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

Improved UTE-based attenuation correction for cranial PET-MR using dynamic magnetic field monitoring.

Purpose: Ultrashort echo time (UTE) MRI has been proposed as a way to produce segmented attenuation maps for PET, as it provides contrast between bone, air, and soft tissue. However, UTE sequences require samples to be acquired during rapidly changing gradient fields, which makes the resulting images prone to eddy current artifacts. In this work it is demonstrated that this can lead to misclassification of tissues in segmented attenuation maps (AC maps) and that these effects can be corrected for by measuring the true k-space trajectories using a magnetic field camera. Methods: The k-space trajectories during a dual echo UTE sequence were measured using a dynamic magnetic field camera. UTE images were reconstructed using nominal trajectories and again using the measured trajectories. A numerical phantom was used to demonstrate the effect of reconstructing with incorrect trajectories. Images of an ovine leg phantom were reconstructed and segmented and the resulting attenuation maps were compared to a segmented map derived from a CT scan of the same phantom, using the Dice similarity measure. The feasibility of the proposed method was demonstrated in in vivo cranial imaging in five healthy volunteers. Simulated PET data were generated for one volunteer to show the impact of misclassifications on the PET reconstruction. Results: Images of the numerical phantom exhibited blurring and edge artifacts on the bone-tissue and air-tissue interfaces when nominal k-space trajectories were used, leading to misclassification of soft tissue as bone and misclassification of bone as air. Images of the tissue phantom and the in vivo cranial images exhibited the same artifacts. The artifacts were greatly reduced when the measured trajectories were used. For the tissue phantom, the Dice coefficient for bone in MR relative to CT was 0.616 using the nominal trajectories and 0.814 using the measured trajectories. The Dice coefficients for soft tissue were 0.933 and 0.934 for the nominal and measured cases, respectively. For air the corresponding figures were 0.991 and 0.993. Compared to an unattenuated reference image, the mean error in simulated PET uptake in the brain was 9.16% when AC maps derived from nominal trajectories was used, with errors in the SUV max for simulated lesions in the range of 7.17%-12.19%. Corresponding figures when AC maps derived from measured trajectories were used were 0.34% (mean error) and -0.21% to +1.81% (lesions). CONCLUSIONS: Eddy current artifacts in UTE imaging can be corrected for by measuring the true k-space trajectories during a calibration scan and using them in subsequent image reconstructions. This improves the accuracy of segmented PET attenuation maps derived from UTE sequences and subsequent PET reconstruction

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

Reactive Oxygen Species Suppress Cardiac NaV1.5 Expression through Foxo1

NaV1.5 is a cardiac voltage-gated Na+ channel αsubunit and is encoded by the SCN5a gene. The activity of this channel determines cardiac depolarization and electrical conduction. Channel defects, including mutations and decrease of channel protein levels, have been linked to the development of cardiac arrhythmias. The molecular mechanisms underlying the regulation of NaV1.5 expression are largely unknown. Forkhead box O (Foxo) proteins are transcriptional factors that bind the consensus DNA sequences in their target gene promoters and regulate the expression of these genes. Comparative analysis revealed conserved DNA sequences, 5′-CAAAACA-3′ (insulin responsive element, IRE), in rat, mouse and human SCN5a promoters with the latter two containing two overlapping Foxo protein binding IREs, 5′-CAAAACAAAACA-3′. This finding led us to hypothesize that Foxo1 regulates NaV1.5 expression by directly binding the SCN5a promoter and affecting its transcriptional activity. In the present study, we determined whether Foxo1 regulates NaV1.5 expression at the transcriptional level and also defined the role of Foxo1 in hydrogen peroxide (H2O2)-mediated NaV1.5 suppression in HL-1 cardiomyocytes using chromatin immunoprecipitation (ChIP), constitutively nuclear Foxo1 expression, and RNAi Foxo1 knockdown as well as whole cell voltage-clamp recordings. ChIP with anti-Foxo1 antibody and follow-up semi-quantitative PCR with primers flanking Foxo1 binding sites in the proximal SCN5a promoter region clearly demonstrated enrichment of DNA, confirming Foxo1 recruitment to this consensus sequence. Foxo1 mutant (T24A/S319A-GFP, Foxo1-AA-GFP) was retained in nuclei, leading to a decrease of NaV1.5 expression and Na+ current, while silencing of Foxo1 expression by RNAi resulted in the augmentation of NaV1.5 expression. H2O2 significantly reduced NaV1.5 expression by promoting Foxo1 nuclear localization and this reduction was prevented by RNAi silencing Foxo1 expression. These studies indicate that Foxo1 negatively regulates NaV1.5 expression in cardiomyocytes and reactive oxygen species suppress NaV1.5 expression through Foxo1