Markov Random Field Segmentation of Brain MR Images

We describe a fully-automatic 3D-segmentation technique for brain MR images. Using Markov random fields the segmentation algorithm captures three important MR features, i.e. non-parametric distributions of tissue intensities, neighborhood correlations and signal inhomogeneities. Detailed simulations and real MR images demonstrate the performance of the segmentation algorithm. The impact of noise, inhomogeneity, smoothing and structure thickness is analyzed quantitatively. Even single echo MR images are well classified into gray matter, white matter, cerebrospinal fluid, scalp-bone and background. A simulated annealing and an iterated conditional modes implementation are presented. Keywords: Magnetic Resonance Imaging, Segmentation, Markov Random FieldsComment: 34 pages, 10 figures; the paper (published in 1997) has introduced the concept of Markov random field to the segmentation of medical MR images. For the published version see http://dx.doi.org/10.1109/42.65088

Excitatory-inhibitory balance within EEG microstates and resting-state fMRI networks: assessed via simultaneous trimodal PET-MR-EEG imaging

The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and γ-aminobutyric acid (GABA) and the receptor availability (RA) of GABAA and mGluR5, remains unexplored. This research investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data. The trimodal data were acquired from three studies using different radio-tracers such as, [11C]ABP688 (ABP) (N = 9), [11C]Flumazenil (FMZ) (N = 10) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) (N = 10) targeted to study the mGluR5, GABAA receptors and glucose metabolism respectively. Glucose metabolism and neuroreceptor binding availability (non-displaceable binding potential (BPND)) of GABAA and mGluR5 were found to be significantly higher and closely linked within core resting-state networks (RSNs). The neuronal generators of EEG microstates and the fMRI measures were most tightly associated with the BPND of GABAA relative to mGluR5 BPND and the glucose metabolism, emphasising a predominance of inhibitory processes within in the core RSNs at rest. Changes in the neuroreceptors leading to an altered coupling with glucose metabolism may render the RSNs vulnerable to psychiatric conditions. The paradigm employed here will likely help identify the precise neurobiological mechanisms behind these alterations in fMRI functional connectivity and EEG oscillations, potentially benefitting individualised healthcare treatment measures

mGluR5 receptor availability is associated with lower levels of negative symptoms and better cognition in male patients with chronic schizophrenia

Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [11 C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F[27,1] = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability. Keywords: chronic schizophrenia; cognition; mGluR5 receptor; negative symptoms; positron emission tomography

Treating a GAD65 Antibody-Associated Limbic Encephalitis with Basiliximab: A Case Study

Background: Antibodies (ABs) against the 65-kDa isoform of the intracellular enzymeglutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) andother neurological conditions. The direct significance of anti-GAD65-ABs for epilepsyis unclear. However, in histological preparations from biopsies of resective epilepsysurgeries, predominantly cytotoxic T-lymphocytes were detected making close contactsto neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeuticinterleukin-2 receptor Abs, such as basiliximab.Case presentation: We report of a 25-year-old male patient with epilepsy since theage of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebro-spinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapiesthat were initially administered for 6 months failed to improve his condition. Subsequentflow-cytometry analysis of CSF showed especially an increased fraction of activatedHLA-DR+CD8+T-lymphocytes (fCD8+TL) when compared to controls. Thus, a second,intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/monthwas started. After 3 months, the fCD8+TL in the CSF normalized; after 6 months, thepsychological impulse-control deficits normalized; and after 11 months the patientwas seizure free. However, 7 weeks later, seizures and, later on, psychological deficitsrecurred and fCD8+TL was once again present in the CSF. Flumazenil PET, magneticresonance imaging-volumetry, and neuropsychological changes during therapy aredescribed.Conclusion: The correlation of the fCD8+TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximabstrongly argues in favor of the putative pathogenic role fCD8+TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation ofhuman anti-drug ABs, a well-known complication of therapy with chimeric ABs

Permeation von Wasserstoff durch Metallmembranen

Experiments show that the permeant flux of hydrogen through a metal membrane at low driving pressures ( $\le$ 1 mbar typically) becomes directly proportional to the pressure and not to the square root of it as it is expected from Richardson's equation. The validity of this equation is usually used for the interpretation of permeation experiments and the determination of the diffusion constant. The observations can well be described in terms of a model which takes into account that the concentrations of the hydrogen atoms in the surface near layers show a time evolution and that the rate of molecules released to the outside increases quadratically with the concentration. Thus, additionally to the diffusion constant D, the release rate constant k$_{r}$ is introduced into the model as a new material constant and the rate equations are given. After the description of the wall pump effect, a variety of different limiting cases are discussed for a symmetrical permeation membrane. This is modified to the asymmetric case and to the influence of particle implantation. The permeation number W turns out to be a dimensionless quantity which characterizes the permeation range andpredicts the permeant flux in steady state

Comparison of Template-Based Versus CT-Based Attenuation Correction for Hybrid MR/PET Scanners

Attenuation correction (AC) of cerebral PET data acquired in hybrid MR/PET scanners is still a challenge. To overcome this problem we previously proposed a correction method by obtaining template-based attenuation maps (AM) using MR and ECAT EXACT HR+ transmission scans. In the present study we investigated (a) the basic difference between template-based and CT-based AC methods and (b) their influence on reconstructed PET images. The data of 11 subjects undergoing 18FDG imaging in the Siemens 3T MR-BrainPET scanner were used. Additionally, from all participants a CT scan of the whole head was acquired at the same day. These CT images were transformed to CT-based AMs. They were filtered by a 3D Gaussian kernel with 3 mm (BrainPET resolution) filter width, which was considered as reference. Comparisons between both AMs (CT-based and template-based) were performed by estimating the Dice coefficients D and calculating the numbers of true positive, true negative and false negative voxels. The BrainPET emission data were reconstructed with both AMs ( AMCT3mm and AMTemplate). All reconstructed PET images were scaled to standardized uptake values (SUVs) and normalized to the MNI brain for using the AAL-VOI Atlas analysis. Correlation plots with regression equation, coefficients of determination R2 and relative differences (RD) between AMCT3mm and the AMTemplate were derived. The fraction of the overall true positive voxels averaged over the 11 subjects was 80.4 ±7.5% for AMTemplate compared to AMCT3mm ( Dbone = 0.63 ±0.08; Dsoft - tissue = 0.85 ±0.08; Dair = 0.79 ±0.04). A misclassification of bone as soft tissue and vice versa was evident in the comparison. The correlation plot of all VOIs considered (1,276 values) showed a mean R2 of 0.964 and a slope of 1.02. A mean RD of 1.33 ±0.95% ( min = - 0.12%, max = 2.85%) was found. The template-based AC method proposed by our group shows considerable differences in comparison to the higher resolution CT-based AM with respect to the Dice coefficients, in particular in the classification of bone and soft tissue. However, this has no major influence on the reconstructed 18FDG PET data

PET motion correction using PRESTO with ITK motion estimation

The Siemens BrainPET scanner is a hybrid MRI/PET system. PET images are prone to motion artefacts which degrade the image quality. Therefore, motion correction is essential. The library PRESTO converts motion-corrected LORs into highly accurate generic projection data [1], providing high-resolution PET images. ITK is an open-source software used for registering multidimensional data [2]. ITK provides motion estimation necessary to PREST