Publications by Year: 2013

Deficits in self monitoring are a core feature of cognitive dysfunction in schizophrenia, and may be the basis for disturbances of self and lack of insight, ultimately impacting social functioning. However, the functional and structural neural correlates of such deficits in self monitoring are not well understood. We investigated this issue using measurements of neurophysiological and structural brain indices, i.e., error-related and correct-response negativity (ERN & CRN) of event-related potentials, and gray matter volume of the anterior cingulate cortex (ACC), and tested whether the association between these indices is altered in patients with schizophrenia. Participants consisted of 18 male patients with chronic schizophrenia and 18 healthy male controls. The 2 groups did not differ in ERN amplitude. In contrast, schizophrenia patients showed significantly larger CRN amplitudes than did healthy subjects. Although the 2 groups did not significantly differ in gray matter volume of the ACC subregions, a significant negative correlation was found between ERN amplitudes at the frontocentral electrodes and absolute gray matter volumes of the left cognitive region of ACC only in healthy controls. These results suggest a disruption of function-structure coupling of the brain regions sub-serving self monitoring in schizophrenia.

BACKGROUND: Previous voxelwise Diffusion Tensor Imaging (DTI) investigations of white matter in first-episode schizophrenia (FESZ) have been limited to the analysis of Fractional Anisotropy (FA) and mean diffusivity (MD), with their findings inconsistent in terms of the anatomical locations and extent of abnormalities. This study examines white matter abnormalities in FESZ, compared with healthy controls, using a tract-based spatial statistics (TBSS) approach applied to multiple measures of tract integrity, and correlates these findings with symptom severity. METHODS: Seventeen first-episode patients with schizophrenia and seventeen age- and gender-matched healthy controls (HC) participated in this imaging study where FA, MD, and axial and radial diffusivities were compared between the two groups using TBSS. RESULTS: First-episode patients with schizophrenia showed lower FA values in the genu and body of corpus callosum, the internal capsule, the external capsule, the fornix, the superior, inferior fronto-occipital fasciculus, the cingulum, and the uncinate fasciculus compared with HC. Increased MD and radial diffusivity were shown in virtually all white matter regions. There was no significant difference, however, observed for axial diffusivity between the two groups. Pearson correlation analysis showed that the FA values of the right inferior fronto-occipital fasciculus were positively correlated with positive symptoms, negative symptoms, and total correct items of the Wisconsin Card Sorting Test. FA values of right external capsule also showed significant positive correlation with category completed scores of the WCST. CONCLUSIONS: These data suggest extensive, possibly myelin related white matter disruptions in FESZ.

Reliable measurements of spinal deformities in idiopathic scoliosis are vital, since they are used for assessing the degree of scoliosis, deciding upon treatment and monitoring the progression of the disease. However, commonly used two dimensional methods (e.g. the Cobb angle) do not fully capture the three dimensional deformity at hand in scoliosis, of which axial vertebral rotation (AVR) is considered to be of great importance. There are manual methods for measuring the AVR, but they are often time-consuming and related with a high intra- and inter-observer variability. In this paper, we present a fully automatic method for estimating the AVR in images from computed tomography. The proposed method is evaluated on four scoliotic patients with 17 vertebrae each and compared with manual measurements performed by three observers using the standard method by Aaro-Dahlborn. The comparison shows that the difference in measured AVR between automatic and manual measurements are on the same level as the inter-observer difference. This is further supported by a high intraclass correlation coefficient (0.971-0.979), obtained when comparing the automatic measurements with the manual measurements of each observer. Hence, the provided results and the computational performance, only requiring approximately 10 to 15 s for processing an entire volume, demonstrate the potential clinical value of the proposed method.

Volumetric change in glioblastoma multiforme (GBM) over time is a critical factor in treatment decisions. Typically, the tumor volume is computed on a slice-by-slice basis using MRI scans obtained at regular intervals. (3D)Slicer - a free platform for biomedical research - provides an alternative to this manual slice-by-slice segmentation process, which is significantly faster and requires less user interaction. In this study, 4 physicians segmented GBMs in 10 patients, once using the competitive region-growing based GrowCut segmentation module of Slicer, and once purely by drawing boundaries completely manually on a slice-by-slice basis. Furthermore, we provide a variability analysis for three physicians for 12 GBMs. The time required for GrowCut segmentation was on an average 61% of the time required for a pure manual segmentation. A comparison of Slicer-based segmentation with manual slice-by-slice segmentation resulted in a Dice Similarity Coefficient of 88.43 ± 5.23% and a Hausdorff Distance of 2.32 ± 5.23 mm.

Despite the enormous potential for pharmaceutical applications, there is still a lack of understanding of the molecular details that can contribute to increased permeability of the stratum corneum (SC). To investigate the influence of hydration and heating on the SC, we record the natural-abundance (13)C signal of SC using polarization transfer solid-state NMR methods. Resonance lines from all major SC components are assigned. Comparison of the signal intensities obtained with the INEPT and CP pulse sequences gives information on the molecular dynamics of SC components. The majority of the lipids are rigid at 32°C, and those lipids co-exist with a small pool of mobile lipids. The ratio between mobile and rigid lipids increases with hydration. An abrupt change of keratin filament dynamics occurs at RH = 80-85%, from completely rigid to a structure with rigid backbone and mobile protruding terminals. Heating has a strong effect on the lipid mobility, but only a weak influence on the keratin filaments. The results provide novel molecular insight into how the SC constituents are affected by hydration and heating, and improve the understanding of enhanced SC permeability, which is associated with elevated temperatures and SC hydration.

The concentration of cholesterol in cell membranes affects membrane fluidity and thickness, and might regulate different processes such as the formation of lipid rafts. Since interpreting experimental data from biological membranes is rather intricate, investigations on simple models with biological relevance are necessary to understand the natural systems. We study the effect of cholesterol on the molecular structure of multi-lamellar vesicles (MLVs) composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a phospholipid ubiquitous in cell membranes, with compositions in the range 0-60 mol% cholesterol. Order parameters, |S(CH)|, are experimentally determined by using (1)H-(13)C solid-state nuclear magnetic resonance (NMR) spectroscopy with segmental detail for all parts of both the cholesterol and POPC molecules, namely the ring system and alkyl chain of the sterol, as well as the glycerol backbone, choline headgroup and the sn-1 and sn-2 acyl chains of POPC. With increasing cholesterol concentration the acyl chains gradually adopt a more extended conformation while the orientation and dynamics of the polar groups are rather unaffected. Additionally, we perform classical molecular dynamics simulations on virtual bilayers mimicking the POPC-cholesterol MLVs investigated by NMR. Good agreement between experiments and simulations is found for the cholesterol alignment in the bilayer and for the |S(CH)| profiles of acyl chains below 15 mol% cholesterol. Deviations occur for the choline headgroup and glycerol backbone parts of POPC, as well as for the phospholipid and cholesterol alkyl chains at higher cholesterol concentrations. The unprecedented detail of the NMR data enables a more complete comparison between simulations and experiments on POPC-cholesterol bilayers and may aid in developing more realistic model descriptions of biological membranes.

We examined variability in performance on widely-used neuropsychological Wechsler tests of intelligence and memory in a large sample of persons with chronic schizophrenia, a subset of whom had also undergone prior studies of magnetic resonance imaging (MRI) of the orbital frontal cortex (OFC) gray matter and diffusion tensor imaging (DTI) of the cingulum bundle (CB) and the uncinate fasiculus (UF) white matter. In comparison to controls, persons with schizophrenia showed lower scores across neuropsychological tests, with most pronounced drops in processing speed and immediate memory, in relation to oral reading. For patients, greater declines in intelligence and memory each correlated with reduced CB white matter fractional anisotropy and reduced OFC gray matter, respectively. However, only memory decline correlated with severity of negative symptoms. Taken together, these data raise the intriguing question as to whether communication and motivational deficits expressed in negative symptoms may contribute to the relationship of auditory memory decline and OFC volume observed in this patient sample.

We present the first in vivo application of the filter-exchange imaging protocol for diffusion MRI. The protocol allows noninvasive mapping of the rate of water exchange between microenvironments with different self-diffusivities, such as the intracellular and extracellular spaces in tissue. Since diffusional water exchange across the cell membrane is a fundamental process in human physiology and pathophysiology, clinically feasible and noninvasive imaging of the water exchange rate would offer new means to diagnose disease and monitor treatment response in conditions such as cancer and edema. The in vivo use of filter-exchange imaging was demonstrated by studying the brain of five healthy volunteers and one intracranial tumor (meningioma). Apparent exchange rates in white matter range from 0.8±0.08 s(-1) in the internal capsule, to 1.6±0.11 s(-1) for frontal white matter, indicating that low values are associated with high myelination. Solid tumor displayed values of up to 2.9±0.8 s(-1). In white matter, the apparent exchange rate values suggest intra-axonal exchange times in the order of seconds, confirming the slow exchange assumption in the analysis of diffusion MRI data. We propose that filter-exchange imaging could be used clinically to map the water exchange rate in pathologies. Filter-exchange imaging may also be valuable for evaluating novel therapies targeting the function of aquaporins.

INTRODUCTION: The middle longitudinal fascicle (MdLF) is a long association fiber connecting the superior temporal gyrus (STG) and temporal pole with the angular gyrus through the white matter of the STG, structures which are known to play a crucial role in the pathology of schizophrenia. Functions of MdLF are thought to be related to language and thought processing in the left hemisphere, and with attention in the right hemisphere. While deficits of these functions are core clinical features of schizophrenia, no study has investigated the structural abnormalities of MdLF in schizophrenia. METHOD: 3T diffusion tensor data was acquired from twenty-six patients with schizophrenia and twenty-five healthy control subjects. Streamline tractography technique was used to extract MdLF. Fractional anisotropy (FA) was compared between the two groups. In addition, relationships were investigated between FA in the left MdLF and the Disorganized Thoughts Factor derived from the Positive and Negative Symptom Scale five factor model, and between FA in the right MdLF and the Poor Attention. RESULT: Relative to control subjects, the patients with chronic schizophrenia showed significant mean FA reductions in the bilateral MdLF. The FA of the left MdLF demonstrated a significant negative association with the Disorganized Thoughts Factor, and the FA of the right MdLF showed a significant negative relationship with the Poor Attention. CONCLUSIONS: This study provides new evidence for structural deficits in the bilateral MdLF in patients with chronic schizophrenia. It further demonstrates the contribution of these abnormalities to the core clinical features - especially to disorganization and attention deficit.

Deep brain stimulation (DBS) is an established procedure for the treatment of movement and affective disorders. Patients with DBS may benefit from magnetic resonance imaging (MRI) to evaluate injuries or comorbidities. However, the MRI radio-frequency (RF) energy may cause excessive tissue heating particularly near the electrode. This paper studies how the accuracy of numerical modeling of the RF field inside a DBS patient varies with spatial resolution and corresponding anatomical detail of the volume surrounding the electrodes. A multiscale model (MS) was created by an atlas-based segmentation using a 1 mm(3) head model (mRes) refined in the basal ganglia by a 200 μ m(2) ex-vivo dataset. Four DBS electrodes targeting the left globus pallidus internus were modeled. Electromagnetic simulations at 128 MHz showed that the peak of the electric field of the MS doubled (18.7 kV/m versus 9.33 kV/m) and shifted 6.4 mm compared to the mRes model. Additionally, the MS had a sixfold increase over the mRes model in peak-specific absorption rate (SAR of 43.9 kW/kg versus 7 kW/kg). The results suggest that submillimetric resolution and improved anatomical detail in the model may increase the accuracy of computed electric field and local SAR around the tip of the implant.