed subjects have shown asymmetrical patterns of activation in primary motor cortex. Some studies have measured a similar asymmetry in the supplementary motor area (SMA), but others have not. To shed more light on the symmetry of function in the SMA, we used path analysis of functional MRI data to investigate effective connectivity during a unilateral finger movement task. We observed a slight asymmetry in task activation: left SMA was equally active during movement of either hand, while right SMA was more active for left-hand movement, suggesting a dominant role of left SMA. In addition, we tested for a corresponding asymmetry in the influence of SMA on sensorimotor cortex (SMC) using a path model based on the well-established principle that SMA is involved in motor control and SMC in execution. We observed that the influence of left SMA on left SMC increased during right-hand movement, and the influence of left SMA on right SMC increased during left-hand movement. However, there was no significant hand-dependent change in the influences of the right SMA. This asymmetry in connectivity implies that left SMA does play a dominant role in unilateral movements of either hand in right handers. The experiment also provides a basis for further studies of motor system connectivity in healthy or patient populations.

Adult↗

Functional MRI neuroanatomic correlates of the Hooper Visual Organization Test.

The Hooper Visual Organization Test (VOT), a commonly applied neuropsychological test of visual spatial ability, is used for assessing patients with suspected right hemisphere, or parietal lobe involvement. A controversy has developed over whether the inferences of this test metric can be assumed to involve global, lateralized, or regional functionality. In this study, the characteristic visual organization and object naming aspects of the VOT task presentation were adapted to a functional MR imaging (fMRI) paradigm to probe the neuroanatomic correlates of this neuropsychological test. Whole brain fMRI mapping results are reported on a cohort of normal subjects. Bilateral fMRI responses were found predominantly in the posterior brain, in regions of superior parietal lobules, ventral temporal-occipital cortex, and posterior visual association areas, and to a lesser extent, the frontal eye fields bilaterally, and left dorsolateral prefrontal cortex. The results indicate a general brain region or network in which VOT impairment, due to its visuospatial and object identification demands, is possible to be detected. Discussion is made of interpretive limitations when adapting neuropsychological tests to fMRI analysis.

Adult↗

Power spectrum ranked independent component analysis of a periodic fMRI complex motor paradigm.

Independent component analysis (ICA) has been demonstrated to be an effective data-driven method for analyzing fMRI data. However, a method for objective differentiation of task-related components from those that are artifactually non-relevant is needed. We propose a method of constant-cycle (periodic) fMRI task paradigm combined with ranking of spatial ICA components by the magnitude contribution of their temporal aspects to the fundamental task frequency. Power spectrum ranking shares some similarity to correlation with an a priori hemodynamic response, but without a need to presume an exact timing or duration of the fMRI response. When applied to a complex motor task paradigm with auditory cues, multiple task-related activations are successfully identified and separated from artifactual components. These activations include sensorimotor, auditory, and superior parietal areas. Comparisons of task-related component time courses indicate the temporal relationship of fMRI responses in functionally involved regions. Results indicate the sensitivity of ICA to short-duration hemodynamics, and the efficacy of a power spectrum ranking method for identification of task-related components.

Acoustic Stimulation↗

White matter tractography using diffusion tensor deflection.

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions.

Algorithms↗

Optimal spline smoothing of fMRI time series by generalized cross-validation.

Linear parametric regression models of fMRI time series have correlated residuals. One approach to address this problem is to condition the autocorrelation structure by temporal smoothing. Smoothing splines with the degree of smoothing selected by generalized cross-validation (GCV-spline) provide a method to find an optimal smoother for an fMRI time series. The purpose of this study was to determine if GCV-spline of fMRI time series yields unbiased variance estimates of linear regression model parameters. GCV-spline was evaluated with a real fMRI data set and bias of the variance estimator was computed for simulated time series with autocorrelation structures derived from fMRI data. This study only considered fMRI experimental designs of boxcar type. The results from the real data suggest that GCV-spline determines appropriate amounts of smoothing. The simulations show that the variance estimates are, on average, unbiased. The unbiased variance estimates come at some cost to signal detection efficiency. This study demonstrates that GCV-spline is an appropriate method for smoothing fMRI time series.

Bias↗

On the incorporation of multi-modality image registration into the radiotherapy treatment planning process.

A technique is presented that allows the direct use of physiological image sets in the radiation therapy treatment planning process. When fused to the treatment planning CT, physiological image studies may allow one to define physiological tumor subvolumes consisting of areas of possible chronic hypoxia, areas of high perfusion, areas of high diffusion, and areas containing high choline concentrations. These physiological tumor subvolumes could be selectively boosted to increase local control of malignant brain tumors once one has determined which of these physiological tumor subvolumes predicts for local tumor recurrence after conventional radiotherapy. In this technique a user assisted automatic registration technique is used that is based on an analytical estimate for the transformation matrix needed to register two rigid bodies. The only user input needed is three non-collinear points selected based on landmarks in the primary image and the corresponding three points in the secondary image. Since this registration technique uses two sets of at least three user-defined landmark points each of which has some selection error associated with it, the final registration will have an error that depends only on the selection error associated with the point sets. Since physiological image studies are acquired at the same setting as the T1- w MRI their spatial orientation with respect to the T1- w MRI is known. Therefore, the registration of multiple physiological image studies to the treatment planning CT can be accomplished by first correlating them to the T1- w MRI, and in a second step the T1- w MRI is then registered to the treatment planning CT. The desired registration of the physiological image studies to the treatment planning CT is then accomplished by simply composing the appropriate transformation matrices.

Brain Neoplasms↗

Role of the corpus callosum in functional connectivity.

BACKGROUND AND PURPOSE: Regional cerebral blood flow fluctuates synchronously in corresponding brain regions between the hemispheres. This synchrony implies neuronal connections between brain regions. The synchrony of blood flow changes is defined operationally as functional connectivity. Our purpose was to measure functional connectivity in patients with corpus callosal agenesis, in whom the interhemispheric connectivity is hypothetically diminished. METHODS: In three patients with agenesis of the corpus callosum, functional MR imaging was performed while patients performed text-listening and finger-tapping tasks. Functional images were also acquired while the patients performed no specific task (resting state). Regions of activation temporally correlated with the performance of the tasks were identified by cross-correlating the task data with a reference function. Voxel clusters (seed voxels) that corresponded to regions of activation in the task-activation data set were selected in the resting data set. All the voxels in the resting 3D data set that had a correlation coefficient exceeding 0.4 were identified. The number of these voxels in the ipsilateral and contralateral hemispheres was tabulated. RESULTS: In all patients, technically adequate functional MR and functional connectivity MR maps were obtained. For both tasks, activation was found in both hemispheres. For all of the seed voxels, significantly more functionally connected voxels were found in the ipsilateral hemisphere than in the contralateral hemisphere. For most seed voxels, no functionally connected voxels were found in the contralateral hemisphere. CONCLUSION: Interhemispheric functional connectivity in the motor and auditory cortices is diminished in patients with agenesis of the corpus callosum compared with that of healthy subjects.

Adult↗

Supplementary motor area activation in patients with frontal lobe tumors and arteriovenous malformations.

BACKGROUND AND PURPOSE: Some patients who undergo surgical resection of portions of the supplementary motor area (SMA) have severe postoperative motor and language deficits, whereas others have no deficits. We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA. METHODS: Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumors or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group. RESULTS: None of the control subjects performing a right hand motor task activated predominantly the right SMA. Fifty percent of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. Fifty-seven percent of control subjects performing the left hand motor task activated the left SMA predominantly. One hundred percent of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Differences between patients and controls were statistically significant. CONCLUSION: A lesion that contacts or overlaps the SMA is associated with an increased functional MR imaging response within the contralateral SMA.

Adolescent↗

Characterizing instantaneous phase relationships in whole-brain fMRI activation data.

Typically, fMRI data is processed in the time domain with linear methods such as regression and correlation analysis. We propose that the theory of phase synchronization may be used to more completely understand the dynamics of interacting systems, and can be applied to fMRI data as a novel method of detecting activation. Generalized synchronization is a phenomenon that occurs when there is a nonlinear functional relationship present between two or more coupled, oscillatory systems, whereas phase synchronization is defined as the locking of the phases while the amplitudes may vary. In this study, we developed an application of phase synchronization analysis that is appropriate for fMRI data, in which the phase locking condition is investigated between a voxel time series and the reference function of the task performed. A synchronization index is calculated to quantify the level of phase locking, and a nonparametric permutation test is used to determine the statistical significance of the results. We performed the phase synchronization analysis on the data from five volunteers for an event-related finger-tapping task. Functional maps were created that provide information on the interrelations between the instantaneous phases of the reference function and the voxel time series in a whole-brain fMRI activation data set. We conclude that this method of analysis is useful for revealing additional information on the complex nature of the fMRI time series.

Adult↗

Changes in oxygenation of intracranial tumors with carbogen: a BOLD MRI and EPR oximetry study.

PURPOSE: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. MATERIALS AND METHODS: The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R(2)*. On a different group of 9L tumors, tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. RESULTS: The average decline in R(2)* with carbogen breathing was 13 +/- 1 s(-1) in the CNS-1 tumors and 29 +/- 4 s(-1) in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO(2) in the two 9L tumors measured was 8.6 +/- 0.5 and 3.6 +/- 0.6 mmHg during air breathing, and rose to 20 +/- 7 and 16 +/- 4 mmHg (mean +/- SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO(2) and R(2)* continued in some subjects over the entire 40 minutes. CONCLUSION: EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors.

Animals↗

Independent component analysis applied to diffusion tensor MRI.

The accuracy of the outcome in a diffusion tensor imaging (DTI) experiment depends on the acquisition scheme as well as the postprocessing methods used. In the present study, the DTI results acquired after applying different combinations of diffusion-weighted (DW) gradient orientations were initially compared. Then, spatially independent component analysis (ICA) was applied to the T(2) and DW images. In all cases a single component was detected that was similar to the map of the trace of the diffusion tensor, but contained a reduced amount of noise. Furthermore, when no correction for eddy current artifacts was used in the image acquisition scheme, the effects of eddy currents were separated by ICA into independent components. After these components were removed, conventional estimation of the diffusion tensor was performed on the modified data. No artifact was contained in the final rotationally invariant scalar quantities that describe the intrinsic diffusion properties. Additionally, independent components that mapped major white matter fiber tracts in the human brain were identified. Finally, the noise included in the original T(2) and DW images was also separated by ICA into independent components. These components were subsequently removed and a reduction of noise in the final DTI results was achieved.

Adult↗

Application of image registration to measurement of intervertebral rotation in the lumbar spine.

In this study, the precision and accuracy of a new method for measuring axial rotations of the lumbar vertebrae, which are thought to be increased in patients with degenerative spinal instability, were estimated. A standard image registration algorithm involving a user-selected center of rotation was adapted for this purpose. Accuracy was tested on a phantom containing a rotating lumbar vertebra. Calculated rotations were compared to the known values. Images were also obtained in subjects, using a tilting table that provided rotation between thorax and hips. For these measurements precision was estimated by varying the center of rotation. In the phantom the method had an accuracy of 0.2 degrees. In the human subject measurements the precision was 0.60-1.5 degrees. The method measured rotations of lumbar vertebrae with sufficient accuracy and precision to detect clinically significant differences in patients with back pain.

Biomechanical Phenomena↗

Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm.

OBJECT: Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. METHODS: Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. CONCLUSIONS: Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

Adenocarcinoma↗