Publications

Corpus callosum (CC) area abnormalities have been reported in magnetic resonance imaging (MRI) studies of adults and youths with bipolar disorder (BPD), suggesting interhemispheric communication may be abnormal in BPD and may be present early in the course of illness and affect normal neuromaturation of this structure throughout the lifecycle. Neuroimaging scans from 44 youths with DSM-IV BPD and 22 healthy controls (HC) were analyzed using cross-sectional area measurements and a novel method of volumetric parcellation. Univariate analyses of variance were conducted on CC subregions using both volume and traditional area measurements. Youths with BPD had smaller middle and posterior callosal regions, and reduced typical age-related increases in CC size. The cross-sectional area and novel volumetric methodologies resulted in similar findings. Future longitudinal assessments of CC development would track the evolution of callosal abnormalities in youths with BPD and allow exploration of the functional significance of these findings.

Clinical blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is becoming increasingly valuable in, e.g., presurgical planning, but the commonly used gradient-echo echo-planar imaging (GE-EPI) technique is sometimes hampered by macroscopic field inhomogeneities. This can affect the degree of signal change that will occur in the GE-EPI images as a response to neural activation and the subsequent blood oxygenation changes, i.e., the BOLD sensitivity (BS). In this study, quantitative BS maps were calculated directly from gradient-echo field maps obtainable on most clinical scanners. In order to validate the accuracy of the calculated BS-maps, known shim gradients were applied and field maps and GE-EPI images of a phantom were acquired. Measured GE-EPI image intensity was then compared with the calculated (predicted) image intensity (pII) which was obtained from the field maps using theoretical expressions for image-intensity loss. The validated expressions for pII were used to calculate the corresponding predicted BOLD sensitivity (pBS) maps in healthy volunteers. Since the field map is assumed to be valid throughout an entire fMRI experiment, the influence of subject motion on the pBS maps was also assessed. To demonstrate the usefulness of such maps, pBS was investigated for clinically important functional areas including hippocampus, Broca’s area and primary motor cortex. A systematic left/right pBS difference was observed in Broca’s area and in the hippocampus, most likely due to magnetic field inhomogeneity of the particular MRI-system used in this study. For all subjects, the hippocampus showed pBS values above unity with a clear anterior-posterior gradient and with an abrupt drop to zero pBS in the anterior parts of hippocampus. It is concluded that GE field maps can be used to accurately predict BOLD sensitivity and that this parameter is useful to assess spatial variations which will influence fMRI experiments.

OBJECTIVE: Data-driven methods for fMRI analysis are useful, for example, when an a priori model of signal variations is unavailable. However, activation sources are typically assumed to be linearly mixed, although non-linear properties of fMRI data, including resting-state data, have been observed. In this work, the non-linear locally linear embedding (LLE) algorithm is introduced for dimensionality reduction of fMRI time series data. MATERIALS AND METHODS: LLE performance was optimised and tested using simulated and volunteer data for task-evoked responses. LLE was compared with principal component analysis (PCA) as a preprocessing step to independent component analysis (ICA). Using an example data set with known non-linear properties, LLE-ICA was compared with PCA-ICA and non-linear PCA-ICA. A resting-state data set was analysed to compare LLE-ICA and PCA-ICA with respect to identifying resting-state networks. RESULTS: LLE consistently found task-related components as well as known resting-state networks, and the algorithm compared well to PCA. The non-linear example data set demonstrated that LLE, unlike PCA, can separate non-linearly modulated sources in a low-dimensional subspace. Given the same target dimensionality, LLE also performed better than non-linear PCA. CONCLUSION: LLE is promising for fMRI data analysis and has potential advantages compared with PCA in terms of its ability to find non-linear relationships.

OBJECTIVE: Although attention deficit hyperactivity disorder (ADHD) in adults is associated with significant morbidity and dysfunction and afflicts both sexes, relatively few imaging studies have examined female subjects and none have had sufficient power to adequately examine sex differences. The authors examined sex differences in the neural functioning of adults with ADHD during performance of a verbal working memory task. METHOD: The participants were 44 adults with ADHD matched on age, sex, and estimated IQ to 49 comparison subjects. Accuracy and reaction time on an N-back task were measured to assess working memory. The blood-oxygen-level-dependent functional MRI response was used as a measure of neural activity. RESULTS: A group-by-sex analysis of variance showed no between-group differences in either reaction time or percent correct for the working memory task. For both sexes combined, the adults with ADHD showed less activity than comparison subjects in prefrontal regions. However, sex-by-group analyses revealed an interaction, such that male ADHD subjects showed significantly less activity in right frontal, temporal, and subcortical regions and left occipital and cerebellar regions relative to male comparison subjects, whereas female ADHD subjects showed no differences from female comparison subjects. Exploratory correlation analyses revealed negative associations between working-memory-related activation and number of hyperactive symptoms for men and number of inattentive symptoms for women. CONCLUSIONS: Male but not female adults with ADHD showed significantly altered patterns of neural activity during a verbal working memory task. Men and women showed different associations between neural activity and ADHD symptoms.

A multiple hypothesis tracking approach to the segmentation of small 3D vessel structures is presented. By simultaneously tracking multiple hypothetical vessel trajectories, low contrast passages can be traversed, leading to an improved tracking performance in areas of low contrast. This work also contributes a novel mathematical vessel template model, with which an accurate vessel centerline extraction is obtained. The tracking is fast enough for interactive segmentation and can be combined with other segmentation techniques to form robust hybrid methods. This is demonstrated by segmenting both the liver arteries in CT angiography data, which is known to pose great challenges, and the coronary arteries in 32 CT cardiac angiography data sets in the Rotterdam Coronary Artery Algorithm Evaluation Framework, for which ground-truth centerlines are available.

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women’s menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.

The quantitative assessment of the anatomic consequences of cerebral infarction is critical in the study of the etiology and therapeutic response in patients with stroke. We present here an overview of the operation of "WebParc," a computational system that provides measures of stroke lesion volume and location with respect to canonical forebrain neural systems nomenclature. Using a web-based interface, clinical imaging data can be registered to a template brain that contains a comprehensive set of anatomic structures. Upon delineation of the lesion, we can express the size and localization of the lesion in terms of the regions that are intersected within the template. We demonstrate the application of the system using MRI-based diffusion-weighted imaging and document measures of the validity and reliability of its uses. Intra- and inter-rater reliability is demonstrated, and characterized relative to the various classes of anatomic regions that can be assessed. The WebParc system has been developed to meet criteria of both efficiency and intuitive operator use in the real time analysis of stroke anatomy, so as to be useful in support of clinical care and clinical research studies. This article is an overview of its base-line operation with quantitative anatomic characterization of lesion size and location in terms of stroke distribution within the separate gray and white matter compartments of the brain.

We performed cerebellum segmentation and parcellation on magnetic resonance images from right-handed boys, aged 6-13 years, including 22 boys with autism [16 with language impairment (ALI)], 9 boys with Specific Language Impairment (SLI), and 11 normal controls. Language-impaired groups had reversed asymmetry relative to unimpaired groups in posterior-lateral cerebellar lobule VIIIA (right side larger in unimpaired groups, left side larger in ALI and SLI), contralateral to previous findings in inferior frontal cortex language areas. Lobule VIIA Crus I was smaller in SLI than in ALI. Vermis volume, particularly anterior I-V, was decreased in language-impaired groups. Language performance test scores correlated with lobule VIIIA asymmetry and with anterior vermis volume. These findings suggest ALI and SLI subjects show abnormalities in neurodevelopment of fronto-corticocerebellar circuits that manage motor control and the processing of language, cognition, working memory, and attention.

We present an advanced software tool designed for visualization and quantitative analysis of Diffusion Tensor Imaging (DTI) called Saturn. The software is specially developed to help clinicians and researchers in neuroimaging, and includes a complete set of visualization capabilities to browse and analyze efficiently DTI data, making this application a powerful tool also for diagnosis purposes. The software includes a robust quantification method for DTI data, using an atlas-based method to automatically obtain equivalent anatomical fiber bundles and regions of interest among different DTI data sets. Consequently, a set of measurements is also implemented to perform robust group studies among subjects affected by neurological disorders and control groups in order to look for significant differences. Finally, a comparison study with five similar DTI applications is presented, showing the advantages offered by this tool.

In this work, we propose to use fiber tracking in order to analyze and quantify the state of the pyramidal tracts in patients affected by tumors. We introduce a framework that includes an automatic method to obtain the fibers involved in the pyramidal tract of any subject, in order to compare robustly fiber bundles affected by tumors with healthy fiber tracts from control subjects and also to quantify the relative state of degeneration between the fiber tracts in the two hemispheres of the same patient. The comparative analyses proposed in our methodology are based on a new set of measures on the pyramidal tract, which take into account intrinsic properties of the fibers involved in the bundle as well as the similarity with the pyramidal tract of a standard healthy subject, modeled as the average of a set of controls. In order to perform better comparison studies and to take into account more information of the whole bundle, a mapping technique is used to represent the fiber tracts in 2D. Here, we show a set of experiments using 5 tumor patients and 10 control subjects, including pre- and post-operative studies in patients that have been treated with partial or total tumor resection. The results obtained indicate the usefulness of the method showing good overall performance. A reproducibility study using several acquisitions of the same patient is also presented to validate the techniques employed.