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

phenoPET: A dedicated PET Scanner for Plant Research based on digital SiPMs

In the frame of the German Plant Phenotyping Project (DPPN) we developed a novel PET scanner. In contrary to a clinical or preclinical PET scanner the detector rings of the Plant System are oriented in a horizontal plane. The final system will be equipped with three rings covering a Field of View (FOV) of 18 cm diameter and 20 cm axial height. One detector ring is formed by 12 modules. Each module contains four 8×8 pixel digital SiPM devices DPC-3200-22-44 (Philips Digital Photon Counting) connected to a PCB and four scintillator matrices with 16×16 individual LYSO scintillators. Crystal size is 1.85×1.85×10 mm3. The matrices are composed with both reflective and transparent contact faces between the crystals in order to optimize crystal identification. A cooling system keeps the detectors below 5°C and limits the dark count rate. Data are already preprocessed by the Cyclone FPGA (Altera) in the module and transmitted from there at 50MiB/s to the base board. The base board collects the data from all modules and allows coincidence detection performed on a Kintex-7 FPGA (Xilinx). Finally the data link to the computer system for image reconstruction is realized via an USB 3.0 connection. Due to the fast photodetectors the system is dedicated to work with rather high activities. Preliminary measurements showed a coincidence peak of 250 ps FWHM between two detector elements and an energy resolution ΔE/E = 12%. This paper will present first results from a one ring system with a FOV of 18 cm diameter and 6.5 cm axial height

Suche nach Kontakt-Wechselwirkungen und Gravitoneffekten in der tief-inelastischen Streuung bei HERA

Neutral current events in deep inelastic scattering at HERA taken with the H1 detector are examined with respect to standard model expectations. The measured inclusive cross section ds/dQ2 for Q2>200 GeV2 in reactions e±p-->e±X is analysed in terms of contact interactions or graviton effects in combination with large extra dimensions. The total amount of analysed data corresponds to an integrated luminosity of L_int=115 pb-1. The comparison of all data sets to their corresponding standard model expectation shows no evidence for new phenomena. Therefore exclusion limits are derived for the mentioned physical scenarios beyond the standard model. The combination of all data sets leads to maximum sensitivity and significantly improved limits compared to earlier results of H1

CHAPTER 7. PET Quantification

A major benefit of the three-dimensional (3D) PET imaging technique in neuroscience, as well as in clinical applications, is that it offers the possibility of dynamically quantifying metabolic processes with a sensitivity of up to 10−12 mol L−1 for the tracer concentration. However, all positron emission tomographs provide biased data with complex dependencies, which means that to obtain quantitative activity distributions in 3D, it is necessary to make several corrections. For example, inhomogeneous detector efficiencies, photon attenuation, Compton scattering, and random coincidences need to be corrected. Furthermore, dynamic imaging represents a challenge, because a high temporal resolution requires short acquisition time frames with rather poor statistics of recorded events from the radioactive decay. Apart from the necessary corrections, the applied reconstruction method has an important impact on the achievable image quality in PET. In this respect, iterative reconstruction methods are becoming the state-of-the-art techniques as they offer superior image quality when compared to analytical methods. Although iterative reconstruction is associated with higher computational demand, the higher calculation effort can be moderated by using a range of optimisation strategies and has been further helped by the remarkable boost in computational resources over the last two decades

High performance volume-of-intersection projectors for 3D-PET image reconstruction based on polar symmetries and SIMD vectorisation

For high-resolution, iterative 3D PET image reconstruction the efficient implementation of forward-backward projectors is essential to minimise the calculation time. Mathematically, the projectors are summarised as a system response matrix (SRM) whose elements define the contribution of image voxels to lines-of-response (LORs). In fact, the SRM easily comprises billions of non-zero matrix elements to evaluate the tremendous number of LORs as provided by state-of-the-art PET scanners. Hence, the performance of iterative algorithms, e.g. maximum-likelihood-expectation-maximisation (MLEM), suffers from severe computational problems due to the intensive memory access and huge number of floating point operations.Here, symmetries occupy a key role in terms of efficient implementation. They reduce the amount of independent SRM elements, thus allowing for a significant matrix compression according to the number of exploitable symmetries. With our previous work, the PET REconstruction Software TOolkit (PRESTO), very high compression factors (>300) are demonstrated by using specific non-Cartesian voxel patterns involving discrete polar symmetries. In this way, a pre-calculated memory-resident SRM using complex volume-of-intersection calculations can be achieved. However, our original ray-driven implementation suffers from addressing voxels, projection data and SRM elements in disfavoured memory access patterns. As a consequence, a rather limited numerical throughput is observed due to the massive waste of memory bandwidth and inefficient usage of cache respectively.In this work, an advantageous symmetry-driven evaluation of the forward-backward projectors is proposed to overcome these inefficiencies. The polar symmetries applied in PRESTO suggest a novel organisation of image data and LOR projection data in memory to enable an efficient single instruction multiple data vectorisation, i.e. simultaneous use of any SRM element for symmetric LORs. In addition, the calculation time is further reduced by using simultaneous multi-threading (SMT). A global speedup factor of 11 without SMT and above 100 with SMT has been achieved for the improved CPU-based implementation while obtaining equivalent numerical results

Corrections for Quantitative Image Reconstruction with <i>pheno</i>PET, a Plant Dedicated PET Scanner

Positron Emission Tomography (PET) allows the in vivo measurement of transport and allocation of recently produced photo-assimilates in plants, which are labeled with $^{11}$C. We operate the plant dedicated system phenoPET which consists of lutetium-yttrium oxyorthosilicate crystals readout with digital Silicon photomultiplier (Digital Photon Counter (DPC) by Phillips). The horizontal Field-of-View (FOV) with a diameter of 180$\,$mm and a height of 200$\,$mm allows the measurements of plants in their natural orientation. Raw data are analyzed offline and reconstructed with Ordinary Poisson Maximum Likelihood Expectation-Maximization (OP-MLEM) provided by PET Reconstruction Software Toolkit (PRESTO). We will present the implemented corrections to reconstruct quantitative images and approaches to speed-up those image reconstructions

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

MR-Based PET Motion Correction Procedure for Simultaneous MR-PET Neuroimaging of Human Brain

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