Human Metabolome Changes after a Single Dose of 3,4-Methylenedioxymethamphetamine (MDMA) with Special Focus on Steroid Metabolism and Inflammation Processes

The intake of 3,4-methylenedioxymethamphetamine (MDMA) is known to increase several endogenous substances involved in steroid and inflammation pathways. Untargeted metabolomics screening approaches can determine biochemical changes after drug exposure and can reveal new pathways, which might be involved in the pharmacology and toxicology of a drug of abuse. We analyzed plasma samples from a placebo-controlled crossover study of a single intake of MDMA. Plasma samples from a time point before and three time points after the intake of a single dose of 125 mg MDMA were screened for changes of endogenous metabolites. An untargeted metabolomics approach on a high-resolution quadrupole time-of-flight mass spectrometer coupled to liquid chromatography with two different chromatographic systems (reversed-phase and hydrophobic interaction liquid chromatography) was applied. Over 10 000 features of the human metabolome were detected. Hence, 28 metabolites were identified, which showed significant changes after administration of MDMA compared with placebo. The analysis revealed an upregulation of cortisol and pregnenolone sulfate 4 h after MDMA intake, suggesting increased stress and serotonergic activity. Furthermore, calcitriol levels were decreased after the intake of MDMA. Calcitriol is involved in the upregulation of trophic factors, which have protective effects on brain dopamine neurons. The inflammation mediators hydroxyeicosatetraenoic acid, dihydroxyeicosatetraenoic acid, and octadecadienoic acid were found to be upregulated after the intake of MDMA compared with placebo, which suggested a stimulation of inflammation pathways

Read-out electronics for digital silicon photomultiplier modules

A new kind of a PET-Scanner (PET = positron emission tomography) for plant research is developed asa joint project of the Forschungszentrum Jülich and Philips Digital Photon Counting (PDPC). Thisscanner will utilize digital silicon photomultiplier (dSiPM) for plant phenotyping for the very first time.The goal of this work is to get a further knowledge of the operation of digital silicon photomultiplier.On this account a test-facility for this new photo detectors has been installed at the central instituteof engineering, electronics and analytics (ZEA-2 electronic systems) to determine the usage of thissensors, having regard to use them as scintillation detectors in a PET-Scanner later on.This work has its focus on the development of a fast read-out electronic for the used photo sensorsDPC3200-22-44. As there will be high data rates a fast USB 3.0 interface has been used. All thenecessary processing and data handling has been implemented in a state of the art FPGA

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

Temperature dependency of digital SiPMs

During the last years a new device for photon detection has been developed by Philips Digital Photon Counting, combining Silicon-PMT techniques with integrated logic, to get a fully digital photo sensor (dSiPM). An Evaluation Kit for dSiPMs has been installed at the Central Institute for Electronics at the Forschungszentrum Jülich. First measurements show, that the chip temperature is a factor that has to be controlled by the operator, since the higher integrated electronics on the die heat up the sensor. In this work, we present our first results focusing the influence of the temperature on the digital SiPMs. A test setup with a high power Peltier element has been set up to cool down the sensor device below -10°C. Several measurements have been done with the dSiPM evaluation kit to show the behaviour of the breakdown-voltage and the dark count rate under different temperature conditions

Design Concept of a FPGA based DAQ for digital SiPMs using USB 3.0

The presentation will show a concept of a read-out system for Philips digital SiPM's. It utilizes a Spartan 6 FPGA to connect and to transfer data from these photon counting device. A USB 3.0 interface is used as a high-speed link of up to 5 Gbit/s to transfer the sensor data to a PC

Temperature dependency of digital SiPM‘s

During the last years a new device for photon detection has been developed by Philips Digital Photon Counting, combining Silicon-PMT techniques with integrated logic, to get a fully digital photo sensor (dSiPM). An Evaluation Kit for dSiPMs has been installed at the Central Institute for Electronics at the Forschungszentrum Jülich. First measurements show, that the chip temperature is a factor that has to be controlled by the operator, since the higher integrated electronics on the die heat up the sensor. In this work, we present our first results focusing the influence of the temperature on the digital SiPMs. A test setup with a high power Peltier element has been set up to cool down the sensor device below -10°C. Several measurements have been done with the dSiPM evaluation kit to show the behaviour of the breakdown-voltage and the dark count rate under different temperature conditions

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