Comparison of the disparity between Talairach and MNI coordinates in functional neuroimaging data: validation of the Lancaster transform.

Spatial normalization of neuroimaging data is a standard step when assessing group effects. As a result of divergent analysis procedures due to different normalization algorithms or templates, not all published coordinates refer to the same neuroanatomical region. Specifically, the literature is populated with results in the form of MNI or Talairach coordinates, and their disparity can impede the comparison of results across different studies. This becomes particularly problematic in coordinate-based meta-analyses, wherein coordinate disparity should be corrected to reduce error and facilitate literature reviews. In this study, a quantitative comparison was performed on two corrections, the Brett transform (i.e., "mni2tal"), and the Lancaster transform (i.e., "icbm2tal"). Functional magnetic resonance imaging (fMRI) data acquired during a standard paired associates task indicated that the disparity between MNI and Talairach coordinates was better reduced via the Lancaster transform, as compared to the Brett transform. In addition, an activation likelihood estimation (ALE) meta-analysis of the paired associates literature revealed that a higher degree of concordance was obtained when using the Lancaster transform in the form of fewer, smaller, and more intense clusters. Based on these results, we recommend that the Lancaster transform be adopted as the community standard for reducing disparity between results reported as MNI or Talairach coordinates, and suggest that future spatial normalization strategies be designed to minimize this variability in the literature.

Self-paced working memory: validation of verbal variations of the n-back paradigm.

Self-paced versions of many paradigms could have utility in probing cognitive systems. To validate several self-paced n-back paradigms, fourteen subjects performed four variations of the working memory task using visually presented letters as stimuli. Several areas in the frontal lobe, the anterior cingulate and a parietal network were consistently activated in the four variations: identity of black letters, location of black letters, color of colored letters and identity of colored letters. Since the n-back task is one of the more popular methods of investigating working memory, we validated the utility of several self-paced versions in normal subjects via quantitative, coordinate-based meta-analyses. The self-paced results agree well with meta-analyses and other published results, giving confidence that a self-paced n-back paradigm is robust in multiple variations. Behavioral results differ from other published reports, perhaps offering insight into true working memory strategy in normal subjects.

An objective method for combining multi-parametric MRI datasets to characterize malignant tumors.

Medical imaging has made significant contributions to the characterization of malignant tumors. In many cases, however, maps from multiple modalities may be required for more complete tumor mapping. In this manuscript we propose an objective method for combining multiple imaging datasets with the goal of characterizing malignant tumors. We refer to the proposed technique as the percent overlap method (POM). To demonstrate the power and flexibility of the POM analysis, we present four patients with recurrent glioblastoma multiforme. Each patient had multiple magnetic resonance imaging procedures resulting in seven different parameter maps. Chemical shift imaging was used to provide three metabolite ratio maps (Cho:NAA, Cho:Cre, Lac:Cre). A perfusion scan provided regional cerebral blood volume and permeability maps. Diffusion and carbogen-based hypoxia mapping data were also acquired. Composite maps were formed for each patient using POM, then were compared to results from the ISODATA clustering technique. The POM maps of likely recurrent tumor regions were found to be consistent with the ISODATA clustering method. This manuscript presents an objective method for combining parameters from multiple physiologic imaging techniques into a single composite map. The accuracy of the map depends strongly on the sensitivity of the chosen imaging parameters to the disease process at the time of image acquisition. Further validation of this method may be achieved by correlation with histological data.

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.

T2 detection of tumor invasion within segmented components of glioblastoma multiforme.

PURPOSE: To use T2-weighted images to detect tumor invasion when comparing normal individuals to groups of gliomablastoma multiforme (GBM) patients with varying levels of CXCR4, a chemokine receptor that promotes tumor migration. MATERIALS AND METHODS: T2-weighted images were acquired preoperatively in 22 treatment-naïve GBM patients. Two groups were formed based on the expression levels of CXCR4. A third group of normal volunteers was used for comparison. Each image was segmented to obtain four different clusters for tissue types identified as white matter, basal ganglia, gray matter/edema and cerebrospinal fluid (CSF)/tumor. Signal intensity histograms were formed for each cluster and compared between groups. RESULTS: In every cluster the GBM groups displayed significantly higher standard deviations of intensity distributions when compared to normal subjects. Significant differences in skewness were found between normal subjects and GBM patients in the white matter, basal ganglia, and CSF/tumor. Further, when the two groups of GBM patients were compared the CXCR4-high group was found to have a significant shift in the median intensity values in the cluster containing gray matter and peritumoral edema. CONCLUSION: T2 signal intensity histograms in normal subjects differ significantly from those obtained from GBM groups, suggesting widespread dissemination of disease.

CXCR4 expression is elevated in glioblastoma multiforme and correlates with an increase in intensity and extent of peritumoral T2-weighted magnetic resonance imaging signal abnormalities.

OBJECTIVE: With the objective of investigating the utility of CXCR4, a chemokine receptor known to mediate glioma cell invasiveness, as a molecular marker for peritumoral disease extent in high-grade gliomas, we sought to characterize the expression profile of CXCR4 in a large panel of tumor samples and determine whether CXCR4 expression levels within glioblastoma multiforme might correlate with radiological evidence of a more extensive disease process. METHODS: Freshly resected tumor tissue samples were processed for immunohistochemical and quantitative polymerase chain reaction analyses to identify and quantify expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast and T2-weighted magnetic resonance imaging brain scans were used to generate voxel signal intensity histograms that were quantitatively analyzed to determine the extent and intensity of peritumoral signal abnormality as a marker of disseminated disease in the brain. RESULTS: CXCR4 expression was markedly elevated in Grade III and IV tumors compared with Grade II gliomas. Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas. CONCLUSION: Our data confirm that high-grade gliomas robustly express CXCR4 and demonstrate a correlative relationship between expression levels of the CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and more extensive disease process in the brain. CXCR4 expression status may, therefore, prove useful as a marker of disseminated disease in patients with glioblastoma multiforme.

N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies.

One of the most popular experimental paradigms for functional neuroimaging studies of working memory has been the n-back task, in which subjects are asked to monitor the identity or location of a series of verbal or nonverbal stimuli and to indicate when the currently presented stimulus is the same as the one presented n trials previously. We conducted a quantitative meta-analysis of 668 sets of activation coordinates in Talairach space reported in 24 primary studies of n-back task variants manipulating process (location vs. identity monitoring) and content (verbal or nonverbal) of working memory. We found the following cortical regions were activated robustly (voxelwise false discovery rate = 1%): lateral premotor cortex; dorsal cingulate and medial premotor cortex; dorsolateral and ventrolateral prefrontal cortex; frontal poles; and medial and lateral posterior parietal cortex. Subsidiary meta-analyses based on appropriate subsets of the primary data demonstrated broadly similar activation patterns for identity monitoring of verbal stimuli and both location and identity monitoring of nonverbal stimuli. There was also some evidence for distinct frontoparietal activation patterns in response to different task variants. The functional specializations of each of the major cortical components in the generic large-scale frontoparietal system are discussed. We conclude that quantitative meta-analysis can be a powerful tool for combining results of multiple primary studies reported in Talairach space. Here, it provides evidence both for broadly consistent activation of frontal and parietal cortical regions by various versions of the n-back working memory paradigm, and for process- and content-specific frontoparietal activation by working memory.

A comparison of label-based review and ALE meta-analysis in the Stroop task.

Meta-analysis is an important tool for interpreting results of functional neuroimaging studies and is highly influential in predicting and testing new outcomes. Although traditional label-based review can be used to search for agreement across multiple studies, a new function-location meta-analysis technique called activation likelihood estimation (ALE) offers great improvements over conventional methods. In ALE, reported foci are modeled as Gaussian functions and pooled to create a statistical whole-brain image. ALE meta-analysis and the label-based review were used to investigate the Stroop task in normal subjects, a paradigm known for its effect of producing conflict and response inhibition due to subjects' tendency to perform word reading as opposed to color naming. Both methods yielded similar activation patterns that were dominated by response in the anterior cingulate and the inferior frontal gyrus. ALE showed greater involvement of the anterior cingulate as compared to that in the label-based technique; however, this was likely due to the increased spatial level of distinction allowed with the ALE method. With ALE, further analysis of the anterior cingulate revealed evidence for somatotopic mapping within the rostral and caudal cingulate zones, an issue that has been the source of some conflict in previous reviews of the anterior cingulate cortex.

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.