Improving Depth, Energy and Timing Estimation in PET Detectors with Deconvolution and Maximum Likelihood Pulse Shape Discrimination.

PubMed

Berg, Eric; Roncali, Emilie; Hutchcroft, Will; Qi, Jinyi; Cherry, Simon R

2016-11-01

In a scintillation detector, the light generated in the scintillator by a gamma interaction is converted to photoelectrons by a photodetector and produces a time-dependent waveform, the shape of which depends on the scintillator properties and the photodetector response. Several depth-of-interaction (DOI) encoding strategies have been developed that manipulate the scintillator's temporal response along the crystal length and therefore require pulse shape discrimination techniques to differentiate waveform shapes. In this work, we demonstrate how maximum likelihood (ML) estimation methods can be applied to pulse shape discrimination to better estimate deposited energy, DOI and interaction time (for time-of-flight (TOF) PET) of a gamma ray in a scintillation detector. We developed likelihood models based on either the estimated detection times of individual photoelectrons or the number of photoelectrons in discrete time bins, and applied to two phosphor-coated crystals (LFS and LYSO) used in a previously developed TOF-DOI detector concept. Compared with conventional analytical methods, ML pulse shape discrimination improved DOI encoding by 27% for both crystals. Using the ML DOI estimate, we were able to counter depth-dependent changes in light collection inherent to long scintillator crystals and recover the energy resolution measured with fixed depth irradiation (~11.5% for both crystals). Lastly, we demonstrated how the Richardson-Lucy algorithm, an iterative, ML-based deconvolution technique, can be applied to the digitized waveforms to deconvolve the photodetector's single photoelectron response and produce waveforms with a faster rising edge. After deconvolution and applying DOI and time-walk corrections, we demonstrated a 13% improvement in coincidence timing resolution (from 290 to 254 ps) with the LFS crystal and an 8% improvement (323 to 297 ps) with the LYSO crystal.

Characterization studies of silicon photomultipliers and crystals matrices for a novel time of flight PET detector

NASA Astrophysics Data System (ADS)

Auffray, E.; Ben Mimoun Bel Hadj, F.; Cortinovis, D.; Doroud, K.; Garutti, E.; Lecoq, P.; Liu, Z.; Martinez, R.; Paganoni, M.; Pizzichemi, M.; Silenzi, A.; Xu, C.; Zvolský, M.

2015-06-01

This paper describes the characterization of crystal matrices and silicon photomultiplier arrays for a novel Positron Emission Tomography (PET) detector, namely the external plate of the EndoTOFPET-US system. The EndoTOFPET-US collaboration aims to integrate Time-Of-Flight PET with ultrasound endoscopy in a novel multimodal device, capable to support the development of new biomarkers for prostate and pancreatic tumors. The detector consists in two parts: a PET head mounted on an ultrasound probe and an external PET plate. The challenging goal of 1 mm spatial resolution for the PET image requires a detector with small crystal size, and therefore high channel density: 4096 LYSO crystals individually readout by Silicon Photomultipliers (SiPM) make up the external plate. The quality and properties of these components must be assessed before the assembly. The dark count rate, gain, breakdown voltage and correlated noise of the SiPMs are measured, while the LYSO crystals are evaluated in terms of light yield and energy resolution. In order to effectively reduce the noise in the PET image, high time resolution for the gamma detection is mandatory. The Coincidence Time Resolution (CTR) of all the SiPMs assembled with crystals is measured, and results show a value close to the demanding goal of 200 ps FWHM. The light output is evaluated for every channel for a preliminary detector calibration, showing an average of about 1800 pixels fired on the SiPM for a 511 keV interaction. Finally, the average energy resolution at 511 keV is about 13 %, enough for effective Compton rejection.

A comparative study of the luminescence properties of LYSO:Ce, LSO:Ce, GSO:Ce and BGO single crystal scintillators for use in medical X-ray imaging.

PubMed

Valais, I; Michail, C; David, S; Nomicos, C D; Panayiotakis, G S; Kandarakis, I

2008-06-01

The present study is a comparative investigation of the luminescence properties of (Lu,Y)(2)SiO(5):Ce (LYSO:Ce), Lu(2)SiO(5):Ce (LSO:Ce), Gd(2)SiO(5):Ce (GSO:Ce) and (Bi(4)Ge(3)O(12)) BGO single crystal scintillators under medical X-ray excitation. All scintillating crystals have dimensions of 10 x 10 x 10 mm(3) are non-hygroscopic exhibiting high radiation absorption efficiency in the energy range used in medical imaging applications. The comparative investigation was performed by determining the absolute luminescence efficiency (emitted light flux over incident X-ray exposure) in X-ray energies employed in general X-ray imaging (40-140 kV) and in mammographic X-ray imaging (22-49 kV). Additionally, light emission spectra of crystals at various X-ray energies were measured, in order to determine the spectral compatibility to optical photon detectors incorporated in medical imaging systems and the overall efficiency (effective efficiency) of a scintillator-optical detector combination. The light emission performance of LYSO:Ce and LSO:Ce scintillators studied was found very high for X-ray imaging.

Comparison of acrylic polymer adhesive tapes and silicone optical grease in light sharing detectors for positron emission tomography

NASA Astrophysics Data System (ADS)

Van Elburg, Devin J.; Noble, Scott D.; Hagey, Simone; Goertzen, Andrew L.

2018-03-01

Optical coupling is an important factor in detector design as it improves optical photon transmission by mitigating internal reflections at light-sharing boundaries. In this work we compare optical coupling materials, namely double-sided acrylic polymer tapes and silicone optical grease (SiG), in the context of positron emission tomography. Four double-sided tapes from 3 M of varying thicknesses (0.229 mm-1.016 mm) and adhesive materials (‘100MP’, ‘A100’, and ‘GPA’) were characterized with spectrophotometer measurements as well as photopeak amplitude and energy resolution measurements using lutetium-yttrium oxy-orthosilicate (LYSO) coupled to photomultiplier tubes (PMT) or silicon photomultipliers (SiPMs). Transmission spectra from the spectrophotometer showed over 80% transmission for all tapes at 420 nm and above, with 89.6% and 88.8% transmission for the 0.508 mm and 1.016 mm thick GPA tapes, respectively, at 420 nm. Measurements with single-pixel LYSO-PMT and 4  ×  4 array (one-to-one coupled) LYSO-SiPM setups determined that SiG had the greatest photopeak amplitude, with tapes showing 2.1%-14.8% reduction in photopeak amplitude with respect to SiG. Energy resolution changed by less than 4% on a relative basis between tapes and SiG with PMT measurements, however for the SiPM array measurements the energy resolution improved from 15.6%  ±  2.7% full-width at half-maximum to 11.4%  ±  1.2% for SiG and 1 mm GPA respectively. Data acquired with dual-layer offset LYSO arrays (light sharing detector designs) demonstrated that a detector coupled with 1 mm thick GPA tape produced equivalent detector flood histograms to those from a design coupled with SiG and a 1 mm thick glass lightguide. No significant degradation in photopeak amplitude and energy resolution was observed over five months of measurements, indicating the tapes maintain their coupling integrity over several months. Though minimal photopeak amplitude degradation compared to SiG occurs, double-sided tapes are convenient alternatives for optical coupling materials since they diffuse light intrinsically, acting as a light guide, offer mechanical support and durability, are easily applied and removed from scintillators/photodetectors, and are relatively inexpensive and readily available.

Comparison of acrylic polymer adhesive tapes and silicone optical grease in light sharing detectors for positron emission tomography.

PubMed

Van Elburg, Devin J; Noble, Scott D; Hagey, Simone; Goertzen, Andrew L

2018-02-26

Optical coupling is an important factor in detector design as it improves optical photon transmission by mitigating internal reflections at light-sharing boundaries. In this work we compare optical coupling materials, namely double-sided acrylic polymer tapes and silicone optical grease (SiG), in the context of positron emission tomography. Four double-sided tapes from 3 M of varying thicknesses (0.229 mm-1.016 mm) and adhesive materials ('100MP', 'A100', and 'GPA') were characterized with spectrophotometer measurements as well as photopeak amplitude and energy resolution measurements using lutetium-yttrium oxy-orthosilicate (LYSO) coupled to photomultiplier tubes (PMT) or silicon photomultipliers (SiPMs). Transmission spectra from the spectrophotometer showed over 80% transmission for all tapes at 420 nm and above, with 89.6% and 88.8% transmission for the 0.508 mm and 1.016 mm thick GPA tapes, respectively, at 420 nm. Measurements with single-pixel LYSO-PMT and 4  ×  4 array (one-to-one coupled) LYSO-SiPM setups determined that SiG had the greatest photopeak amplitude, with tapes showing 2.1%-14.8% reduction in photopeak amplitude with respect to SiG. Energy resolution changed by less than 4% on a relative basis between tapes and SiG with PMT measurements, however for the SiPM array measurements the energy resolution improved from 15.6%  ±  2.7% full-width at half-maximum to 11.4%  ±  1.2% for SiG and 1 mm GPA respectively. Data acquired with dual-layer offset LYSO arrays (light sharing detector designs) demonstrated that a detector coupled with 1 mm thick GPA tape produced equivalent detector flood histograms to those from a design coupled with SiG and a 1 mm thick glass lightguide. No significant degradation in photopeak amplitude and energy resolution was observed over five months of measurements, indicating the tapes maintain their coupling integrity over several months. Though minimal photopeak amplitude degradation compared to SiG occurs, double-sided tapes are convenient alternatives for optical coupling materials since they diffuse light intrinsically, acting as a light guide, offer mechanical support and durability, are easily applied and removed from scintillators/photodetectors, and are relatively inexpensive and readily available.

LYSO crystal testing for an EDM polarimeter

NASA Astrophysics Data System (ADS)

Müller, F.; Keshelashvili, I.; Mchedlishvili, D.; JEDI Collaboration

2017-11-01

Four detector modules, built from three different LYSO crystals and two different types of light sensors (PMTs and SiPM arrays), have been tested with a deuteron beam from 100 MeV - 270 MeV at the COSY accelerator facility for the srEDM project at the Forschungszentrum Jülich in Germany. The detector modules were arranged in a cluster hand mounted on a positioning table. The deuteron beam was targeted at the center of each individual crystal for data analysis. The signals were digitized using a 14 bit, 250 MS/s flash ADC. Further, the energy spectra were calibrated using the known beam energies from the accelerator. From the calibrated spectra, the energy resolution was calculated. A resolution of 3% for the low energies and down to 1% for the high energy of 270 MeV was achieved. A deuteron reconstruction efficiency of almost 100% for low energies and around 70% for high energies was achieved. The SiPM light sensor showed a very good performance and will be used for the next generation of detector modules.

Design, development and evaluation of a resistor-based multiplexing circuit for a 20×20 SiPM array

NASA Astrophysics Data System (ADS)

Wang, Zhonghai; Sun, Xishan; Lou, Kai; Meier, Joseph; Zhou, Rong; Yang, Chaowen; Zhu, Xiaorong; Shao, Yiping

2016-04-01

One technical challenge in developing a large-size scintillator detector with multiple Silicon Photomultiplier (SiPM) arrays is to read out a large number of detector output channels. To achieve this, different signal multiplexing circuits have been studied and applied with different performances and cost-effective tradeoffs. Resistor-based multiplexing circuits exhibit simplicity and signal integrity, but also present the disadvantage of timing shift among different channels. In this study, a resistor-based multiplexing circuit for a large-sized SiPM array readout was developed and evaluated by simulation and experimental studies. Similarly to a multiplexing circuit used for multi-anode PMT, grounding and branching resistors were connected to each SiPM output channel. The grounding resistor was used to simultaneously reduce the signal crosstalk among different channels and to improve timing performance. Both grounding and branching resistor values were optimized to maintain a balanced performance of the event energy, timing, and positioning. A multiplexing circuit was implemented on a compact PCB and applied for a flat-panel detector which consisted of a 32×32 LYSO scintillator crystals optically coupled to 5×5 SiPM arrays for a total 20×20 output channels. Test results showed excellent crystal identification for all 1024 LYSO crystals (each with 2×2×30 mm3 size) with 22Na flood-source irradiation. The measured peak-to-valley ratio from typical crystal map profile is around 3:1 to 6.6:1, an average single crystal energy resolution of about 17.3%, and an average single crystal timing resolution of about 2 ns. Timing shift among different crystals, as reported in some other resistor-based multiplexing circuit designs, was not observed. In summary, we have designed and implemented a practical resistor-based multiplexing circuit that can be readily applied for reading out a large SiPM array with good detector performance.

A Hand-Held, Intra-Operative Positron Imaging Probe for Surgical Applications

NASA Astrophysics Data System (ADS)

Sabet, Hamid; Stack, Brendan C.; Nagarkar, Vivek V.

2015-10-01

We have developed a prototype intra-operative β+ imaging probe to help tumor removal and malignant tissue resection. The probe can be used during surgery to provide clear delineation of malignant tissues. Our probe consists of a hybrid scintillator coupled to a silicon photomultiplier (SiPM) array with associated front-end electronics encapsulated in an ergonomic aluminum housing. Pulse shape discrimination electronics has been implemented and integrated into the downstream data acquisition system. The field of view of the probe is 10 ×10 mm2 realized by a 0.4 mm thick CsI:Tl scintillator coupled to a 1 mm thick LYSO. While CsI:Tl layer acts as β+ sensitive detector, LYSO detects gamma radiation where the gamma response can be subtracted from the total signal to improve SNR and contrast. The thickness of the LYSO scintillator is optimized such that it acts as light diffuser to spread the scintillation light generated in CsI:Tl over multiple SiPM pixels for accurate estimation of the β+ interaction location. The probe shows FWHM spatial resolution in the presence of large background radiation. The probe was used to study rabbits with tongue tumors. The experimental results show that the probe can successfully locate the tongue tumors in its active imaging area.

A new detector for mass spectrometry: direct detection of low energy ions using a multi-pixel photon counter.

PubMed

Wilman, Edward S; Gardiner, Sara H; Nomerotski, Andrei; Turchetta, Renato; Brouard, Mark; Vallance, Claire

2012-01-01

A new type of ion detector for mass spectrometry and general detection of low energy ions is presented. The detector consists of a scintillator optically coupled to a single-photon avalanche photodiode (SPAD) array. A prototype sensor has been constructed from a LYSO (Lu(1.8)Y(0.2)SiO(5)(Ce)) scintillator crystal coupled to a commercial SPAD array detector. As proof of concept, the detector is used to record the time-of-flight mass spectra of butanone and carbon disulphide, and the dependence of detection sensitivity on the ion kinetic energy is characterised.

How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?

PubMed

Auray-Blais, Christiane; Ntwari, Aimé; Clarke, Joe T R; Warnock, David G; Oliveira, João Paulo; Young, Sarah P; Millington, David S; Bichet, Daniel G; Sirrs, Sandra; West, Michael L; Casey, Robin; Hwu, Wuh-Liang; Keutzer, Joan M; Zhang, X Kate; Gagnon, René

2010-12-14

Fabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb(3)), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb(3)), is increased in patients with the disease. Until now, lyso-Gb(3) was not detectable in urine, possibly because of the presence of interfering compounds. We undertook to: 1) characterize lyso-Gb(3) in urine; 2) develop a method to quantitate urinary lyso-Gb(3) by mass spectrometry; 3) evaluate urinary lyso-Gb(3) as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb(3) is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb(3) from 83 Fabry patients and 77 healthy age-matched controls. The intraday and interday bias and precision of the method were <15%. Increases in lyso-Gb(3)/creatinine correlated with the concentrations of Gb(3) (r(2)=0.43), type of mutations (p=0.0006), gender (p<0.0001) and enzyme replacement therapy status (p=0.0012). Urine from healthy controls contained no detectable lyso-Gb(3). Lyso-Gb(3) did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb(3) of Fabry patients correlated well with a number of indicators of disease severity. Lyso-Gb(3) is a reliable independent biomarker for clinically important characteristics of Fabry disease. Copyright © 2010 Elsevier B.V. All rights reserved.

A PET detector prototype based on digital SiPMs and GAGG scintillators.

PubMed

Schneider, Florian R; Shimazoe, Kenji; Somlai-Schweiger, Ian; Ziegler, Sibylle I

2015-02-21

Silicon Photomultipliers (SiPM) are interesting light sensors for Positron Emission Tomography (PET). The detector signal of analog SiPMs is the total charge of all fired cells. Energy and time information have to be determined with dedicated readout electronics. Philips Digital Photon Counting has developed a SiPM with added electronics on cell level delivering a digital value of the time stamp and number of fired cells. These so called Digital Photon Counters (DPC) are fully digital devices. In this study, the feasibility of using DPCs in combination with LYSO (Lutetium Yttrium Oxyorthosilicate) and GAGG (Gadolinium Aluminum Gallium Garnet) scintillators for PET is tested. Each DPC module has 64 channels with 3.2 × 3.8775 mm(2), comprising 3200 cells each. GAGG is a recently developed scintillator (Zeff = 54, 6.63 g cm(-3), 520 nm peak emission, 46 000 photons MeV(-1), 88 ns (92%) and 230 ns (8%) decay times, non-hygroscopic, chemically and mechanically stable). Individual crystals of 2 × 2 × 6 mm(3) were coupled onto each DPC pixel. LYSO coupled to the DPC results in a coincidence time resolution (CTR) of 171 ps FWHM and an energy resolution of 12.6% FWHM at 511 keV. Using GAGG, coincidence timing is 310 ps FWHM and energy resolution is 8.5% FWHM. A PET detector prototype with 2 DPCs equipped with a GAGG array matching the pixel size (3.2 × 3.8775 × 8 mm(3)) was assembled. To emulate a ring of 10 modules, objects are rotated in the field of view. CTR of the PET is 619 ps and energy resolution is 9.2% FWHM. The iterative MLEM reconstruction is based on system matrices calculated with an analytical detector response function model. A phantom with rods of different diameters filled with (18)F was used for tomographic tests.

A PET detector prototype based on digital SiPMs and GAGG scintillators

NASA Astrophysics Data System (ADS)

Schneider, Florian R.; Shimazoe, Kenji; Somlai-Schweiger, Ian; Ziegler, Sibylle I.

2015-02-01

Silicon Photomultipliers (SiPM) are interesting light sensors for Positron Emission Tomography (PET). The detector signal of analog SiPMs is the total charge of all fired cells. Energy and time information have to be determined with dedicated readout electronics. Philips Digital Photon Counting has developed a SiPM with added electronics on cell level delivering a digital value of the time stamp and number of fired cells. These so called Digital Photon Counters (DPC) are fully digital devices. In this study, the feasibility of using DPCs in combination with LYSO (Lutetium Yttrium Oxyorthosilicate) and GAGG (Gadolinium Aluminum Gallium Garnet) scintillators for PET is tested. Each DPC module has 64 channels with 3.2 × 3.8775 mm2, comprising 3200 cells each. GAGG is a recently developed scintillator (Zeff = 54, 6.63 g cm-3, 520 nm peak emission, 46 000 photons MeV-1, 88 ns (92%) and 230 ns (8%) decay times, non-hygroscopic, chemically and mechanically stable). Individual crystals of 2 × 2 × 6 mm3 were coupled onto each DPC pixel. LYSO coupled to the DPC results in a coincidence time resolution (CTR) of 171 ps FWHM and an energy resolution of 12.6% FWHM at 511 keV. Using GAGG, coincidence timing is 310 ps FWHM and energy resolution is 8.5% FWHM. A PET detector prototype with 2 DPCs equipped with a GAGG array matching the pixel size (3.2 × 3.8775 × 8 mm3) was assembled. To emulate a ring of 10 modules, objects are rotated in the field of view. CTR of the PET is 619 ps and energy resolution is 9.2% FWHM. The iterative MLEM reconstruction is based on system matrices calculated with an analytical detector response function model. A phantom with rods of different diameters filled with 18F was used for tomographic tests.

A microwave-mediated saponification of galactosylceramide and galactosylceramide I3-sulfate and identification of their lyso-compounds by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

PubMed

Taketomi, T; Hara, A; Uemura, K; Kurahashi, H; Sugiyama, E

1996-07-16

Small amounts of galactosylceramide (cerebroside) and galactosylceramide I3-sulfate (sulfatide) obtained from porcine spinal cord and equine kidney were deacylated by a rapid method of microwave-mediated saponification to prepare their lyso-compounds. Mass spectra of their protonated or deprotonated molecular ion peaks were detected by recently developed new technology of a delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometer with reflector detector in positive or negative ion mode. Long chain bases of lysocerebroside and lysosulfatide were different between porcine spinal cord and equine kidney, but similar to each other in the same organ, suggesting their common synthetic pathway. It is noted that the new rapid method can be similarly applied to the deacylation of both cerebroside and sulfatide in contrast to our classical method which was able to be applied to cerebroside, but not to sulfatide.

LYSO based precision timing calorimeters

NASA Astrophysics Data System (ADS)

Bornheim, A.; Apresyan, A.; Ronzhin, A.; Xie, S.; Duarte, J.; Spiropulu, M.; Trevor, J.; Anderson, D.; Pena, C.; Hassanshahi, M. H.

2017-11-01

In this report we outline the study of the development of calorimeter detectors using bright scintillating crystals. We discuss how timing information with a precision of a few tens of pico seconds and below can significantly improve the reconstruction of the physics events under challenging high pileup conditions to be faced at the High-Luminosity LHC or a future hadron collider. The particular challenge in measuring the time of arrival of a high energy photon lies in the stochastic component of the distance of initial conversion and the size of the electromagnetic shower. We present studies and measurements from test beams for calorimeter based timing measurements to explore the ultimate timing precision achievable for high energy photons of 10 GeV and above. We focus on techniques to measure the timing with a high precision in association with the energy of the photon. We present test-beam studies and results on the timing performance and characterization of the time resolution of LYSO-based calorimeters. We demonstrate time resolution of 30 ps is achievable for a particular design.

Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout

PubMed Central

Bircher, Chad; Shao, Yiping

2012-01-01

Purpose: Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. Methods: The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators’ internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 × 1.5 and 2.0 × 2.0 mm2 cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. Results: All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. Conclusions: The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems. PMID:22320787

Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout.

PubMed

Bircher, Chad; Shao, Yiping

2012-02-01

Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 × 1.5 and 2.0 × 2.0 mm(2) cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems.

Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bircher, Chad; Shao Yiping

Purpose: Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method couldmore » be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. Methods: The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 x 1.5 and 2.0 x 2.0 mm{sup 2} cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. Results: All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. Conclusions: The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems.« less

Detection of high energy muons with sub-20 ps timing resolution using L(Y)SO crystals and SiPM readout

NASA Astrophysics Data System (ADS)

Benaglia, A.; Gundacker, S.; Lecoq, P.; Lucchini, M. T.; Para, A.; Pauwels, K.; Auffray, E.

2016-09-01

Precise timing capability will be a key aspect of particle detectors at future high energy colliders, as the time information can help in the reconstruction of physics events at the high collision rate expected there. Other than being used in detectors for PET, fast scintillating crystals coupled to compact Silicon Photomultipliers (SiPMs) constitute a versatile system that can be exploited to realize an ad-hoc timing device to be hosted in a larger high energy physics detector. In this paper, we present the timing performance of LYSO:Ce and LSO:Ce codoped 0.4% Ca crystals coupled to SiPMs, as measured with 150 GeV muons at the CERN SPS H2 extraction line. Small crystals, with lengths ranging from 5 mm up to 30 mm and transverse size of 2 × 2mm2 or 3 × 3mm2 , were exposed to a 150 GeV muon beam. SiPMs from two different companies (Hamamatsu and FBK) were used to detect the light produced in the crystals. The best coincidence time resolution value of (14.5 ± 0.5) ps , corresponding to a single-detector time resolution of about 10 ps, is demonstrated for 5 mm long LSO:Ce,Ca crystals coupled to FBK SiPMs, when time walk corrections are applied.

Simultaneous Profiling of Lysoglycerophospholipids in Rice (Oryza sativa L.) Using Direct Infusion-Tandem Mass Spectrometry with Multiple Reaction Monitoring.

PubMed

Lim, Dong Kyu; Mo, Changyeun; Long, Nguyen Phuoc; Kim, Giyoung; Kwon, Sung Won

2017-03-29

White rice is the final product after the hull and bran layers have been removed during the milling process. Although lysoglycerophospholipids (lysoGPLs) only occupy a small proportion in white rice, they are essential for evaluating rice authenticity and quality. In this study, we developed a high-throughput and targeted lipidomics approach that involved direct infusion-tandem mass spectrometry with multiple reaction monitoring to simultaneously profile lysoGPLs in white rice. The method is capable of characterizing 17 lysoGPLs within 1 min. In addition, unsupervised and supervised analyses exhibited a considerably large diversity of lysoGPL concentrations in white rice from different origins. In particular, a classification model was built using identified lysoGPLs that can differentiate white rice from Korea, China, and Japan. Among the discriminatory lysoGPLs, for the lysoPE(16:0) and lysoPE(18:2) compositions, there were relatively small within-group variations, and they were considerably different among the three countries. In conclusion, our proposed method provides a rapid, high-throughput, and comprehensive format for profiling lysoGPLs in rice samples.

The Road to the Common PET/CT Detector

NASA Astrophysics Data System (ADS)

Nassalski, Antoni; Moszynski, Marek; Szczesniak, Tomasz; Wolski, Dariusz; Batsch, Tadeusz

2007-10-01

Growing interest in the development of dual modality positron emission/X-rays tomography (PET/CT) systems prompts researchers to face a new challenge: to acquire both the anatomical and functional information in the same measurement, simultaneously using the same detection system and electronics. The aim of this work was to study a detector consisting of LaBr3, LSO or LYSO pixel crystals coupled to an avalanche photodiode (APD). The measurements covered tests of the detectors in PET and CT modes, respectively. The measurements included the determination of light output, energy resolution, the non-proportionality of the light yield and the time resolution for 511 keV annihilation quanta; analysis also included characterizing the PET detector, and determining the dependence of counting rate versus mean current of the APD in the X-ray detection. In the present experiment, the use of counting and current modes in the CT detection increases the dynamic range of the measured dose of X-rays by a factor of 20, compared to the counting mode alone.

A prototype MR insertable brain PET using tileable GAPD arrays.

PubMed

Hong, Key Jo; Choi, Yong; Jung, Jin Ho; Kang, Jihoon; Hu, Wei; Lim, Hyun Keong; Huh, Yoonsuk; Kim, Sangsu; Jung, Ji Woong; Kim, Kyu Bom; Song, Myung Sung; Park, Hyun-Wook

2013-04-01

The aim of this study was to develop a prototype magnetic resonance (MR)-compatible positron emission tomography (PET) that can be inserted into a MR imager and that allows simultaneous PET and MR imaging of the human brain. This paper reports the initial results of the authors' prototype brain PET system operating within a 3-T magnetic resonance imaging (MRI) system using newly developed Geiger-mode avalanche photodiode (GAPD)-based PET detectors, long flexible flat cables, position decoder circuit with high multiplexing ratio, and digital signal processing with field programmable gate array-based analog to digital converter boards. A brain PET with 72 detector modules arranged in a ring was constructed and mounted in a 3-T MRI. Each PET module was composed of cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled to a tileable GAPD. The GAPD output charge signals were transferred to preamplifiers using 3 m long flat cables. The LYSO and GAPD were located inside the MR bore and all electronics were positioned outside the MR bore. The PET detector performance was investigated both outside and inside the MRI, and MR image quality was evaluated with and without the PET system. The performance of the PET detector when operated inside the MRI during MR image acquisition showed no significant change in energy resolution and count rates, except for a slight degradation in timing resolution with an increase from 4.2 to 4.6 ns. Simultaneous PET/MR images of a hot-rod and Hoffman brain phantom were acquired in a 3-T MRI. Rods down to a diameter of 3.5 mm were resolved in the hot-rod PET image. The activity distribution patterns between the white and gray matter in the Hoffman brain phantom were well imaged. The hot-rod and Hoffman brain phantoms on the simultaneously acquired MR images obtained with standard sequences were observed without any noticeable artifacts, although MR image quality requires some improvement. These results demonstrate that the simultaneous acquisition of PET and MR images is feasible using the MR insertable PET developed in this study.

Development and performance test of an online blood sampling system for determination of the arterial input function in rats.

PubMed

Roehrbacher, Friedrich; Bankstahl, Jens P; Bankstahl, Marion; Wanek, Thomas; Stanek, Johann; Sauberer, Michael; Muellauer, Julia; Schroettner, Thales; Langer, Oliver; Kuntner, Claudia

2015-12-01

For positron emission tomography (PET) kinetic modelling, an accurate determination of the arterial input function is required. In this study, a blood sampling system was developed and tested using different radiotracers in rats. The detector consists of pairs of lutetium yttrium oxyorthosilicate (LYSO) detectors, photomultiplier tubes and lead shield assembled within a steel casing working in coincidence mode. Rats were cannulated with microtubes in the femoral artery and vein for arterial blood sampling as well as administration of the PET tracers. Connected PTFE microtubes were centred between the LYSO crystals using a special holder. To enhance sensitivity, three layers with two coils were used. A flexible tube pump was used to ensure a constant blood flow. Performance of the detector was assessed with [(18)F]fludeoxyglucose (FDG), [(18)F]ciprofloxacin, (R)-[(11)C]verapamil, [(11)C]tariquidar, [(11)C]mephobarbital and [(11)C]MC113. Obtained input function curves were compared with manual samples drawn every 5 s during the first 3 min and further on at 5, 10, 20, 30, 40, 50 and 60 min after radiotracer injection. After manual sampling, an arterio/venous shunt was established. Shape and area-under-the-curve (AUC; Bq/μl*h) of the input functions were evaluated. The developed detector system provided an absolute sensitivity of 6.5%. Maximum peak values agreed well between manual samples and the detector with a mean difference of -0.4% ± 7.0% (max 12.0%, min -9.9%). AUC values also exhibited an excellent correlation (R = 0.996) between manual sampling and detector measurements with a mean difference of 9.3% ± 9.7% (max 24.1%, min -3.2%). The system was able to measure peak blood activity concentration levels of 110 to 2,000 Bq/μl which corresponds to injected activities from 5.5 to 100 MBq depending on the used radiotracer, applied volume and weight of the animal. This study demonstrates that the developed blood sampling system can be used for in vivo small animal PET studies in rats in a reliable way. The usage of the systems enhances the accuracy of the input curve as handling of small blood samples especially with low activity (as for C-11) is prone to measurement errors. Additionally, the radiation dose of the experimenters can be reduced, as it is not required anymore to continuously draw samples where the personal is in close contact to the radioactive animals and blood.

Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout

NASA Astrophysics Data System (ADS)

Bläckberg, L.; El Fakhri, G.; Sabet, H.

2017-11-01

A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to  >42%, and for rough interfaces  >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout.

PubMed

Bläckberg, L; El Fakhri, G; Sabet, H

2017-10-19

A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to  >42%, and for rough interfaces  >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

Time-over-threshold for pulse shape discrimination in a time-of-flight phoswich PET detector.

PubMed

Chang, Chen-Ming; Cates, Joshua W; Levin, Craig S

2017-01-07

It is well known that a PET detector capable of measuring both photon time-of-flight (TOF) and depth-of-interaction (DOI) improves the image quality and accuracy. Phoswich designs have been realized in PET detectors to measure DOI for more than a decade. However, PET detectors based on phoswich designs put great demand on the readout circuits, which have to differentiate the pulse shape produced by different crystal layers. A simple pulse shape discrimination approach is required to realize the phoswich designs in a clinical PET scanner, which consists of thousands of scintillation crystal elements. In this work, we studied time-over-threshold (ToT) as a pulse shape parameter for DOI. The energy, timing and DOI performance were evaluated for a phoswich detector design comprising [Formula: see text] mm LYSO:Ce crystal optically coupled to [Formula: see text] mm calcium co-doped LSO:Ce,Ca(0.4%) crystal read out by a silicon photomultiplier (SiPM). A DOI accuracy of 97.2% has been achieved for photopeak events using the proposed time-over-threshold (ToT) processing. The energy resolution without correction for SiPM non-linearity was [Formula: see text]% and [Formula: see text]% FWHM at 511 keV for LYSO and LSO crystal layers, respectively. The coincidence time resolution for photopeak events ranges from 164.6 ps to 183.1 ps FWHM, depending on the layer combinations. The coincidence time resolution for inter-crystal scatter events ranges from 214.6 ps to 418.3 ps FWHM, depending on the energy windows applied. These results show great promises of using ToT for pulse shape discrimination in a TOF phoswich detector since a ToT measurement can be easily implemented in readout electronics.

Neutrophils Regulate Tissue Neutrophilia in Inflammation via the Oxidant-modified Lipid Lysophosphatidylserine*

PubMed Central

Frasch, S. Courtney; Fernandez-Boyanapalli, Ruby F.; Berry, Karin A. Zemski; Murphy, Robert C.; Leslie, Christina C.; Nick, Jerry A.; Henson, Peter M.; Bratton, Donna L.

2013-01-01

Resolution of neutrophilia characteristic of acute inflammation requires cessation of neutrophil recruitment and removal of tissue neutrophils. Based on in vitro studies, a role in these events was hypothesized for oxidant-generated lysophosphatidylserine (lyso-PS) on recruited neutrophils signaling via the G2A receptor on macrophages. Peritoneal exudate neutrophils harvested from wild type (WT) mice had 5-fold more lyso-PS (lyso-PShigh) than those of gp91phox−/− (lyso-PSlow) mice. Ex vivo engulfment of lyso-PShigh neutrophils (95% viable) by WT peritoneal macrophages was quantitatively similar to UV-irradiated apoptotic blood neutrophils, although the signaling pathway for the former was uniquely dependent on macrophage G2A. In contrast, lyso-PSlow neutrophils were poorly engulfed unless presented with exogenous lyso-PS. Enhanced clearance of lyso-PShigh neutrophils was also seen in vivo following their adoptive transfer into inflamed peritonea of WT but not G2A−/− mice, further supporting a requirement for signaling via G2A. To investigate downstream effects of lyso-PS/G2A signaling, antibody blockade of G2A in WT mice reduced macrophage CD206 expression and efferocytosis during peritonitis. Conversely, adoptive transfer of lyso-PShigh neutrophils early in inflammation in gp91phox−/− mice led to accelerated development of efferocytichigh and CD206high macrophages. This macrophage reprogramming was associated with suppressed production of pro-inflammatory mediators and reduced neutrophilia. These effects were not seen if G2A was blocked or lyso-PSlow neutrophils were transferred. Taken together, the results demonstrate that oxidant-generated lyso-PS made by viable tissue neutrophils is an endogenous anti-inflammatory mediator working in vivo to orchestrate the “early” and rapid clearance of recruited neutrophils as well as the reprogramming of “resolving” macrophages. PMID:23293064

LYSO based precision timing calorimeters

DOE PAGES

Bornheim, A.; Apresyan, A.; Ronzhin, A.; ...

2017-11-01

In this report we outline the study of the development of calorimeter detectors using bright scintillating crystals. We discuss how timing information with a precision of a few tens of pico seconds and below can significantly improve the reconstruction of the physics events under challenging high pileup conditions to be faced at the High-Luminosity LHC or a future hadron collider. The particular challenge in measuring the time of arrival of a high energy photon lies in the stochastic component of the distance of initial conversion and the size of the electromagnetic shower. We present studies and measurements from test beamsmore » for calorimeter based timing measurements to explore the ultimate timing precision achievable for high energy photons of 10 GeV and above. We focus on techniques to measure the timing with a high precision in association with the energy of the photon. We present test-beam studies and results on the timing performance and characterization of the time resolution of LYSO-based calorimeters. We demonstrate time resolution of 30 ps is achievable for a particular design.« less

The activities of acyl-CoA:1-acyl-lysophospholipid acyltransferase(s) in human platelets.

PubMed Central

Bakken, A M; Farstad, M

1992-01-01

The activities of acyl-CoA:1-acyl-lysophospholipid acyltransferases (EC 2.3.1.23) have been studied in human platelet lysates by using endogenously formed [14C]acyl-CoA from [14C]fatty acid, ATP and CoA in the presence of 1-acyl-lysophosphatidyl-choline (lysoPC), -ethanolamine (lysoPE), -serine (lysoPS) or -inositol (lysoPI). Linoleic acid as fatty acid substrate had the highest affinity to acyl-CoA:1-acyl-lysophospholipid acyltransferase with lysoPC as variable substrate, followed by eicosapentaenoic acid (EPA) and arachidonic acid (AA). The activity at optimal conditions was 7.4, 7.3 and 7.2 nmol/min per 10(9) platelets with lysoPC as substrate, with linoleic acid, AA and EPA respectively. EPA and AA were incorporated into all lyso-forms. Linoleic acid was also incorporated into lysoPE at a high rate, but less into lysoPS and lysoPI. DHA was incorporated into lysoPC and lysoPE, but only slightly into lysoPI and lysoPS. Whereas incorporation of all fatty acids tested was maximal for lysoPC and lysoPI at 200 and 80 microM respectively, maximal incorporation needed over 500 microM for lysoPE and lysoPS. The optimal concentration for [14C]fatty acid substrates was in the range 15-150 microM for all lysophospholipids. Competition experiments with equimolar concentrations of either lysoPC and lysoPI or lysoPE resulted in formation of [14C]PC almost as if lysoPI or lysoPE were not added to the assay medium. PMID:1471991

Development of depth encoding small animal PET detectors using dual-ended readout of pixelated scintillator arrays with SiPMs.

PubMed

Kuang, Zhonghua; Sang, Ziru; Wang, Xiaohui; Fu, Xin; Ren, Ning; Zhang, Xianming; Zheng, Yunfei; Yang, Qian; Hu, Zhanli; Du, Junwei; Liang, Dong; Liu, Xin; Zheng, Hairong; Yang, Yongfeng

2018-02-01

The performance of current small animal PET scanners is mainly limited by the detector performance and depth encoding detectors are required to develop PET scanner to simultaneously achieve high spatial resolution and high sensitivity. Among all depth encoding PET detector approaches, dual-ended readout detector has the advantage to achieve the highest depth of interaction (DOI) resolution and spatial resolution. Silicon photomultiplier (SiPM) is believed to be the photodetector of the future for PET detector due to its excellent properties as compared to the traditional photodetectors such as photomultiplier tube (PMT) and avalanche photodiode (APD). The purpose of this work is to develop high resolution depth encoding small animal PET detector using dual-ended readout of finely pixelated scintillator arrays with SiPMs. Four lutetium-yttrium oxyorthosilicate (LYSO) arrays with 11 × 11 crystals and 11.6 × 11.6 × 20 mm 3 outside dimension were made using ESR, Toray and BaSO 4 reflectors. The LYSO arrays were read out with Hamamatsu 4 × 4 SiPM arrays from both ends. The SiPM array has a pixel size of 3 × 3 mm 2 , 0.2 mm gap in between the pixels and a total active area of 12.6 × 12.6 mm 2 . The flood histograms, DOI resolution, energy resolution and timing resolution of the four detector modules were measured and compared. All crystals can be clearly resolved from the measured flood histograms of all four arrays. The BaSO 4 arrays provide the best and the ESR array provides the worst flood histograms. The DOI resolution obtained from the DOI profiles of the individual crystals of the four array is from 2.1 to 2.35 mm for events with E > 350 keV. The DOI ratio variation among crystals is bigger for the BaSO 4 arrays as compared to both the ESR and Toray arrays. The BaSO 4 arrays provide worse detector based DOI resolution. The photopeak amplitude of the Toray array had the maximum change with depth, it provides the worst energy resolution of 21.3%. The photopeak amplitude of the BaSO 4 array with 80 μm reflector almost doesn't change with depth, it provides the best energy resolution of 12.9%. A maximum timing shift of 1.37 ns to 1.61 ns among the corner and the center crystals in the four arrays was obtained due to the use of resistor network readout. A crystal based timing resolution of 0.68 ns to 0.83 ns and a detector based timing resolution of 1.26 ns to 1.45 ns were obtained for the four detector modules. Four high resolution depth encoding small animal PET detectors were developed using dual-ended readout of pixelated scintillator arrays with SiPMs. The performance results show that those detectors can be used to build a small animal PET scanner to simultaneously achieve uniform high spatial resolution and high sensitivity. © 2017 American Association of Physicists in Medicine.

Preliminary studies of PQS PET detector module for dose verification of carbon beam therapy

NASA Astrophysics Data System (ADS)

Kim, H.-I.; An, S. Jung; Lee, C. Y.; Jo, W. J.; Min, E.; Lee, K.; Kim, Y.; Joung, J.; Chung, Y. H.

2014-05-01

PET imaging can be used to verify dose distributions of therapeutic particle beams such as carbon ion beams. The purpose of this study was to develop a PET detector module which was designed for an in-beam PET scanner geometry integrated into a carbon beam therapy system, and to evaluate its feasibility as a monitoring system of patient dose distribution. A C-shaped PET geometry was proposed to avoid blockage of the carbon beam by the detector modules. The proposed PET system consisted of 14 detector modules forming a bore with 30.2 cm inner diameter for brain imaging. Each detector module is composed of a 9 × 9 array of 4.0 mm × 4.0 mm × 20.0 mm LYSO crystal module optically coupled with four 29 mm diameter PMTs using Photomultiplier-quadrant-sharing (PQS) technique. Because the crystal pixel was identified based upon the distribution of scintillation lights of four PMTs, the design of the reflector between crystal elements should be well optimized. The optical design of reflectors was optimized using DETECT2000, a Monte Carlo code for light photon transport. A laser-cut reflector set was developed using the Enhanced Specular Reflector (ESR, 3M Co.) mirror-film with a high reflectance of 98% and a thickness of 0.064 mm. All 81 crystal elements of detector module were identified. Our result demonstrates that the C-shaped PET system is under development and we present the first reconstructed image.

Development of a Monte Carlo Simulation for APD-Based PET Detectors Using a Continuous Scintillating Crystal

NASA Astrophysics Data System (ADS)

Clowes, P.; Mccallum, S.; Welch, A.

2006-10-01

We are currently developing a multilayer avalanche photodiode (APD)-based detector for use in positron emission tomography (PET), which utilizes thin continuous crystals. In this paper, we developed a Monte Carlo-based simulation to aid in the design of such detectors. We measured the performance of a detector comprising a single thin continuous crystal (3.1 mm times 9.5 mm times 9.5 mm) of lutetium yttrium ortho-silicate (LYSO) and an APD array (4times4) elements; each element 1.6 mm2 and on a 2.3 mm pitch. We showed that a spatial resolution of better than 2.12 mm is achievable throughout the crystal provided that we adopt a Statistics Based Positioning (SBP) Algorithm. We then used Monte Carlo simulation to model the behavior of the detector. The accuracy of the Monte Carlo simulation was verified by comparing measured and simulated parent datasets (PDS) for the SBP algorithm. These datasets consisted of data for point sources at 49 positions uniformly distributed over the detector area. We also calculated the noise in the detector circuit and verified this value by measurement. The noise value was included in the simulation. We show that the performance of the simulation closely matches the measured performance. The simulations were extended to investigate the effect of different noise levels on positioning accuracy. This paper showed that if modest improvements could be made in the circuit noise then positioning accuracy would be greatly improved. In summary, we have developed a model that can be used to simulate the performance of a variety of APD-based continuous crystal PET detectors

Time-over-threshold for pulse shape discrimination in a time-of-flight phoswich PET detector

PubMed Central

Chang, Chen-Ming; Cates, Joshua W.; Levin, Craig S.

2016-01-01

It is well known that a PET detector capable of measuring both photon time-of-flight (TOF) and depth-of-interaction (DOI) improves the image quality and accuracy. Phoswich designs have been realized in PET detectors to measure DOI for more than a decade. However, PET detectors based on phoswich designs put great demand on the readout circuits, which have to differentiate the pulse shape produced by different crystal layers. A simple pulse shape discrimination approach is required to realize the phoswich designs in a clinical PET scanner, which consists of thousands of scintillation crystal elements. In this work, we studied time-over-threshold (ToT) as a pulse shape parameter for DOI. The energy, timing and DOI performance were evaluated for a phoswich detector design comprising 3 mm × 3 mm × 10 mm LYSO:Ce crystal optically coupled to 3 mm × 3 mm × 10 mm calcium co-doped LSO:Ce,Ca(0.4%) crystal read out by a silicon photomultiplier (SiPM). A DOI accuracy of 97.2% has been achieved for photopeak events using the proposed time-over-threshold (ToT) processing. The energy resolution without correction for SiPM non-linearity was 9.7 ± 0.2% and 11.3 ± 0.2% FWHM at 511 keV for LYSO and LSO crystal layers, respectively. The coincidence time resolution for photopeak events ranges from 164.6 ps to 183.1 ps FWHM, depending on the layer combinations. The coincidence time resolution for inter-crystal scatter events ranges from 214.6 ps to 418.3 ps FWHM, depending on the energy windows applied. These results show great promises of using ToT for pulse shape discrimination in a TOF phoswich detector since a ToT measurement can be easily implemented in readout electronics. PMID:27991437

Development of capacitive multiplexing circuit for SiPM-based time-of-flight (TOF) PET detector

NASA Astrophysics Data System (ADS)

Choe, Hyeok-Jun; Choi, Yong; Hu, Wei; Yan, Jianhua; Jung, Jin Ho

2017-04-01

There has been great interest in developing a time-of-flight (TOF) PET to improve the signal-to-noise ratio of PET image relative to that of non-TOF PET. Silicon photomultiplier (SiPM) arrays have attracted attention for use as a fast TOF PET photosensor. Since numerous SiPM arrays are needed to construct a modern human PET, a multiplexing method providing both good timing performance and high channel reduction capability is required to develop a SiPM-based TOF PET. The purpose of this study was to develop a capacitive multiplexing circuit for the SiPM-based TOF PET. The proposed multiplexing circuit was evaluated by measuring the coincidence resolving time (CRT) and the energy resolution as a function of the overvoltage using three different capacitor values of 15, 30, and 51 pF. A flood histogram was also obtained and quantitatively assessed. Experiments were performed using a 4× 4 array of 3× 3 mm2 SiPMs. Regarding the capacitor values, the multiplexing circuit using a smaller capacitor value showed the best timing performance. On the other hand, the energy resolution and flood histogram quality of the multiplexing circuit deteriorated as the capacitor value became smaller. The proposed circuit was able to achieve a CRT of 260+/- 4 ps FWHM and an energy resolution of 17.1 % with a pair of 2× 2× 20 mm3 LYSO crystals using a capacitor value of 30 pF at an overvoltage of 3.0 V. It was also possible to clearly resolve a 6× 6 array of LYSO crystals in the flood histogram using the multiplexing circuit. The experiment results indicate that the proposed capacitive multiplexing circuit is useful to obtain an excellent timing performance and a crystal-resolving capability in the flood histogram with a minimal degradation of the energy resolution, as well as to reduce the number of the readout channels of the SiPM-based TOF PET detector.

Side readout of long scintillation crystal elements with digital SiPM for TOF-DOI PET.

PubMed

Yeom, Jung Yeol; Vinke, Ruud; Levin, Craig S

2014-12-01

Side readout of scintillation light from crystal elements in positron emission tomography (PET) is an alternative to conventional end-readout configurations, with the benefit of being able to provide accurate depth-of-interaction (DOI) information and good energy resolution while achieving excellent timing resolution required for time-of-flight PET. This paper explores different readout geometries of scintillation crystal elements with the goal of achieving a detector that simultaneously achieves excellent timing resolution, energy resolution, spatial resolution, and photon sensitivity. The performance of discrete LYSO scintillation elements of different lengths read out from the end/side with digital silicon photomultipliers (dSiPMs) has been assessed. Compared to 3 × 3 × 20 mm(3) LYSO crystals read out from their ends with a coincidence resolving time (CRT) of 162 ± 6 ps FWHM and saturated energy spectra, a side-readout configuration achieved an excellent CRT of 144 ± 2 ps FWHM after correcting for timing skews within the dSiPM and an energy resolution of 11.8% ± 0.2% without requiring energy saturation correction. Using a maximum likelihood estimation method on individual dSiPM pixel response that corresponds to different 511 keV photon interaction positions, the DOI resolution of this 3 × 3 × 20 mm(3) crystal side-readout configuration was computed to be 0.8 mm FWHM with negligible artifacts at the crystal ends. On the other hand, with smaller 3 × 3 × 5 mm(3) LYSO crystals that can also be tiled/stacked to provide DOI information, a timing resolution of 134 ± 6 ps was attained but produced highly saturated energy spectra. The energy, timing, and DOI resolution information extracted from the side of long scintillation crystal elements coupled to dSiPM have been acquired for the first time. The authors conclude in this proof of concept study that such detector configuration has the potential to enable outstanding detector performance in terms of timing, energy, and DOI resolution.

Side readout of long scintillation crystal elements with digital SiPM for TOF-DOI PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeom, Jung Yeol, E-mail: yeomjy@kumoh.ac.kr, E-mail: cslevin@stanford.edu; Vinke, Ruud; Levin, Craig S., E-mail: yeomjy@kumoh.ac.kr, E-mail: cslevin@stanford.edu

Purpose: Side readout of scintillation light from crystal elements in positron emission tomography (PET) is an alternative to conventional end-readout configurations, with the benefit of being able to provide accurate depth-of-interaction (DOI) information and good energy resolution while achieving excellent timing resolution required for time-of-flight PET. This paper explores different readout geometries of scintillation crystal elements with the goal of achieving a detector that simultaneously achieves excellent timing resolution, energy resolution, spatial resolution, and photon sensitivity. Methods: The performance of discrete LYSO scintillation elements of different lengths read out from the end/side with digital silicon photomultipliers (dSiPMs) has been assessed.more » Results: Compared to 3 × 3 × 20 mm{sup 3} LYSO crystals read out from their ends with a coincidence resolving time (CRT) of 162 ± 6 ps FWHM and saturated energy spectra, a side-readout configuration achieved an excellent CRT of 144 ± 2 ps FWHM after correcting for timing skews within the dSiPM and an energy resolution of 11.8% ± 0.2% without requiring energy saturation correction. Using a maximum likelihood estimation method on individual dSiPM pixel response that corresponds to different 511 keV photon interaction positions, the DOI resolution of this 3 × 3 × 20 mm{sup 3} crystal side-readout configuration was computed to be 0.8 mm FWHM with negligible artifacts at the crystal ends. On the other hand, with smaller 3 × 3 × 5 mm{sup 3} LYSO crystals that can also be tiled/stacked to provide DOI information, a timing resolution of 134 ± 6 ps was attained but produced highly saturated energy spectra. Conclusions: The energy, timing, and DOI resolution information extracted from the side of long scintillation crystal elements coupled to dSiPM have been acquired for the first time. The authors conclude in this proof of concept study that such detector configuration has the potential to enable outstanding detector performance in terms of timing, energy, and DOI resolution.« less

Rapid screening for lipid storage disorders using biochemical markers. Expert center data and review of the literature.

PubMed

Voorink-Moret, M; Goorden, S M I; van Kuilenburg, A B P; Wijburg, F A; Ghauharali-van der Vlugt, J M M; Beers-Stet, F S; Zoetekouw, A; Kulik, W; Hollak, C E M; Vaz, F M

2018-02-01

In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and oxysterols, which, combined with chitotriosidase activity may represent a rapid first tier screening for lipid storage disorders. A lysosphingolipid panel consisting of lysoglobotriaosylceramide (LysoGb3), lysohexosylceramide (LysoHexCer: both lysoglucosylceramide and lysogalactosylceramide), lysosphingomyelin (LysoSM) and its carboxylated analogue lysosphingomyelin-509 (LysoSM-509) was measured in control subjects and plasma samples of predominantly untreated patients affected with lipid storage disorders (n=74). In addition, the oxysterols cholestane-3β,5α,6β-triol and 7-ketocholesterol were measured in a subset of these patients (n=36) as well as chitotriosidase activity (n=43). A systematic review of the literature was performed to assess the usefulness of these biochemical markers. Specific elevations of metabolites, i.e. without overlap between controls and other lipid storage disorders, were found for several lysosomal storage diseases: increased LysoSM levels in acid sphingomyelinase deficiency (Niemann-Pick disease type A/B), LysoGb3 levels in males with classical phenotype Fabry disease and LysoHexCer (i.e. lysoglucosylceramide/lysogalactosylceramide) in Gaucher and Krabbe diseases. While elevated levels of LysoSM-509 and cholestane-3β,5α,6β-triol did not discriminate between Niemann Pick disease type C and acid sphingomyelinase deficiency, LysoSM-509/LysoSM ratio was specifically elevated in Niemann-Pick disease type C. In Gaucher disease type I, mild increases in several lysosphingolipids were found including LysoGb3 with levels in the range of non-classical Fabry males and females. Chitotriosidase showed specific elevations in symptomatic Gaucher disease, and was mildly elevated in all other lipid storage disorders. Review of the literature identified 44 publications. Most findings were in line with our cohort. Several moderate elevations of biochemical markers were found across a wide range of other, mainly inherited metabolic, diseases. Measurement in plasma of LysoSLs and oxysterols by UPLC-MS/MS in combination with activity of chitotriosidase provides a useful first tier screening of patients suspected of lipid storage disease. The LysoSM-509/LysoSM ratio is a promising parameter in Niemann-Pick disease type C. Further studies in larger groups of untreated patients and controls are needed to improve the specificity of the findings. Copyright © 2018 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisenberger, Andrew G.; Kross, Brian J.; Lee, Seung Joo

The ability to detect the emissions of radioactive isotopes through radioactive decay (e.g. beta particles, x-rays and gamma-rays) has been used for over 80 years as a tracer method for studying natural phenomena. More recently a positron emitting radioisotope of carbon: {sup 11}C has been utilized as a {sup 11}CO{sub 2} tracer for plant ecophysiology research. Because of its ease of incorporation into the plant via photosynthesis, the {sup 11}CO{sub 2} radiotracer is a powerful tool for use in plant biology research. Positron emission tomography (PET) imaging has been used to study carbon transport in live plants using {sup 11}CO{submore » 2}. Presently there are several groups developing and using new PET instrumentation for plant based studies. Thomas Jefferson National Accelerator Facility (Jefferson Lab) in collaboration with the Duke University Phytotron and the Triangle Universities Nuclear Laboratory (TUNL) is involved in PET detector development for plant imaging utilizing technologies developed for nuclear physics research. The latest developments of the use of a LYSO scintillator based PET detector system for {sup 11}CO{sub 2} tracer studies in plants will be briefly outlined.« less

A depth-encoding PET detector that uses light sharing and single-ended readout with silicon photomultipliers

NASA Astrophysics Data System (ADS)

Kuang, Zhonghua; Yang, Qian; Wang, Xiaohui; Fu, Xin; Ren, Ning; Sang, Ziru; Wu, San; Zheng, Yunfei; Zhang, Xianming; Hu, Zhanli; Du, Junwei; Liang, Dong; Liu, Xin; Zheng, Hairong; Yang, Yongfeng

2018-02-01

Detectors with depth-encoding capability and good timing resolution are required to develop high-performance whole-body or total-body PET scanners. In this work, depth-encoding PET detectors that use light sharing between two discrete crystals and single-ended readout with silicon photomultipliers (SiPMs) were manufactured and evaluated. The detectors consisted of two unpolished 3  ×  3  ×  20 mm3 LYSO crystals with different coupling materials between them and were read out by Hamamatsu 3  ×  3 mm2 SiPMs with one-to-one coupling. The ratio of the energy of one SiPM to the total energy of two SiPMs was used to measure the depth of interaction (DOI). Detectors with different coupling materials in-between the crystals were measured in the singles mode in an effort to obtain detectors that can provide good DOI resolution. The DOI resolution and energy resolution of three types of detector were measured and the timing resolution was measured for the detector with the best DOI and energy resolution. The optimum detector, with 5 mm optical glue, a 9 mm triangular ESR and a 6 mm rectangular ESR in-between the unpolished crystals, provides a DOI resolution of 2.65 mm, an energy resolution of 10.0% and a timing resolution of 427 ps for events of E  >  400 keV. The detectors simultaneously provide good DOI and timing resolution, and show great promise for the development of high-performance whole-body and total-body PET scanners.

Improved spatial resolution in PET scanners using sampling techniques

PubMed Central

Surti, Suleman; Scheuermann, Ryan; Werner, Matthew E.; Karp, Joel S.

2009-01-01

Increased focus towards improved detector spatial resolution in PET has led to the use of smaller crystals in some form of light sharing detector design. In this work we evaluate two sampling techniques that can be applied during calibrations for pixelated detector designs in order to improve the reconstructed spatial resolution. The inter-crystal positioning technique utilizes sub-sampling in the crystal flood map to better sample the Compton scatter events in the detector. The Compton scatter rejection technique, on the other hand, rejects those events that are located further from individual crystal centers in the flood map. We performed Monte Carlo simulations followed by measurements on two whole-body scanners for point source data. The simulations and measurements were performed for scanners using scintillators with Zeff ranging from 46.9 to 63 for LaBr3 and LYSO, respectively. Our results show that near the center of the scanner, inter-crystal positioning technique leads to a gain of about 0.5-mm in reconstructed spatial resolution (FWHM) for both scanner designs. In a small animal LYSO scanner the resolution improves from 1.9-mm to 1.6-mm with the inter-crystal technique. The Compton scatter rejection technique shows higher gains in spatial resolution but at the cost of reduction in scanner sensitivity. The inter-crystal positioning technique represents a modest acquisition software modification for an improvement in spatial resolution, but at a cost of potentially longer data correction and reconstruction times. The Compton scatter rejection technique, while also requiring a modest acquisition software change with no increased data correction and reconstruction times, will be useful in applications where the scanner sensitivity is very high and larger improvements in spatial resolution are desirable. PMID:19779586

Lysophosphatidylcholine-induced cytotoxicity in osteoblast-like MG-63 cells: involvement of transient receptor potential vanilloid 2 (TRPV2) channels.

PubMed

Fallah, Abdallah; Pierre, Rachel; Abed, Elie; Moreau, Robert

2013-01-01

Epidemiological studies indicate that patients suffering from atherosclerosis are predisposed to develop osteoporosis. Accordingly, atherogenic determinants such as oxidized low density lipoprotein (OxLDL) particles have been shown to alter bone cell functions. In this work, we investigated the cytotoxicity of lysophosphatidylcholine (lysoPC), a major phospholipid component generated upon LDL oxidation, on bone-forming MG-63 osteoblast-like cells. Cell viability was reduced by lysoPC in a concentration-dependent manner with a LC50 of 18.7±0.7 μM. LysoPC-induced cell death was attributed to induction of both apoptosis and necrosis. Since impairment of intracellular calcium homeostasis is often involved in mechanism of cell death, we determined the involvement of calcium in lysoPC-induced cytotoxicity. LysoPC promoted a rapid and transient increase in intracellular calcium attributed to mobilization from calcium stores, followed by a sustained influx. Intracellular calcium mobilization was associated to phospholipase C (PLC)-dependent mobilization of calcium from the endoplasmic reticulum since inhibition of PLC or calcium depletion of reticulum endoplasmic with thapsigargin prevented the calcium mobilization. The calcium influx induced by lysoPC was abolished by inhibition of transient receptor potential vanilloid (TRPV) channels with ruthenium red whereas gadolinium, which inhibits canonical TRP (TRPC) channels, was without effect. Accordingly, expression of TRPV2 and TRPV4 were shown in MG-63 cells. The addition of TRPV2 inhibitor Tranilast in the incubation medium prevent the calcium influx triggered by lysoPC and reduced lysoPC-induced cytotoxicity whereas TRPV4 inhibitor RN 1734 was without effect, which confirms the involvement of TRPV2 activation in lysoPC-induced cell death.

HIGH-RESOLUTION L(Y)SO DETECTORS USING PMT-QUADRANT-SHARING FOR HUMAN & ANIMAL PET CAMERAS

PubMed Central

Ramirez, Rocio A.; Liu, Shitao; Liu, Jiguo; Zhang, Yuxuan; Kim, Soonseok; Baghaei, Hossain; Li, Hongdi; Wang, Yu; Wong, Wai-Hoi

2009-01-01

We developed high resolution L(Y)SO detectors for human and animal PET applications using Photomultiplier-quadrant-sharing (PQS) technology. The crystal sizes were 1.27 × 1.27 × 10 mm3 for the animal PQS-blocks and 3.25 × 3.25 × 20 mm3 for human ones. Polymer mirror film patterns (PMR) were placed between crystals as reflector. The blocks were assembled together using optical grease and wrapped by Teflon tape. The blocks were coupled to regular round PMT’s of 19/51 mm in PQS configuration. List-mode data of Ga-68 source (511 KeV) were acquired with our high yield pileup-event recovery (HYPER) electronics and data acquisition software. The high voltage bias was 1100V. Crystal decoding maps and individual crystal energy resolutions were extracted from the data. To investigate the potential imaging resolution of the PET cameras with these blocks, we used GATE (Geant4 Application for Tomographic Emission) simulation package. GATE is a GEANT4 based software toolkit for realistic simulation of PET and SPECT systems. The packing fractions of these blocks were found to be 95.6% and 98.2%. From the decoding maps, all 196 and 225 crystals were clearly identified. The average energy resolutions were 14.0% and 15.6%. For small animal PET systems, the detector ring diameter was 16.5 cm with an axial field of view (AFOV) of 11.8 cm. The simulation data suggests that a reconstructed radial (tangential) spatial resolution of 1.24 (1.25) mm near the center is potentially achievable. For the wholebody human PET systems, the detector ring diameter was 86 cm. The simulation data suggests that a reconstructed radial (tangential) spatial resolution of 3.09(3.38) mm near the center is potentially achievable. From this study we can conclude that PQS design could achieve high spatial resolutions and excellent energy resolutions on human and animal PET systems with substantially lower production costs and inexpensive readout devices. PMID:19946463

Evaluation of a silicon photomultiplier PET insert for simultaneous PET and MR imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, Guen Bae; Kim, Kyeong Yun; Yoon, Hyun Suk

2016-01-15

Purpose: In this study, the authors present a silicon photomultiplier (SiPM)-based positron emission tomography (PET) insert dedicated to small animal imaging with high system performance and robustness to temperature change. Methods: The insert consists of 64 LYSO-SiPM detector blocks arranged in 4 rings of 16 detector blocks to yield a ring diameter of 64 mm and axial field of view of 55 mm. Each detector block consists of a 9 × 9 array of LYSO crystals (1.2 × 1.2 × 10 mm{sup 3}) and a monolithic 4 × 4 SiPM array. The temperature of each monolithic SiPM is monitored, andmore » the proper bias voltage is applied according to the temperature reading in real time to maintain uniform performance. The performance of this PET insert was characterized using National Electrical Manufacturers Association NU 4-2008 standards, and its feasibility was evaluated through in vivo mouse imaging studies. Results: The PET insert had a peak sensitivity of 3.4% and volumetric spatial resolutions of 1.92 (filtered back projection) and 0.53 (ordered subset expectation maximization) mm{sup 3} at center. The peak noise equivalent count rate and scatter fraction were 42.4 kcps at 15.08 MBq and 16.5%, respectively. By applying the real-time bias voltage adjustment, an energy resolution of 14.2% ± 0.3% was maintained and the count rate varied ≤1.2%, despite severe temperature changes (10–30 °C). The mouse imaging studies demonstrate that this PET insert can produce high-quality images useful for imaging studies on the small animals. Conclusions: The developed MR-compatible PET insert is designed for insertion into a narrow-bore magnetic resonance imaging scanner, and it provides excellent imaging performance for PET/MR preclinical studies.« less

Energy and Timing Measurement with Time-Based Detector Readout for PET Applications: Principle and Validation with Discrete Circuit Components

PubMed Central

Sun, Xishan; Lan, Allan K.; Bircher, Chad; Deng, Zhi; Liu, Yinong; Shao, Yiping

2011-01-01

A new signal processing method for PET application has been developed, with discrete circuit components to measure energy and timing of a gamma interaction based solely on digital timing processing without using an amplitude-to-digital convertor (ADC) or a constant fraction discriminator (CFD). A single channel discrete component time-based readout (TBR) circuit was implemented in a PC board. Initial circuit functionality and performance evaluations have been conducted. Accuracy and linearity of signal amplitude measurement were excellent, as measured with test pulses. The measured timing accuracy from test pulses reached to less than 300 ps, a value limited mainly by the timing jitter of the prototype electronics circuit. Both suitable energy and coincidence timing resolutions (~18% and ~1.0 ns) have been achieved with 3 × 3 × 20 mm3 LYSO scintillator and photomultiplier tube-based detectors. With its relatively simple circuit and low cost, TBR is expected to be a suitable front-end signal readout electronics for compact PET or other radiation detectors requiring the reading of a large number of detector channels and demanding high performance for energy and timing measurement. PMID:21743761

Role of protein kinase A and class II phosphatidylinositol 3-kinase C2β in the downregulation of KCa3.1 channel synthesis and membrane surface expression by lyso-globotriaosylceramide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Ju Yeon; Park, Seonghee, E-mail: sp@ewha.ac.kr

The intermediate conductance calcium-activated potassium channel (KCa3.1) mediates proliferation of many cell types including fibroblasts, and is a molecular target for intervention in various cell proliferative diseases. Our previous study showed that reduction of KCa3.1 channel expression by lyso-globotriaosylceramide (lyso-Gb3) inhibits differentiation into myofibroblasts and collagen synthesis, which might lead to development of ascending thoracic aortic aneurysm secondary to Fabry disease. However, how lyso-Gb3 downregulates KCa3.1 channel expression is unknown. Therefore, we aimed to investigate the underlying mechanisms of lyso-Gb3-mediated KCa3.1 channel downregulation, focusing on the cAMP signaling pathway. We found that lyso-Gb3 increased the intracellular cAMP concentration by upregulationmore » of adenylyl cyclase 6 and inhibited ERK 1/2 phosphorylation through the protein kinase A (PKA) pathway, leading to the inhibition of KCa3.1 channel synthesis, not the exchange protein directly activated by cAMP (Epac) pathway. Moreover, lyso-Gb3 suppressed expression of class II phosphatidylinositol 3-kinase C2β (PI3KC2β) by PKA activation, which reduces the production of phosphatidylinositol 3-phosphate [PI(3)P], and the reduced membrane surface expression of KCa3.1 channel was recovered by increasing the intracellular levels of PI(3)P. Consequently, our findings that lyso-Gb3 inhibited both KCa3.1 channel synthesis and surface expression by increasing intracellular cAMP, and controlled surface expression through changes in PI3KC2β-mediated PI(3)P production, suggest that modulation of PKA and PI3KC2β activity to control of KCa3.1 channel expression can be an alternative important target to attenuate ascending thoracic aortic aneurysms in Fabry disease. - Highlights: • Lyso-Gb3 causes elevation of intracellular cAMP. • Lyso-Gb3 inhibits the ERK 1/2 phosphorylation through PKA, thereby reducing KCa3.1 channel synthesis. • Lyso-Gb3 reduces PI3KC2β-mediated intracellular PI(3)P production. • Lyso-Gb3 reduces both surface and total expression of the KCa3.1 channel. • Increasing intracellular levels of PI(3)P only recovers the reduced surface expression.« less

The High Energy Particle Detector on Board of the China Seismo-Electromagnetic Satellite

NASA Astrophysics Data System (ADS)

Sparvoli, Roberta; Palma, Francesco; Panico, Beatrice; Sotgiu, Alessandro; Vitale, Vincenzo

2016-08-01

The study of the Van Allen belts temporal stability is among the main objectives of the China Seismo- Electromagnetic Satellite (CSES) space mission, as well as the study of other electromagnetic disturbances with possible seismic origin. In parallel to this, the CSES mission will address issues of heliospheric and magnetospheric physics, by measuring the cosmic radiation around the Earth.The CSES satellite, developed by a Chinese-Italian collaboration, will be launched in the first half of 2017 and inserted into a circular Sun-synchronous orbit with 98° inclination and 500 km altitude. The expected lifetime is 5 years. CSES hosts several instruments on board: 2 magnetometers, an electric field detector, a plasma analyser, a Langmuir probe and a High-Energy Particle Detector (HEPD). The HEPD detector, responsibility of the Italian side of the CSES collaboration, will measure electrons (3 - 100 MeV) and protons (30 - 300 MeV) along CSES orbit. It consists of a segmented layer of plastic scintillators for the trigger and a calorimeter constituted by a tower of plastic scintillator counters and a LYSO plane. The direction of the incident particle is provided by two planes of double-side silicon micro-strip detectors placed in front of the trigger. Topic of this talk is the technical description of the HEPD and its main characteristics.

Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy.

PubMed

van Breemen, Mariëlle J; Rombach, Saskia M; Dekker, Nick; Poorthuis, Ben J; Linthorst, Gabor E; Zwinderman, Aeilko H; Breunig, Frank; Wanner, Christoph; Aerts, Johannes M; Hollak, Carla E

2011-01-01

Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.2mg/kg, agalsidase beta at 0.2mg/kg or at 1.0mg/kg bodyweight. Each treatment regimen led to prominent reductions of plasma lysoGb3 in Fabry males within 3 months (P=0.0313), followed by relative stability later on. Many males developed antibodies against α-galactosidase A, particularly those treated with agalsidase beta. Patients with antibodies tended towards smaller correction in plasma lysoGb3 concentration, whereas treatment with high dose agalsidase beta allowed a reduction comparable to patients without antibodies. Pre-treatment plasma lysoGb3 concentrations of Fabry females were relatively low. In all females and with each treatment regimen, ERT gave reduction or stabilisation of plasma lysoGb3. Our investigation revealed that ERT of Fabry patients reduces plasma lysoGb3, regardless of the recombinant enzyme used. This finding shows that ERT can correct a characteristic biochemical abnormality in Fabry patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Performance characterization of high quantum efficiency metal package photomultiplier tubes for time-of-flight and high-resolution PET applications.

PubMed

Ko, Guen Bae; Lee, Jae Sung

2015-01-01

Metal package photomultiplier tubes (PMTs) with a metal channel dynode structure have several advanced features for devising such time-of-flight (TOF) and high spatial resolution positron emission tomography (PET) detectors, thanks to their high packing density, large effective area ratio, fast time response, and position encoding capability. Here, we report on an investigation of new metal package PMTs with high quantum efficiency (QE) for high-resolution PET and TOF PET detector modules. The latest metal package PMT, the Hamamatsu R11265 series, is served with two kinds of photocathodes that have higher quantum efficiency than normal bialkali (typical QE ≈ 25%), super bialkali (SBA; QE ≈ 35%), and ultra bialkali (UBA; QE ≈ 43%). In this study, the authors evaluated the performance of the new PMTs with SBA and UBA photocathodes as a PET detector by coupling various crystal arrays. They also investigated the performance improvements of high QE, focusing in particular on a block detector coupled with a lutetium-based scintillator. A single 4 × 4 × 10 mm(3) LYSO, a 7 × 7 array of 3 × 3 × 20 mm(3) LGSO, a 9 × 9 array of 1.2 × 1.2 × 10 mm(3) LYSO, and a 6 × 6 array of 1.5 × 1.5 × 7 mm(3) LuYAP were used for evaluation. All coincidence data were acquired with a DRS4 based fast digitizer. This new PMT shows promising crystal positioning accuracy, energy and time discrimination performance for TOF, and high-resolution PET applications. The authors also found that a metal channel PMT with SBA was enough for both TOF and high-resolution application, although UBA gave a minor improvement to time resolution. However, significant performance improvement was observed in relative low light output crystals (LuYAP) coupled with UBA. The results of this study will be of value as a useful reference to select PMTs for high-performance PET detectors.

Performance of a SiPM based semi-monolithic scintillator PET detector

NASA Astrophysics Data System (ADS)

Zhang, Xianming; Wang, Xiaohui; Ren, Ning; Kuang, Zhonghua; Deng, Xinhan; Fu, Xin; Wu, San; Sang, Ziru; Hu, Zhanli; Liang, Dong; Liu, Xin; Zheng, Hairong; Yang, Yongfeng

2017-10-01

A depth encoding PET detector module using semi-monolithic scintillation crystal single-ended readout by a SiPM array was built and its performance was measured. The semi-monolithic scintillator detector consists of 11 polished LYSO slices measuring 1  ×  11.6  ×  10 mm3. The slices are glued together with enhanced specular reflector (ESR) in between and outside of the slices. The bottom surface of the slices is coupled to a 4  ×  4 SiPM array with a 1 mm light guide and silicon grease between them. No reflector is used on the top surface and two sides of the slices to reduce the scintillation photon reflection. The signals of the 4  ×  4 SiPM array are grouped along rows and columns separately into eight signals. Four SiPM column signals are used to identify the slices according to the center of the gravity of the scintillation photon distribution in the pixelated direction. Four SiPM row signals are used to estimate the y (monolithic direction) and z (depth of interaction) positions according to the center of the gravity and the width of the scintillation photon distribution in the monolithic direction, respectively. The detector was measured with 1 mm sampling interval in both the y and z directions with electronic collimation by using a 0.25 mm diameter 22Na point source and a 1  ×  1  ×  20 mm3 LYSO crystal detector. An average slice based energy resolution of 14.9% was obtained. All slices of 1 mm thick were clearly resolved and a detector with even thinner slices could be used. The y positions calculated with the center of gravity method are different for interactions happening at the same y, but different z positions due to depth dependent edge effects. The least-square minimization and the maximum likelihood positioning algorithms were developed and both methods improved the spatial resolution at the edges of the detector as compared with the center of gravity method. A mean absolute error (MAE) which is defined as the probability-weighted mean of the absolute value of the positioning error is used to evaluate the spatial resolution. An average MAE spatial resolution of ~1.15 mm was obtained in both y and z directions without rejection of the multiple scattering events. The average MAE spatial resolution was ~0.7 mm in both y and z directions after the multiple scattering events were rejected. The timing resolution of the detector is 575 ps. In the next step, long rectangle detector will be built to reduce edge effects and improve the spatial resolution of the semi-monolithic detector. Thick detector up to 20 mm will be explored and the positioning algorithms will be further optimized.

Performance of a SiPM based semi-monolithic scintillator PET detector.

PubMed

Zhang, Xianming; Wang, Xiaohui; Ren, Ning; Kuang, Zhonghua; Deng, Xinhan; Fu, Xin; Wu, San; Sang, Ziru; Hu, Zhanli; Liang, Dong; Liu, Xin; Zheng, Hairong; Yang, Yongfeng

2017-09-21

A depth encoding PET detector module using semi-monolithic scintillation crystal single-ended readout by a SiPM array was built and its performance was measured. The semi-monolithic scintillator detector consists of 11 polished LYSO slices measuring 1  ×  11.6  ×  10 mm 3 . The slices are glued together with enhanced specular reflector (ESR) in between and outside of the slices. The bottom surface of the slices is coupled to a 4  ×  4 SiPM array with a 1 mm light guide and silicon grease between them. No reflector is used on the top surface and two sides of the slices to reduce the scintillation photon reflection. The signals of the 4  ×  4 SiPM array are grouped along rows and columns separately into eight signals. Four SiPM column signals are used to identify the slices according to the center of the gravity of the scintillation photon distribution in the pixelated direction. Four SiPM row signals are used to estimate the y (monolithic direction) and z (depth of interaction) positions according to the center of the gravity and the width of the scintillation photon distribution in the monolithic direction, respectively. The detector was measured with 1 mm sampling interval in both the y and z directions with electronic collimation by using a 0.25 mm diameter 22 Na point source and a 1  ×  1  ×  20 mm 3 LYSO crystal detector. An average slice based energy resolution of 14.9% was obtained. All slices of 1 mm thick were clearly resolved and a detector with even thinner slices could be used. The y positions calculated with the center of gravity method are different for interactions happening at the same y, but different z positions due to depth dependent edge effects. The least-square minimization and the maximum likelihood positioning algorithms were developed and both methods improved the spatial resolution at the edges of the detector as compared with the center of gravity method. A mean absolute error (MAE) which is defined as the probability-weighted mean of the absolute value of the positioning error is used to evaluate the spatial resolution. An average MAE spatial resolution of ~1.15 mm was obtained in both y and z directions without rejection of the multiple scattering events. The average MAE spatial resolution was ~0.7 mm in both y and z directions after the multiple scattering events were rejected. The timing resolution of the detector is 575 ps. In the next step, long rectangle detector will be built to reduce edge effects and improve the spatial resolution of the semi-monolithic detector. Thick detector up to 20 mm will be explored and the positioning algorithms will be further optimized.

MO-F-CAMPUS-J-03: Development of a Human Brain PET for On-Line Proton Beam-Range Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Yiping

Purpose: To develop a prototype PET for verifying proton beam-range before each fractionated therapy that will enable on-line re-planning proton therapy. Methods: Latest “edge-less” silicon photomultiplier arrays and customized ASIC readout electronics were used to develop PET detectors with depth-of-interaction (DOI) measurement capability. Each detector consists of one LYSO array with each end coupled to a SiPM array. Multiple detectors can be seamlessly tiled together to form a large detector panel. Detectors with 1.5×1.5 and 2.0×2.0 mm crystals at 20 or 30 mm lengths were studied. Readout of individual SiPM or signal multiplexing was used to transfer 3D interaction position-codedmore » analog signals through flexible-print-circuit cables or PCB board to dedicated ASIC front-end electronics to output digital timing pulses that encode interaction information. These digital pulses can be transferred to, through standard LVDS cables, and decoded by a FPGA-based data acquisition of coincidence events and data transfer. The modular detector and scalable electronics/data acquisition will enable flexible PET system configuration for different imaging geometry. Results: Initial detector performance measurement shows excellent crystal identification even with 30 mm long crystals, ∼18% and 2.8 ns energy and timing resolutions, and around 2–3 mm DOI resolution. A small prototype PET scanner with one detector ring has been built and evaluated, validating the technology and design. A large size detector panel has been fabricated by scaling up from modular detectors. Different designs of resistor and capacitor based signal multiplexing boards were tested and selected based on optimal crystal identification and timing performance. Stackable readout electronics boards and FPGA-based data acquisition boards were developed and tested. A brain PET is under construction. Conclusion: Technology of large-size DOI detector based on SiPM array and advanced readout has been developed. PET imaging performance and initial phantom studies of on-line proton beam-range measurement will be conducted and reported. NIH grant R21CA187717; Cancer Prevention and Research Institute of Texas grant RP120326.« less

The MINDView brain PET detector, feasibility study based on SiPM arrays

NASA Astrophysics Data System (ADS)

González, Antonio J.; Majewski, Stan; Sánchez, Filomeno; Aussenhofer, Sebastian; Aguilar, Albert; Conde, Pablo; Hernández, Liczandro; Vidal, Luis F.; Pani, Roberto; Bettiol, Marco; Fabbri, Andrea; Bert, Julien; Visvikis, Dimitris; Jackson, Carl; Murphy, John; O'Neill, Kevin; Benlloch, Jose M.

2016-05-01

The Multimodal Imaging of Neurological Disorders (MINDView) project aims to develop a dedicated brain Positron Emission Tomography (PET) scanner with sufficient resolution and sensitivity to visualize neurotransmitter pathways and their disruptions in mental disorders for diagnosis and follow-up treatment. The PET system should be compact and fully compatible with a Magnetic Resonance Imaging (MRI) device in order to allow its operation as a PET brain insert in a hybrid imaging setup with most MRI scanners. The proposed design will enable the currently-installed MRI base to be easily upgraded to PET/MRI systems. The current design for the PET insert consists of a 3-ring configuration with 20 modules per ring and an axial field of view of ~15 cm and a geometrical aperture of ~33 cm in diameter. When coupled to the new head Radio Frequency (RF) coil, the inner usable diameter of the complete PET-RF coil insert is reduced to 26 cm. Two scintillator configurations have been tested, namely a 3-layer staggered array of LYSO with 1.5 mm pixel size, with 35×35 elements (6 mm thickness each) and a black-painted monolithic LYSO block also covering about 50×50 mm2 active area with 20 mm thickness. Laboratory test results associated with the current MINDView PET module concept are presented in terms of key parameters' optimization, such as spatial and energy resolution, sensitivity and Depth of Interaction (DOI) capability. It was possible to resolve all pixel elements from the three scintillator layers with energy resolutions as good as 10%. The monolithic scintillator showed average detector resolutions varying from 3.5 mm in the entrance layer to better than 1.5 mm near the photosensor, with average energy resolutions of about 17%.

Thermal regulation for APDs in a 1 mm(3) resolution clinical PET camera: design, simulation and experimental verification.

PubMed

Zhai, Jinjian; Vandenbroucke, Arne; Levin, Craig S

2014-07-21

We are developing a 1 mm(3) resolution positron emission tomography camera dedicated to breast imaging. The camera collects high energy photons emitted from radioactively labeled agents introduced in the patients in order to detect molecular signatures of breast cancer. The camera comprises many layers of lutetium yttrium oxyorthosilicate (LYSO) scintillation crystals coupled to position sensitive avalanche photodiodes (PSAPDs). The main objectives of the studies presented in this paper are to investigate the temperature profile of the layers of LYSO-PSAPD detectors (a.k.a. 'fins') residing in the camera and to use these results to present the design of the thermal regulation system for the front end of the camera. The study was performed using both experimental methods and simulation. We investigated a design with a heat-dissipating fin. Three fin configurations are tested: fin with Al windows (FwW), fin without Al windows (FwoW) and fin with alumina windows (FwAW). A Fluent® simulation was conducted to study the experimentally inaccessible temperature of the PSAPDs. For the best configuration (FwW), the temperature difference from the center to a point near the edge is 1.0 K when 1.5 A current was applied to the Peltier elements. Those of FwoW and FwAW are 2.6 K and 1.7 K, respectively. We conclude that the design of a heat-dissipating fin configuration with 'aluminum windows' (FwW) that borders the scintillation crystal arrays of 16 adjacent detector modules has better heat dissipation capabilities than the design without 'aluminum windows' (FwoW) and the design with 'alumina windows' (FwAW), respectively.

Optimized light sharing for high-resolution TOF PET detector based on digital silicon photomultipliers.

PubMed

Marcinkowski, R; España, S; Van Holen, R; Vandenberghe, S

2014-12-07

The majority of current whole-body PET scanners are based on pixelated scintillator arrays with a transverse pixel size of 4 mm. However, recent studies have shown that decreasing the pixel size to 2 mm can significantly improve image spatial resolution. In this study, the performance of Digital Photon Counter (DPC) from Philips Digital Photon Counting (PDPC) was evaluated to determine their potential for high-resolution whole-body time of flight (TOF) PET scanners. Two detector configurations were evaluated. First, the DPC3200-44-22 DPC array was coupled to a LYSO block of 15 × 15 2 × 2 × 22 mm(3) pixels through a 1 mm thick light guide. Due to light sharing among the dies neighbour logic of the DPC was used. In a second setup the same DPC was coupled directly to a scalable 4 × 4 LYSO matrix of 1.9 × 1.9 × 22 mm(3) crystals with a dedicated reflector arrangement allowing for controlled light sharing patterns inside the matrix. With the first approach an average energy resolution of 14.5% and an average CRT of 376 ps were achieved. For the second configuration an average energy resolution of 11% and an average CRT of 295 ps were achieved. Our studies show that the DPC is a suitable photosensor for a high-resolution TOF-PET detector. The dedicated reflector arrangement allows one to achieve better performances than the light guide approach. The count loss, caused by dark counts, is overcome by fitting the matrix size to the size of DPC single die.

Imaging properties of pixellated scintillators with deep pixels

PubMed Central

Barber, H. Bradford; Fastje, David; Lemieux, Daniel; Grim, Gary P.; Furenlid, Lars R.; Miller, Brian W.; Parkhurst, Philip; Nagarkar, Vivek V.

2015-01-01

We have investigated the light-transport properties of scintillator arrays with long, thin pixels (deep pixels) for use in high-energy gamma-ray imaging. We compared 10×10 pixel arrays of YSO:Ce, LYSO:Ce and BGO (1mm × 1mm × 20 mm pixels) made by Proteus, Inc. with similar 10×10 arrays of LSO:Ce and BGO (1mm × 1mm × 15mm pixels) loaned to us by Saint-Gobain. The imaging and spectroscopic behaviors of these scintillator arrays are strongly affected by the choice of a reflector used as an inter-pixel spacer (3M ESR in the case of the Proteus arrays and white, diffuse-reflector for the Saint-Gobain arrays). We have constructed a 3700-pixel LYSO:Ce Prototype NIF Gamma-Ray Imager for use in diagnosing target compression in inertial confinement fusion. This system was tested at the OMEGA Laser and exhibited significant optical, inter-pixel cross-talk that was traced to the use of a single-layer of ESR film as an inter-pixel spacer. We show how the optical cross-talk can be mapped, and discuss correction procedures. We demonstrate a 10×10 YSO:Ce array as part of an iQID (formerly BazookaSPECT) imager and discuss issues related to the internal activity of 176Lu in LSO:Ce and LYSO:Ce detectors. PMID:26236070

Imaging properties of pixellated scintillators with deep pixels

NASA Astrophysics Data System (ADS)

Barber, H. Bradford; Fastje, David; Lemieux, Daniel; Grim, Gary P.; Furenlid, Lars R.; Miller, Brian W.; Parkhurst, Philip; Nagarkar, Vivek V.

2014-09-01

We have investigated the light-transport properties of scintillator arrays with long, thin pixels (deep pixels) for use in high-energy gamma-ray imaging. We compared 10x10 pixel arrays of YSO:Ce, LYSO:Ce and BGO (1mm x 1mm x 20 mm pixels) made by Proteus, Inc. with similar 10x10 arrays of LSO:Ce and BGO (1mm x 1mm x 15mm pixels) loaned to us by Saint-Gobain. The imaging and spectroscopic behaviors of these scintillator arrays are strongly affected by the choice of a reflector used as an inter-pixel spacer (3M ESR in the case of the Proteus arrays and white, diffuse-reflector for the Saint-Gobain arrays). We have constructed a 3700-pixel LYSO:Ce Prototype NIF Gamma-Ray Imager for use in diagnosing target compression in inertial confinement fusion. This system was tested at the OMEGA Laser and exhibited significant optical, inter-pixel cross-talk that was traced to the use of a single-layer of ESR film as an inter-pixel spacer. We show how the optical cross-talk can be mapped, and discuss correction procedures. We demonstrate a 10x10 YSO:Ce array as part of an iQID (formerly BazookaSPECT) imager and discuss issues related to the internal activity of 176Lu in LSO:Ce and LYSO:Ce detectors.

MO-G-17A-01: Innovative High-Performance PET Imaging System for Preclinical Imaging and Translational Researches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, X; Lou, K; Rice University, Houston, TX

Purpose: To develop a practical and compact preclinical PET with innovative technologies for substantially improved imaging performance required for the advanced imaging applications. Methods: Several key components of detector, readout electronics and data acquisition have been developed and evaluated for achieving leapfrogged imaging performance over a prototype animal PET we had developed. The new detector module consists of an 8×8 array of 1.5×1.5×30 mm{sup 3} LYSO scintillators with each end coupled to a latest 4×4 array of 3×3 mm{sup 2} Silicon Photomultipliers (with ∼0.2 mm insensitive gap between pixels) through a 2.0 mm thick transparent light spreader. Scintillator surface andmore » reflector/coupling were designed and fabricated to reserve air-gap to achieve higher depth-of-interaction (DOI) resolution and other detector performance. Front-end readout electronics with upgraded 16-ch ASIC was newly developed and tested, so as the compact and high density FPGA based data acquisition and transfer system targeting 10M/s coincidence counting rate with low power consumption. The new detector module performance of energy, timing and DOI resolutions with the data acquisition system were evaluated. Initial Na-22 point source image was acquired with 2 rotating detectors to assess the system imaging capability. Results: No insensitive gaps at the detector edge and thus it is capable for tiling to a large-scale detector panel. All 64 crystals inside the detector were clearly separated from a flood-source image. Measured energy, timing, and DOI resolutions are around 17%, 2.7 ns and 1.96 mm (mean value). Point source image is acquired successfully without detector/electronics calibration and data correction. Conclusion: Newly developed advanced detector and readout electronics will be enable achieving targeted scalable and compact PET system in stationary configuration with >15% sensitivity, ∼1.3 mm uniform imaging resolution, and fast acquisition counting rate capability for substantially improved imaging and quantification performance for small animal imaging and image-guided radiotherapy applications. This work was supported by a research award RP120326 from Cancer Prevention and Research Institute of Texas.« less

An edge-readout, multilayer detector for positron emission tomography.

PubMed

Li, Xin; Ruiz-Gonzalez, Maria; Furenlid, Lars R

2018-06-01

We present a novel gamma-ray-detector design based on total internal reflection (TIR) of scintillation photons within a crystal that addresses many limitations of traditional PET detectors. Our approach has appealing features, including submillimeter lateral resolution, DOI positioning from layer thickness, and excellent energy resolution. The design places light sensors on the edges of a stack of scintillator slabs separated by small air gaps and exploits the phenomenon that more than 80% of scintillation light emitted during a gamma-ray event reaches the edges of a thin crystal with polished faces due to TIR. Gamma-ray stopping power is achieved by stacking multiple layers, and DOI is determined by which layer the gamma ray interacts in. The concept of edge readouts of a thin slab was verified by Monte Carlo simulation of scintillation light transport. An LYSO crystal of dimensions 50.8 mm × 50.8 mm × 3.0 mm was modeled with five rectangular SiPMs placed along each edge face. The mean-detector-response functions (MDRFs) were calculated by simulating signals from 511 keV gamma-ray interactions in a grid of locations. Simulations were carried out to study the influence of choice of scintillator material and dimensions, gamma-ray photon energies, introduction of laser or mechanically induced optical barriers (LIOBs, MIOBs), and refractive indices of optical-coupling media and SiPM windows. We also analyzed timing performance including influence of gamma-ray interaction position and presence of optical barriers. We also modeled and built a prototype detector, a 27.4 mm × 27.4 mm × 3.0 mm CsI(Tl) crystal with 4 SiPMs per edge to experimentally validate the results predicted by the simulations. The prototype detector used CsI(Tl) crystals from Proteus outfitted with 16 Hamamatsu model S13360-6050PE MPPCs read out by an AiT-16-channel readout. The MDRFs were measured by scanning the detector with a collimated beam of 662-keV photons from a 137 Cs source. The spatial resolution was experimentally determined by imaging a tungsten slit that created a beam of 0.44 mm (FWHM) width normal to the detector surface. The energy resolution was evaluated by analyzing list-mode data from flood illumination by the 137 Cs source. We find that in a block-detector-sized LYSO layer read out by five SiPMs per edge, illuminated by 511-keV photons, the average resolution is 1.49 mm (FWHM). With the introduction of optical barriers, average spatial resolution improves to 0.56 mm (FWHM). The DOI resolution is the layer thickness of 3.0 mm. We also find that optical-coupling media and SiPM-window materials have an impact on spatial resolution. The timing simulation with LYSO crystal yields a coincidence resolving time (CRT) of 200-400 ps, which is slightly position dependent. And the introduction of optical barriers has minimum influence. The prototype CsI(Tl) detector, with a smaller area and fewer SiPMs, was measured to have central-area spatial resolutions of 0.70 and 0.39 mm without and with optical barriers, respectively. These results match well with our simulations. An energy resolution of 6.4% was achieved at 662 keV. A detector design based on a stack of monolithic scintillator layers that uses edge readouts offers several advantages over current block detectors for PET. For example, there is no tradeoff between spatial resolution and detection sensitivity since no reflector material displaces scintillator crystal, and submillimeter resolution can be achieved. DOI information is readily available, and excellent timing and energy resolutions are possible. © 2018 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Opposing Effects of Platelet-Activating Factor and Lyso-Platelet-Activating Factor on Neutrophil and Platelet ActivationS⃞

PubMed Central

Welch, Emily J.; Naikawadi, Ram P.; Li, Zhenyu; Lin, Phoebe; Ishii, Satoshi; Shimizu, Takao; Tiruppathi, Chinnaswamy; Du, Xiaoping; Subbaiah, Papasani V.; Ye, Richard D.

2009-01-01

Platelet-activating factor (PAF) is a potent, bioactive phospholipid that acts on multiple cells and tissues through its G protein-coupled receptor (GPCR). PAF is not stored but is rapidly generated via enzymatic acetylation of the precursor 1-O-hexadecyl-2-hydroxy-sn-glycero-3-phosphocholine (lysoPAF). The bioactivity of PAF is effectively and tightly regulated by PAF acetylhydrolases, which convert PAF back to lysoPAF. Previous studies report that lysoPAF is an inactive precursor and metabolite of PAF. However, lysoPAF has not been carefully studied in its own context. Here we report that lysoPAF has an opposing effect of PAF in the activation of neutrophils and platelets. Whereas PAF potentiates neutrophil NADPH oxidase activation, lysoPAF dose-dependently inhibits this function. Inhibition by lysoPAF is not affected by the use of a PAF receptor antagonist or genetic deletion of the PAF receptor gene. The mechanism of lysoPAF-mediated inhibition of neutrophils involves an elevation in the intracellular cAMP level, and pharmacological blockade of adenylyl cyclase completely reverses the inhibitory effect of lysoPAF. In addition, lysoPAF increases intracellular cAMP levels in platelets and inhibits thrombin-induced platelet aggregation, which can be reversed by inhibition of protein kinase A. These findings identify lysoPAF as a bioactive lipid with opposing functions of PAF and suggest a novel and intrinsic regulatory mechanism for balance of the potent activity of PAF. PMID:18931035

Baicalin promotes the bacteriostatic activity of lysozyme on S. aureus in mammary glands and neutrophilic granulocytes in mice

PubMed Central

Zhang, Zecai; Shen, Peng; Yang, Zhengtao; Zhang, Naisheng

2017-01-01

Staphylococcus aureus causes mastitis as a result of community-acquired or nosocomial infections. Lysozyme (LYSO) is an enzyme that is upregulated in many organisms during the innate immune response against infection by bacterial pathogens. Baicalin is a bioactive flavonoid that can bind to enzymes, often to potentiate their effect. Here we tested the effects of baicalin on the activity of LYSO using the S. aureus mastitis mouse model and neutrophilic granulocyte model of S. aureus infection. In our experiments, S. aureus counts decreased with increasing baicalin concentration. Furthermore, qPCR and western blot analyses showed that LYSO expression was unaffected by baicalin, while fluorescence quenching and UV fluorescence spectral analyses showed that baicalin binds to LYSO. To test whether this binding increased LYSO activity, we assessed LYSO-induced bacteriostasis in the presence of baicalin. Our results showed that LYSO-induced S. aureus bacteriostasis increased with increasing concentrations of baicalin, and that baicalin binding to LYSO synergistically increased the antibacterial activity of LYSO. These results demonstrate that baicalin enhances LYSO-induced bacteriostasis during the innate immune response to S. aureus. They suggest baicalin is a potentially useful therapeutic agent for the treatment of bacterial infections. PMID:28184027

Depth of interaction determination in monolithic scintillator with double side SiPM readout.

PubMed

Morrocchi, Matteo; Ambrosi, Giovanni; Bisogni, Maria Giuseppina; Bosi, Filippo; Boretto, Marco; Cerello, Piergiorgio; Ionica, Maria; Liu, Ben; Pennazio, Francesco; Piliero, Maria Antonietta; Pirrone, Giovanni; Postolache, Vasile; Wheadon, Richard; Del Guerra, Alberto

2017-12-01

Monolithic scintillators read out by arrays of photodetectors represent a promising solution to obtain high spatial resolution and the depth of interaction (DOI) of the annihilation photon. We have recently investigated a detector geometry composed of a monolithic scintillator readout on two sides by silicon photomultiplier (SiPM) arrays, and we have proposed two parameters for the DOI determination: the difference in the number of triggered SiPMs on the two sides of the detector and the difference in the maximum collected signal on a single SiPM on each side. This work is focused on the DOI calibration and on the determination of the capability of our detector. For the DOI calibration, we studied a method which can be implemented also in detectors mounted in a full PET scanner. We used a PET detector module composed of a monolithic 20 × 20 × 10 mm 3 LYSO scintillator crystal coupled on two opposite faces to two arrays of SiPMs. On each side, the scintillator was coupled to 6 × 6 SiPMs. In this paper, the two parameters previously proposed for the DOI determination were calibrated with two different methods. The first used a lateral scan of the detector with a collimated 511 keV pencil beam at steps of 0.5 mm to study the detector DOI capability, while the second used the background radiation of the 176 Lu in the scintillator. The DOI determination capability was tested on different regions of the detector using each parameter and the combination of the two. With both parameters for the DOI determination, in the lateral scan, the bias between the mean reconstructed DOI and the real beam position was lower than 0.3 mm, and the DOI distribution had a standard deviation of about 1.5 mm. When using the calibration with the radioactivity of the LYSO, the mean bias increased of about 0.2 mm but with no degradation of the standard deviation of the DOI distribution. The two parameters allow to achieve a DOI resolution comparable with the state of the art, giving a continuous information about the three-dimensional interaction position of the scintillation. These results were obtained by using simple estimators and a detector scalable to a whole PET system. The DOI calibration obtained using lutetium natural radioactivity gives results comparable to the other standard method but appears more readily applicable to detectors mounted in a full PET scanner.

Addendum: Measurement of charged particle yields from PMMA irradiated by a 220 MeV/u ¹²C beam.

PubMed

Mattei, Ilaria; Battistoni, Giuseppe; Collini, Francesco; De Lucia, Erika; Durante, Marco; Fiore, Salvatore; Latessa, Chiara; Mancini-Terracciano, Carlo; Marafini, Michela; Mirabelli, Riccardo; Muraro, Silvia; Paramatti, Riccardo; Piersanti, Luca; Rucinski, Antoni; Russomando, Andrea; Sarti, Alessio; Schuy, Christoph; Sciubba, Adalberto; Solfaroli Camillocci, Elena; Toppi, Marco; Traini, Giacomo; Valle, Serena Marta; Vanstalle, Marie; Patera, Vincenzo

2017-09-08

In this paper we report the re-analysis of the data published in (Piersanti et al. 2014) documenting the charged secondary particles production induced by the interaction of a 220 MeV/u 12C ion beam impinging on a polymethyl methacrylate (PMMA) target, measured in 2012 at the GSI facility in Darmstadt (Germany). This re-analysis takes into account the inhomogeneous light response of the LYSO crystal in the experimental setup measured in a subsequent experiment (2014) performed in the Heidelberg Ion- Beam Therapy Center. A better description of the detector and re-calculation of the geometrical efficiencies have been implemented as well, based on an improved approach that accounts also for the energy dependence of the emission spectrum. The new analysis has small effect on the total secondary charged flux, but has an impact on the production yield and emission velocity distributions of the different particle species (protons, deuterons and tritons) at different angles with respect to the beam direction (60° and 90°). All these observables indeed depend on the particle identification algorithms and hence on the LYSO detector energy response. The results of the data re-analysis presented here are intended to supersede and replace the results published in (Piersanti et al. 2014). © 2017 Institute of Physics and Engineering in Medicine.

A scintillator geometry suitable for very small PET gantries

NASA Astrophysics Data System (ADS)

Gonzalez, A. J.; Gonzalez-Montoro, A.; Aguilar, A.; Cañizares, G.; Martí, R.; Iranzo, S.; Lamprou, E.; Sanchez, S.; Sanchez, F.; Benlloch, J. M.

2017-12-01

In this work we are describing a novel approach to the scintillator crystal configuration as used in nuclear medicine imaging. Our design is related to the coupling in one PET module of the two separate crystal configurations used so far there: monolithic and crystal arrays. The particular design we have studied is based on a two-layer scintillator approach (hybrid) composed of a monolithic LYSO crystal (5-6 mm thickness) and a LYSO crystal array with 4-5 mm height (0.8 and 1 mm pixels). We show here the detector block performance, in terms of spatial, energy and DOI information, to be used as a module in the design of PET scanners. The design we propose allows one to achieve accurate three-dimensional spatial resolution (including DOI information) while assuring high detection efficiency at reasonable cost. Moreover, the proposed design improves the spatial response uniformity across the whole detector module, and especially at the edge region. The crystal arrays are mounted in the front and were well resolved. The monolithic crystal inserted between crystal array and the photosensor, provided measured FWHM resolution as good as 1.5-1.7 mm including the 1 mm source size. The monolithic block achieved a DOI resolution (FWHM) nearing 3 mm. We compared these results with an approach in which we use a single monolithic block with total volume equals to the hybrid approach. In general, comparable performances were obtained.

Addendum: Measurement of charged particle yields from PMMA irradiated by a 220 MeV/u 12C beam

NASA Astrophysics Data System (ADS)

Mattei, I.; Battistoni, G.; Collini, F.; De Lucia, E.; Durante, M.; Fiore, S.; La Tessa, C.; Mancini-Terracciano, C.; Marafini, M.; Mirabelli, R.; Muraro, S.; Paramatti, R.; Piersanti, L.; Rucinski, A.; Russomando, A.; Sarti, A.; Schuy, C.; Sciubba, A.; Solfaroli Camillocci, E.; Toppi, M.; Traini, G.; Valle, S. M.; Vanstalle, M.; Patera, V.

2017-11-01

In this paper we report the re-analysis of the data published in Piersanti et al (2014 Phys. Med. Biol. 59 1857) documenting the charged secondary particles production induced by the interaction of a 220 MeV/u 12C ion beam impinging on a polymethyl methacrylate (PMMA) target, measured in 2012 at the GSI facility in Darmstadt (Germany). This re-analysis takes into account the inhomogeneous light response of the LYSO crystal in the experimental setup measured in a subsequent experiment (2014) performed in the Heidelberg Ion-Beam Therapy Center. A better description of the detector and re-calculation of the geometrical efficiencies have been implemented as well, based on an improved approach that accounts also for the energy dependence of the emission spectrum. The new analysis has little effect on the total secondary charged flux, but has an impact on the production yield and emission velocity distributions of the different particle species (protons, deuterons and tritons) at different angles with respect to the beam direction (60^\\circ and 90^\\circ ). All these observables indeed depend on the particle identification algorithms and hence on the LYSO detector energy response. The results of the data re-analysis presented here are intended to supersede and replace the results published in Piersanti et al (2014 Phys. Med. Biol. 59 1857).

Lyso-GM2 ganglioside: a possible biomarker of Tay-Sachs disease and Sandhoff disease.

PubMed

Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-Ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

2011-01-01

To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease.

Lyso-GM2 Ganglioside: A Possible Biomarker of Tay-Sachs Disease and Sandhoff Disease

PubMed Central

Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

2011-01-01

To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease. PMID:22205997

Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful Biomarker for Fabry Disease

PubMed Central

Sueoka, Hideaki; Ichihara, Junji; Tsukimura, Takahiro; Togawa, Tadayasu; Sakuraba, Hitoshi

2015-01-01

Biomarkers useful for diagnosis and evaluation of treatment for patients with Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and its analogues are extremely low or below the detection limits in some Fabry patients as well as in healthy subjects. In this paper, we introduce the novel application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC-MS/MS requires smaller amounts of samples and is more sensitive than conventional techniques. Using this method, we measured the plasma concentrations of lyso-Gb3 and its analogues in 40 healthy subjects, 5 functional variants (males with E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later-onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry patient subgroups were statistically higher, especially in the classic Fabry males, than those in the functional variants and healthy subjects. The plasma concentrations of lyso-Gb3 and its analogues in healthy subjects, functional variants, and some Fabry patients with specific mutations (R112H and M296I) that cannot be established by conventional techniques were successfully determined by means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male patients with these mutations were lower than those in most Fabry patients having other mutations, but higher than those in the functional variants and healthy subjects. This new method is expected to be useful for sensitive determination of the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for the diagnosis of Fabry disease. PMID:25965380

A feasibility study of a PET/MRI insert detector using strip-line and waveform sampling data acquisition.

PubMed

Kim, H; Chen, C-T; Eclov, N; Ronzhin, A; Murat, P; Ramberg, E; Los, S; Wyrwicz, Alice M; Li, Limin; Kao, C-M

2015-06-01

We are developing a time-of-flight Positron Emission Tomography (PET) detector by using silicon photo-multipliers (SiPM) on a strip-line and high speed waveform sampling data acquisition. In this design, multiple SiPMs are connected on a single strip-line and signal waveforms on the strip-line are sampled at two ends of the strip to reduce readout channels while fully exploiting the fast time response of SiPMs. In addition to the deposited energy and time information, the position of the hit SiPM along the strip-line is determined by the arrival time difference of the waveform. Due to the insensitivity of the SiPMs to magnetic fields and the compact front-end electronics, the detector approach is highly attractive for developing a PET insert system for a magnetic resonance imaging (MRI) scanner to provide simultaneous PET/MR imaging. To investigate the feasibility, experimental tests using prototype detector modules have been conducted inside a 9.4 Tesla small animal MRI scanner (Bruker BioSpec 94/30 imaging spectrometer). On the prototype strip-line board, 16 SiPMs (5.2 mm pitch) are installed on two strip-lines and coupled to 2 × 8 LYSO scintillators (5.0 × 5.0 × 10.0 mm 3 with 5.2 mm pitch). The outputs of the strip-line boards are connected to a Domino-Ring-Sampler (DRS4) evaluation board for waveform sampling. Preliminary experimental results show that the effect of interference on the MRI image due to the PET detector is negligible and that PET detector performance is comparable with the results measured outside the MRI scanner.

A 32 mm  ×  32 mm  ×  22 mm monolithic LYSO:Ce detector with dual-sided digital photon counter readout for ultrahigh-performance TOF-PET and TOF-PET/MRI

NASA Astrophysics Data System (ADS)

Borghi, Giacomo; Peet, Bart Jan; Tabacchini, Valerio; Schaart, Dennis R.

2016-07-01

New applications for positron emission tomography (PET) and combined PET/magnetic resonance imaging (MRI) are currently emerging, for example in the fields of neurological, breast, and pediatric imaging. Such applications require improved image quality, reduced dose, shorter scanning times, and more precise quantification. This can be achieved by means of dedicated scanners based on ultrahigh-performance detectors, which should provide excellent spatial resolution, precise depth-of-interaction (DOI) estimation, outstanding time-of-flight (TOF) capability, and high detection efficiency. Here, we introduce such an ultrahigh-performance TOF/DOI PET detector, based on a 32 mm  ×  32 mm  ×  22 mm monolithic LYSO:Ce crystal. The 32 mm  ×  32 mm front and back faces of the crystal are coupled to a digital photon counter (DPC) array, in so-called dual-sided readout (DSR) configuration. The fully digital detector offers a spatial resolution of ~1.1 mm full width at half maximum (FWHM)/~1.2 mm mean absolute error, together with a DOI resolution of ~2.4 mm FWHM, an energy resolution of 10.2% FWHM, and a coincidence resolving time of 147 ps FWHM. The time resolution closely approaches the best results (135 ps FWHM) obtained to date with small crystals made from the same material coupled to the same DPC arrays, illustrating the excellent correction for optical and electronic transit time spreads that can be achieved in monolithic scintillators using maximum-likelihood techniques for estimating the time of interaction. The performance barely degrades for events with missing data (up to 6 out of 32 DPC dies missing), permitting the use of almost all events registered under realistic acquisition conditions. Moreover, the calibration procedures and computational methods used for position and time estimation follow recently made improvements that make them fast and practical, opening up realistic perspectives for using DSR monolithic scintillator detectors in TOF-PET and TOF-PET/MRI systems.

Development of an LYSO based gamma camera for positron and scinti-mammography

NASA Astrophysics Data System (ADS)

Liang, H.-C.; Jan, M.-L.; Lin, W.-C.; Yu, S.-F.; Su, J.-L.; Shen, L.-H.

2009-08-01

In this research, characteristics of combination of PSPMTs (position sensitive photo-multiplier tube) to form a larger detection area is studied. A home-made linear divider circuit was built for merging signals and readout. Borosilicate glasses were chosen for the scintillation light sharing in the crossover region. Deterioration effect caused by the light guide was understood. The influences of light guide and crossover region on the separable crystal size were evaluated. According to the test results, a gamma camera with a crystal block of 90 × 90 mm2 covered area, composed of 2 mm LYSO crystal pixels, was designed and fabricated. Measured performances showed that this camera worked fine in both 511 keV and lower energy gammas. The light loss behaviour within the crossover region was analyzed and realized. Through count rate measurements, the 176Lu nature background didn't show severe influence on the single photon imaging and exhibited an amount of less than 1/3 of all the events acquired. These results show that with using light sharing techniques, combination of multiple PSPMTs in both X and Y directions to build a large area imaging detector is capable to be achieved. Also this camera design is feasible to keep both the abilities for positron and single photon breast imaging applications. Separable crystal size is 2 mm with 2 mm thick glass applied for the light sharing in current status.

Characterization of highly multiplexed monolithic PET / gamma camera detector modules.

PubMed

Pierce, L A; Pedemonte, S; DeWitt, D; MacDonald, L; Hunter, W C J; Van Leemput, K; Miyaoka, R

2018-03-29

PET detectors use signal multiplexing to reduce the total number of electronics channels needed to cover a given area. Using measured thin-beam calibration data, we tested a principal component based multiplexing scheme for scintillation detectors. The highly-multiplexed detector signal is no longer amenable to standard calibration methodologies. In this study we report results of a prototype multiplexing circuit, and present a new method for calibrating the detector module with multiplexed data. A [Formula: see text] mm 3 LYSO scintillation crystal was affixed to a position-sensitive photomultiplier tube with [Formula: see text] position-outputs and one channel that is the sum of the other 64. The 65-channel signal was multiplexed in a resistive circuit, with 65:5 or 65:7 multiplexing. A 0.9 mm beam of 511 keV photons was scanned across the face of the crystal in a 1.52 mm grid pattern in order to characterize the detector response. New methods are developed to reject scattered events and perform depth-estimation to characterize the detector response of the calibration data. Photon interaction position estimation of the testing data was performed using a Gaussian Maximum Likelihood estimator and the resolution and scatter-rejection capabilities of the detector were analyzed. We found that using a 7-channel multiplexing scheme (65:7 compression ratio) with 1.67 mm depth bins had the best performance with a beam-contour of 1.2 mm FWHM (from the 0.9 mm beam) near the center of the crystal and 1.9 mm FWHM near the edge of the crystal. The positioned events followed the expected Beer-Lambert depth distribution. The proposed calibration and positioning method exhibited a scattered photon rejection rate that was a 55% improvement over the summed signal energy-windowing method.

Optical delay encoding for fast timing and detector signal multiplexing in PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grant, Alexander M.; Levin, Craig S., E-mail: cslevin@stanford.edu; Molecular Imaging Program at Stanford

2015-08-15

Purpose: The large number of detector channels in modern positron emission tomography (PET) scanners poses a challenge in terms of readout electronics complexity. Multiplexing schemes are typically implemented to reduce the number of physical readout channels, but often result in performance degradation. Novel methods of multiplexing in PET must be developed to avoid this data degradation. The preservation of fast timing information is especially important for time-of-flight PET. Methods: A new multiplexing scheme based on encoding detector interaction events with a series of extremely fast overlapping optical pulses with precise delays is demonstrated in this work. Encoding events in thismore » way potentially allows many detector channels to be simultaneously encoded onto a single optical fiber that is then read out by a single digitizer. A two channel silicon photomultiplier-based prototype utilizing this optical delay encoding technique along with dual threshold time-over-threshold is demonstrated. Results: The optical encoding and multiplexing prototype achieves a coincidence time resolution of 160 ps full width at half maximum (FWHM) and an energy resolution of 13.1% FWHM at 511 keV with 3 × 3 × 5 mm{sup 3} LYSO crystals. All interaction information for both detectors, including timing, energy, and channel identification, is encoded onto a single optical fiber with little degradation. Conclusions: Optical delay encoding and multiplexing technology could lead to time-of-flight PET scanners with fewer readout channels and simplified data acquisition systems.« less

Development of a Compton camera for safeguards applications in a pyroprocessing facility

NASA Astrophysics Data System (ADS)

Park, Jin Hyung; Kim, Young Su; Kim, Chan Hyeong; Seo, Hee; Park, Se-Hwan; Kim, Ho-Dong

2014-11-01

The Compton camera has a potential to be used for localizing nuclear materials in a large pyroprocessing facility due to its unique Compton kinematics-based electronic collimation method. Our R&D group, KAERI, and Hanyang University have made an effort to develop a scintillation-detector-based large-area Compton camera for safeguards applications. In the present study, a series of Monte Carlo simulations was performed with Geant4 in order to examine the effect of the detector parameters and the feasibility of using a Compton camera to obtain an image of the nuclear material distribution. Based on the simulation study, experimental studies were performed to assess the possibility of Compton imaging in accordance with the type of the crystal. Two different types of Compton cameras were fabricated and tested with a pixelated type of LYSO (Ce) and a monolithic type of NaI(Tl). The conclusions of this study as a design rule for a large-area Compton camera can be summarized as follows: 1) The energy resolution, rather than position resolution, of the component detector was the limiting factor for the imaging resolution, 2) the Compton imaging system needs to be placed as close as possible to the source location, and 3) both pixelated and monolithic types of crystals can be utilized; however, the monolithic types, require a stochastic-method-based position-estimating algorithm for improving the position resolution.

Improved event positioning in a gamma ray detector using an iterative position-weighted centre-of-gravity algorithm.

PubMed

Liu, Chen-Yi; Goertzen, Andrew L

2013-07-21

An iterative position-weighted centre-of-gravity algorithm was developed and tested for positioning events in a silicon photomultiplier (SiPM)-based scintillation detector for positron emission tomography. The algorithm used a Gaussian-based weighting function centred at the current estimate of the event location. The algorithm was applied to the signals from a 4 × 4 array of SiPM detectors that used individual channel readout and a LYSO:Ce scintillator array. Three scintillator array configurations were tested: single layer with 3.17 mm crystal pitch, matched to the SiPM size; single layer with 1.5 mm crystal pitch; and dual layer with 1.67 mm crystal pitch and a ½ crystal offset in the X and Y directions between the two layers. The flood histograms generated by this algorithm were shown to be superior to those generated by the standard centre of gravity. The width of the Gaussian weighting function of the algorithm was optimized for different scintillator array setups. The optimal width of the Gaussian curve was found to depend on the amount of light spread. The algorithm required less than 20 iterations to calculate the position of an event. The rapid convergence of this algorithm will readily allow for implementation on a front-end detector processing field programmable gate array for use in improved real-time event positioning and identification.

Globotriaosylsphingosine (Lyso-Gb3) as a biomarker for cardiac variant (N215S) Fabry disease.

PubMed

Alharbi, Fahad J; Baig, Shanat; Auray-Blais, Christiane; Boutin, Michel; Ward, Douglas G; Wheeldon, Nigel; Steed, Rick; Dawson, Charlotte; Hughes, Derralynn; Geberhiwot, Tarekegn

2018-03-01

Fabry disease (FD) is a multi-systemic X-linked lysosomal disorder caused by the deficient activity of α-galactosidase-A enzyme, which leads to accumulation of glycosphingolipids in various body tissues. The N215S mutation is a known variant of FD, with a late onset cardiac phenotype. Consensus guidelines acknowledged the use of globotriaosylsphingosine (Lyso-Gb 3 ) as a diagnostic marker for classical FD but its utility for cardiac variant FD is not clear. We aim to characterize the clinical features and evaluate the diagnostic accuracy of plasma and urinary Lyso-Gb 3 levels in N215S cardiac variant FD patients. Thirty-four FD patients with the late-onset N215S cardiac variant mutation were enrolled along with 62 classical FD patients and 109 healthy controls. Plasma and urinary Lyso-Gb 3 and its analogues were analyzed by LC-MS/MS. Both FD males and females with N215S mutation showed Lyso-Gb 3 levels of (mean ± SEM) 9.7 ± 1.0 and 5.4 ± 0.8 nM, respectively. These levels were significantly higher than healthy control and lower than classical FD patients (p < 0.0001). Plasma Lyso-Gb 3 levels equal to or higher than 2.7 nM yielded a diagnostic sensitivity and specificity of 100% (AUC = 1, p < 0.0001). Cardiac involvement was frequent with 16/34 (47%) developing left ventricular hypertrophy. Three patients who underwent renal biopsy had the characteristic sphingolipid deposition in the podocytes while 6/19 (32%) had evidence of white matter changes or infarct on brain MRI. Taken together, cardiac variant N215S mutation is rather an attenuated form of classical FD. Plasma Lyso-Gb 3 is a diagnostic hallmark to differentiate N215S variant phenotype from subjects with no FD.

Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes, and brain: Sensitive targets of conserved specificity for organophosphorus delayed neurotoxicants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vose, Sarah C.; Center for Children's Environmental Health Research, School of Public Health, University of California, Berkeley, CA 94720; Holland, Nina T.

2007-10-01

Brain neuropathy target esterase (NTE), associated with organophosphorus (OP)-induced delayed neuropathy, has the same OP inhibitor sensitivity and specificity profiles assayed in the classical way (paraoxon-resistant, mipafox-sensitive hydrolysis of phenyl valerate) or with lysophosphatidylcholine (LysoPC) as the substrate. Extending our earlier observation with mice, we now examine human erythrocyte, lymphocyte, and brain LysoPC hydrolases as possible sensitive targets for OP delayed neurotoxicants and insecticides. Inhibitor profiling of human erythrocytes and lymphocytes gave the surprising result of essentially the same pattern as with brain. Human erythrocyte LysoPC hydrolases are highly sensitive to OP delayed neurotoxicants, with in vitro IC{sub 50} valuesmore » of 0.13-85 nM for longer alkyl analogs, and poorly sensitive to the current OP insecticides. In agricultural workers, erythrocyte LysoPC hydrolyzing activities are similar for newborn children and their mothers and do not vary with paraoxonase status but have high intersample variation that limits their use as a biomarker. Mouse erythrocyte LysoPC hydrolase activity is also of low sensitivity in vitro and in vivo to the OP insecticides whereas the delayed neurotoxicant ethyl n-octylphosphonyl fluoride inhibits activity in vivo at 1-3 mg/kg. Overall, inhibition of blood LysoPC hydrolases is as good as inhibition of brain NTE as a predictor of OP inducers of delayed neuropathy. NTE and lysophospholipases (LysoPLAs) both hydrolyze LysoPC, yet they are in distinct enzyme families with no sequence homology and very different catalytic sites. The relative contributions of NTE and LysoPLAs to LysoPC hydrolysis and clearance from erythrocytes, lymphocytes, and brain remain to be defined.« less

Color sensitive silicon photomultiplers with micro-cell level encoding for DOI PET detectors

NASA Astrophysics Data System (ADS)

Shimazoe, Kenji; Koyama, Akihiro; Takahashi, Hiroyuki; Ganka, Thomas; Iskra, Peter; Marquez Seco, Alicia; Schneider, Florian; Wiest, Florian

2017-11-01

There have been many studies on Depth Of Interaction (DOI) identification for high resolution Positron Emission Tomography (PET) systems, including those on phoswich detectors, double-sided readout, light sharing methods, and wavelength discrimination. The wavelength discrimination method utilizes the difference in wavelength of stacked scintillators and requires a color sensitive photodetector. Here, a new silicon photomultiplier (SiPM) coupled to a color filter (colorSiPM) was designed and fabricated for DOI detection. The fabricated colorSiPM has two anode readouts that are sensitive to blue and green color. The colorSiPM's response and DOI identification capability for stacked GAGG and LYSO crystals are characterized. The fabricated colorSiPM is sensitive enough to detect a peak of 662 keV from a 137 Cs source.

A High-Resolution Time-of-Flight Clinical PET Detection System Using a Gapless PMT-Quadrant-Sharing Method

NASA Astrophysics Data System (ADS)

Wong, Wai-Hoi; Li, Hongdi; Zhang, Yuxuan; Ramirez, Rocio; An, Shaohui; Wang, Chao; Liu, Shitao; Dong, Yun; Baghaei, Hossain

2015-10-01

We developed a high-resolution Photomultiplier-Quadrant-Sharing (PQS) PET system for human imaging. This system is made up of 24 detector panels. Each panel (bank) consists of 3 ×7 detector blocks, and each block has 16 ×16 LYSO crystals of 2.35 ×2.35 ×15.2 mm3. We used a novel detector-grinding scheme that is compatible with the PQS detector-pixel-decoding requirements to make a gapless cylindrical detector ring for maximizing detection efficiency while delivering an ultrahigh spatial-resolution for a whole-body PET camera with a ring diameter of 87 cm and axial field of view of 27.6 cm. This grinding scheme enables two adjacent gapless panels to share one row of the PMTs to extend the PQS configuration beyond one panel and thus maximize the economic benefit (in PMT usage) of the PQS design. The entire detector ring has 129,024 crystals, all of which are clearly decoded using only 576 PMTs (38-mm diameter). Thus, each PMT on average decodes 224 crystals to achieve a high crystal-pitch resolution of 2.44 mm ×2.44 mm. The detector blocks were mass-produced with our slab-sandwich-slice technique using a set of optimized mirror-film patterns (between crystals) to maximize light output and achieve high spatial and timing resolution. This detection system with time-of-flight capability was placed in a human PET/CT gantry. The reconstructed image resolution of the system was about 2.87 mm using 2D-filtered back-projection. The time-of-flight resolution was 473 ps. The preliminary images of phantoms and clinical studies presented in this work demonstrate the capability of this new PET/CT system to produce high-quality images.

Effect of lysophosphatidylcholine on the filtration coefficient in intact dog lungs

NASA Technical Reports Server (NTRS)

Butler, B. D.; Davies, I.; Drake, R. E.

1989-01-01

Lysophosphatidylcholine (lyso-Pc) is a lysophospholipid normally found in low concentrations in the lung. At high concentrations lyso-Pc, instilled into the airways, causes pulmonary edema. The hypothesis was tested that the edema caused by lyso-Pc was due to an increase in pulmonary microvascular membrane permeability. In 11 anesthetized dogs, the left lower lobes (LLL) were continuously weighed while lyso-Pc (20 mM) was instilled into the LLL airways. After 30 min, the microvascular membrane fluid filtration coefficient (Kf) was determined from the relationship between the rate of LLL weight gain and the pulmonary microvascular pressure. Kf was not significantly different between the lyso-Pc-treated lobes vs control lobes. The data do not support the hypothesis that lyso-Pc, instilled into the airways, causes an increase in pulmonary microvascular permeability.

A defect in inducible beta-galactosidase of B lymphocytes in the osteopetrotic (mi/mi) mouse.

PubMed Central

Yamamoto, N; Naraparaju, V R

1996-01-01

Macrophages were activated by administration of an inflammatory lipid metabolite, lysophosphatidylcholine (lyso-Pc), to wild type mice but not murine (microphthalmic) osteopetrotic (mi/mi) mutant mice. In vitro treatment of wild type mouse peritoneal cells with lyso-Pc efficiently activated macrophages whereas lyso-Pc-treatment of mi mutant mouse peritoneal cells resulted in no activation of macrophages. Generation of macrophage activating factor requires a precursor protein, serum vitamin D binding protein (DBP), and participation of lyso-Pc-inducible beta-galactosidase of B lymphocytes. Lyso-Pc-inducible beta-galactosidase of B lymphocytes was found to be defective in mi mutant mice. PMID:8881764

Development of a multiplexed readout with high position resolution for positron emission tomography

NASA Astrophysics Data System (ADS)

Lee, Sangwon; Choi, Yong; Kang, Jihoon; Jung, Jin Ho

2017-04-01

Detector signals for positron emission tomography (PET) are commonly multiplexed to reduce the number of digital processing channels so that the system can remain cost effective while also maintaining imaging performance. In this work, a multiplexed readout combining Anger position estimation algorithm and position decoder circuit (PDC) was developed to reduce the number of readout channels by a factor of 24, 96-to-4. The data acquisition module consisted of a TDC (50 ps resolution), 4-channel ADCs (12 bit, 105 MHz sampling rate), 2 GB SDRAM and USB3.0. The performance of the multiplexed readout was assessed with a high-resolution PET detector block composed of 2×3 detector modules, each consisting of an 8×8 array of 1.52×1.52×6 mm3 LYSO, a 4×4 array of 3×3 mm2 silicon photomultiplier (SiPM) and 13.4×13.4 mm2 light guide with 0.7 mm thickness. The acquired flood histogram showed that all 384 crystals could be resolved. The average energy resolution at 511 keV was 13.7±1.6% full-width-at-half-maximum (FWHM) and the peak-to-valley ratios of the flood histogram on the horizontal and vertical lines were 18.8±0.8 and 22.8±1.3, respectively. The coincidence resolving time of a pair of detector blocks was 6.2 ns FWHM. The reconstructed phantom image showed that rods down to a diameter of 1.6 mm could be resolved. The results of this study indicate that the multiplexed readout would be useful in developing a PET with a spatial resolution less than the pixel size of the photosensor, such as a SiPM array.

Investigation of spatial resolution improvement by use of a mouth-insert detector in the helmet PET scanner.

PubMed

Ahmed, Abdella M; Tashima, Hideaki; Yamaya, Taiga

2018-03-01

The dominant factor limiting the intrinsic spatial resolution of a positron emission tomography (PET) system is the size of the crystal elements in the detector. To increase sensitivity and achieve high spatial resolution, it is essential to use advanced depth-of-interaction (DOI) detectors and arrange them close to the subject. The DOI detectors help maintain high spatial resolution by mitigating the parallax error caused by the thickness of the scintillator near the peripheral regions of the field-of-view. As an optimal geometry for a brain PET scanner, with high sensitivity and spatial resolution, we proposed and developed the helmet-chin PET scanner using 54 four-layered DOI detectors consisting of a 16 × 16 × 4 array of GSOZ scintillator crystals with dimensions of 2.8 × 2.8 × 7.5 mm 3 . All the detectors used in the helmet-chin PET scanner had the same spatial resolution. In this study, we conducted a feasibility study of a new add-on detector arrangement for the helmet PET scanner by replacing the chin detector with a segmented crystal cube, having high spatial resolution in all directions, which can be placed inside the mouth. The crystal cube (which we have named the mouth-insert detector) has an array of 20 × 20 × 20 LYSO crystal segments with dimensions of 1 × 1 × 1 mm 3 . Thus, the scanner is formed by the combination of the helmet and mouth-insert detectors, and is referred to as the helmet-mouth-insert PET scanner. The results show that the helmet-mouth-insert PET scanner has comparable sensitivity and improved spatial resolution near the center of the hemisphere, compared to the helmet-chin PET scanner.

High resolution phoswich gamma-ray imager utilizing monolithic MPPC arrays with submillimeter pixelized crystals

NASA Astrophysics Data System (ADS)

Kato, T.; Kataoka, J.; Nakamori, T.; Kishimoto, A.; Yamamoto, S.; Sato, K.; Ishikawa, Y.; Yamamura, K.; Kawabata, N.; Ikeda, H.; Kamada, K.

2013-05-01

We report the development of a high spatial resolution tweezers-type coincidence gamma-ray camera for medical imaging. This application consists of large-area monolithic Multi-Pixel Photon Counters (MPPCs) and submillimeter pixelized scintillator matrices. The MPPC array has 4 × 4 channels with a three-side buttable, very compact package. For typical operational gain of 7.5 × 105 at + 20 °C, gain fluctuation over the entire MPPC device is only ± 5.6%, and dark count rates (as measured at the 1 p.e. level) amount to <= 400 kcps per channel. We selected Ce-doped (Lu,Y)2(SiO4)O (Ce:LYSO) and a brand-new scintillator, Ce-doped Gd3Al2Ga3O12 (Ce:GAGG) due to their high light yield and density. To improve the spatial resolution, these scintillators were fabricated into 15 × 15 matrices of 0.5 × 0.5 mm2 pixels. The Ce:LYSO and Ce:GAGG scintillator matrices were assembled into phosphor sandwich (phoswich) detectors, and then coupled to the MPPC array along with an acrylic light guide measuring 1 mm thick, and with summing operational amplifiers that compile the signals into four position-encoded analog outputs being used for signal readout. Spatial resolution of 1.1 mm was achieved with the coincidence imaging system using a 22Na point source. These results suggest that the gamma-ray imagers offer excellent potential for applications in high spatial medical imaging.

A PET Design Based on SiPM and Monolithic LYSO Crystals: Performance Evaluation

NASA Astrophysics Data System (ADS)

González, Antonio J.; Aguilar, Albert; Conde, Pablo; Hernández, Liczandro; Moliner, Laura; Vidal, Luis F.; Sánchez, Filomeno; Sánchez, Sebastián; Correcher, Carlos; Molinos, César; Barberá, Julio; Lankes, Konrad; Junge, Sven; Bruckbauer, Thomas; Bruyndonckx, Peter; Benlloch, Jose M.

2016-10-01

A new small animal PET based on SiPM and monolithic LYSO crystals has been developed. Eight detector modules form the PET ring, each mounting an array of 12 × 12 SiPMs coupled to a readout providing the summed signals of the pixels on each of the 12 rows and 12 columns of the SiPM array. This design makes it possible to accurately determine the centroid of the scintillation light distribution with about 1.6 mm full width at half maximum (FWHM) resolution without correction for the 1 mm source size, and the photon depth of interaction (DOI) with nearly 2 mm FWHM. This single ring PET system has a homogeneous spatial resolution across the entire 80 mm transaxial field of view (FOV) of about 1 mm FWHM. The noise equivalent count rate (NECR) peak is estimated to occur at around 39.2 MBq with a rate of approximately 82.7 kcps for the mouse-like phantom and 22 kcps at 48.1 MBq for the rat-like phantom. Following the NEMA protocol, the peak absolute sensitivity in the center of the FOV is 2.8% for a 30% peak energy window. A pilot test injecting NaF to a mouse of 20 grams is also presented. Finally, the PET ring has been tested in front of a high field 15.2 T Magnetic Resonance (MR). No significant variation on energy and spatial resolution across the FOV has been observed due to the presence of the magnetic field.

Precision Timing Calorimeter for High Energy Physics

DOE PAGES

Anderson, Dustin; Apresyan, Artur; Bornheim, Adolf; ...

2016-04-01

Here, we present studies on the performance and characterization of the time resolution of LYSO-based calorimeters. Results for an LYSO sampling calorimeter and an LYSO-tungsten Shashlik calorimeter are presented. We also demonstrate that a time resolution of 30 ps is achievable for the LYSO sampling calorimeter. Timing calorimetry is described as a tool for mitigating the effects due to the large number of simultaneous interactions in the high luminosity environment foreseen for the Large Hadron Collider.

Clinical significance of plasma globotriaosylsphingosine levels in Chinese patients with Fabry disease.

PubMed

Ouyang, Yan; Chen, Bing; Pan, Xiaoxia; Wang, Zhaohui; Ren, Hong; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Yang, Li; Chen, Nan

2018-04-01

Although plasma globotriaosylsphingosine (lyso-Gb3) is a promising biomarker of Fabry disease (FD), few studies have assessed the impact of lyso-Gb3 in patients with FD. A total of 38 patients diagnosed with FD at Ruijin Hospital between January 2012 and December 2014 were recruited in the current study. An additional 120 unrelated healthy individuals were selected as healthy controls. A simplified liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was performed to determine lyso-Gb3 levels in plasma. Protein precipitation and glycolipid extraction were conducted using acetone/methanol. Clinical performance, including diagnostic value and disease surveillance, were compared between plasma lyso-Gb3 levels and α-galactosidase A (α-gal A) enzyme activity. The overall coefficient of variation values between inter- and intra-days varied between 2.8 and 18.9% and linearity correlation coefficients were ≥0.99 for all assays. Therefore, the effectiveness of the LC-MS/MS method was validated. Furthermore, a cut-off value of 0.81 ng/ml plasma lyso-Gb3 was able to separate patients with FD from healthy individuals. The sensitivity of this cut-off was 94.7% and the specificity was 100%. Compared with α-gal A enzyme activity, the diagnostic rate of patients assessed using plasma lyso-Gb3 levels was similar; however, there was a tighter correlation between plasma lyso-Gb3 levels and the mainz severity score index score in male patients (r=0.711 vs. r=-0.687). The sensitivity of plasma lyso-Gb3 in diagnosing female patients with FD was higher than α-gal A enzyme activity (82.4 vs. 23.5%). To the best of our knowledge, the present study is the first to report the effectiveness of plasma lyso-Gb3 levels in diagnosing Chinese patients with FD. Using α-gal A activity as a reference, the results of current study indicated that plasma lyso-Gb3 levels are more useful at diagnosing female patients with FD. Furthermore, plasma lyso-Gb3 levels are more suitable at determining overall disease severity in male patients.

Non-Proportionality of Electron Response and Energy Resolution of Compton Electrons in Scintillators

NASA Astrophysics Data System (ADS)

Swiderski, L.; Marcinkowski, R.; Szawlowski, M.; Moszynski, M.; Czarnacki, W.; Syntfeld-Kazuch, A.; Szczesniak, T.; Pausch, G.; Plettner, C.; Roemer, K.

2012-02-01

Non-proportionality of light yield and energy resolution of Compton electrons in three scintillators (LaBr3:Ce, LYSO:Ce and CsI:Tl) were studied in a wide energy range from 10 keV up to 1 MeV. The experimental setup was comprised of a High Purity Germanium detector and tested scintillators coupled to a photomultiplier. Probing the non-proportionality and energy resolution curves at different energies was obtained by changing the position of various radioactive sources with respect to both detectors. The distance between both detectors and source was kept small to make use of Wide Angle Compton Coincidence (WACC) technique, which allowed us to scan large range of scattering angles simultaneously and obtain relatively high coincidence rate of 100 cps using weak sources of about 10 μCi activity. The results are compared with those obtained by direct irradiation of the tested scintillators with gamma-ray sources and fitting the full-energy peaks.

A novel single-ended readout depth-of-interaction PET detector fabricated using sub-surface laser engraving.

PubMed

Uchida, H; Sakai, T; Yamauchi, H; Hakamata, K; Shimizu, K; Yamashita, T

2016-09-21

We propose a novel scintillation detector design for positron emission tomography (PET), which has depth of interaction (DOI) capability and uses a single-ended readout scheme. The DOI detector contains a pair of crystal bars segmented using sub-surface laser engraving (SSLE). The two crystal bars are optically coupled to each other at their top segments and are coupled to two photo-sensors at their bottom segments. Initially, we evaluated the performance of different designs of single crystal bars coupled to photomultiplier tubes at both ends. We found that segmentation by SSLE results in superior performance compared to the conventional method. As the next step, we constructed a crystal unit composed of a 3  ×  3  ×  20 mm 3 crystal bar pair, with each bar containing four layers segmented using the SSLE. We measured the DOI performance by changing the optical conditions for the crystal unit. Based on the experimental results, we then assessed the detector performance in terms of the DOI capability by evaluating the position error, energy resolution, and light collection efficiency for various crystal unit designs with different bar sizes and a different number of layers (four to seven layers). DOI encoding with small position error was achieved for crystal units composed of a 3  ×  3  ×  20 mm 3 LYSO bar pair having up to seven layers, and with those composed of a 2  ×  2  ×  20 mm 3 LYSO bar pair having up to six layers. The energy resolution of the segment in the seven-layer 3  ×  3  ×  20 mm 3 crystal bar pair was 9.3%-15.5% for 662 keV gamma-rays, where the segments closer to the photo-sensors provided better energy resolution. SSLE provides high geometrical accuracy at low production cost due to the simplicity of the crystal assembly. Therefore, the proposed DOI detector is expected to be an attractive choice for practical small-bore PET systems dedicated to imaging of the brain, breast, and small animals.

Experimental study of a depth-encoding PET detector inserting horizontal-striped glass between crystal layers

NASA Astrophysics Data System (ADS)

Yang, J.; Kim, K. B.; Choi, Y.; Kang, J.

2018-04-01

A depth-encoding positron emission tomography (PET) detector inserting a horizontal-striped glass between pixilated scintillation crystal layers was developed and experimentally evaluated. The detector consists of 2-layers of 4×4 LYSO array arranged with a 3.37 mm pitch. Horizontal-striped glasses with 1×4 array with different thickness of 3, 4 and 5 mm were inserted between top- and bottom-crystal layers. Bottom surface of bottom-layer was optically coupled to a 4×4 GAPD array. Sixteen output signals from DOI-PET detector were multiplexed by modified resistive charge division (RCD) networks and multiplexed signals were fed into custom-made charge-sensitive preamplifiers. The four amplified signals were digitized and recorded by the custom-made DAQ system based on FPGA. The four digitized outputs were post-processed and converted to flood histograms for each interaction event. Experimental results revealed that all crystal pixels were clearly identified on the 2D flood histogram without overlapping. Patterns of the 2D flood histogram were constituted with arrangements of [bottom–top–bottom–top–\\ldots–top–bottom–top–bottom] crystal responses in X-direction. These could be achieved by employing horizontal-striped glass that controlled the extent of light dispersion towards the X-direction in crystal layers for generation of a different position mapping for each layer and the modified RCD network that controls degree of charge sharing in readout electronics for reduction of identification error. This study demonstrated the proposed DOI-PET detector can extract the 3D γ-ray interaction position without considerable performance degradation of PET detector from the 2D flood histogram.

Maximum likelihood positioning and energy correction for scintillation detectors

NASA Astrophysics Data System (ADS)

Lerche, Christoph W.; Salomon, André; Goldschmidt, Benjamin; Lodomez, Sarah; Weissler, Björn; Solf, Torsten

2016-02-01

An algorithm for determining the crystal pixel and the gamma ray energy with scintillation detectors for PET is presented. The algorithm uses Likelihood Maximisation (ML) and therefore is inherently robust to missing data caused by defect or paralysed photo detector pixels. We tested the algorithm on a highly integrated MRI compatible small animal PET insert. The scintillation detector blocks of the PET gantry were built with the newly developed digital Silicon Photomultiplier (SiPM) technology from Philips Digital Photon Counting and LYSO pixel arrays with a pitch of 1 mm and length of 12 mm. Light sharing was used to readout the scintillation light from the 30× 30 scintillator pixel array with an 8× 8 SiPM array. For the performance evaluation of the proposed algorithm, we measured the scanner’s spatial resolution, energy resolution, singles and prompt count rate performance, and image noise. These values were compared to corresponding values obtained with Center of Gravity (CoG) based positioning methods for different scintillation light trigger thresholds and also for different energy windows. While all positioning algorithms showed similar spatial resolution, a clear advantage for the ML method was observed when comparing the PET scanner’s overall single and prompt detection efficiency, image noise, and energy resolution to the CoG based methods. Further, ML positioning reduces the dependence of image quality on scanner configuration parameters and was the only method that allowed achieving highest energy resolution, count rate performance and spatial resolution at the same time.

Sci-Sat AM(1): Imaging-08: Small animal APD PET detector with submillimetric resolution for molecular imaging.

PubMed

Bérard, P; Bergeron, M; Pepin, C M; Cadorette, J; Tétrault, M-A; Viscogliosi, N; Fontaine, R; Dautet, H; Davies, M; Lecomte, R

2008-07-01

Visualization and quantification of biological processes in mice, the preferred animal model in most preclinical studies, require the best possible spatial resolution in positron emission tomography (PET). A new 64-channel avalanche photodiode (APD) detector module was developed to achieve submillimeter spatial resolution for this purpose. The module consists of dual 4 × 8 APD arrays mounted in a custom ceramic holder. Individual APD pixels having an active area of 1.1 × 1.1 mm2 at a 1.2 mm pitch can be fitted to an 8 × 8 LYSO scintillator block designed to accommodate one-to-one coupling. An analog test board with four 16-channel preamplifier ASICs was designed to be interfaced with the existing LabPET digital processing electronics. At a standard APD operating bias, a mean energy resolution of 27.5 ± 0.6% was typically obtained at 511 keV with a relative standard deviation of 13.8% in signal amplitude for the 64 individual pixels. Crosstalk between pixels was found to be well below the typical lower energy threshold used for PET imaging applications. With two modules in coincidence, a global timing resolution of 5.0 ns FWHM was measured. Finally, an intrinsic spatial resolution of 0.8 mm FWHM was measured by sweeping a 22Na point source between two detector arrays. The proposed detector module demonstrates promising characteristics for dedicated mouse PET imaging at submillimiter resolution. © 2008 American Association of Physicists in Medicine.

A photostable near-infrared fluorescent tracker with pH-independent specificity to lysosomes for long time and multicolor imaging.

PubMed

Zhang, Xinfu; Wang, Chao; Han, Zhuo; Xiao, Yi

2014-12-10

A new boron-dipyrromethene-based lysosome tracker, Lyso-NIR, is facilely synthesized. Besides the intensive near-infrared (NIR) fluorescence and high photostability, Lyso-NIR shows the capability to stably localize in lysosomes, which is independent of the local pH. Lyso-NIR does not have the problematic alkalization effect suffered by the commonly used lysotrackers; thus, it shows ignorable cytotoxicity and slightly affects normal physiological functions of lysosomes. The above advantages of Lyso-NIR make it feasible to track lysosomes' dynamic changes in a relatively long time during the full cellular processes such as apoptosis, heavy metal stimulation, and endocytosis, as is demonstrated in this work. Moreover, Lyso-NIR's narrow NIR emission at 740 nm with a full width at half-maximum smaller than 50 nm makes it easy to avoid the crosstalk with the emissions from other common fluorescent probes, which strengthens Lyso-NIR's competitiveness as a standard lysosome tracker for multicolor bioimaging.

Comparison between Pixelated Scintillators: CsI(Tl), LaCl 3(Ce) and LYSO(Ce) when coupled to a Silicon Photomultipliers Array

NASA Astrophysics Data System (ADS)

Jeong, Manhee; Van, Benjamin; Wells, Byron T.; D'Aries, Lawrence J.; Hammig, Mark D.

2018-06-01

A large area SiPM array is individually coupled to five different types of scintillators in and each is evaluated for the development of a coded aperture imaging system. In order to readout signals from the 144 pixel array, a resistor network with symmetric charge division circuitry was developed, which successfully provides a significant reduction in the multiplicity of the analog outputs and reduces the size of the accumulated data. Energy resolutions at 662 keV for pixelated arrays of dimensions and material types as follows: 3 × 3 × 20 mm3 CsI(Tl), 4 × 4 × 20 mm3 CsI(Tl), 4 × 4 × 5 mm3 LYSO(Ce), 4 × 4 × 10 mm3 LYSO(Ce), and 2 × 2 × 5 mm3 LaCl3(Ce) have been determined. In addition, sub-millimeter FWHM pixel-identification resolutions were acquired from all of the scintillators tested.

SU-G-JeP1-13: Innovative Tracking Detector for Dose Monitoring in Hadron Therapy: Realization and Monte Carlo Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rucinski, A; Mancini-Terracciano, C; Paramatti, R

2016-06-15

Purpose: Development of strategies to monitor range uncertainties is necessary to improve treatment planning in Charged Particle Therapy (CPT) and fully exploit the advantages of ion beams. Our group developed (within the framework of the INSIDE project funded by the Italian research ministry) and is currently building a compact detector Dose Profiler (DP) able to backtrack charged secondary particles produced in the patient during the irradiation. Furthermore we are studying monitoring strategy exploiting charged secondary emission profiles to control the range of the ion beam. Methods: This contribution reports on the DP detector design and construction status. The detector consistsmore » of a charged secondary tracker composed of scintillating fiber layers and a LYSO calorimeter for particles energy measurement.The detector layout has been optimized using the FLUKA Monte Carlo (MC) simulation software. The simulation of a 220 MeV Carbon beam impinging on a PMMA target has been performed to study the detector response, exploiting previous secondary radiation measurements performed by our group. The emission profile of charged secondary particles was reconstructed backtracking the particles to their generation point to benchmark the DP performances. Results: The DP construction status, including the technological details will be presented. The feasibility of range monitoring with DP will be demonstrated by means of MC studies. The correlation of the charged secondary particles emission shape with the position of the Bragg peak (BP) will be shown, as well as the spatial resolution achievable on the BP position estimation (less than 3 mm) in the clinical like conditions. Conclusion: The simulation studies supported the feasibility of an accurate range monitoring technique exploiting the use of charged secondary fragments emitted during the particle therapy treatment. The DP experimental tests are foreseen in 2016, at CNAO particle therapy center in Pavia.« less

Renal metabolic profiling of early renal injury and renoprotective effects of Poria cocos epidermis using UPLC Q-TOF/HSMS/MSE.

PubMed

Zhao, Ying-Yong; Lei, Ping; Chen, Dan-Qian; Feng, Ya-Long; Bai, Xu

2013-01-01

Poria cocos epidermis is one of ancient traditional Chinese medicines (TCMs), which is usually used for the treatment of chronic kidney disease (CKD) for thousands of years in China. A metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry (UPLC Q-TOF/HSMS) and a mass spectrometry(Elevated Energy) (MS(E)) data collection technique was developed to obtained a systematic view of the development and progression of CKD and biochemistry mechanism of therapeutic effects of P. cocos epidermis (Fu-Ling-Pi, FLP). By partial least squares-discriminate analysis, 19 metabolites were identified as potential biomarkers of CKD. Among the 19 biomarkers, 10 biomarkers including eicosapentaenoic acid, docosahexaenoic acid, lysoPC(20:4), lysoPC(18:2), lysoPC(15:0), lysoPE(20:0/0:0), indoxyl sulfate, hippuric acid, p-cresol sulfate and allantoin were reversed to the control level in FLP-treated groups. The study indicates that FLP treatment can ameliorate CKD by intervening in some dominating metabolic pathways, such as fatty acid metabolism, phospholipid metabolism, purine metabolism and tryptophan metabolism. This work was for the first time to investigate the FLP therapeutic effect based on metabonomics technology, which is a potentially powerful tool to study the TCMs. Copyright © 2013 Elsevier B.V. All rights reserved.

A small animal PET based on GAPDs and charge signal transmission approach for hybrid PET-MR imaging

NASA Astrophysics Data System (ADS)

Kang, Jihoon; Choi, Yong; Hong, Key Jo; Hu, Wei; Jung, Jin Ho; Huh, Yoonsuk; Kim, Byung-Tae

2011-08-01

Positron emission tomography (PET) employing Geiger-mode avalanche photodiodes (GAPDs) and charge signal transmission approach was developed for small animal imaging. Animal PET contained 16 LYSO and GAPD detector modules that were arranged in a 70 mm diameter ring with an axial field of view of 13 mm. The GAPDs charge output signals were transmitted to a preamplifier located remotely using 300 cm flexible flat cables. The position decoder circuits (PDCs) were used to multiplex the PET signals from 256 to 4 channels. The outputs of the PDCs were digitized and further-processed in the data acquisition unit. The cross-compatibilities of the PET detectors and MRI were assessed outside and inside the MRI. Experimental studies of the developed full ring PET were performed to examine the spatial resolution and sensitivity. Phantom and mouse images were acquired to examine the imaging performance. The mean energy and time resolution of the PET detector were 17.6% and 1.5 ns, respectively. No obvious degradation on PET and MRI was observed during simultaneous PET-MRI data acquisition. The measured spatial resolution and sensitivity at the CFOV were 2.8 mm and 0.7%, respectively. In addition, a 3 mm diameter line source was clearly resolved in the hot-sphere phantom images. The reconstructed transaxial PET images of the mouse brain and tumor displaying the glucose metabolism patterns were imaged well. These results demonstrate GAPD and the charge signal transmission approach can allow the development of high performance small animal PET with improved MR compatibility.

State of the art timing in TOF-PET detectors with LuAG, GAGG and L(Y)SO scintillators of various sizes coupled to FBK-SiPMs

NASA Astrophysics Data System (ADS)

Gundacker, S.; Acerbi, F.; Auffray, E.; Ferri, A.; Gola, A.; Nemallapudi, M. V.; Paternoster, G.; Piemonte, C.; Lecoq, P.

2016-08-01

Time of flight (TOF) in positron emission tomography (PET) has experienced a revival of interest after its first introduction in the eighties. This is due to a significant progress in solid state photodetectors (SiPMs) and newly developed scintillators (LSO and its derivatives). Latest developments at Fondazione Bruno Kessler (FBK) lead to the NUV-HD SiPM with a very high photon detection efficiency of around 55%. Despite the large area of 4×4 mm2 it achieves a good single photon time resolution (SPTR) of 180±5ps FWHM. Coincidence time resolution (CTR) measurements using LSO:Ce codoped with Ca scintillators yield best values of 73±2ps FWHM for 2×2×3 mm3 and 117±3ps for 2×2×20 mm3 crystal sizes. Increasing the crystal cross-section from 2×2 mm2 to 3×3 mm2 a non negligible CTR deterioration of approximately 7ps FWHM is observed. Measurements with LSO:Ce codoped Ca and LYSO:Ce scintillators with various cross-sections (1×1 mm2 - 4×4 mm2) and lengths (3mm - 30mm) will be a basis for discussing on how the crystal geometry affects timing in TOF-PET. Special attention is given to SiPM parameters, e.g. SPTR and optical crosstalk, and their measured dependency on the crystal cross-section. Additionally, CTR measurements with LuAG:Ce, LuAG:Pr and GGAG:Ce samples are presented and the results are interpreted in terms of their scintillation properties, e.g. rise time, decay time, light yield and emission spectra.

PET/CT alignment calibration with a non-radioactive phantom and the intrinsic 176Lu radiation of PET detector

NASA Astrophysics Data System (ADS)

Wei, Qingyang; Ma, Tianyu; Wang, Shi; Liu, Yaqiang; Gu, Yu; Dai, Tiantian

2016-11-01

Positron emission tomography/computed tomography (PET/CT) is an important tool for clinical studies and pre-clinical researches which provides both functional and anatomical images. To achieve high quality co-registered PET/CT images, alignment calibration of PET and CT scanner is a critical procedure. The existing methods reported use positron source phantoms imaged both by PET and CT scanner and then derive the transformation matrix from the reconstructed images of the two modalities. In this paper, a novel PET/CT alignment calibration method with a non-radioactive phantom and the intrinsic 176Lu radiation of the PET detector was developed. Firstly, a multi-tungsten-alloy-sphere phantom without positron source was designed and imaged by CT and the PET scanner using intrinsic 176Lu radiation included in LYSO. Secondly, the centroids of the spheres were derived and matched by an automatic program. Lastly, the rotation matrix and the translation vector were calculated by least-square fitting of the centroid data. The proposed method was employed in an animal PET/CT system (InliView-3000) developed in our lab. Experimental results showed that the proposed method achieves high accuracy and is feasible to replace the conventional positron source based methods.

Improvement of crystal identification performance for a four-layer DOI detector composed of crystals segmented by laser processing

NASA Astrophysics Data System (ADS)

Mohammadi, Akram; Inadama, Naoko; Yoshida, Eiji; Nishikido, Fumihiko; Shimizu, Keiji; Yamaya, Taiga

2017-09-01

We have developed a four-layer depth of interaction (DOI) detector with single-side photon readout, in which segmented crystals with the patterned reflector insertion are separately identified by the Anger-type calculation. Optical conditions between segmented crystals, where there is no reflector, affect crystal identification ability. Our objective of this work was to improve crystal identification performance of the four-layer DOI detector that uses crystals segmented with a recently developed laser processing technique to include laser processed boundaries (LPBs). The detector consisted of 2 × 2 × 4mm3 LYSO crystals and a 4 × 4 array multianode photomultiplier tube (PMT) with 4.5 mm anode pitch. The 2D position map of the detector was calculated by the Anger calculation method. At first, influence of optical condition on crystal identification was evaluated for a one-layer detector consisting of a 2 × 2 crystal array with three different optical conditions between the crystals: crystals stuck together using room temperature vulcanized (RTV) rubber, crystals with air coupling and segmented crystals with LPBs. The crystal array with LPBs gave the shortest distance between crystal responses in the 2D position map compared with the crystal array coupled with RTV rubber or air due to the great amount of cross-talk between segmented crystals with LPBs. These results were used to find optical conditions offering the optimum distance between crystal responses in the 2D position map for the four-layer DOI detector. Crystal identification performance for the four-layer DOI detector consisting of an 8 × 8 array of crystals segmented with LPBs was examined and it was not acceptable for the crystals in the first layer. The crystal identification was improved for the first layer by changing the optical conditions between all 2 × 2 crystal arrays of the first layer to RTV coupling. More improvement was observed by combining different optical conditions between all crystals of the first layer and some crystals of the second and the third layers of the segmented array.

Characterization of highly multiplexed monolithic PET / gamma camera detector modules

NASA Astrophysics Data System (ADS)

Pierce, L. A.; Pedemonte, S.; DeWitt, D.; MacDonald, L.; Hunter, W. C. J.; Van Leemput, K.; Miyaoka, R.

2018-04-01

PET detectors use signal multiplexing to reduce the total number of electronics channels needed to cover a given area. Using measured thin-beam calibration data, we tested a principal component based multiplexing scheme for scintillation detectors. The highly-multiplexed detector signal is no longer amenable to standard calibration methodologies. In this study we report results of a prototype multiplexing circuit, and present a new method for calibrating the detector module with multiplexed data. A 50 × 50 × 10 mm3 LYSO scintillation crystal was affixed to a position-sensitive photomultiplier tube with 8 × 8 position-outputs and one channel that is the sum of the other 64. The 65-channel signal was multiplexed in a resistive circuit, with 65:5 or 65:7 multiplexing. A 0.9 mm beam of 511 keV photons was scanned across the face of the crystal in a 1.52 mm grid pattern in order to characterize the detector response. New methods are developed to reject scattered events and perform depth-estimation to characterize the detector response of the calibration data. Photon interaction position estimation of the testing data was performed using a Gaussian Maximum Likelihood estimator and the resolution and scatter-rejection capabilities of the detector were analyzed. We found that using a 7-channel multiplexing scheme (65:7 compression ratio) with 1.67 mm depth bins had the best performance with a beam-contour of 1.2 mm FWHM (from the 0.9 mm beam) near the center of the crystal and 1.9 mm FWHM near the edge of the crystal. The positioned events followed the expected Beer–Lambert depth distribution. The proposed calibration and positioning method exhibited a scattered photon rejection rate that was a 55% improvement over the summed signal energy-windowing method.

GPU-based optical propagation simulator of a laser-processed crystal block for the X'tal cube PET detector.

PubMed

Ogata, Yuma; Ohnishi, Takashi; Moriya, Takahiro; Inadama, Naoko; Nishikido, Fumihiko; Yoshida, Eiji; Murayama, Hideo; Yamaya, Taiga; Haneishi, Hideaki

2014-01-01

The X'tal cube is a next-generation DOI detector for PET that we are developing to offer higher resolution and higher sensitivity than is available with present detectors. It is constructed from a cubic monolithic scintillation crystal and silicon photomultipliers which are coupled on various positions of the six surfaces of the cube. A laser-processing technique is applied to produce 3D optical boundaries composed of micro-cracks inside the monolithic scintillator crystal. The current configuration is based on an empirical trial of a laser-processed boundary. There is room to improve the spatial resolution by optimizing the setting of the laser-processed boundary. In fact, the laser-processing technique has high freedom in setting the parameters of the boundary such as size, pitch, and angle. Computer simulation can effectively optimize such parameters. In this study, to design optical characteristics properly for the laser-processed crystal, we developed a Monte Carlo simulator which can model arbitrary arrangements of laser-processed optical boundaries (LPBs). The optical characteristics of the LPBs were measured by use of a setup with a laser and a photo-diode, and then modeled in the simulator. The accuracy of the simulator was confirmed by comparison of position histograms obtained from the simulation and from experiments with a prototype detector composed of a cubic LYSO monolithic crystal with 6 × 6 × 6 segments and multi-pixel photon counters. Furthermore, the simulator was accelerated by parallel computing with general-purpose computing on a graphics processing unit. The calculation speed was about 400 times faster than that with a CPU.

The Crystal Zero Degree Detector at BESIII

NASA Astrophysics Data System (ADS)

Koch, L.; Denig, A.; Drexler, P.; Garillon, B.; Johansson, T.; Kühn, W.; Lange, S.; Lauth, W.; Liang, Y.; Marciniewski, P.; Rathmann, T.; Redmer, C.

2017-07-01

The BESIII experiment at the BEPCII electron positron collider at IHEP (Beijing) is collecting data in the charm-τ mass region. Electron positron collisions are a very well suited environment for the study of initial state radiation (ISR). However, the photons from ISR are strongly peaked towards small polar angles and are currently detected with limited efficiency. In order to increase the detection efficiency of ISR photons, we are developing small-size calorimeters to be placed in the very forward and backward regions. Each detector will consist of two 4×3 arrays of 1×1×14 cm3 LYSO crystals. A 1 cm gap separating each of the two arrays will reduce the contamination from background at very low angles. The scintillation light will be collected by silicon photomultipliers (SiPMs). The expected event rate in the MHz range requires flash ADCs recording the preamplified SiPM outputs.The digitized waveforms will be analyzed in realtime yielding data reduction and pile-up detection. This high bandwidth data stream will be transmitted via optical fibers to FPGA-based hardware performing sub-event building, buffering, and event correlation with the BESIII trigger. The sub-events with a corresponding trigger will be sent to the BESIII event builder via TCP/IP. A single crystal equipped with a SiPM was instrumented as a prototype detector. Tests with radioactive sources were performed successfully.

Lyso-DGTS lipid isolated from microalgae enhances PON1 activities in vitro and in vivo, increases PON1 penetration into macrophages and decreases cellular lipid accumulation.

PubMed

Dahli, Loureen; Atrahimovich, Dana; Vaya, Jacob; Khatib, Soliman

2018-04-16

High-density lipoprotein (HDL) plays an important role in preventing atherosclerosis. The antioxidant effect of HDL is mostly associated with paraoxonase 1 (PON1) activity. Increasing PON1 activity using nutrients might improve HDL function and quality and thus, decrease atherosclerotic risk. We previously isolated and identified a novel active compound, lyso-DGTS (C20:5,0) from Nannochloropsis sp. ethanol extract. In the present study, its effect on PON1 activities was examined and the mechanism by which the compound affects PON1 activity was explored. Lyso-DGTS elevated recombinant PON1 (rePON1) lactonase and esterase activities in a dose- and time-responsive manner, and further stabilized and preserved rePON1 lactonase activity. Incubation of lyso-DGTS with human serum for 4 h at 37°C also increased PON1 lactonase activity in a dose-responsive manner. Using tryptophan-fluorescence-quenching assay, lyso-DGTS was found to interact with rePON1 spontaneously with negative free energy (ΔG = -22.87 kJ mol -1 at 25°C). Thermodynamic parameters and molecular modeling calculations showed that the main interaction of lyso-DGTS with the enzyme is through a hydrogen bond with supporting van der Waals interactions. Furthermore, lyso-DGTS significantly increased rePON1 influx into macrophages and prevented lipid accumulation in macrophages stimulated with oxidized low-density lipid dose-dependently. In vivo supplementation of lyso-DGTS to the circulation of mice fed a high-fat diet via osmotic mini-pumps implanted subcutaneously significantly increased serum PON1 lactonase activity and decreased serum glucose concentrations to the level of mice fed a normal diet. Our findings suggest a beneficial effect of lyso-DGTS on increasing PON1 activity and thus, improving HDL quality and atherosclerotic risk factors. © 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Two-Photon Fluorescent Probe for Monitoring Autophagy via Fluorescence Lifetime Imaging.

PubMed

Hou, Liling; Ning, Peng; Feng, Yan; Ding, Yaqi; Bai, Lei; Li, Lin; Yu, Haizhu; Meng, Xiangming

2018-06-19

We reported the first lysosome targeted two-photon fluorescent probe (Lyso-NP) as a viscosity probe for monitoring autophagy. The fluorescence lifetime of Lyso-NP exhibited an excellent linear relationship with viscosity value ( R 2 = 0.99, x = 0.39). Lyso-NP also showed the specific capability for imaging lysosomal viscosity under two-photon excitation at 860 nm along with good biocompatibility. More importantly, Lyso-NP could be used to monitor the autophagy process in living cells by quantitatively detecting lysosomal viscosity changes during the membrane fusion process via two-photon fluorescence lifetime imaging.

Radioactivity measurement of radioactive contaminated soil by using a fiber-optic radiation sensor

NASA Astrophysics Data System (ADS)

Joo, Hanyoung; Kim, Rinah; Moon, Joo Hyun

2016-06-01

A fiber-optic radiation sensor (FORS) was developed to measure the gamma radiation from radioactive contaminated soil. The FORS was fabricated using an inorganic scintillator (Lu,Y)2SiO5:Ce (LYSO:Ce), a mixture of epoxy resin and hardener, aluminum foil, and a plastic optical fiber. Before its real application, the FORS was tested to determine if it performed adequately. The test result showed that the measurements by the FORS adequately followed the theoretically estimated values. Then, the FORS was applied to measure the gamma radiation from radioactive contaminated soil. For comparison, a commercial radiation detector was also applied to measure the same soil samples. The measurement data were analyzed by using a statistical parameter, the critical level to determine if net radioactivity statistically different from background was present in the soil sample. The analysis showed that the soil sample had radioactivity distinguishable from background.

Reflectivity quenching of ESR multilayer polymer film reflector in optically bonded scintillator arrays

NASA Astrophysics Data System (ADS)

Loignon-Houle, Francis; Pepin, Catherine M.; Charlebois, Serge A.; Lecomte, Roger

2017-04-01

The 3M-ESR multilayer polymer film is a widely used reflector in scintillation detector arrays. As specified in the datasheet and confirmed experimentally by measurements in air, it is highly reflective (> 98 %) over the entire visible spectrum (400-1000 nm) for all angles of incidence. Despite these outstanding characteristics, it was previously found that light crosstalk between pixels in a bonded LYSO scintillator array with ESR reflector can be as high as ∼30-35%. This unexplained light crosstalk motivated further investigation of ESR optical performance. Analytical simulation of a multilayer structure emulating the ESR reflector showed that the film becomes highly transparent to incident light at large angles when surrounded on both sides by materials of refractive index higher than air. Monte Carlo simulations indicate that a considerable fraction (∼25-35%) of scintillation photons are incident at these leaking angles in high aspect ratio LYSO scintillation crystals. The film transparency was investigated experimentally by measuring the scintillation light transmission through the ESR film sandwiched between a scintillation crystal and a photodetector with or without layers of silicone grease. Strong light leakage, up to nearly 30%, was measured through the reflector when coated on both sides with silicone, thus elucidating the major cause of light crosstalk in bonded arrays. The reflector transparency was confirmed experimentally for angles of incidence larger than 60 ° using a custom designed setup allowing illumination of the bonded ESR film at selected grazing angles. The unsuspected ESR film transparency can be beneficial for detector arrays exploiting light sharing schemes, but it is highly detrimental for scintillator arrays designed for individual pixel readout.

Crystal identification for a dual-layer-offset LYSO based PET system via Lu-176 background radiation and mean shift algorithm

NASA Astrophysics Data System (ADS)

Wei, Qingyang; Ma, Tianyu; Xu, Tianpeng; Zeng, Ming; Gu, Yu; Dai, Tiantian; Liu, Yaqiang

2018-01-01

Modern positron emission tomography (PET) detectors are made from pixelated scintillation crystal arrays and readout by Anger logic. The interaction position of the gamma-ray should be assigned to a crystal using a crystal position map or look-up table. Crystal identification is a critical procedure for pixelated PET systems. In this paper, we propose a novel crystal identification method for a dual-layer-offset LYSO based animal PET system via Lu-176 background radiation and mean shift algorithm. Single photon event data of the Lu-176 background radiation are acquired in list-mode for 3 h to generate a single photon flood map (SPFM). Coincidence events are obtained from the same data using time information to generate a coincidence flood map (CFM). The CFM is used to identify the peaks of the inner layer using the mean shift algorithm. The response of the inner layer is deducted from the SPFM by subtracting CFM. Then, the peaks of the outer layer are also identified using the mean shift algorithm. The automatically identified peaks are manually inspected by a graphical user interface program. Finally, a crystal position map is generated using a distance criterion based on these peaks. The proposed method is verified on the animal PET system with 48 detector blocks on a laptop with an Intel i7-5500U processor. The total runtime for whole system peak identification is 67.9 s. Results show that the automatic crystal identification has 99.98% and 99.09% accuracy for the peaks of the inner and outer layers of the whole system respectively. In conclusion, the proposed method is suitable for the dual-layer-offset lutetium based PET system to perform crystal identification instead of external radiation sources.

Improved image quality using monolithic scintillator detectors with dual-sided readout in a whole-body TOF-PET ring: a simulation study.

PubMed

Tabacchini, Valerio; Surti, Suleman; Borghi, Giacomo; Karp, Joel S; Schaart, Dennis R

2017-02-13

We have recently built and characterized the performance of a monolithic scintillator detector based on a 32 mm  ×  32 mm  ×  22 mm LYSO:Ce crystal read out by digital silicon photomultiplier (dSiPM) arrays coupled to the crystal front and back surfaces in a dual-sided readout (DSR) configuration. The detector spatial resolution appeared to be markedly better than that of a detector consisting of the same crystal with conventional back-sided readout (BSR). Here, we aim to evaluate the influence of this difference in the detector spatial response on the quality of reconstructed images, so as to quantify the potential benefit of the DSR approach for high-resolution, whole-body time-of-flight (TOF) positron emission tomography (PET) applications. We perform Monte Carlo simulations of clinical PET systems based on BSR and DSR detectors, using the results of our detector characterization experiments to model the detector spatial responses. We subsequently quantify the improvement in image quality obtained with DSR compared to BSR, using clinically relevant metrics such as the contrast recovery coefficient (CRC) and the area under the localized receiver operating characteristic curve (ALROC). Finally, we compare the results with simulated rings of pixelated detectors with DOI capability. Our results show that the DSR detector produces significantly higher CRC and increased ALROC values than the BSR detector. The comparison with pixelated systems indicates that one would need to choose a crystal size of 3.2 mm with three DOI layers to match the performance of the BSR detector, while a pixel size of 1.3 mm with three DOI layers would be required to get on par with the DSR detector.

Improved image quality using monolithic scintillator detectors with dual-sided readout in a whole-body TOF-PET ring: a simulation study

NASA Astrophysics Data System (ADS)

Tabacchini, Valerio; Surti, Suleman; Borghi, Giacomo; Karp, Joel S.; Schaart, Dennis R.

2017-03-01

We have recently built and characterized the performance of a monolithic scintillator detector based on a 32 mm  ×  32 mm  ×  22 mm LYSO:Ce crystal read out by digital silicon photomultiplier (dSiPM) arrays coupled to the crystal front and back surfaces in a dual-sided readout (DSR) configuration. The detector spatial resolution appeared to be markedly better than that of a detector consisting of the same crystal with conventional back-sided readout (BSR). Here, we aim to evaluate the influence of this difference in the detector spatial response on the quality of reconstructed images, so as to quantify the potential benefit of the DSR approach for high-resolution, whole-body time-of-flight (TOF) positron emission tomography (PET) applications. We perform Monte Carlo simulations of clinical PET systems based on BSR and DSR detectors, using the results of our detector characterization experiments to model the detector spatial responses. We subsequently quantify the improvement in image quality obtained with DSR compared to BSR, using clinically relevant metrics such as the contrast recovery coefficient (CRC) and the area under the localized receiver operating characteristic curve (ALROC). Finally, we compare the results with simulated rings of pixelated detectors with DOI capability. Our results show that the DSR detector produces significantly higher CRC and increased ALROC values than the BSR detector. The comparison with pixelated systems indicates that one would need to choose a crystal size of 3.2 mm with three DOI layers to match the performance of the BSR detector, while a pixel size of 1.3 mm with three DOI layers would be required to get on par with the DSR detector.

Signature energetic analysis of accelerate electron beam after first acceleration station by accelerating stand of Joint Institute for Nuclear Research

NASA Astrophysics Data System (ADS)

Sledneva, A. S.; Kobets, V. V.

2017-06-01

The linear electron accelerator based on the LINAC - 800 accelerator imported from the Netherland is created at Joint Institute for Nuclear Research in the framework of the project on creation of the Testbed with an electron beam of a linear accelerator with an energy up to 250 MV. Currently two accelerator stations with a 60 MV energy of a beam are put in operation and the work is to put the beam through accelerating section of the third accelerator station. The electron beam with an energy of 23 MeV is used for testing the crystals (BaF2, CsI (native), and LYSO) in order to explore the opportunity to use them in particle detectors in experiments: Muon g-2, Mu2e, Comet, whose preparation requires a detailed study of the detectors properties such as their irradiation by the accelerator beams.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lecomte, Roger; Arpin, Louis; Beaudoin, Jean-Franç

Purpose: LabPET II is a new generation APD-based PET scanner designed to achieve sub-mm spatial resolution using truly pixelated detectors and highly integrated parallel front-end processing electronics. Methods: The basic element uses a 4×8 array of 1.12×1.12 mm{sup 2} Lu{sub 1.9}Y{sub 0.1}SiO{sub 5}:Ce (LYSO) scintillator pixels with one-to-one coupling to a 4×8 pixelated monolithic APD array mounted on a ceramic carrier. Four detector arrays are mounted on a daughter board carrying two flip-chip, 64-channel, mixed-signal, application-specific integrated circuits (ASIC) on the backside interfacing to two detector arrays each. Fully parallel signal processing was implemented in silico by encoding time andmore » energy information using a dual-threshold Time-over-Threshold (ToT) scheme. The self-contained 128-channel detector module was designed as a generic component for ultra-high resolution PET imaging of small to medium-size animals. Results: Energy and timing performance were optimized by carefully setting ToT thresholds to minimize the noise/slope ratio. ToT spectra clearly show resolved 511 keV photopeak and Compton edge with ToT resolution well below 10%. After correction for nonlinear ToT response, energy resolution is typically 24±2% FWHM. Coincidence time resolution between opposing 128-channel modules is below 4 ns FWHM. Initial imaging results demonstrate that 0.8 mm hot spots of a Derenzo phantom can be resolved. Conclusion: A new generation PET scanner featuring truly pixelated detectors was developed and shown to achieve a spatial resolution approaching the physical limit of PET. Future plans are to integrate a small-bore dedicated mouse version of the scanner within a PET/CT platform.« less

Analytical Calculation of the Lower Bound on Timing Resolution for PET Scintillation Detectors Comprising High-Aspect-Ratio Crystal Elements

PubMed Central

Cates, Joshua W.; Vinke, Ruud; Levin, Craig S.

2015-01-01

Excellent timing resolution is required to enhance the signal-to-noise ratio (SNR) gain available from the incorporation of time-of-flight (ToF) information in image reconstruction for positron emission tomography (PET). As the detector’s timing resolution improves, so does SNR, reconstructed image quality, and accuracy. This directly impacts the challenging detection and quantification tasks in the clinic. The recognition of these benefits has spurred efforts within the molecular imaging community to determine to what extent the timing resolution of scintillation detectors can be improved and develop near-term solutions for advancing ToF-PET. Presented in this work, is a method for calculating the Cramér-Rao lower bound (CRLB) on timing resolution for scintillation detectors with long crystal elements, where the influence of the variation in optical path length of scintillation light on achievable timing resolution is non-negligible. The presented formalism incorporates an accurate, analytical probability density function (PDF) of optical transit time within the crystal to obtain a purely mathematical expression of the CRLB with high-aspect-ratio (HAR) scintillation detectors. This approach enables the statistical limit on timing resolution performance to be analytically expressed for clinically-relevant PET scintillation detectors without requiring Monte Carlo simulation-generated photon transport time distributions. The analytically calculated optical transport PDF was compared with detailed light transport simulations, and excellent agreement was found between the two. The coincidence timing resolution (CTR) between two 3×3×20 mm3 LYSO:Ce crystals coupled to analogue SiPMs was experimentally measured to be 162±1 ps FWHM, approaching the analytically calculated lower bound within 6.5%. PMID:26083559

Analytical calculation of the lower bound on timing resolution for PET scintillation detectors comprising high-aspect-ratio crystal elements

NASA Astrophysics Data System (ADS)

Cates, Joshua W.; Vinke, Ruud; Levin, Craig S.

2015-07-01

Excellent timing resolution is required to enhance the signal-to-noise ratio (SNR) gain available from the incorporation of time-of-flight (ToF) information in image reconstruction for positron emission tomography (PET). As the detector’s timing resolution improves, so does SNR, reconstructed image quality, and accuracy. This directly impacts the challenging detection and quantification tasks in the clinic. The recognition of these benefits has spurred efforts within the molecular imaging community to determine to what extent the timing resolution of scintillation detectors can be improved and develop near-term solutions for advancing ToF-PET. Presented in this work, is a method for calculating the Cramér-Rao lower bound (CRLB) on timing resolution for scintillation detectors with long crystal elements, where the influence of the variation in optical path length of scintillation light on achievable timing resolution is non-negligible. The presented formalism incorporates an accurate, analytical probability density function (PDF) of optical transit time within the crystal to obtain a purely mathematical expression of the CRLB with high-aspect-ratio (HAR) scintillation detectors. This approach enables the statistical limit on timing resolution performance to be analytically expressed for clinically-relevant PET scintillation detectors without requiring Monte Carlo simulation-generated photon transport time distributions. The analytically calculated optical transport PDF was compared with detailed light transport simulations, and excellent agreement was found between the two. The coincidence timing resolution (CTR) between two 3× 3× 20 mm3 LYSO:Ce crystals coupled to analogue SiPMs was experimentally measured to be 162+/- 1 ps FWHM, approaching the analytically calculated lower bound within 6.5%.

Buffer-induced swelling and vesicle budding in binary lipid mixtures of dioleoylphosphatidylcholine:dioleoylphosphatidylethanolamine and dioleoylphosphatidylcholine:lysophosphatidylcholine using small-angle X-ray scattering and ³¹P static NMR.

PubMed

Barriga, Hanna M G; Bazin, Richard; Templer, Richard H; Law, Robert V; Ces, Oscar

2015-03-17

A large variety of data exists on lipid phase behavior; however, it is mostly in nonbuffered systems over nonbiological temperature ranges. We present biophysical data on lipid mixtures of dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE), and lysophosphatidylcholine (LysoPC) examining their behaviors in excess water and buffer systems over the temperature range 4-34 °C. These mixtures are commonly used to investigate the effects of spontaneous curvature on integral membrane proteins. Using small-angle X-ray scattering (SAXS) and (31)P NMR, we observed lamellar and vesicle phases, with the buffer causing an increase in the layer spacing. Increasing amounts of DOPE in a DOPC bilayer decreased the layer spacing of the mesophase, while the opposite trend was observed for increasing amounts of LysoPC. (31)P static NMR was used to analyze the DOPC:LysoPC samples to investigate the vesicle sizes present, with evidence of vesicle budding observed at LysoPC concentrations above 30 mol %. NMR line shapes were fitted using an adapted program accounting for the distortion of the lipids within the magnetic field. The distortion of the vesicle, because of magnetic susceptibility, varied with LysoPC content, and a discontinuity was found in both the water and buffer samples. Generally, the distortion increased with LysoPC content; however, at a ratio of DOPC:LysoPC 60:40, the sample showed a level of distortion of the vesicle similar to that of pure DOPC. This implies an increased flexibility in the membrane at this point. Commonly, the assumption is that for increasing LysoPC concentration there is a reduction in membrane tension, implying that estimations of membrane tension based on spontaneous curvature assumptions may not be accurate.

Two-Dimensional Nuclear Magnetic Resonance Structure Determination Module for Introductory Biochemistry: Synthesis and Structural Characterization of Lyso-Glycerophospholipids

ERIC Educational Resources Information Center

Garrett, Teresa A.; Rose, Rebecca L.; Bell, Sidney M.

2013-01-01

In this laboratory module, introductory biochemistry students are exposed to two-dimensional [superscript 1]H-nuclear magnetic resonance of glycerophospholipids (GPLs). Working in groups of three, students enzymatically synthesized and purified a variety of 2-acyl lyso GPLs. The structure of the 2-acyl lyso GPL was verified using [superscript…

Water soluble two-photon fluorescent organic probes for long-term imaging of lysosomes in live cells and tumor spheroids.

PubMed

Kumari, Pratibha; Verma, Sanjay K; Mobin, Shaikh M

2018-01-11

The morphological alteration of lysosomes is a powerful indicator of various pathological disorders. In this regard, we have designed and synthesized a new water soluble fluorescent Schiff-base ligand (L-lyso) containing two hydroxyl groups. L-lyso exhibits excellent two-photon properties with tracking of lysosomes in live cells as well as in 3D tumor spheroids. Furthermore, it can label lysosomes for more than 3 days. Thus, L-lyso has an edge over the commercially available expensive LysoTracker probes and also over other reported probes in terms of its long-term imaging, water solubility and facile synthesis.

Data acquisition electronics for gamma ray emission tomography using width-modulated leading-edge discriminators

NASA Astrophysics Data System (ADS)

Lage, E.; Tapias, G.; Villena, J.; Desco, M.; Vaquero, J. J.

2010-08-01

We present a new high-performance and low-cost approach for implementing radiation detection acquisition systems. The basic elements used are charge-integrating ADCs and a set of components encapsulated in an HDL (hardware definition language) library which makes it possible to implement several acquisition tasks such as time pickoff and coincidence detection using a new and simple trigger technique that we name WMLET (width-modulated leading-edge timing). As proof of concept, a 32-channel hybrid PET/SPECT acquisition system based on these elements was developed and tested. This demonstrator consists of a master module responsible for the generation and distribution of trigger signals, 2 × 16-channel ADC cards (12-bit resolution) for data digitization and a 32-bit digital I/O PCI card for handling data transmission to a personal computer. System characteristics such as linearity, maximum transmission rates or timing resolution in coincidence mode were evaluated with test and real detector signals. Imaging capabilities of the prototype were also evaluated using different detector configurations. The performance tests showed that this implementation is able to handle data rates in excess of 600k events s-1 when acquiring simultaneously 32 channels (96-byte events). ADC channel linearity is >98.5% in energy quantification. Time resolution in PET mode for the tested configurations ranges from 3.64 ns FWHM to 7.88 ns FWHM when signals from LYSO-based detectors are used. The measured energy resolution matched the expected values for the detectors evaluated and single elements of crystal matrices can be neatly separated in the acquired flood histograms.

Data acquisition electronics for gamma ray emission tomography using width-modulated leading-edge discriminators.

PubMed

Lage, E; Tapias, G; Villena, J; Desco, M; Vaquero, J J

2010-08-07

We present a new high-performance and low-cost approach for implementing radiation detection acquisition systems. The basic elements used are charge-integrating ADCs and a set of components encapsulated in an HDL (hardware definition language) library which makes it possible to implement several acquisition tasks such as time pickoff and coincidence detection using a new and simple trigger technique that we name WMLET (width-modulated leading-edge timing). As proof of concept, a 32-channel hybrid PET/SPECT acquisition system based on these elements was developed and tested. This demonstrator consists of a master module responsible for the generation and distribution of trigger signals, 2 x 16-channel ADC cards (12-bit resolution) for data digitization and a 32-bit digital I/O PCI card for handling data transmission to a personal computer. System characteristics such as linearity, maximum transmission rates or timing resolution in coincidence mode were evaluated with test and real detector signals. Imaging capabilities of the prototype were also evaluated using different detector configurations. The performance tests showed that this implementation is able to handle data rates in excess of 600k events s(-1) when acquiring simultaneously 32 channels (96-byte events). ADC channel linearity is >98.5% in energy quantification. Time resolution in PET mode for the tested configurations ranges from 3.64 ns FWHM to 7.88 ns FWHM when signals from LYSO-based detectors are used. The measured energy resolution matched the expected values for the detectors evaluated and single elements of crystal matrices can be neatly separated in the acquired flood histograms.

A flexible, small positron emission tomography prototype for resource-limited laboratories

NASA Astrophysics Data System (ADS)

Miranda-Menchaca, A.; Martínez-Dávalos, A.; Murrieta-Rodríguez, T.; Alva-Sánchez, H.; Rodríguez-Villafuerte, M.

2015-05-01

Modern small-animal PET scanners typically consist of a large number of detectors along with complex electronics to provide tomographic images for research in the preclinical sciences that use animal models. These systems can be expensive, especially for resource-limited educational and academic institutions in developing countries. In this work we show that a small-animal PET scanner can be built with a relatively reduced budget while, at the same time, achieving relatively high performance. The prototype consists of four detector modules each composed of LYSO pixelated crystal arrays (individual crystal elements of dimensions 1 × 1 × 10 mm3) coupled to position-sensitive photomultiplier tubes. Tomographic images are obtained by rotating the subject to complete enough projections for image reconstruction. Image quality was evaluated for different reconstruction algorithms including filtered back-projection and iterative reconstruction with maximum likelihood-expectation maximization and maximum a posteriori methods. The system matrix was computed both with geometric considerations and by Monte Carlo simulations. Prior to image reconstruction, Fourier data rebinning was used to increase the number of lines of response used. The system was evaluated for energy resolution at 511 keV (best 18.2%), system sensitivity (0.24%), spatial resolution (best 0.87 mm), scatter fraction (4.8%) and noise equivalent count-rate. The system can be scaled-up to include up to 8 detector modules, increasing detection efficiency, and its price may be reduced as newer solid state detectors become available replacing the traditional photomultiplier tubes. Prototypes like this may prove to be very valuable for educational, training, preclinical and other biological research purposes.

Monitoring Energy Calibration Drift Using the Scintillator Background Radiation

NASA Astrophysics Data System (ADS)

Conti, Maurizio; Eriksson, Lars; Hayden, Charles

2011-06-01

Scintillating materials commonly used in nuclear medicine can contain traces of isotopes that naturally emit gamma or beta radiation. Examples of these are 138La contained in LaBr3 and other Lanthanum based scintillators, and 176Lu contained in LSO, LYSO, LuYAP and other Lutetium based scintillators. In particular,176Lu decays into 176Hf and emits a beta particle with maximum energy 589 keV, and a cascade of gamma rays of energies 307 keV, 202 keV and 88 keV. We propose to use the background radiation for monitoring of detector calibration drift and for self-calibration of detectors in complex detector systems. A calibration drift due to random or systematic changes in photomultiplier tube (PMT) gain was studied in a Siemens PET scanner, based on LSO blocks. Both a conventional radioactive source (68Ge, 511 keV photons from electron-positron annihilation) and the LSO background radiation were used for calibration. The difference in the calibration peak shift at 511 keV estimated with the two methods was less than 10%.

Features of Different Inorganic Scintillators Used in Neutron-Radiation Systems for Illegal Substance Detection

NASA Astrophysics Data System (ADS)

Batyaev, V. F.; Belichenko, S. G.; Bestaev, R. R.

2016-04-01

The work is devoted to a quantitative comparison of different inorganic scintillators to be used in neutron-radiation inspection systems. Such systems can be based on the tagged neutron (TN) method and have a significant potential in different applications such as detection of explosives, drugs, mines, identification of chemical warfare agents, assay of nuclear materials and human body composition [1]-[3]. The elemental composition of an inspected object is determined via spectrometry of gammas from the object bombarded by neutrons which are tagged by an alpha-detector built inside a neutron generator. This creates a task to find a quantitative indicator of the object identification quality (via elemental composition) as a function of basic parameters of the γ-detectors, such as their efficiency, energy and time resolutions, which in turn are generally defined by a scintillator of the detector. We have tried to solve the task for a set of four scintillators which are often used in the study of TN method, namely BGO, LaBr3, LYSO, NaI(Tl), whose basic parameters are well known [4]-[7].

In-beam PET data characterization with the large area DoPET prototype

NASA Astrophysics Data System (ADS)

Sportelli, G.; Belcari, N.; Camarlinghi, N.; Ciocca, M.; Collini, F.; Molinelli, S.; Pullia, M.; Zaccaro, E.; Del Guerra, A.; Rosso, V.

2016-02-01

Range verification with in-beam PET techniques is a powerful tool for monitoring the correctness of dose delivery in particle therapy. Among the major limitations of in-beam PET systems are the limited detectors size due to the constrained space in which they can be placed to allow the irradiation, and the necessity of a high read-out modularization, due to high activity rates during the irradiation. In this work we present the data acquired at the CNAO (Centro Nazionale di Adroterapia Oncologica) treatment center in Pavia, Italy, with the new DoPET system, specifically designed to operate in in-beam conditions. The new prototype consists of two planar 15cm × 15cm LYSO-based detectors, read out by 9 PMT detector modules each. In particular, we test the capability of our system to determine particle range in various irradiation conditions. Several plastic phantoms were irradiated at the CNAO treatment centre with protons and carbon ions of various energies. The used dose in treatment plans is 2 Gy and the monitoring feedback is produced in a few minutes after the end of the treatment.

Measurement of the time resolution of small SiPM-based scintillation counters

NASA Astrophysics Data System (ADS)

Kravchenko, E. A.; Porosev, V. V.; Savinov, G. A.

2017-12-01

In this research, we evaluated the timing resolution of SiPM-based scintillation detector on a 1-GeV electron beam "extracted" from VEPP-4M. We tested small scintillation crystals of pure CsI, YAP, LYSO, and LFS-3 with HAMAMATSU S10362-33-025C and S13360-3050CS. The CsI scintillator together with HAMAMATSU S13360-3050CS demonstrated the best results. Nevertheless, the achieved time resolution of ~80 ps (RMS) relates mainly to the photodetector itself. It makes the silicon photomultiplier an attractive candidate to replace other devices in applications where sub-nanosecond accuracy is required.

The System Design, Engineering Architecture, and Preliminary Results of a Lower-Cost High-Sensitivity High-Resolution Positron Emission Mammography Camera.

PubMed

Zhang, Yuxuan; Ramirez, Rocio A; Li, Hongdi; Liu, Shitao; An, Shaohui; Wang, Chao; Baghaei, Hossain; Wong, Wai-Hoi

2010-02-01

A lower-cost high-sensitivity high-resolution positron emission mammography (PEM) camera is developed. It consists of two detector modules with the planar detector bank of 20 × 12 cm(2). Each bank has 60 low-cost PMT-Quadrant-Sharing (PQS) LYSO blocks arranged in a 10 × 6 array with two types of geometries. One is the symmetric 19.36 × 19.36 mm(2) block made of 1.5 × 1.5 × 10 mm(3) crystals in a 12 × 12 array. The other is the 19.36 × 26.05 mm(2) asymmetric block made of 1.5 × 1.9 × 10 mm(3) crystals in 12 × 13 array. One row (10) of the elongated blocks are used along one side of the bank to reclaim the half empty PMT photocathode in the regular PQS design to reduce the dead area at the edge of the module. The bank has a high overall crystal packing fraction of 88%, which results in a very high sensitivity. Mechanical design and electronics have been developed for low-cost, compactness, and stability purposes. Each module has four Anger-HYPER decoding electronics that can handle a count-rate of 3 Mcps for single events. A simple two-module coincidence board with a hardware delay window for random coincidences has been developed with an adjustable window of 6 to 15 ns. Some of the performance parameters have been studied by preliminary tests and Monte Carlo simulations, including the crystal decoding map and the 17% energy resolution of the detectors, the point source sensitivity of 11.5% with 50 mm bank-to-bank distance, the 1.2 mm-spatial resolutions, 42 kcps peak Noise Equivalent Count Rate at 7.0-mCi total activity in human body, and the resolution phantom images. Those results show that the design goal of building a lower-cost, high-sensitivity, high-resolution PEM detector is achieved.

An algorithm for automatic crystal identification in pixelated scintillation detectors using thin plate splines and Gaussian mixture models

NASA Astrophysics Data System (ADS)

Schellenberg, Graham; Stortz, Greg; Goertzen, Andrew L.

2016-02-01

A typical positron emission tomography detector is comprised of a scintillator crystal array coupled to a photodetector array or other position sensitive detector. Such detectors using light sharing to read out crystal elements require the creation of a crystal lookup table (CLUT) that maps the detector response to the crystal of interaction based on the x-y position of the event calculated through Anger-type logic. It is vital for system performance that these CLUTs be accurate so that the location of events can be accurately identified and so that crystal-specific corrections, such as energy windowing or time alignment, can be applied. While using manual segmentation of the flood image to create the CLUT is a simple and reliable approach, it is both tedious and time consuming for systems with large numbers of crystal elements. In this work we describe the development of an automated algorithm for CLUT generation that uses a Gaussian mixture model paired with thin plate splines (TPS) to iteratively fit a crystal layout template that includes the crystal numbering pattern. Starting from a region of stability, Gaussians are individually fit to data corresponding to crystal locations while simultaneously updating a TPS for predicting future Gaussian locations at the edge of a region of interest that grows as individual Gaussians converge to crystal locations. The algorithm was tested with flood image data collected from 16 detector modules, each consisting of a 409 crystal dual-layer offset LYSO crystal array readout by a 32 pixel SiPM array. For these detector flood images, depending on user defined input parameters, the algorithm runtime ranged between 17.5-82.5 s per detector on a single core of an Intel i7 processor. The method maintained an accuracy above 99.8% across all tests, with the majority of errors being localized to error prone corner regions. This method can be easily extended for use with other detector types through adjustment of the initial template model used.

Examination of Triacylglycerol Biosynthetic Pathways via De Novo Transcriptomic and Proteomic Analyses in an Unsequenced Microalga

DTIC Science & Technology

2011-10-17

analysis results. The components of the TAG biosynthetic pathway, including glycerol-3-phosphate acyl- transferase (GPAT), lyso- phosphatidic acid ...acyltransferase (LPAAT), phosphatidic acid phosphatase (PAP), lyso-phosphati- dylcholine acyltransferase (LPAT), and diacylglycerol acyltransfer- ase (DGAT...transfer to position one of G3P results in the formation of lyso- phosphatidic acid (LPA), in a reaction catalyzed by GPAT. Subsequent acyl transfer to

Biomarkers of Morbid Obesity and Prediabetes by Metabolomic Profiling of Human Discordant Phenotypes.

PubMed

Tulipani, Sara; Palau-Rodriguez, Magali; Miñarro Alonso, Antonio; Cardona, Fernando; Marco-Ramell, Anna; Zonja, Bozo; Lopez de Alda, Miren; Muñoz-Garach, Araceli; Sanchez-Pla, Alejandro; Tinahones, Francisco J; Andres-Lacueva, Cristina

2016-12-01

Metabolomic studies aimed to dissect the connection between the development of type 2 diabetes and obesity are still scarce. In the present study, fasting serum from sixty-four adult individuals classified into four sex-matched groups by their BMI [non-obese versus morbid obese] and the increased risk of developing diabetes [prediabetic insulin resistant state versus non-prediabetic non-insulin resistant] was analyzed by LC- and FIA-ESI-MS/MS-driven metabolomic approaches. Altered levels of [lyso]glycerophospholipids was the most specific metabolic trait associated to morbid obesity, particularly lysophosphatidylcholines acylated with margaric, oleic and linoleic acids [lysoPC C17:0: R=-0.56, p=0.0003; lysoPC C18:1: R=-0.61, p=0.0001; lysoPC C18:2 R=-0.64, p<0.0001]. Several amino acids were biomarkers of risk of diabetes onset associated to obesity. For instance, glutamate significantly associated with fasting insulin [R=0.5, p=0.0019] and HOMA-IR [R=0.46, p=0.0072], while glycine showed negative associations [fasting insulin: R=-0.51, p=0.0017; HOMA-IR: R=-0.49, p=0.0033], and the branched chain amino acid valine associated to prediabetes and insulin resistance in a BMI-independent manner [fasting insulin: R=0.37, p=0.0479; HOMA-IR: R=0.37, p=0.0468]. Minority sphingolipids including specific [dihydro]ceramides and sphingomyelins also associated with the prediabetic insulin resistant state, hence deserving attention as potential targets for early diagnosis or therapeutic intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Algorithms for Photon Depth of Interaction Estimation for the TRIMAGE PET Component

NASA Astrophysics Data System (ADS)

Camarlinghi, Niccolò; Belcari, Nicola; Cerello, Piergiorgio; Pennazio, Francesco; Sportelli, Giancarlo; Zaccaro, Emanuele; Del Guerra, Alberto

2016-02-01

The TRIMAGE consortium aims to develop a multimodal PET/MR/EEG brain scanner dedicated to the early diagnosis of schizophrenia and other mental health disorders. The TRIMAGE PET component features a full ring made of 18 detectors, each one consisting of twelve 8 ×8 Silicon PhotoMultipliers (SiPMs) tiles coupled to two segmented LYSO crystal matrices with staggered layers. The identification of the pixel where a photon interacted is performed on-line at the front-end level, thus allowing the FPGA board to emit fully digital event packets. This allows to increase the effective bandwidth, but imposes restrictions on the complexity of the algorithms to be implemented. In this work, two algorithms, whose implementation is feasible directly on an FPGA, are presented and evaluated. The first algorithm is driven by physical considerations, while the other consists in a two-class linear Support Vector Machine (SVM). The validation of the algorithm performance is carried out by using simulated data generated with the GAMOS Monte Carlo. The obtained results show that the achieved accuracy in layer identification is above 90% for both the proposed approaches. The feasibility of tagging and rejecting events that underwent multiple interactions within the detector is also discussed.

Use of LysoTracker dyes: a flow cytometric study of autophagy.

PubMed

Chikte, Shaheen; Panchal, Neelam; Warnes, Gary

2014-02-01

The flow cytometric use of LysoTracker dyes was employed to investigate the autophagic process and to compare this with the upregulation of autophagy marker, the microtubule-associated protein LC3B. Although the mechanism of action of LysoTracker dyes is not fully understood, they have been used in microscopy to image acidic spherical organelles, and their use in flow cytometry has not been thoroughly investigated in the study of autophagy. This investigation uses numerous autophagy-inducing agents including chloroquine (CQ), rapamycin, low serum (<1%) RPMI, and nutrient starvation to induce autophagy in Jurkat T-cell leukemia and K562 erythromyeloid cell lines. LC3B showed an increase with CQ treatment although this was different to LysoTracker signals in terms of dose and time. Rapamycin, low serum (<1%) RPMI, and nutrient starvation induction of autophagy also induced an increase in LysoTracker and LC3B signals. CQ also induced apoptosis in cell lines, which was blocked by pan-caspase inhibitor z-VAD resulting in a reduction in cells undergoing apoptosis and a subsequent upregulation of autophagic markers LC3B and lysosomal dye signals. Given that LC3B and LysoTracker are measuring different biological events in the autophagic process, they surprisingly both upregulated during autophagic process. This study, however, shows that although LysoTracker dyes do not specifically label lysosomes or autophagosomes within the cell, they allow the simultaneous measurement of an autophagy-related process and other live-cell functions, which are not possible with the standard LC3B antibody-labeling technique. This method has the advantage of other live-cell LCB-GFP-tagged experiments in that be used to analyze patient cells as well as easier to use and significantly less costly. Copyright © 2013 International Society for Advancement of Cytometry.

Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

PubMed Central

Ferreira, Susana; Auray-Blais, Christiane; Boutin, Michel; Lavoie, Pamela; Nunes, José Pedro; Martins, Elisabete; Garman, Scott; Oliveira, João Paulo

2016-01-01

Recent data have shown that lyso-Gb3, the deacylated derivative of globotriaosylceramide (Gb3), is possibly involved in the pathogenesis of Fabry disease (FD) and might be a clinically useful biomarker of its metabolic load. To test this hypothesis, we assayed Gb3 and lyso-Gb3 and related analogs in plasma and/or urine samples of 12 clinically well-characterized subjects carrying several different GLA variant alleles associated with a wide range of residual α-galactosidase A activities. Urinary Gb3 was measured by HPLC–MS/MS; plasma and urinary lyso-Gb3 and related analogs were measured by UPLC–MS/MS. Individual profiles of Gb3 and lyso-Gb3 and related analogs closely correlated with the phenotypic data for each subject, discerning the classical FD patient from the two patients carrying cardiac variants as well as these from all the others without FD. The lyso-Gb3 analog at m/z 836 was found at increased levels only in patients manifesting clinically severe heart disease, irrespective of the pathogenicity of the GLA variant they carried. This finding suggests that this lyso-Gb3 analog might be an earlier biomarker of progressive heart disease, non-specific of the FD cardiomyopathy. The possibility that urinary Gb3 is a specific marker of kidney involvement in FD deserves further study. PMID:26070511

A compact high resolution flat panel PET detector based on the new 4-side buttable MPPC for biomedical applications.

PubMed

Wang, Qiang; Wen, Jie; Ravindranath, Bosky; O'Sullivan, Andrew W; Catherall, David; Li, Ke; Wei, Shouyi; Komarov, Sergey; Tai, Yuan-Chuan

2015-09-11

Compact high-resolution panel detectors using virtual pinhole (VP) PET geometry can be inserted into existing clinical or pre-clinical PET systems to improve regional spatial resolution and sensitivity. Here we describe a compact panel PET detector built using the new Though Silicon Via (TSV) multi-pixel photon counters (MPPC) detector. This insert provides high spatial resolution and good timing performance for multiple bio-medical applications. Because the TSV MPPC design eliminates wire bonding and has a package dimension which is very close to the MPPC's active area, it is 4-side buttable. The custom designed MPPC array (based on Hamamatsu S12641-PA-50(x)) used in the prototype is composed of 4 × 4 TSV-MPPC cells with a 4.46 mm pitch in both directions. The detector module has 16 × 16 lutetium yttrium oxyorthosilicate (LYSO) crystal array, with each crystal measuring 0.92 × 0.92 × 3 mm 3 with 1.0 mm pitch. The outer diameter of the detector block is 16.8 × 16.8 mm 2 . Thirty-two such blocks will be arranged in a 4 × 8 array with 1 mm gaps to form a panel detector with detection area around 7 cm × 14 cm in the full-size detector. The flood histogram acquired with Ge-68 source showed excellent crystal separation capability with all 256 crystals clearly resolved. The detector module's mean, standard deviation, minimum (best) and maximum (worst) energy resolution were 10.19%, +/-0.68%, 8.36% and 13.45% FWHM, respectively. The measured coincidence time resolution between the block detector and a fast reference detector (around 200 ps single photon timing resolution) was 0.95 ns. When tested with Siemens Cardinal electronics the performance of the detector blocks remain consistent. These results demonstrate that the TSV-MPPC is a promising photon sensor for use in a flat panel PET insert composed of many high resolution compact detector modules.

Simulation of π 0-γ separation study for proposed CMS forward electromagnetic calorimeter

DOE PAGES

Roy, Ashim; Jain, Shilpi; Banerjee, Sunanda; ...

2016-11-11

The Forward Electromagnetic Calorimeter of the CMS detector is going to be upgraded in the high luminosity running as the energy of the present Electromagnetic Calorimeter (PbWO4) will degrade in the high luminosity (luminosity 10 34 cm -2 s -1) running due to extensive radiation (hadron flux 10 13 neutrons cm, -2). Shashlik Electromagnetic Calorimeter which consists of alternate layers of 1.5 mm LYSO(Ce) crystal plates and 2.5 mm Tungsten absorbers, was a proposal for high luminosity running. One of the performance points for any electromagnetic calorimeter is the ability to separate π 0 s from true photons, since finalmore » states with photons are a clean and one of the most important final states in proton-proton collisions at the LHC. As a result, the objective of this project is to study the possibility of π 0 and γ separation in the Shashlik detector using Multivariate Analysis (MVA) technique.« less

Simulation of π 0-γ separation study for proposed CMS forward electromagnetic calorimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy, Ashim; Jain, Shilpi; Banerjee, Sunanda

The Forward Electromagnetic Calorimeter of the CMS detector is going to be upgraded in the high luminosity running as the energy of the present Electromagnetic Calorimeter (PbWO4) will degrade in the high luminosity (luminosity 10 34 cm -2 s -1) running due to extensive radiation (hadron flux 10 13 neutrons cm, -2). Shashlik Electromagnetic Calorimeter which consists of alternate layers of 1.5 mm LYSO(Ce) crystal plates and 2.5 mm Tungsten absorbers, was a proposal for high luminosity running. One of the performance points for any electromagnetic calorimeter is the ability to separate π 0 s from true photons, since finalmore » states with photons are a clean and one of the most important final states in proton-proton collisions at the LHC. As a result, the objective of this project is to study the possibility of π 0 and γ separation in the Shashlik detector using Multivariate Analysis (MVA) technique.« less

Design of the PET-MR system for head imaging of the DREAM Project

NASA Astrophysics Data System (ADS)

González, A. J.; Conde, P.; Hernández, L.; Herrero, V.; Moliner, L.; Monzó, J. M.; Orero, A.; Peiró, A.; Rodríguez-Álvarez, M. J.; Ros, A.; Sánchez, F.; Soriano, A.; Vidal, L. F.; Benlloch, J. M.

2013-02-01

In this paper we describe the overall design of a PET-MR system for head imaging within the framework of the DREAM Project as well as the first detector module tests. The PET system design consists of 4 rings of 16 detector modules each and it is expected to be integrated in a head dedicated radio frequency coil of an MR scanner. The PET modules are based on monolithic LYSO crystals coupled by means of optical devices to an array of 256 Silicon Photomultipliers. These types of crystals allow to preserve the scintillation light distribution and, thus, to recover the exact photon impact position with the proper characterization of such a distribution. Every module contains 4 Application Specific Integrated Circuits (ASICs) which return detailed information of several light statistical momenta. The preliminary tests carried out on this design and controlled by means of ASICs have shown promising results towards the suitability of hybrid PET-MR systems.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PubMed

Maruyama, Hiroki; Miyata, Kaori; Mikame, Mariko; Taguchi, Atsumi; Guili, Chu; Shimura, Masaru; Murayama, Kei; Inoue, Takeshi; Yamamoto, Saori; Sugimura, Koichiro; Tamita, Koichi; Kawasaki, Toshihiro; Kajihara, Jun; Onishi, Akifumi; Sugiyama, Hitoshi; Sakai, Teiko; Murata, Ichijiro; Oda, Takamasa; Toyoda, Shigeru; Hanawa, Kenichiro; Fujimura, Takeo; Ura, Shigehisa; Matsumura, Mimiko; Takano, Hideki; Yamashita, Satoshi; Matsukura, Gaku; Tazawa, Ryushi; Shiga, Tsuyoshi; Ebato, Mio; Satoh, Hiroshi; Ishii, Satoshi

2018-03-15

PurposePlasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females.MethodsBetween 1 July 2014 and 31 December 2015, we screened 2,360 patients (1,324 males) referred from 169 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively.ResultsOf 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml -1 ) and low α-Gal A activity (≤4.0 nmol h -1  ml -1 ), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 15 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 8 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance).ConclusionPlasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.Genet Med advance online publication, 15 March 2018; doi:10.1038/gim.2018.31.

Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS).

PubMed

Kim, Ji Young; Park, Ju Yeon; Kim, Oh Yoen; Ham, Bo Mi; Kim, Hyun-Jin; Kwon, Dae Young; Jang, Yangsoo; Lee, Jong Ho

2010-09-03

Obesity is currently epidemic in many countries worldwide and is strongly related to diabetes and cardiovascular disease. This study investigated the differences in metabolomic profiling between overweight/obese and normal-weight men. Overweight/obese (n=30) and age-matched, normal-weight men (n=30) were included. Anthropometric parameters, conventional metabolites, and biomarkers were measured. Metabolomic profiling was analyzed with UPLC-Q-TOF MS. Overweight/obese men showed higher levels of HOMA-IR, triglycerides, total cholesterol, and LDL-cholesterol, and lower levels of HDL-cholesterol and adiponectin than lean men. Overweight/obese men showed higher proportion of stearic acid and lower proportion of oleic acid in serum phospholipids. Additionally, overweight/obese individuals showed higher fat intake and lower ratio of polyunsaturated fatty acids to saturated fatty acids. We identified three lyso-phosphatidylcholine (lysoPC) as potential plasma markers and confirmed eight known metabolites for overweight/obesity men. Especially, overweight/obese subjects showed higher levels of lysoPC C14:0 and lysoPC C18:0 and lower levels of lysoPC C18:1 than lean subjects. Results confirmed abnormal metabolism of two branched-chain amino acids, two aromatic amino acids, and fatty acid synthesis and oxidation in overweight/obese men. Additionally, the amount of dietary saturated fat may influence the proportion of saturated fatty acids in serum phospholipids and the degree of saturation of the constituent acyl group of plasma lysoPC.

Novel enzymatic method for assaying Lp-PLA2 in serum.

PubMed

Yamaura, Saki; Sakasegawa, Shin-Ichi; Koguma, Emisa; Ueda, Shigeru; Kayamori, Yuzo; Sugimori, Daisuke; Karasawa, Ken

2018-06-01

Measurement of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) can be used as an adjunct to traditional cardiovascular risk factors for identifying individuals at higher risk of cardiovascular events. This can be performed by quantification of the protein concentration using an ELISA platform or by measuring Lp-PLA 2 activity using platelet-activating factor (PAF) analog as substrate. Here, an enzymatic Lp-PLA 2 activity assay method using 1-O-Hexadecyl-2-acetyl-rac-glycero-3-phosphocholine (rac C 16 PAF) was developed. The newly revealed substrate specificity of lysoplasmalogen-specific phospholipase D (lysophospholipase D (LysoPLD)) was exploited. Lp-PLA 2 hydrolyzes 1-O-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C 16 PAF) to 1-O-Hexadecyl-2-hydroxy-sn-glycero-3-phosphocholine (LysoPAF). LysoPLD acted on LysoPAF, and the hydrolytically released choline was detected by choline oxidase. Regression analysis of Lp-PLA 2 activity measured by the enzymatic Lp-PLA 2 activity assay vs. two chemical Lp-PLA 2 activity assays, i.e. LpPLA 2 FS and PLAC® test, and ELISA, gave the following correlation coefficients: 0.990, 0.893 and 0.785, respectively (n = 30). Advantages of this enzymatic Lp-PLA 2 activity assay compared with chemical Lp-PLA 2 methods include the following; (i) only requires two reagents enabling a simple two-point linear calibration method with one calibrator (ii) no need for inhibitors of esterase-like activity in serum. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats.

PubMed

Zhu, Lei; Zhao, Zhi Jun; Ren, Xiao Bin; Li, Qiang; Ding, Hua; Sun, Zhou; Kao, Qing Jun; Wang, Li Hua

2018-01-01

The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats.

PubMed

Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N

1994-05-15

Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

Partial synthesis of ganglioside and lysoganglioside lipoforms as internal standards for MS quantification.

PubMed

Gantner, Martin; Schwarzmann, Günter; Sandhoff, Konrad; Kolter, Thomas

2014-12-01

Within recent years, ganglioside patterns have been increasingly analyzed by MS. However, internal standards for calibration are only available for gangliosides GM1, GM2, and GM3. For this reason, we prepared homologous internal standards bearing nonnatural fatty acids of the major mammalian brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, and of the tumor-associated gangliosides GM2 and GD2. The fatty acid moieties were incorporated after selective chemical or enzymatic deacylation of bovine brain gangliosides. For modification of the sphingoid bases, we developed a new synthetic method based on olefin cross metathesis. This method was used for the preparation of a lyso-GM1 and a lyso-GM2 standard. The total yield of this method was 8.7% for the synthesis of d17:1-lyso-GM1 from d20:1/18:0-GM1 in four steps. The title compounds are currently used as calibration substances for MS quantification and are also suitable for functional studies. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Studying the energy dependence of intrinsic conversion efficiency of single crystal scintillators under X-ray excitation

NASA Astrophysics Data System (ADS)

Kalyvas, N.; Valais, I.; David, S.; Michail, Ch.; Fountos, G.; Liaparinos, P.; Kandarakis, I.

2014-05-01

Single crystal scintilators are used in various radiation detectors applications. The efficiency of the crystal can be determined by the Detector Optical Gain (DOG) defined as the ratio of the emitted optical photon flux over the incident radiation photons flux. A parameter affecting DOG is the intrinsic conversion efficiency ( n C ) giving the percentage of the X-ray photon power converted to optical photon power. n C is considered a constant value for X-ray energies in the order of keV although a non-proportional behavior has been reported. In this work an analytical model, has been utilized to single crystals scintillators GSO:Ce, LSO:Ce and LYSO:Ce to examine whether the intrinsic conversion efficiency shows non proportional behavior under X-ray excitation. DOG was theoretically calculated as a function of the incident X-ray spectrum, the X-ray absorption efficiency, the energy of the produced optical photons and the light transmission efficiency. The theoretical DOG values were compared with experimental data obtained by irradiating the crystals with X-rays at tube voltages from 50 to 140 kV and by measuring the light energy flux emitted from the irradiated screen. An initial value for n C (calculated from literature data) was assumed for the X-ray tube voltage of 50 kV. For higher X-ray tube voltages the optical photon propagation phenomena was assumed constant and any deviations between experimental and theoretical data were associated with changes in the intrinsic conversion efficiency. The experimental errors were below 7% for each experimental setup. The behavior of n C values for LSO:Ce and LYSO:Ce were found very similar, i.e., ranging with values from 0.089 at 50 kV to 0.015 at 140 kV, while for GSO:Ce, n C demonstrated a peak at 80 kV.

Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis.

PubMed

Zhou, Lina; Shi, Mengchen; Zhao, Lu; Lin, Zhipeng; Tang, Zeli; Sun, Hengchang; Chen, Tingjin; Lv, Zhiyue; Xu, Jin; Huang, Yan; Yu, Xinbing

2017-06-17

Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liver fibrosis induced by the liver fluke Clonorchis sinensis are poorly understood. Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and pathogenesis of parasites and fungi; however, the roles of C. sinensis lysophospholipase A (CsLysoPLA) in C. sinensis-induced liver fibrosis remain unknown. A mouse macrophage cell line (RAW264.7) was cultured and treated with CsLysoPLA. IL-25 and members of its associated signaling pathway were detected by performing quantitative real-time PCR, Western blotting and immunofluorescent staining. A human hepatic stellate cell line (LX-2) was cultured and exposed to IL-25. LX-2 cell activation markers were examined via quantitative real-time PCR, Western blotting and immunofluorescent staining. Migration was analyzed in transwell plates. Treating RAW264.7 cells with CsLysoPLA significantly induced IL-25 expression. Elevated PKA, B-Raf, and ERK1/2 mRNA levels and phosphorylated B-Raf and ERK1/2 were detected in CsLysoPLA-stimulated RAW264.7 cells. The PKA inhibitor H-89 weakened B-Raf and ERK1/2 phosphorylation whereas the AKT activator SC79 attenuated ERK1/2 phosphorylation in RAW264.7 cells. Both H-89 and SC79 inhibited CsLysoPLA-induced IL-25 upregulation. In addition, stimulation of LX-2 cells with IL-25 upregulated the expression of mesenchymal cell markers, including α-smooth muscle actin (α-SMA) and collagen type I (Collagen-I), and promoted cell migration. CsLysoPLA activates HSCs by upregulating IL-25 in macrophages through the PKA-dependent B-Raf/ERK1/2 pathway and potentially promotes hepatic fibrosis during C. sinensis infection.

Optimization of a LSO-Based Detector Module for Time-of-Flight PET

NASA Astrophysics Data System (ADS)

Moses, W. W.; Janecek, M.; Spurrier, M. A.; Szupryczynski, P.; Choong, W.-S.; Melcher, C. L.; Andreaco, M.

2010-06-01

We have explored methods for optimizing the timing resolution of an LSO-based detector module for a single-ring, “demonstration” time-of-flight PET camera. By maximizing the area that couples the scintillator to the PMT and minimizing the average path length that the scintillation photons travel, a single detector timing resolution of 218 ps fwhm is measured, which is considerably better than the 385 ps fwhm obtained by commercial LSO or LYSO TOF detector modules. We explored different surface treatments (saw-cut, mechanically polished, and chemically etched) and reflector materials (Teflon tape, ESR, Lumirror, Melinex, white epoxy, and white paint), and found that for our geometry, a chemically etched surface had 5% better timing resolution than the saw-cut or mechanically polished surfaces, and while there was little dependence on the timing resolution between the various reflectors, white paint and white epoxy were a few percent better. Adding co-dopants to LSO shortened the decay time from 40 ns to 30 ns but maintained the same or higher total light output. This increased the initial photoelectron rate and so improved the timing resolution by 15%. Using photomultiplier tubes with higher quantum efficiency (blue sensitivity index of 13.5 rather than 12) improved the timing resolution by an additional 5%. By choosing the optimum surface treatment (chemically etched), reflector (white paint), LSO composition (co-doped), and PMT (13.5 blue sensitivity index), the coincidence timing resolution of our detector module was reduced from 309 ps to 220 ps fwhm.

LysoTracker and MitoTracker Red are transport substrates of P-glycoprotein: implications for anticancer drug design evading multidrug resistance.

PubMed

Zhitomirsky, Benny; Farber, Hodaya; Assaraf, Yehuda G

2018-04-01

LysoTracker and MitoTracker Red are fluorescent probes widely used for viable cell staining of lysosomes and mitochondria, respectively. They are utilized to study organelle localization and their resident proteins, assess organelle functionality and quantification of organelle numbers. The ATP-driven efflux transporter P-glycoprotein (P-gp) is expressed in normal and malignant tissues and extrudes structurally distinct endogenous and exogenous cytotoxic compounds. Thus, once aromatic hydrophobic compounds such as the above-mentioned fluorescent probes are recognized as transport substrates, efflux pumps including P-gp may abolish their ability to reach their cellular target organelles. Herein, we show that LysoTracker and MitoTracker Red are expelled from P-gp-overexpressing cancer cells, thus hindering their ability to fluorescently mark target organelles. We further demonstrate that tariquidar, a potent P-gp transport inhibitor, restores LysoTracker and MitoTracker Red cell entry. We conclude that LysoTracker and MitoTracker Red are P-gp transport substrates, and therefore, P-gp expression must be taken into consideration prior to cellular applications using these probes. Importantly, as MitoTracker was a superior P-gp substrate than LysoTracker Red, we discuss the implications for the future design of chemotherapeutics evading cancer multidrug resistance. Furthermore, restoration of MitoTracker Red fluorescence in P-gp-overexpressing cells may facilitate the identification of potent P-gp transport inhibitors (i.e. chemosensitizers). © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Performance evaluation of a compact PET/SPECT/CT tri-modality system for small animal imaging applications

NASA Astrophysics Data System (ADS)

Wei, Qingyang; Wang, Shi; Ma, Tianyu; Wu, Jing; Liu, Hui; Xu, Tianpeng; Xia, Yan; Fan, Peng; Lyu, Zhenlei; Liu, Yaqiang

2015-06-01

PET, SPECT and CT imaging techniques are widely used in preclinical small animal imaging applications. In this paper, we present a compact small animal PET/SPECT/CT tri-modality system. A dual-functional, shared detector design is implemented which enables PET and SPECT imaging with a same LYSO ring detector. A multi-pinhole collimator is mounted on the system and inserted into the detector ring in SPECT imaging mode. A cone-beam CT consisting of a micro focus X-ray tube and a CMOS detector is implemented. The detailed design and the performance evaluations are reported in this paper. In PET imaging mode, the measured NEMA based spatial resolution is 2.12 mm (FWHM), and the sensitivity at the central field of view (CFOV) is 3.2%. The FOV size is 50 mm (∅)×100 mm (L). The SPECT has a spatial resolution of 1.32 mm (FWHM) and an average sensitivity of 0.031% at the center axial, and a 30 mm (∅)×90 mm (L) FOV. The CT spatial resolution is 8.32 lp/mm @10%MTF, and the contrast discrimination function value is 2.06% with 1.5 mm size cubic box object. In conclusion, a compact, tri-modality PET/SPECT/CT system was successfully built with low cost and high performance.

A new PET detector concept for compact preclinical high-resolution hybrid MR-PET

NASA Astrophysics Data System (ADS)

Berneking, Arne; Gola, Alberto; Ferri, Alessandro; Finster, Felix; Rucatti, Daniele; Paternoster, Giovanni; Jon Shah, N.; Piemonte, Claudio; Lerche, Christoph

2018-04-01

This work presents a new PET detector concept for compact preclinical hybrid MR-PET. The detector concept is based on Linearly-Graded SiPM produced with current FBK RGB-HD technology. One 7.75 mm x 7.75 mm large sensor chip is coupled with optical grease to a black coated 8 mm x 8 mm large and 3 mm thick monolithic LYSO crystal. The readout is obtained from four readout channels with the linear encoding based on integrated resistors and the Center of Gravity approach. To characterize the new detector concept, the spatial and energy resolutions were measured. Therefore, the measurement setup was prepared to radiate a collimated beam to 25 different points perpendicular to the monolithic scintillator crystal. Starting in the center point of the crystal at 0 mm / 0 mm and sampling a grid with a pitch of 1.75 mm, all significant points of the detector were covered by the collimator beam. The measured intrinsic spatial resolution (FWHM) was 0.74 +/- 0.01 mm in x- and 0.69 +/- 0.01 mm in the y-direction at the center of the detector. At the same point, the measured energy resolution (FWHM) was 13.01 +/- 0.05 %. The mean intrinsic spatial resolution (FWHM) over the whole detector was 0.80 +/- 0.28 mm in x- and 0.72 +/- 0.19 mm in y-direction. The energy resolution (FWHM) of the detector was between 13 and 17.3 % with an average energy resolution of 15.7 +/- 1.0 %. Due to the reduced thickness, the sensitivity of this gamma detector is low but still higher than pixelated designs with the same thickness due to the monolithic crystals. Combining compact design, high spatial resolution, and high sensitivity, the detector concept is particularly suitable for applications where the scanner bore size is limited and high resolution is required - as is the case in small animal hybrid MR-PET.

Apical sorting of lysoGPI-anchored proteins occurs independent of association with detergent-resistant membranes but dependent on their N-glycosylation.

PubMed

Castillon, Guillaume Alain; Michon, Laetitia; Watanabe, Reika

2013-06-01

Most glycosylphosphatidylinositol-anchored proteins (GPI-APs) are located at the apical surface of epithelial cells. The apical delivery of GPI-APs is believed to result from their association with lipid rafts. We find that overexpression of C-terminally tagged PGAP3 caused predominant production of lysoGPI-APs, an intermediate precursor in the GPI lipid remodeling process in Madin-Darby canine kidney cells. In these cells, produced lysoGPI-APs are not incorporated into detergent-resistant membranes (DRMs) but still are delivered apically, suggesting that GPI-AP association with DRMs is not necessary for apical targeting. In contrast, apical transport of both fully remodeled and lyso forms of GPI-APs is dependent on N-glycosylation, confirming a general role of N-glycans in apical protein transport. We also find that depletion of cholesterol causes apical-to-basolateral retargeting not only of fully remodeled GPI-APs, but also of lysoGPI-APs, as well as endogenous soluble and transmembrane proteins that would normally be targeted to the apical membrane. These findings confirm the essential role for cholesterol in the apical protein targeting and further demonstrate that the mechanism of cholesterol-dependent apical sorting is not related to DRM association of GPI-APs.

Development of brain PET using GAPD arrays.

PubMed

Jung, Jin Ho; Choi, Yong; Hong, Key Jo; Kang, Jihoon; Hu, Wei; Lim, Hyun Keong; Huh, Yoonsuk; Kim, Sangsu; Jung, Jiwoong; Kim, Kyu Bom

2012-03-01

In recent times, there has been great interest in the use of Geiger-mode avalanche photodiodes (GAPDs) as scintillator readout in positron emission tomography (PET) detectors because of their advantages, such as high gain, compact size, low power consumption, and magnetic field insensitivity. The purpose of this study was to develop a novel PET system based on GAPD arrays for brain imaging. The PET consisted of 72 detector modules arranged in a ring of 330 mm diameter. Each PET module was composed of a 4 × 4 matrix of 3 × 3 × 20 mm(3) cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled with a 4 × 4 array three-side tileable GAPD. The signals from each PET module were fed into preamplifiers using a 3 m long flat cable and then sent to a position decoder circuit (PDC), which output a digital address and an analog pulse of the interacted channel among 64 preamplifier signals transmitted from four PET detector modules. The PDC outputs were fed into field programmable gate array (FPGA)-embedded data acquisition (DAQ) boards. The analog signal was then digitized, and arrival time and energy of the signal were calculated and stored. The energy and coincidence timing resolutions measured for 511 keV gamma rays were 18.4 ± 3.1% and 2.6 ns, respectively. The transaxial spatial resolution and sensitivity in the center of field of view (FOV) were 3.1 mm and 0.32% cps/Bq, respectively. The rods down to a diameter of 2.5 mm were resolved in a hot-rod phantom image, and activity distribution patterns between the white and gray matters in the Hoffman brain phantom were well imaged. Experimental results indicate that a PET system can be developed using GAPD arrays and the GAPD-based PET system can provide high-quality PET imaging.

Phosphatidylcholine catabolism in the MCF-7 cell cycle.

PubMed

Lin, Weiyang; Arthur, Gilbert

2006-10-01

The catabolism of phosphatidylcholine (PtdCho) appears to play a key role in regulating the net accumulation of the lipid in the cell cycle. Current protocols for measuring the degradation of PtdCho at specific cell-cycle phases require prolonged periods of incubation with radiolabelled choline. To measure the degradation of PtdCho at the S and G2 phases in the MCF-7 cell cycle, protocols were developed with radiolabelled lysophosphatidylcholine (lysoPtdCho), which reduces the labelling period and minimizes the recycling of labelled components. Although most of the incubated lysoPtdCho was hydrolyzed to glycerophosphocholine (GroPCho) in the medium, the kinetics of the incorporation of label into PtdCho suggests that the labelled GroPCho did not contribute significantly to cellular PtdCho formation. A protocol which involved exposing the cells twice to hydroxyurea, was also developed to produce highly synchronized MCF-7 cells with a profile of G1:S:G2/M of 90:5:5. An analysis of PtdCho catabolism in the synchronized cells following labelling with lysoPtdCho revealed that there was increased degradation of PtdCho in early to mid-S phase, which was attenuated in the G2/M phase. The results suggest that the net accumulation of PtdCho in MCF-7 cells may occur in the G2 phase of the cell cycle.

Novel technique for generating macrophage foam cells for in vitro reverse cholesterol transport studies[S

PubMed Central

Sengupta, Bhaswati; Narasimhulu, Chandrakala Aluganti; Parthasarathy, Sampath

2013-01-01

Generation of foam cells, an essential step for reverse cholesterol transport studies, uses the technique of receptor-dependent macrophage loading with radiolabeled acetylated LDL. In this study, we used the ability of a biologically relevant detergent molecule, lysophosphatidylcholine (lyso-PtdCho), to form mixed micelles with cholesterol or cholesteryl ester (CE) to generate macrophage foam cells. Fluorescent or radiolabeled cholesterol/lyso-PtdCho mixed micelles were prepared and incubated with RAW 264.7 or mouse peritoneal macrophages. Results showed that such micelles were quite stable at 4°C and retained the solubilized cholesterol during one month of storage. Macrophages incubated with cholesterol or CE (unlabeled, fluorescently labeled, or radiolabeled)/lyso-PtdCho mixed micelles accumulated CE as documented by microscopy, lipid staining, labeled oleate incorporation, and by TLC. Such foam cells unloaded cholesterol when incubated with HDL but not with oxidized HDL. We propose that stable cholesterol or CE/lyso-PtdCho micelles would offer advantages over existing methods. PMID:24115226

A compact high resolution flat panel PET detector based on the new 4-side buttable MPPC for biomedical applications

PubMed Central

Wang, Qiang; Wen, Jie; Ravindranath, Bosky; O’Sullivan, Andrew W.; Catherall, David; Li, Ke; Wei, Shouyi; Komarov, Sergey; Tai, Yuan-Chuan

2015-01-01

Compact high-resolution panel detectors using virtual pinhole (VP) PET geometry can be inserted into existing clinical or pre-clinical PET systems to improve regional spatial resolution and sensitivity. Here we describe a compact panel PET detector built using the new Though Silicon Via (TSV) multi-pixel photon counters (MPPC) detector. This insert provides high spatial resolution and good timing performance for multiple bio-medical applications. Because the TSV MPPC design eliminates wire bonding and has a package dimension which is very close to the MPPC’s active area, it is 4-side buttable. The custom designed MPPC array (based on Hamamatsu S12641-PA-50(x)) used in the prototype is composed of 4 × 4 TSV-MPPC cells with a 4.46 mm pitch in both directions. The detector module has 16 × 16 lutetium yttrium oxyorthosilicate (LYSO) crystal array, with each crystal measuring 0.92 × 0.92 × 3 mm3 with 1.0 mm pitch. The outer diameter of the detector block is 16.8 × 16.8 mm2. Thirty-two such blocks will be arranged in a 4 × 8 array with 1 mm gaps to form a panel detector with detection area around 7 cm × 14 cm in the full-size detector. The flood histogram acquired with Ge-68 source showed excellent crystal separation capability with all 256 crystals clearly resolved. The detector module’s mean, standard deviation, minimum (best) and maximum (worst) energy resolution were 10.19%, +/−0.68%, 8.36% and 13.45% FWHM, respectively. The measured coincidence time resolution between the block detector and a fast reference detector (around 200 ps single photon timing resolution) was 0.95 ns. When tested with Siemens Cardinal electronics the performance of the detector blocks remain consistent. These results demonstrate that the TSV-MPPC is a promising photon sensor for use in a flat panel PET insert composed of many high resolution compact detector modules. PMID:26085702

Preliminary results of a prototype C-shaped PET designed for an in-beam PET system

NASA Astrophysics Data System (ADS)

Kim, Hyun-Il; Chung, Yong Hyun; Lee, Kisung; Kim, Kyeong Min; Kim, Yongkwon; Joung, Jinhun

2016-06-01

Positron emission tomography (PET) can be utilized in particle beam therapy to verify the dose distribution of the target volume as well as the accuracy of the treatment. We present an in-beam PET scanner that can be integrated into a particle beam therapy system. The proposed PET scanner consisted of 14 detector modules arranged in a C-shape to avoid blockage of the particle beam line by the detector modules. Each detector module was composed of a 9×9 array of 4.0 mm×4.0 mm×20.0 mm LYSO crystals optically coupled to four 29-mm-diameter PMTs using the photomultiplier-quadrant-sharing (PQS) technique. In this study, a Geant4 Application for Tomographic Emission (GATE) simulation study was conducted to design a C-shaped PET scanner and then experimental evaluation of the proposed design was performed. The spatial resolution and sensitivity were measured according to NEMA NU2-2007 standards and were 6.1 mm and 5.61 cps/kBq, respectively, which is in good agreement with our simulation, with an error rate of 12.0%. Taken together, our results demonstrate the feasibility of the proposed C-shaped in-beam PET system, which we expect will be useful for measuring dose distribution in particle therapy.

A Submillimeter Resolution PET Prototype Evaluated With an 18F Inkjet Printed Phantom

NASA Astrophysics Data System (ADS)

Schneider, Florian R.; Hohberg, Melanie; Mann, Alexander B.; Paul, Stephan; Ziegler, Sibylle I.

2015-10-01

This work presents a submillimeter resolution PET (Positron Emission Tomography) scanner prototype based on SiPM/MPPC arrays (Silicon Photomultiplier/Multi Pixel Photon Counter). Onto each active area a 1 ×1 ×20 mm3 LYSO (Lutetium-Yttrium-Oxyorthosilicate) scintillator crystal is coupled one-to-one. Two detector modules facing each other in a distance of 10.0 cm have been set up with in total 64 channels that are digitized by SADCs (Sampling Analog to Digital Converters) with 80 MHz, 10 bit resolution and FPGA (Field Programmable Gate Array) based extraction of energy and time information. Since standard phantoms are not sufficient for testing submillimeter resolution at which positron range is an issue, a 18F inkjet printed phantom has been used to explore the limit in spatial resolution. The phantom could be successfully reconstructed with an iterative MLEM (Maximum Likelihood Expectation Maximization) and an analytically calculated system matrix based on the DRF (Detector Response Function) model. The system yields a coincidence time resolution of 4.8 ns FWHM, an energy resolution of 20%-30% FWHM and a spatial resolution of 0.8 mm.

Impact of 4-epi-oxytetracycline on the gut microbiota and blood metabolomics of Wistar rats

PubMed Central

Han, Hongxing; Xiao, Hailong; Zhang, Kai; Lu, Zhenmei

2016-01-01

The impact of 4-epi-oxytetracycline (4-EOTC), one of the main oxytetracycline (OTC) metabolites, on the gut microbiota and physiological metabolism of Wistar rats was analyzed to explore the dynamic alterations apparent after repeated oral exposure (0.5, 5.0 or 50.0 mg/kg bw) for 15 days as shown by 16S rRNA pyrosequencing and UPLC-Q-TOF/MS analysis. Both principal component analysis and cluster analysis showed consistently altered patterns with distinct differences in the treated groups versus the control groups. 4-EOTC treatment at 5.0 or 50.0 mg/kg increased the relative abundance of the Actinobacteria, specifically Bifidobacteriaceae, and improved the synthesis of lysophosphatidylcholine (LysoPC), as shown by the lipid biomarkers LysoPC(16:0), LysoPC(18:3), LysoPC(20:3), and LysoPC(20:4). The metabolomic analysis of urine samples also identified four other decreased metabolites: diacylglycerol, sphingomyelin, triacylglycerol, and phosphatidylglycerol. Notably, the significant changes observed in these biomarkers demonstrated the ongoing disorder induced by 4-EOTC. Blood and urine analysis revealed that residual 4-EOTC accumulated in the rats, even two weeks after oral 4-EOTC administration, ceased. Thus, through thorough analysis, it can be concluded that the alteration of the gut microbiota and disorders in blood metabolomics are correlated with 4-EOTC treatment. PMID:26976662

Impact of 4-epi-oxytetracycline on the gut microbiota and blood metabolomics of Wistar rats.

PubMed

Han, Hongxing; Xiao, Hailong; Zhang, Kai; Lu, Zhenmei

2016-03-15

The impact of 4-epi-oxytetracycline (4-EOTC), one of the main oxytetracycline (OTC) metabolites, on the gut microbiota and physiological metabolism of Wistar rats was analyzed to explore the dynamic alterations apparent after repeated oral exposure (0.5, 5.0 or 50.0 mg/kg bw) for 15 days as shown by 16S rRNA pyrosequencing and UPLC-Q-TOF/MS analysis. Both principal component analysis and cluster analysis showed consistently altered patterns with distinct differences in the treated groups versus the control groups. 4-EOTC treatment at 5.0 or 50.0 mg/kg increased the relative abundance of the Actinobacteria, specifically Bifidobacteriaceae, and improved the synthesis of lysophosphatidylcholine (LysoPC), as shown by the lipid biomarkers LysoPC(16:0), LysoPC(18:3), LysoPC(20:3), and LysoPC(20:4). The metabolomic analysis of urine samples also identified four other decreased metabolites: diacylglycerol, sphingomyelin, triacylglycerol, and phosphatidylglycerol. Notably, the significant changes observed in these biomarkers demonstrated the ongoing disorder induced by 4-EOTC. Blood and urine analysis revealed that residual 4-EOTC accumulated in the rats, even two weeks after oral 4-EOTC administration, ceased. Thus, through thorough analysis, it can be concluded that the alteration of the gut microbiota and disorders in blood metabolomics are correlated with 4-EOTC treatment.

Quantification of cardiolipin by liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Garrett, Teresa A; Kordestani, Reza; Raetz, Christian R H

2007-01-01

Cardiolipin (CL), a tetra-acylated glycerophospholipid composed of two phosphatidyl moieties linked by a bridging glycerol, plays an important role in mitochondrial function in eukaryotic cells. Alterations to the content and acylation state of CL cause mitochondrial dysfunction and may be associated with pathologies such as ischemia, hypothyrodism, aging, and heart failure. The structure of CL is very complex because of microheterogeneity among its four acyl chains. Here we have developed a method for the quantification of CL molecular species by liquid chromatography-electrospray ionization mass spectrometry. We quantify the [M-2H](2-) ion of a CL of a given molecular formula and identify the CLs by their total number of carbons and unsaturations in the acyl chains. This method, developed using mouse macrophage RAW 264.7 tumor cells, is broadly applicable to other cell lines, tissues, bacteria and yeast. Furthermore, this method could be used for the quantification of lyso-CLs and bis-lyso-CLs.

The MiniPET: a didactic PET system

NASA Astrophysics Data System (ADS)

Pedro, R.; Silva, J.; Gurriana, L.; Silva, J. M.; Maio, A.; Soares Augusto, J.

2013-03-01

The MiniPET project aims to design and build a small PET system. It consists of two 4 × 4 matrices of 16 LYSO scintillator crystals and two PMTs with 16 channels resulting in a low cost system with the essential functionality of a clinical PET instrument. It is designed to illustrate the physics of the PET technique and to provide a didactic platform for the training of students and nuclear imaging professionals as well as for scientific outreach. The PET modules can be configured to test for the coincidence of 511 keV gamma rays. The model has a flexible mechanical setup [1] and can simulate 14 diferent ring geometries, from a configuration with as few as 18 detectors per ring (ring radius phi=51 mm), up to a geometry with 70 detectors per ring (phi=200 mm). A second version of the electronic system [2] allowed measurement and recording of the energy deposited in 4 detector channels by photons from a 137Cs radioactive source and by photons resulting of the annihilation of positrons from a 22Na radioactive source. These energy spectra are used for detector performance studies, as well as angular dependency studies. In this paper, the mechanical setup, the front-end high-speed analog electronics, the digital acquisition and control electronics implemented in a FPGA, as well as the data-transfer interface between the FPGA board and a host PC are described. Recent preliminary results obtained with the 4 active channels in the prototype are also presented.

A multiplexed TOF and DOI capable PET detector using a binary position sensitive network.

PubMed

Bieniosek, M F; Cates, J W; Levin, C S

2016-11-07

Time of flight (TOF) and depth of interaction (DOI) capabilities can significantly enhance the quality and uniformity of positron emission tomography (PET) images. Many proposed TOF/DOI PET detectors require complex readout systems using additional photosensors, active cooling, or waveform sampling. This work describes a high performance, low complexity, room temperature TOF/DOI PET module. The module uses multiplexed timing channels to significantly reduce the electronic readout complexity of the PET detector while maintaining excellent timing, energy, and position resolution. DOI was determined using a two layer light sharing scintillation crystal array with a novel binary position sensitive network. A 20 mm effective thickness LYSO crystal array with four 3 mm  ×  3 mm silicon photomultipliers (SiPM) read out by a single timing channel, one energy channel and two position channels achieved a full width half maximum (FWHM) coincidence time resolution of 180  ±  2 ps with 10 mm of DOI resolution and 11% energy resolution. With sixteen 3 mm  ×  3 mm SiPMs read out by a single timing channel, one energy channel and four position channels a coincidence time resolution 204  ±  1 ps was achieved with 10 mm of DOI resolution and 15% energy resolution. The methods presented here could significantly simplify the construction of high performance TOF/DOI PET detectors.

Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain.

PubMed

Jung, Jin Ho; Choi, Yong; Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun; Oh, Chang Hyun; Park, Hyun-wook; Kim, Kyung Min; Kim, Jong Guk

2015-05-01

The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired. Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.

A simulation study of a C-shaped in-beam PET system for dose verification in carbon ion therapy

NASA Astrophysics Data System (ADS)

Jung An, Su; Beak, Cheol-Ha; Lee, Kisung; Hyun Chung, Yong

2013-01-01

The application of hadrons such as carbon ions is being developed for the treatment of cancer. The effectiveness of such a technique is due to the eligibility of charged particles in delivering most of their energy near the end of the range, called the Bragg peak. However, accurate verification of dose delivery is required since misalignment of the hadron beam can cause serious damage to normal tissue. PET scanners can be utilized to track the carbon beam to the tumor by imaging the trail of the hadron-induced positron emitters in the irradiated volume. In this study, we designed and evaluated (through Monte Carlo simulations) an in-beam PET scanner for monitoring patient dose in carbon beam therapy. A C-shaped PET and a partial-ring PET were designed to avoid interference between the PET detectors and the therapeutic carbon beam delivery. Their performance was compared with that of a full-ring PET scanner. The C-shaped, partial-ring, and full-ring scanners consisted of 14, 12, and 16 detector modules, respectively, with a 30.2 cm inner diameter for brain imaging. Each detector module was composed of a 13×13 array of 4.0 mm×4.0 mm×20.0 mm LYSO crystals and four round 25.4 mm diameter PMTs. To estimate the production yield of positron emitters such as 10C, 11C, and 15O, a cylindrical PMMA phantom (diameter, 20 cm; thickness, 20 cm) was irradiated with 170, 290, and 350 AMeV 12C beams using the GATE code. Phantom images of the three types of scanner were evaluated by comparing the longitudinal profile of the positron emitters, measured along the carbon beam as it passed a simulated positron emitter distribution. The results demonstrated that the development of a C-shaped PET scanner to characterize carbon dose distribution for therapy planning is feasible.

Globotriaosylsphingosine (lyso-Gb3) might not be a reliable marker for monitoring the long-term therapeutic outcomes of enzyme replacement therapy for late-onset Fabry patients with the Chinese hotspot mutation (IVS4+919G>A)

PubMed Central

2014-01-01

Background In Taiwan, DNA-based newborn screening showed a surprisingly high incidence (1/875 in males and 1/399 in females) of a cardiac Fabry mutation (IVS4 + 919G > A). However, the natural course, long-term treatment outcomes and suitable biomarkers for monitoring the therapeutic outcomes of these patients are largely unknown. Methods Fabry disease (FD) patients who had received enzyme replacement therapy (ERT) for more than 1 year were enrolled in this study from December 2008 to April 2013. Periodic echocardiography and serum globotriaosylsphingosine (lyso-Gb3) analysis were carried out. Before and after ERT, left ventricular mass index (LVMI) and serum lyso-Gb3 level were compared and the correlation between the change of LVMI and the change of serum lyso-Gb3 were also analyzed. Results Thirty-six patients, in four patient groups, were enrolled: (1) 16 males with IVS4 + 919G > A mutation; (2) 7 females with IVS4 + 919G > A mutation; (3) 2 males with classical mutations; and (4) 11 females with classical mutations. The follow-up period was 13–46 months. There were significant LVMI reductions after ERT in all four groups after excluding confounding factors. However, interestingly, serum lyso-Gb3 decreased significantly in the early period after ERT in all groups, but increased gradually after an average of 11.1 months after ERT in late-onset male and female Fabry groups, even when their LVMI still decreased or remained stable. Furthermore, there was no correlation between the change of serum lyso-Gb3 and the change of LVMI in both classical and IVS4 + 919G > A FD patients. Conclusion Although lyso-Gb3 has a high diagnostic sensitivity in late-onset Fabry patients and has a good response to ERT during the early stages, it might not be a reliable marker for monitoring the long-term therapeutic outcomes of ERT for late-onset Fabry patients with the Chinese hotspot mutation (IVS4 + 919G > A). PMID:25047006

MR-compatibility of a high-resolution small animal PET insert operating inside a 7 T MRI.

PubMed

Thiessen, J D; Shams, E; Stortz, G; Schellenberg, G; Bishop, D; Khan, M S; Kozlowski, P; Retière, F; Sossi, V; Thompson, C J; Goertzen, A L

2016-11-21

A full-ring PET insert consisting of 16 PET detector modules was designed and constructed to fit within the 114 mm diameter gradient bore of a Bruker 7 T MRI. The individual detector modules contain two silicon photomultiplier (SiPM) arrays, dual-layer offset LYSO crystal arrays, and high-definition multimedia interface (HDMI) cables for both signal and power transmission. Several different RF shielding configurations were assessed prior to construction of a fully assembled PET insert using a combination of carbon fibre and copper foil for RF shielding. MR-compatibility measurements included field mapping of the static magnetic field (B 0 ) and the time-varying excitation field (B 1 ) as well as acquisitions with multiple pulse sequences: spin echo (SE), rapid imaging with refocused echoes (RARE), fast low angle shot (FLASH) gradient echo, and echo planar imaging (EPI). B 0 field maps revealed a small degradation in the mean homogeneity (+0.1 ppm) when the PET insert was installed and operating. No significant change was observed in the B 1 field maps or the image homogeneity of various MR images, with a 9% decrease in the signal-to-noise ratio (SNR) observed only in EPI images acquired with the PET insert installed and operating. PET detector flood histograms, photopeak amplitudes, and energy resolutions were unchanged in individual PET detector modules when acquired during MRI operation. There was a small baseline shift on the PET detector signals due to the switching amplifiers used to power MRI gradient pulses. This baseline shift was observable when measured with an oscilloscope and varied as a function of the gradient duty cycle, but had no noticeable effect on the performance of the PET detector modules. Compact front-end electronics and effective RF shielding led to minimal cross-interference between the PET and MRI systems. Both PET detector and MRI performance was excellent, whether operating as a standalone system or a hybrid PET/MRI.

Design and evaluation of a SiPM-based large-area detector module for positron emission imaging

NASA Astrophysics Data System (ADS)

Alva-Sánchez, H.; Murrieta-Rodríguez, T.; Calva-Coraza, E.; Martínez-Dávalos, A.; Rodríguez-Villafuerte, M.

2018-03-01

The design and evaluation of a large-area detector module for positron emission imaging applications, is presented. The module features a SensL ArrayC-60035-64P-PCB solid state detector (8×8 array of tileable silicon photomultipliers by SensL, 7.2 mm pitch) covering a total area of 57.4×57.4 mm2. The detector module was formed using a pixelated array of 40×40 lutetium-yttrium oxyorthosilicate (LYSO) scintillator crystal elements with 1.43 mm pitch. A 7 mm thick coupling light guide was used to allow light sharing between adjacent SiPM. A 16-channel symmetric charge division (SCD) readout board was designed to multiplex the number of signals from 64 to 16 (8 columns and 8 rows) and a center-of-gravity algorithm to identify the position. Data acquisition and digitization was accomplished using a custom-made system based on FPGAs boards. Crystal maps were obtained using 18F-positron sources and Voronoi diagrams were used to correct for geometric distortions and to generate a non-uniformity correction matrix. All measurements were taken at a controlled room temperature of 22oC. The crystal maps showed minor distortion, 90% of the 1600 total crystal elements could be identified, a mean peak-to-valley ratio of 4.3 was obtained and a 10.8% mean energy resolution for 511 keV annihilation photons was determined. The performance of the detector using our own readout board was compared to that using two different commercially readout boards using the same detector module arrangement. We show that these large-area SiPM arrays, combined with a 16-channel SCD readout board, can offer high spatial resolution, excellent energy resolution and detector uniformity and thus, can be used for positron emission imaging applications.

MR-compatibility of a high-resolution small animal PET insert operating inside a 7 T MRI

NASA Astrophysics Data System (ADS)

Thiessen, J. D.; Shams, E.; Stortz, G.; Schellenberg, G.; Bishop, D.; Khan, M. S.; Kozlowski, P.; Retière, F.; Sossi, V.; Thompson, C. J.; Goertzen, A. L.

2016-11-01

A full-ring PET insert consisting of 16 PET detector modules was designed and constructed to fit within the 114 mm diameter gradient bore of a Bruker 7 T MRI. The individual detector modules contain two silicon photomultiplier (SiPM) arrays, dual-layer offset LYSO crystal arrays, and high-definition multimedia interface (HDMI) cables for both signal and power transmission. Several different RF shielding configurations were assessed prior to construction of a fully assembled PET insert using a combination of carbon fibre and copper foil for RF shielding. MR-compatibility measurements included field mapping of the static magnetic field (B 0) and the time-varying excitation field (B 1) as well as acquisitions with multiple pulse sequences: spin echo (SE), rapid imaging with refocused echoes (RARE), fast low angle shot (FLASH) gradient echo, and echo planar imaging (EPI). B 0 field maps revealed a small degradation in the mean homogeneity (+0.1 ppm) when the PET insert was installed and operating. No significant change was observed in the B 1 field maps or the image homogeneity of various MR images, with a 9% decrease in the signal-to-noise ratio (SNR) observed only in EPI images acquired with the PET insert installed and operating. PET detector flood histograms, photopeak amplitudes, and energy resolutions were unchanged in individual PET detector modules when acquired during MRI operation. There was a small baseline shift on the PET detector signals due to the switching amplifiers used to power MRI gradient pulses. This baseline shift was observable when measured with an oscilloscope and varied as a function of the gradient duty cycle, but had no noticeable effect on the performance of the PET detector modules. Compact front-end electronics and effective RF shielding led to minimal cross-interference between the PET and MRI systems. Both PET detector and MRI performance was excellent, whether operating as a standalone system or a hybrid PET/MRI.

Laser pixelation of thick scintillators for medical imaging applications: x-ray studies

NASA Astrophysics Data System (ADS)

Sabet, Hamid; Kudrolli, Haris; Marton, Zsolt; Singh, Bipin; Nagarkar, Vivek V.

2013-09-01

To achieve high spatial resolution required in nuclear imaging, scintillation light spread has to be controlled. This has been traditionally achieved by introducing structures in the bulk of scintillation materials; typically by mechanical pixelation of scintillators and fill the resultant inter-pixel gaps by reflecting materials. Mechanical pixelation however, is accompanied by various cost and complexity issues especially for hard, brittle and hygroscopic materials. For example LSO and LYSO, hard and brittle scintillators of interest to medical imaging community, are known to crack under thermal and mechanical stress; the material yield drops quickly with large arrays with high aspect ratio pixels and therefore the pixelation process cost increases. We are utilizing a novel technique named Laser Induced Optical Barriers (LIOB) for pixelation of scintillators that overcomes the issues associated with mechanical pixelation. In this technique, we can introduce optical barriers within the bulk of scintillator crystals to form pixelated arrays with small pixel size and large thickness. We applied LIOB to LYSO using a high-frequency solid-state laser. Arrays with different crystal thickness (5 to 20 mm thick), and pixel size (0.8×0.8 to 1.5×1.5 mm2) were fabricated and tested. The width of the optical barriers were controlled by fine-tuning key parameters such as lens focal spot size and laser energy density. Here we report on LIOB process, its optimization, and the optical crosstalk measurements using X-rays. There are many applications that can potentially benefit from LIOB including but not limited to clinical/pre-clinical PET and SPECT systems, and photon counting CT detectors.

NBD-labelled phospholipid accelerates apolipoprotein C-II amyloid fibril formation but is not incorporated into mature fibrils

PubMed Central

Ryan, Timothy M.; Griffin, Michael D. W.; Bailey, Michael F.; Schuck, Peter; Howlett, Geoffrey J.

2014-01-01

Human apolipoprotein (apo) C-II is one of several lipid-binding proteins that self-assemble into fibrils and accumulate in disease-related amyloid deposits. A general characteristic of these amyloid deposits is the presence of lipids, known to modulate individual steps in amyloid fibril formation. ApoC-II fibril formation is activated by sub-micellar phospholipids but inhibited by micellar lipids. We examined the mechanism for the activation by sub-micellar lipids using the fluorescently-labelled, short-chain phospholipid, 1-dodecyl-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]-2-hydroxy-glycero-3-phosphocholine (NBD-lyso-12-PC). Addition of submicellar NBD-lyso-12-PC increased the rate of fibril formation by apoC-II approximately two-fold. Stopped flow kinetic analysis using fluorescence detection and low, non-fibril forming concentrations of apoC-II indicated NBD-Lyso-12-PC binds rapidly, in the millisecond timescale, followed by the slower formation of discrete apoC-II tetramers. Sedimentation velocity analysis showed NBD-Lyso-12-PC binds to both apoC-II monomers and tetramers at approximately 5 sites per monomer with an average dissociation constant of approximately 10 μM. Mature apoC-II fibrils formed in the presence of NBD-Lyso-12-PC were devoid of lipid indicating a purely catalytic role for sub-micellar lipids in the activation of apoC-II fibril formation. These studies demonstrate the catalytic potential of small amphiphilic molecules to control protein folding and fibril assembly pathways. PMID:21985034

Dietary Components Affect the Plasma and Tissue Levels of Lutein in Aged Rats with Lutein Deficiency--A Repeated Gavage and Dietary Study.

PubMed

Sheshappa, Mamatha Bangera; Ranganathan, Arunkumar; Bhatiwada, Nidhi; Talahalli, Ramprasad Ravichandra; Vallikannan, Baskaran

2015-10-01

The aim of this study was to find out the influence of selected dietary components on plasma and tissue response of repeated micellar and dietary lutein in aged rats with lutein deficiency. In repeated (16 d) gavage study, micellar lutein was co-ingested with either phosphatidylcholine (PC), lyso-phosphatidylcholine (lysoPC), β-carotene, dietary fiber or vegetable fat (3% soybean oil). In dietary study, rats were fed (4 wk) semi-synthetic diet either with lutein + PC, lutein + dietary fiber or B. alba (lutein source) + PC. The post-prandial plasma and tissue response of lutein was measured by HPLC. Results showed that micellar fat, PC and lysoPC significantly (P ≤ 0.05) increased the lutein levels in plasma (31.1%, 26.8%, and 34.9%), liver (27.4%, 29.5%, and 8.6%), and eyes (63.5%, 90.2%, and 86%) compared to the control group (group gavaged micelles with no dietary components studied). Similarly, dietary study showed an enhanced plasma, liver, and eye lutein levels by 44.8%, 24.1%, and 42.0% (lutein + PC group) and 51.7%, 39.8%, and 31.7% (B.alba + PC group), respectively compared to control. The activity of antioxidant enzymes in plasma and liver of both the studies were also affected compared to control. Result reveals, that PC enhance the intestinal absorption of both micellar and dietary lutein which is either in free or bound form with food matrices in aged rats with lutein deficiency. Hence, PC at a concentration used in this study can be considered to improve the lutein bioavailability in lutein deficiency. Lutein and zeaxanthin are macular pigments acquired mostly from greens, that play an significant role in protecting vision from Age related macular degeneration (AMD). However, their biological availability is poor and affected by dietary components. This study demonstrates the positive influence of dietary PC and lyso PC in improving intestinal uptake of lutein. Our previous and present finding shows there is a possibility of developing functional/supplemental foods with PC and lyso PC targeted to elderly populace thus minimizing or delaying the vision complication associated like AMD. © 2015 Institute of Food Technologists®

Timing performance of the silicon PET insert probe

PubMed Central

Studen, A.; Burdette, D.; Chesi, E.; Cindro, V.; Clinthorne, N. H.; Cochran, E.; Grošičar, B.; Kagan, H.; Lacasta, C.; Linhart, V.; Mikuž, M.; Stankova, V.; Weilhammer, P.; Žontar, D.

2010-01-01

Simulation indicates that PET image could be improved by upgrading a conventional ring with a probe placed close to the imaged object. In this paper, timing issues related to a PET probe using high-resistivity silicon as a detector material are addressed. The final probe will consist of several (four to eight) 1-mm thick layers of silicon detectors, segmented into 1 × 1 mm2 pads, each pad equivalent to an independent p + nn+ diode. A proper matching of events in silicon with events of the external ring can be achieved with a good timing resolution. To estimate the timing performance, measurements were performed on a simplified model probe, consisting of a single 1-mm thick detector with 256 square pads (1.4 mm side), coupled with two VATAGP7s, application-specific integrated circuits. The detector material and electronics are the same that will be used for the final probe. The model was exposed to 511 keV annihilation photons from an 22Na source, and a scintillator (LYSO)–PMT assembly was used as a timing reference. Results were compared with the simulation, consisting of four parts: (i) GEANT4 implemented realistic tracking of electrons excited by annihilation photon interactions in silicon, (ii) calculation of propagation of secondary ionisation (electron–hole pairs) in the sensor, (iii) estimation of the shape of the current pulse induced on surface electrodes and (iv) simulation of the first electronics stage. A very good agreement between the simulation and the measurements were found. Both indicate reliable performance of the final probe at timing windows down to 20 ns. PMID:20215445

Timing performance of the silicon PET insert probe.

PubMed

Studen, A; Burdette, D; Chesi, E; Cindro, V; Clinthorne, N H; Cochran, E; Grosicar, B; Kagan, H; Lacasta, C; Linhart, V; Mikuz, M; Stankova, V; Weilhammer, P; Zontar, D

2010-01-01

Simulation indicates that PET image could be improved by upgrading a conventional ring with a probe placed close to the imaged object. In this paper, timing issues related to a PET probe using high-resistivity silicon as a detector material are addressed. The final probe will consist of several (four to eight) 1-mm thick layers of silicon detectors, segmented into 1 x 1 mm(2) pads, each pad equivalent to an independent p + nn+ diode. A proper matching of events in silicon with events of the external ring can be achieved with a good timing resolution. To estimate the timing performance, measurements were performed on a simplified model probe, consisting of a single 1-mm thick detector with 256 square pads (1.4 mm side), coupled with two VATAGP7s, application-specific integrated circuits. The detector material and electronics are the same that will be used for the final probe. The model was exposed to 511 keV annihilation photons from an (22)Na source, and a scintillator (LYSO)-PMT assembly was used as a timing reference. Results were compared with the simulation, consisting of four parts: (i) GEANT4 implemented realistic tracking of electrons excited by annihilation photon interactions in silicon, (ii) calculation of propagation of secondary ionisation (electron-hole pairs) in the sensor, (iii) estimation of the shape of the current pulse induced on surface electrodes and (iv) simulation of the first electronics stage. A very good agreement between the simulation and the measurements were found. Both indicate reliable performance of the final probe at timing windows down to 20 ns.

Chronic elevation of phosphocholine containing lipids in mice exposed to Gulf War agents pyridostigmine bromide and permethrin.

PubMed

Abdullah, Laila; Evans, James E; Montague, Hannah; Reed, Jon M; Moser, Ann; Crynen, Gogce; Gonzalez, Ariel; Zakirova, Zuchra; Ross, Ivan; Mullan, Chris; Mullan, Michael; Ait-Ghezala, Ghania; Crawford, Fiona

2013-01-01

For two decades, 25% of the veterans who served in the 1991 Gulf War (GW) have been living with Gulf War Illness (GWI), a chronic multisymptom illness. Evidence suggests that brain structures involved in cognitive function may be affected in GWI. Gulf War agents such as the acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and the pesticide permethrin (PER) are considered key etiogenic factors in GWI. We therefore developed a mouse model of GW agent exposure by co-administering PB and PER and showed that this model exhibits cognitive impairment and anxiety, and increased astrogliosis at chronic post-exposure time-points. Since GW agents inhibit AChE, we hypothesized that PB+PER exposure will modulate phosphatidylcholine (PC) and sphingomyelin (SM), which are reservoirs of phosphocholine required for endogenous ACh synthesis. Lipidomic analyses showed that PC and SM were elevated in the brains of exposed compared to control mice. Brain ether PC (ePC) species were increased but lyso-platelet activating factors (lyso-PAF) that are products of ePC were decreased in exposed animals compared to controls. Catalase expression (a marker for peroxisomes) was increased in GW agent exposed mice compared to controls. Ether PC and lyso-PAF modulation was also evident in the plasma of GW agent exposed mice compared to controls. These studies suggest peroxisomal and lysosomal dysfunction in the brain at a chronic post-exposure timepoint following GW agent exposure. Our studies provide a new direction for GWI research, which will be useful for developing suitable therapies for treating GWI. © 2013 Elsevier Inc. All rights reserved.

Two-photon imaging of formaldehyde in live cells and animals utilizing a lysosome-targetable and acidic pH-activatable fluorescent probe.

PubMed

Xie, Xilei; Tang, Fuyan; Shangguan, Xiaoyan; Che, Shiyi; Niu, Jinye; Xiao, Yongsheng; Wang, Xu; Tang, Bo

2017-06-13

Lyso-TPFP presents lysosomal targetability and an acidic pH-activatable response toward formaldehyde. Thus, it exclusively visualizes lysosomal formaldehyde and is immune against it in neutral cytosol and other organelles. In addition, two-photon fluorescence imaging endows Lyso-TPFP with the capability of in situ tracking formaldehyde in live cells and animals.

Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients.

PubMed

Smid, Bouwien E; Rombach, Saskia M; Aerts, Johannes M F G; Kuiper, Symen; Mirzaian, Mina; Overkleeft, Hermen S; Poorthuis, Ben J H M; Hollak, Carla E M; Groener, Johanna E M; Linthorst, Gabor E

2011-10-31

Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m), or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow). An assessment report from the European Medicines Agency (EMA) raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3) in Dutch Fabry patients. The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36) and brief pain inventory (BPI) questionnaires were analysed. All thirty-five Dutch Fabry patients using agalsidase beta (17 males) were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p = 0.68). In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5-29.2) after 1 year of shortage (p = 0.001). Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases. No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase beta shortage. Increases in lysoGb3, however, suggest recurrence of disease activity.

Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

PubMed Central

2011-01-01

Background Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m), or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow). An assessment report from the European Medicines Agency (EMA) raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3) in Dutch Fabry patients. Methods The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36) and brief pain inventory (BPI) questionnaires were analysed. Results All thirty-five Dutch Fabry patients using agalsidase beta (17 males) were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p = 0.68). In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5 - 29.2) after 1 year of shortage (p = 0.001). Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases. Conclusions No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase beta shortage. Increases in lysoGb3, however, suggest recurrence of disease activity. PMID:22041095

Design study of an in situ PET scanner for use in proton beam therapy

NASA Astrophysics Data System (ADS)

Surti, S.; Zou, W.; Daube-Witherspoon, M. E.; McDonough, J.; Karp, J. S.

2011-05-01

Proton beam therapy can deliver a high radiation dose to a tumor without significant damage to surrounding healthy tissue or organs. One way of verifying the delivered dose distribution is to image the short-lived positron emitters produced by the proton beam as it travels through the patient. A potential solution to the limitations of PET imaging in proton beam therapy is the development of a high sensitivity, in situ PET scanner that starts PET imaging almost immediately after patient irradiation while the patient is still lying on the treatment bed. A partial ring PET design is needed for this application in order to avoid interference between the PET detectors and the proton beam, as well as restrictions on patient positioning on the couch. A partial ring also allows us to optimize the detector separation (and hence the sensitivity) for different patient sizes. Our goal in this investigation is to evaluate an in situ PET scanner design for use in proton therapy that provides tomographic imaging in a partial ring scanner design using time-of-flight (TOF) information and an iterative reconstruction algorithm. GEANT4 simulation of an incident proton beam was used to produce a positron emitter distribution, which was parameterized and then used as the source distribution inside a water-filled cylinder for EGS4 simulations of a PET system. Design optimization studies were performed as a function of crystal type and size, system timing resolution, scanner angular coverage and number of positron emitter decays. Data analysis was performed to measure the accuracy of the reconstructed positron emitter distribution as well as the range of the positron emitter distribution. We simulated scanners with varying crystal sizes (2-4 mm) and type (LYSO and LaBr3) and our results indicate that 4 mm wide LYSO or LaBr3 crystals (resulting in 4-5 mm spatial resolution) are adequate; for a full-ring, non-TOF scanner we predict a low bias (<0.6 mm) and a good precision (<1 mm) in the estimated range relative to the simulated positron distribution. We then varied the angular acceptance of the scanner ranging from 1/2 to 2/3 of 2π a partial ring TOF imaging with good timing resolution (<=600 ps) is necessary to produce accurate tomographic images. A two-third ring scanner with 300 ps timing resolution leads to a bias of 1.0 mm and a precision of 1.4 mm in the range estimate. With a timing resolution of 600 ps, the bias increases to 2.0 mm while the precision in the range estimate is similar. For a half-ring scanner design, more distortions are present in the image, which is characterized by the increased error in the profile difference estimate. We varied the number of positron decays imaged by the PET scanner by an order of magnitude and we observe some decrease in the precision of the range estimate for lower number of decays, but all partial ring scanner designs studied have a precision <=1.5 mm. The largest number tested, 150 M total positron decays, is considered realistic for a clinical fraction of delivered dose, while the range of positron decays investigated in this work covers a variable number of situations corresponding to delays in scan start time and the total scan time. Thus, we conclude that for partial ring systems, an angular acceptance of at least 1/2 (of 2π) together with timing resolution of 300 ps is needed to achieve accurate and precise range estimates. With 600 ps timing resolution an angular acceptance of 2/3 (of 2π) is required to achieve satisfactory range estimates. These results indicate that it would be feasible to develop a partial-ring dedicated PET scanner based on either LaBr3 or LYSO to accurately characterize the proton dose for therapy planning.

Altered activity of lysophospholipase D, which produces bioactive lysophosphatidic acid and choline, in serum from women with pathological pregnancy.

PubMed

Tokumura, A; Kume, T; Taira, S; Yasuda, K; Kanzaki, H

2009-05-01

Altered lipid metabolism is associated with human abnormal pregnancy, such as pre-eclampsia and preterm labor, and potentially leads to fetus loss. A causative factor for the onset and progress of the systemic multifactorial syndromes associated with the pathological pregnancy is oxidized low-density lipoprotein, an active identity of which was postulated to be lysophosphatidic acid (LPA). We previously found that LPA is produced extracellularly by plasma lysophospholipase D (lysoPLD) activity of autotaxin, a tumor cell motility-stimulating protein. In this study, a convenient assay based on the choline released from endogenous substrate or exogenous lysophosphatidylcholine (LPC) was used for comparison of serum lysoPLD activity among patients with normal and abnormal pregnancy. The serum choline-producing activity was found to be mainly due to autotaxin, and dependent on its dilution rate. There was some association between low dilution dependency of serum lysoPLD activity toward an exogenous LPC and high lysoPLD activity toward endogenous substrates in cases of patients with preterm labor and pre-eclampsia. However, there was no difference in the serum level of LPC between women with normal pregnancy and those with pathological pregnancy. These results indicate that production of bioactive LPA by lysoPLD activity is elevated by an unknown mechanism that may be related to increased availability of endogenous substrates LPC, but not its concentration in human serum. If the level of LPA in blood circulation is elevated in the pathological pregnancies in vivo, it may play a role in induction and/or progression of systemic vascular dysfunction seen patients with preterm labor or pre-eclampsia.

Rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabolomics approach to study the effects of jieduquyuziyin prescription on systemic lupus erythematosus.

PubMed

Ding, Xinghong; Hu, Jinbo; Wen, Chengping; Ding, Zhishan; Yao, Li; Fan, Yongsheng

2014-01-01

Jieduquyuziyin prescription (JP), a traditional Chinese medicine (TCM) prescription, has been widely used for the clinical treatment of systemic lupus erythematosus (SLE). However, the complex chemical constituents of JP and the multifactorial pathogenesis of SLE make research on the therapeutic mechanism of JP in SLE challenging. In this paper, a serum metabolomics approach based on rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF/MS) was employed to acquire the metabolic characteristics of serum samples obtained from mice in the SLE model group, JP-treated group, prednisone acetate (PA)-treated group and control group. The orthogonal partial least squares (OPLS) was applied to recognize metabolic patterns, and an obvious separation of groups was obtained. Thirteen metabolites, namely, phosphatidylethanolamine (PE 20:3), hepoxilin B3, lyso- phosphatidylethanolamine (lyso-PE 22:6), 12S-hydroxypentaenoic acid (12S-HEPE), traumatic acid, serotonin, platelet-activating factor (PAF), phosphatidylcholine (PC 20:5),eicosapentaenoic acid (EPA), 12(S)-hydroxyei- cosatetraenoic acid (12S-HETE), 14-hydroxy docosahexaenoic acid (14-HDOHE), lyso-phosphatidylcholine (lyso-PC 20:4), and indole acetaldehyde, were identified and characterized as differential metabolites involved in the pathogenesis of SLE. After treatment with JP, the relative content of 12(S)-HETE, PAF, 12(S)-HEPE, EPA, PE (20:3), Lyso-PE(22:6), and 14-HDOHE were effectively regulated, which suggested that the therapeutic effects of JP on SLE may involve regulating disturbances to the metabolism of unsaturated fatty acid, tryptophan and phospholipid. This research also demonstrated that metabolomics is a powerful tool for researching complex disease mechanisms and evaluating the mechanism of action of TCM.

Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugita, Kazuya; Yamamura, Chiaki; Tabata, Ken-ichi

2013-01-04

Highlights: Black-Right-Pointing-Pointer Expression of GPR174 in CHO cells induces morphological changes and proliferation delay. Black-Right-Pointing-Pointer These are due to increase in intracellular cAMP concentration. Black-Right-Pointing-Pointer Lysophosphatidylserine was identified to stimulate GPR174 leading to activate ACase. Black-Right-Pointing-Pointer The potencies of fatty acid moiety on LysoPS were oleoyl Greater-Than-Or-Slanted-Equal-To stearoyl > palmitoyl. Black-Right-Pointing-Pointer We propose that GPR174 is a lysophosphatidylserine receptor. -- Abstract: We established cell lines that stably express orphan GPCR GPR174 using CHO cells, and studied physiological and pharmacological features of the receptor. GPR174-expressing cells showed cell-cell adhesion with localization of actin filaments to cell membrane, and revealed significant delaymore » of cell proliferation. Since the morphological changes of GPR174-cells were very similar to mock CHO cells treated with cholera toxin, we measured the concentration of intracellular cAMP. The results showed the concentration was significantly elevated in GPR174-cells. By measuring intracellular cAMP concentration in GPR174-cells, we screened lipids and nucleotides to identify ligands for GPR174. We found that lysophosphatidylserine (LysoPS) stimulated increase in intracellular cAMP in a dose-dependent manner. Moreover, phosphorylation of Erk was elevated by LysoPS in GPR174 cells. These LysoPS responses were inhibited by NF449, an inhibitor of G{alpha}{sub s} protein. These results suggested that GPR174 was a putative LysoPS receptor conjugating with G{alpha}{sub s}, and its expression induced morphological changes in CHO cells by constitutively activating adenylyl cycles accompanied with cell conjunctions and delay of proliferation.« less

Inhibitory effects of palmitoylcarnitine and lysophosphatidylcholine on the sodium current of cardiac ventricular cells.

PubMed

Sato, T; Kiyosue, T; Arita, M

1992-01-01

We investigated the effects of ischemia-related amphipathic compounds, palmitoylcarnitine (PamCar, 0.5-50 microM) and lysophosphatidylcholine (lysoPtdCho, 5-50 microM) on sodium current (INa) of guinea-pig ventricular myocytes. The cells were perfused with low-Na+ (60 mM) Tyrode's solution, and Ca2+ and K+ currents were blocked by external Co2+ (3 mM) and internal Cs+ (140 mM), respectively. INa was elicited by depolarizing voltage steps from a holding potential of -100 mV at a temperature of 33 degrees C. PamCar (5 microM) decreased the peak INa (attained at -20 mV or -30 mV) from 6.1 +/- 2.1 nA to 3.9 +/- 1.4 nA (n = 11), or by 36.1% within 2 min, and shifted the curve of steady-state INa inactivation by 5.4 mV in the positive direction (from -76.3 +/- 4.6 mV, control to -70.9 +/- 4.0 mV, in PamCar, n = 4). Partial restoration of the amplitude and the shift of the steady-state inactivation curve of INa was attained after washout of PamCar. In contrast, lysoPtdCho at concentrations over 10 microM irreversibly depressed the INa within 0.5-3 min and the reduction of INa was followed by cell contracture or cell death (n = 9). The survival time, defined as a period from the start of lysoPtdCho application to the time of the last successful recording of the INa (before evolution of sudden changes in the holding current), depended on the concentrations of lysoPtdCho. Both PamCar and lysoPtdCho retarded the time course of activation and inactivation of INa.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of the minocycline with extracelluar protein and intracellular protein by multi-spectral techniques and molecular docking

NASA Astrophysics Data System (ADS)

Fang, Qing; Wang, Yirun; Hu, Taoying; Liu, Ying

2017-02-01

The interaction of minocyeline (MNC) with extracelluar protein (lysozyme, LYSO) or intracellular protein (bovine hemoglobin, BHb) was investigated using multi-spectral techniques and molecular docking in vitro. Fluorescence studies suggested that MNC quenched LYSO/BHb fluorescence in a static mode with binding constants of 2.01 and 0.26 × 104 L•mol-1 at 298 K, respectively. The LYZO-MNC system was more easily influenced by temperature (298 and 310 K) than the BHb-MNC system. The thermodynamic parameters demonstrated that hydrogen bonds and van der Waals forces played the major role in the binding process. Based on the Förster theory of nonradiative energy transfer, the binding distances between MNC and the inner tryptophan residues of LYSO and BHb were calculated to be 4.34 and 3.49 nm, respectively. Furthermore, circular dichroism spectra (CD), Fourier transforms infrared (FTIR), UV-vis, and three-dimensional fluorescence spectra results indicated the secondary structures of LYSO and BHb were partially destroyed by MNC with the α-helix percentage of LYZO-MNC increased (17.8-28.6%) while that of BHb-MNC was decreased (41.6-39.6%). UV-vis spectral results showed these binding interactions could cause conformational and some micro-environmental changes of LYSO and BHb. In accordance with the results of molecular docking, In LYZO-MNC system, MNC was mainly bound in the active site hinge region where Trp-62 and Trp-63 are located, and in MNC-BHb system, MNC was close to the subunit α 1 of BHb, molecular docking analysis supported the thermodynamic results well. The work contributes to clarify the mechanism of MNC with two proteins at molecular level.

Impact of event positioning algorithm on performance of a whole-body PET scanner using one-to-one coupled detectors

NASA Astrophysics Data System (ADS)

Surti, S.; Karp, J. S.

2018-03-01

The advent of silicon photomultipliers (SiPMs) has introduced the possibility of increased detector performance in commercial whole-body PET scanners. The primary advantage of these photodetectors is the ability to couple a single SiPM channel directly to a single pixel of PET scintillator that is typically 4 mm wide (one-to-one coupled detector design). We performed simulation studies to evaluate the impact of three different event positioning algorithms in such detectors: (i) a weighted energy centroid positioning (Anger logic), (ii) identifying the crystal with maximum energy deposition (1st max crystal), and (iii) identifying the crystal with the second highest energy deposition (2nd max crystal). Detector simulations performed with LSO crystals indicate reduced positioning errors when using the 2nd max crystal positioning algorithm. These studies are performed over a range of crystal cross-sections varying from 1  ×  1 mm2 to 4  ×  4 mm2 as well as crystal thickness of 1 cm to 3 cm. System simulations were performed for a whole-body PET scanner (85 cm ring diameter) with a long axial FOV (70 cm long) and show an improvement in reconstructed spatial resolution for a point source when using the 2nd max crystal positioning algorithm. Finally, we observe a 30-40% gain in contrast recovery coefficient values for 1 and 0.5 cm diameter spheres when using the 2nd max crystal positioning algorithm compared to the 1st max crystal positioning algorithm. These results show that there is an advantage to implementing the 2nd max crystal positioning algorithm in a new generation of PET scanners using one-to-one coupled detector design with lutetium based crystals, including LSO, LYSO or scintillators that have similar density and effective atomic number as LSO.

Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.

PubMed

Xu, Jin; Casas-Ferreira, Ana M; Ma, Yun; Sen, Arundhuti; Kim, Min; Proitsi, Petroula; Shkodra, Maltina; Tena, Maria; Srinivasan, Parthi; Heaton, Nigel; Jassem, Wayel; Legido-Quigley, Cristina

2015-12-04

Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.

Activation of PAF-synthesizing enzymes in rat brain stem slices after LTP induction in the medial vestibular nuclei.

PubMed

Francescangeli, Ermelinda; Grassi, Silvarosa; Pettorossi, Vito E; Goracci, Gianfrancesco

2002-11-01

LysoPAF acetyltransferase (lysoPAF-AT) and PAF-synthesizing phosphocholinetransferase (PAF-PCT) are the two enzymes which catalyze the final reactions for the synthesis of PAF. Their activities, assayed in the homogenate of rat brain stem slices and under their optimal conditions, increased 5 min after high frequency stimulation of vestibular afferents, inducing LTP in the medial vestibular nuclei. The activity of phosphatidylcholine-synthesizing phosphocholinetransferase, was not affected. Sixty minutes from the induction of LTP, PAF-PCT activity, but not that of lysoPAF-AT, was still significantly higher with respect to 5 min test stimulated control. We used AP-5 to verify whether this increase was strictly dependent upon LTP induction, which requires NMDA receptor activation. In AP-5 treated slices, lysoPAF-acetyltransferase and PAF-synthesizing phosphocholinetransferase activities increased, but they were reduced after high frequency stimulation under AP-5. In conclusion, we have demonstrated that the activities of PAF-synthesizing enzymes are activated soon after the induction of LTP and that this effect is linked to the activation of NMDA-receptors. We suggest that the enzyme activation by AP-5, preventing LTP, might be due to glutamate enhancement but, in neurons showing LTP and under normal conditions, the activation of potentiation mechanisms is critical for the enhancement of enzyme activities.

Characterization of an In-Beam PET Prototype for Proton Therapy With Different Target Compositions

NASA Astrophysics Data System (ADS)

Attanasi, Francesca; Belcari, Nicola; Moehrs, Sascha; Rosso, Valeria; Vecchio, Sara; Cirrone, G. A. Pablo; Cuttone, Giacomo; Lojacono, Piero; Romano, Francesco; Lanconelli, Nico; Del Guerra, Alberto

2010-06-01

At the University of Pisa, the DoPET (Dosimetry with a Positron Emission Tomograph) project has focused on the development and characterization of an ad hoc, scalable, dual-head PET prototype for in-beam treatment planning verification of the proton therapy. In this paper we report the first results obtained with our current prototype, consisting of two opposing lutetium yttrium orthosilicate (LYSO) detectors, each one covering an area of 4.5 × 4.5 cm2. We measured the β+-activation induced by 62 MeV proton beams at Catana facility (LNS, Catania, Italy) in several plastic phantoms. Experiments were performed to evaluate the possibility to extract accurate phantom geometrical information from the reconstructed PET images. The PET prototype proved its capability of locating small air cavities in homogeneous PMMA phantoms with a submillimetric accuracy and of distinguishing materials with different 16O and 12C content by back mapping phantom geometry through the separation of the isotope contributions. This could be very useful in the clinical practice as a tool to highlight anatomical or physiological organ variations among different treatment sessions and to discriminate different tissue types, thus providing feedbacks for the accuracy of dose deposition.

Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Jin Ho; Choi, Yong, E-mail: ychoi.image@gmail.com; Jung, Jiwoong

2015-05-15

Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. Themore » PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired. Conclusions: Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.« less

Phosphatidyl derivative of hydroxytyrosol. In vitro intestinal digestion, bioaccessibility, and its effect on antioxidant activity.

PubMed

Martin, Diana; Moran-Valero, Maria I; Casado, Víctor; Reglero, Guillermo; Torres, Carlos F

2014-10-08

Intestinal digestion of phosphatidyl derivatives of HT (PHT) and its bioaccessibility under in vitro conditions was performed. First, an in vitro intestinal digestion model for phospholipids was developed. The impact of digestion in the antioxidant ability of PHT was also assayed. PHT was progressively hydrolyzed to lyso-PHT. However, digestion was slower than the phospholipid control. Nevertheless, most hydrolysis products were found at the micellar phase fraction, meaning a high bioaccessibility. Either PHT or digested PHT showed lower antioxidant activity than HT. However, PHT improved its antioxidant ability after digestion, likely related to lyso-PHT. As a summary, the synthetic phosphatidyl derivative of HT as PHT is recognized by phospholipases during simulation of intestinal digestion, although less efficiently than analogous phospholipids. Nevertheless, taking into account the bioaccessibility and the antioxidant activity of digested PHT, the potential of carriers of HT under the form of phospholipids might be of interest.

New insights into the autotaxin/LPA axis in cancer development and metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leblanc, Raphaël; Peyruchaud, Olivier, E-mail: olivier.peyruchaud@inserm.fr

Lysophosphatidic acid (LPA) is a simple lipid with a single fatty acyl chain linked to a glycerophosphate backbone. Despite the simplicity of its structure but owing to its interactions with a series of at least six G protein-coupled receptors (LPA{sub 1–6}), LPA exerts pleiotropic bioactivities including stimulation of proliferation, migration and survival of many cell types. Autotaxin (ATX) is a unique enzyme with a lysophospholipase D (lysoPLD) activity that is responsible for the levels of LPA in the blood circulation. Both LPA receptor family members and ATX/LysoPLD are aberrantly expressed in many human cancers. This review will present the moremore » striking as well as novel experimental evidences using cell lines, cancer mouse models and transgenic animals identifying the roles for ATX and LPA receptors in cancer progression, tumor cell invasion and metastasis.« less

Characterization of high density SiPM non-linearity and energy resolution for prompt gamma imaging applications

NASA Astrophysics Data System (ADS)

Regazzoni, V.; Acerbi, F.; Cozzi, G.; Ferri, A.; Fiorini, C.; Paternoster, G.; Piemonte, C.; Rucatti, D.; Zappalà, G.; Zorzi, N.; Gola, A.

2017-07-01

Fondazione Bruno Kessler (FBK) (Trento, Italy) has recently introduced High Density (HD) and Ultra High-Density (UHD) SiPMs, featuring very small micro-cell pitch. The high cell density is a very important factor to improve the linearity of the SiPM in high-dynamic-range applications, such as the scintillation light readout in high-energy gamma-ray spectroscopy and in prompt gamma imaging for proton therapy. The energy resolution at high energies is a trade-off between the excess noise factor caused by the non-linearity of the SiPM and the photon detection efficiency of the detector. To study these effects, we developed a new setup that simulates the LYSO light emission in response to gamma photons up to 30 MeV, using a pulsed light source. We measured the non-linearity and energy resolution vs. energy of the FBK RGB-HD e RGB-UHD SiPM technologies. We considered five different cell sizes, ranging from 10 μm up to 25 μm. With the UHD technology we were able to observe a remarkable reduction of the SiPM non-linearity, less than 5% at 5 MeV with 10 μm cells, which should be compared to a non-linearity of 50% with 25 μm-cell HD-SiPMs. With the same setup, we also measured the different components of the energy resolution (intrinsic, statistical, detector and electronic noise) vs. cell size, over-voltage and energy and we separated the different sources of excess noise factor.

Phosphatase-Resistant Analogues of Lysophosphatidic Acid

PubMed Central

Prestwich, Glenn D.; Gajewiak, Joanna; Zhang, Honglu; Xu, Xiaoyu; Yang, Guanghui; Serban, Monica

2008-01-01

Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G protein coupled receptors (GPCRs) have important potential applications in cell biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion, angiogenesis, and also biochemical resistance to chemotherapy- and radiotherapy-induced apoptosis. LPA and its analogues also are feedback inhibitors of the enzyme lysophospholipase D (lysoPLD, a.k.a., autotaxin, ATX), a central regulator of invasion and metastasis. For cancer therapy, the optimal therapeutic profile would be a metabolically stabilized, pan-LPA receptor antagonist that also inhibited lysoPLD. For protection of gastrointestinal mucosa and lymphocytes, LPA agonists would be desirable to minimize or reverse radiation or chemical-induced injury. Analogues of lysophosphatidic acid (LPA) that are chemically modified to be less susceptible to phospholipases and phosphatases show activity as long-lived receptor-specific agonists and antagonists for LPA receptors, as well as inhibitors for the lysoPLD activity of ATX. PMID:18454946

Two-dimensional nuclear magnetic resonance structure determination module for introductory biochemistry: synthesis and structural characterization of lyso-glycerophospholipids.

PubMed

Garrett, Teresa A; Rose, Rebecca L; Bell, Sidney M

2013-01-01

In this laboratory module, introductory biochemistry students are exposed to two-dimensional (1) H-nuclear magnetic resonance of glycerophospholipids (GPLs). Working in groups of three, students enzymatically synthesized and purified a variety of 2-acyl lyso GPLs. The structure of the 2-acyl lyso GPL was verified using (1) H-correlation spectroscopy. Students scored significantly higher on an assessment of NMR knowledge after having participated in this lab module and in comparison to a similar cohort who did not participate. Inaddition, student confidence in their NMR knowledge and abilities increased 62% following the module and correlated with their ability to apply their NMR knowledge. Based on these results, the laboratory module was very effective at providing students with a more extensive understanding of the underlying concepts of NMR as a tool for structural determination. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Oriented 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine/ganglioside membranes: a Fourier transform infrared attenuated total reflection spectroscopic study. Band assignments; orientational, hydrational, and phase behavior; and effects of Ca2+ binding.

PubMed

Müller, E; Giehl, A; Schwarzmann, G; Sandhoff, K; Blume, A

1996-09-01

Fourier transform infrared (FTIR) attenuated total reflection (ATR) spectroscopy was used to elucidate the hydration behavior and molecular order of phospholipid/ganglioside bilayers. We examined dry and hydrated films of the gangliosides GM1, deacetyl-GM1, lyso-GM1, deacetyllyso-GM1, and GM3 and oriented mixed films of these gangliosides with 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) using polarized light. Analysis of the amide I frequencies reveals that the amide groups are involved in intermolecular interactions via hydrogen bonds of varying strengths. The tilt angle of the acyl chains of the lipids in mixed films was determined as a function of ganglioside structure. Deacetylation of the sialic acid in the headgroup has a stronger influence on the tilt angle than the removal of the ganglioside fatty acid. The phase behavior was examined by FTIR ATR spectroscopy and by differential scanning calorimetry (DSC) measurements on lipid suspensions. At the same molar concentration, lyso-gangliosides have less effect on changes of transition temperature compared to the double-chain analogs. Distinct differences in the amide band shapes were observed between mixtures with lyso-gangliosides and normal double-chain gangliosides. Determined from the dicroic ratio RATR, the orientation of the COO- group in all DMPC/ganglioside mixtures was found to be relatively fixed with respect to the membrane normal. In 4:1 mixtures of DMPC with GM1 and deacetyl-GM1, the binding of Ca2+ leads to a slight decrease in chain tilt in the gel phase, probably caused by a dehydration of the membrane-water interface. In mixtures of DMPC with GM3 and deacetyl-lyso-GM1, a slight increase in chain tilt is observed. The chain tilt in DMPC/lyso-GM1 mixtures is unchanged. Analysis of the COO- band reveals that Ca2+ does not bind to the carboxylate group of the sialic acid of GM1 and deacetyl-GM1, the mixtures in which a decrease in chain tilt was observed. Binding to the sialic acid was only observed for mixtures of DMPC with GM3, lyso-GM1, and deacetyl-lyso-GM1. Ca2+ obviously accumulates at the bilayer-water interface and leads to partial dehydration of the headgroup region in the gel as well as in the liquid-crystalline phase. This can be concluded from the changes in the amide I band shapes. With the exception of DMPC/deacetyl-GM1, the effects on the ester C==O bands are small. The addition of Ca2+ has minor effects on the phase behavior, with the exception of the DMPC/GM1 mixture.

Light-Sharing Interface for dMiCE Detectors Using Sub-Surface Laser Engraving

PubMed Central

Hunter, William C. J.; Miyaoka, Robert S.; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K.

2015-01-01

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of a crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for each crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mm3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Silicon photomultiplier arrays. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout while obtaining energy resolutions on the order of 10%. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern. PMID:25914421

Light-Sharing Interface for dMiCE Detectors using Sub-Surface Laser Engraving.

PubMed

Hunter, William C J; Miyaoka, Robert S; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K

2013-10-01

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of this crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for a crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mmˆ3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Geiger-Müller avalanche photodiodes from Hamamatsu. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions events. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern.

Light-Sharing Interface for dMiCE Detectors using Sub-Surface Laser Engraving

PubMed Central

Hunter, William C.J.; Miyaoka, Robert S.; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K.

2014-01-01

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of this crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for a crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mmˆ3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Geiger-Müller avalanche photodiodes from Hamamatsu. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions events. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern. PMID:25506194

Light-Sharing Interface for dMiCE Detectors Using Sub-Surface Laser Engraving.

PubMed

Hunter, William C J; Miyaoka, Robert S; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K

2015-02-06

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of a crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for each crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mm 3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Silicon photomultiplier arrays. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout while obtaining energy resolutions on the order of 10%. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern.

Prototype pre-clinical PET scanner with depth-of-interaction measurements using single-layer crystal array and single-ended readout

NASA Astrophysics Data System (ADS)

Lee, Min Sun; Kim, Kyeong Yun; Ko, Guen Bae; Lee, Jae Sung

2017-05-01

In this study, we developed a proof-of-concept prototype PET system using a pair of depth-of-interaction (DOI) PET detectors based on the proposed DOI-encoding method and digital silicon photomultiplier (dSiPM). Our novel cost-effective DOI measurement method is based on a triangular-shaped reflector that requires only a single-layer pixelated crystal and single-ended signal readout. The DOI detector consisted of an 18  ×  18 array of unpolished LYSO crystal (1.47  ×  1.47  ×  15 mm3) wrapped with triangular-shaped reflectors. The DOI information was encoded by depth-dependent light distribution tailored by the reflector geometry and DOI correction was performed using four-step depth calibration data and maximum-likelihood (ML) estimation. The detector pair and the object were placed on two motorized rotation stages to demonstrate 12-block ring PET geometry with 11.15 cm diameter. Spatial resolution was measured and phantom and animal imaging studies were performed to investigate imaging performance. All images were reconstructed with and without the DOI correction to examine the impact of our DOI measurement. The pair of dSiPM-based DOI PET detectors showed good physical performances respectively: 2.82 and 3.09 peak-to-valley ratios, 14.30% and 18.95% energy resolution, and 4.28 and 4.24 mm DOI resolution averaged over all crystals and all depths. A sub-millimeter spatial resolution was achieved at the center of the field of view (FOV). After applying ML-based DOI correction, maximum 36.92% improvement was achieved in the radial spatial resolution and a uniform resolution was observed within 5 cm of transverse PET FOV. We successfully acquired phantom and animal images with improved spatial resolution and contrast by using the DOI measurement. The proposed DOI-encoding method was successfully demonstrated in the system level and exhibited good performance, showing its feasibility for animal PET applications with high spatial resolution and sensitivity.

A simultaneous beta and coincidence-gamma imaging system for plant leaves

NASA Astrophysics Data System (ADS)

Ranjbar, Homayoon; Wen, Jie; Mathews, Aswin J.; Komarov, Sergey; Wang, Qiang; Li, Ke; O'Sullivan, Joseph A.; Tai, Yuan-Chuan

2016-05-01

Positron emitting isotopes, such as 11C, 13N, and 18F, can be used to label molecules. The tracers, such as 11CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have a higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to poor positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (simultaneous beta-gamma imager). The imager can simultaneously detect positrons ({β+} ) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs beta and gamma images independently to estimate the thickness component of the beta forward model and afterward jointly estimates the radioactivity distribution in the object. We have validated the physics model and reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed 11CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the structural similarity (SSIM) index for comparing the leaf images from the simultaneous beta-gamma imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively.

A simultaneous beta and coincidence-gamma imaging system for plant leaves.

PubMed

Ranjbar, Homayoon; Wen, Jie; Mathews, Aswin J; Komarov, Sergey; Wang, Qiang; Li, Ke; O'Sullivan, Joseph A; Tai, Yuan-Chuan

2016-05-07

Positron emitting isotopes, such as (11)C, (13)N, and (18)F, can be used to label molecules. The tracers, such as (11)CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have a higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to poor positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (simultaneous beta-gamma imager). The imager can simultaneously detect positrons ([Formula: see text]) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs beta and gamma images independently to estimate the thickness component of the beta forward model and afterward jointly estimates the radioactivity distribution in the object. We have validated the physics model and reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed (11)CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the structural similarity (SSIM) index for comparing the leaf images from the simultaneous beta-gamma imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Matthew D., E-mail: Matt.Wilson@stfc.ac.uk; Seller, Paul; Veale, Matthew C.

A novel, “single-shot” fluorescence imaging technique has been demonstrated on the B16 beamline at the Diamond Light Source synchrotron using the HEXITEC energy dispersive imaging detector. A custom made furnace with 200µm thick metal alloy samples was positioned in a white X-ray beam with a hole made in the furnace walls to allow the transmitted beam to be imaged with a conventional X-ray imaging camera consisting of a 500 µm thick single crystal LYSO scintillator, mirror and lens coupled to an AVT Manta G125B CCD sensor. The samples were positioned 45° to the incident beam to enable simultaneous transmission andmore » fluorescence imaging. The HEXITEC detector was positioned at 90° to the sample with a 50 µm pinhole 13 cm from the sample and the detector positioned 2.3m from pinhole. The geometric magnification provided a field of view of 1.1×1.1mm{sup 2} with one of the 80×80 pixels imaging an area equivalent to 13µm{sup 2}. Al-Cu alloys doped with Zr, Ag and Mo were imaged in transmission and fluorescence mode. The fluorescence images showed that the dopant metals could be simultaneously imaged with sufficient counts on all 80x80 pixels within 60 s, with the X-ray flux limiting the fluorescence imaging rate. This technique demonstrated that it is possible to simultaneously image and identify multiple elements on a spatial resolution scale ~10µm or higher without the time consuming need to scan monochromatic energies or raster scan a focused beam of X-rays. Moving to high flux beamlines and using an array of detectors could improve the imaging speed of the technique with element specific imaging estimated to be on a 1 s timescale.« less

Tunable femtosecond near-infrared source based on a Yb:LYSO-laser-pumped optical parametric oscillator

NASA Astrophysics Data System (ADS)

Wen-Long, Tian; Zhao-Hua, Wang; Jiang-Feng, Zhu; Zhi-Yi, Wei

2016-01-01

We demonstrate a widely tunable near-infrared source from 767 nm to 874 nm generated by the intracavity second harmonic generation (SHG) in an optical parametric oscillator pumped by a Yb:LYSO solid-state laser. The home-made Yb:LYSO oscillator centered at 1035 nm delivers an average power of 2 W and a pulse duration as short as 351 fs. Two MgO doped periodically poled lithium niobates (MgO:PPLN) with grating periods of 28.5-31.5 μm in steps of 0.5 μm and 19.5-21.3 μm in steps of 0.2 μm are used for the OPO and intracavity SHG, respectively. The maximum average output power of 180 mW at 798 nm was obtained and the output pulses have pulse duration of 313 fs at 792 nm if a sech2-pulse shape was assumed. In addition, tunable signal femtosecond pulses from 1428 nm to 1763 nm are also realized with the maximum average power of 355 mW at 1628 nm. Project supported by the National Key Basic Research Program of China (Grant No. 2013CB922402), the National Key Scientific Instruments Development Program of China (Grant No. 2012YQ120047), the National Natural Science Foundation of China (Grant Nos. 61205130 and 11174361), and the Key Deployment Project of Chinese Academy of Sciences (Grant No. KJZD-EW-L11-03).

WE-C-217BCD-10: Development of High Performance PET for Animal Imaging and Therapy Applications.

PubMed

Shao, Y; Sun, X; Lan, K; Bircher, C

2012-06-01

A prototype small animal PET is developed with several novel technologies to measure 3D gamma-interaction positions and to substantially improve imaging performance. Each new detector has an 8×8 array of 1.95×1.95×30 mm̂3 LYSO scintillators, with each end optically connected to a solid-state photo multiplier (SSPM) array through a light guide. This dual-ended-readout enables the depth-of-interaction (DOI) measurement. Each SSPM array has 16 SSPMs arranged in a 4×4 matrix. Each SSPM has active area about 3×3 mm̂2, with its output read by an ASIC electronics that directly converts analog signals to digital timing pulses which encode the interaction information for energy, timing, crystal of interaction, and DOI calculations. These digital pulses are transferred to and decoded by FPGA-based TDC for coincident event selection and data acquisition. This independent readout of each SSPM and parallel signal process significantly improve signal-to-noise ratio and permit applying flexible data processing algorithms. The current prototype system consists of two rotating detector panels on a portable gantry, with 4 detectors linearly packed together in each panel to provide ∼16 mm axial and variable trans- axial FOV with adjustable panel-to-panel distance. List-mode OSEM-based image reconstruction with resolution modeling was implemented. Both Na- 22 point source and phantom were used to evaluate the system performance. The measured energy, timing, spatial and DOI resolutions for each crystal were around 16%, 2.6 ns, 2.0 mm and 5.0 mm, respectively. The measured spatial resolutions with DOI were ∼1.7 mm across the entire FOV in all direction, while those without DOI were much worse and non-uniform across the FOV, in the range predominately around 3.0 to 4.0 mm. In addition, images from a F-18 hot-rod phantom with DOI show significantly improved quality compared to those without DOI. DOI- measurable PET shows substantially improved image performance for a compact system. National Institute of Health. University of Texas MD Anderson Cancer Center. © 2012 American Association of Physicists in Medicine.

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy.

PubMed

Franzen, Daniel; Haile, Sarah R; Kasper, David C; Mechtler, Thomas P; Flammer, Andreas J; Krayenbühl, Pierre A; Nowak, Albina

2018-01-01

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations of GLA gene leading to reduced α-galactosidase activity and resulting in a progressive accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Plasma Lyso-Gb3 levels serve as a disease severity and treatment monitoring marker during enzyme replacement therapy (ERT). Adult patients with AFD who had yearly pulmonary function tests between 1999 and 2015 were eligible for this observational study. Primary outcome measures were the change in z-score of forced expiratory volume in the first second (FEV 1 ) and FEV 1 /FVC over time. Plasma Lyso-Gb3 levels and the age of ERT initiation were investigated for their association with lung function decline. Fifty-three patients (42% male, median (range) age at diagnosis of AFD 34 (6-61) years in men, 34 (13-67) in women) were included. The greatest decrease of FEV 1 /FVC z-scores was observed in Classic men (-0.048 per year, 95% CI -0.081 to -0.014), compared with the Later-Onset men (+0.013,95% CI -0.055 to 0.082), Classic women (-0.008, 95% CI -0.035 to +0.020) and Later-Onset women (-0.013, 95% CI -0.084 to +0.058). Cigarette smoking (P=0.022) and late ERT initiation (P=0.041) were independently associated with faster FEV 1 decline. FEV 1 /FVC z-score decrease was significantly reduced after initiation of ERT initiation (-0.045 compared with -0.015, P=0.014). Furthermore, there was a trend towards a relevant influence of Lyso-Gb3 (P=0.098) on airflow limitation with age. Early ERT initiation seems to preserve pulmonary function. Plasma Lyso-Gb3 is maybe a useful predictor for airflow limitation. Classic men need a closer monitoring of the lung function.

Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes.

PubMed

Prieto-Sánchez, María T; Ruiz-Palacios, María; Blanco-Carnero, José E; Pagan, Ana; Hellmuth, Christian; Uhl, Olaf; Peissner, Wolfgang; Ruiz-Alcaraz, Antonio J; Parrilla, Juan J; Koletzko, Berthold; Larqué, Elvira

2017-04-01

Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers. Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM-diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers. Fetal abdominal circumference z-score at 38 weeks tended to higher values in GDM (P = 0.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids (P = 0.029) and lyso-PL (P = 0.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids (r = 0.388, P = 0.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference. In offspring of women with GDM treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce DHA availability. Lyso-PL appear to contribute to materno-fetal DHA transport. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

TDC-based readout electronics for real-time acquisition of high resolution PET bio-images

NASA Astrophysics Data System (ADS)

Marino, N.; Saponara, S.; Ambrosi, G.; Baronti, F.; Bisogni, M. G.; Cerello, P.,; Ciciriello, F.; Corsi, F.; Fanucci, L.; Ionica, M.; Licciulli, F.; Marzocca, C.; Morrocchi, M.; Pennazio, F.; Roncella, R.; Santoni, C.; Wheadon, R.; Del Guerra, A.

2013-02-01

Positron emission tomography (PET) is a clinical and research tool for in vivo metabolic imaging. The demand for better image quality entails continuous research to improve PET instrumentation. In clinical applications, PET image quality benefits from the time of flight (TOF) feature. Indeed, by measuring the photons arrival time on the detectors with a resolution less than 100 ps, the annihilation point can be estimated with centimeter resolution. This leads to better noise level, contrast and clarity of detail in the images either using analytical or iterative reconstruction algorithms. This work discusses a silicon photomultiplier (SiPM)-based magnetic-field compatible TOF-PET module with depth of interaction (DOI) correction. The detector features a 3D architecture with two tiles of SiPMs coupled to a single LYSO scintillator on both its faces. The real-time front-end electronics is based on a current-mode ASIC where a low input impedance, fast current buffer allows achieving the required time resolution. A pipelined time to digital converter (TDC) measures and digitizes the arrival time and the energy of the events with a timestamp of 100 ps and 400 ps, respectively. An FPGA clusters the data and evaluates the DOI, with a simulated z resolution of the PET image of 1.4 mm FWHM.

Qualification test of a MPPC-based PET module for future MRI-PET scanners

NASA Astrophysics Data System (ADS)

Kurei, Y.; Kataoka, J.; Kato, T.; Fujita, T.; Funamoto, H.; Tsujikawa, T.; Yamamoto, S.

2014-11-01

We have developed a high-resolution, compact Positron Emission Tomography (PET) module for future use in MRI-PET scanners. The module consists of large-area, 4×4 ch MPPC arrays (Hamamatsu S11827-3344MG) optically coupled with Ce:LYSO scintillators fabricated into 12×12 matrices of 1×1 mm2 pixels. At this stage, a pair of module and coincidence circuits was assembled into an experimental prototype gantry arranged in a ring of 90 mm in diameter to form the MPPC-based PET system. The PET detector ring was then positioned around the RF coil of the 4.7 T MRI system. We took an image of a point 22Na source under fast spin echo (FSE) and gradient echo (GE), in order to measure interference between the MPPC-based PET and the MRI. We only found a slight degradation in the spatial resolution of the PET image from 1.63 to 1.70 mm (FWHM; x-direction), or 1.48-1.55 mm (FWHM; y-direction) when operating with the MRI, while the signal-to-noise ratio (SNR) of the MRI image was only degraded by 5%. These results encouraged us to develop a more advanced version of the MRI-PET gantry with eight MPPC-based PET modules, whose detailed design and first qualification test are also presented in this paper.

Implementation and analysis of list mode algorithm using tubes of response on a dedicated brain and breast PET

NASA Astrophysics Data System (ADS)

Moliner, L.; Correcher, C.; González, A. J.; Conde, P.; Hernández, L.; Orero, A.; Rodríguez-Álvarez, M. J.; Sánchez, F.; Soriano, A.; Vidal, L. F.; Benlloch, J. M.

2013-02-01

In this work we present an innovative algorithm for the reconstruction of PET images based on the List-Mode (LM) technique which improves their spatial resolution compared to results obtained with current MLEM algorithms. This study appears as a part of a large project with the aim of improving diagnosis in early Alzheimer disease stages by means of a newly developed hybrid PET-MR insert. At the present, Alzheimer is the most relevant neurodegenerative disease and the best way to apply an effective treatment is its early diagnosis. The PET device will consist of several monolithic LYSO crystals coupled to SiPM detectors. Monolithic crystals can reduce scanner costs with the advantage to enable implementation of very small virtual pixels in their geometry. This is especially useful for LM reconstruction algorithms, since they do not need a pre-calculated system matrix. We have developed an LM algorithm which has been initially tested with a large aperture (186 mm) breast PET system. Such an algorithm instead of using the common lines of response, incorporates a novel calculation of tubes of response. The new approach improves the volumetric spatial resolution about a factor 2 at the border of the field of view when compared with traditionally used MLEM algorithm. Moreover, it has also shown to decrease the image noise, thus increasing the image quality.

Measurement of intrinsic rise times for various L(Y)SO and LuAG scintillators with a general study of prompt photons to achieve 10 ps in TOF-PET.

PubMed

Gundacker, Stefan; Auffray, Etiennette; Pauwels, Kristof; Lecoq, Paul

2016-04-07

The coincidence time resolution (CTR) of scintillator based detectors commonly used in positron emission tomography is well known to be dependent on the scintillation decay time (τd) and the number of photons detected (n'), i.e. CTR proportional variant √τd/n'. However, it is still an open question to what extent the scintillation rise time (τr) and other fast or prompt photons, e.g. Cherenkov photons, at the beginning of the scintillation process influence the CTR. This paper presents measurements of the scintillation emission rate for different LSO type crystals, i.e. LSO:Ce, LYSO:Ce, LSO:Ce codoped Ca and LGSO:Ce. For the various LSO-type samples measured we find an average value of 70 ps for the scintillation rise time, although some crystals like LSO:Ce codoped Ca seem to have a much faster rise time in the order of 20 ps. Additional measurements for LuAG:Ce and LuAG:Pr show a rise time of 535 ps and 251 ps, respectively. For these crystals, prompt photons (Cherenkov) can be observed at the beginning of the scintillation event. Furthermore a significantly lower rise time value is observed when codoping with calcium. To quantitatively investigate the influence of the rise time to the time resolution we measured the CTR with the same L(Y)SO samples and compared the values to Monte Carlo simulations. Using the measured relative light yields, rise- and decay times of the scintillators we are able to quantitatively understand the measured CTRs in our simulations. Although the rise time is important to fully explain the CTR variation for the different samples tested we determined its influence on the CTR to be in the order of a few percent only. This result is surprising because, if only photonstatistics of the scintillation process is considered, the CTR would be proportional to the square root of the rise time. The unexpected small rise time influence on the CTR can be explained by the convolution of the scintillation rate with the single photon time resolution (SPTR) of the photodetector and the photon travel spread (PTS) in the crystal. The timing benefits of prompt photons at the beginning of the scintillation process (Cherenkov etc) are further studied, which leads to the conclusion that the scintillation rise time, SPTR and PTS have to be lowered simultaneously to fully profit from these fast photons in order to improve the CTR significantly.

Measurement of intrinsic rise times for various L(Y)SO and LuAG scintillators with a general study of prompt photons to achieve 10 ps in TOF-PET

NASA Astrophysics Data System (ADS)

Gundacker, Stefan; Auffray, Etiennette; Pauwels, Kristof; Lecoq, Paul

2016-04-01

The coincidence time resolution (CTR) of scintillator based detectors commonly used in positron emission tomography is well known to be dependent on the scintillation decay time ({τd} ) and the number of photons detected ({{n}\\prime} ), i.e. CTR\\propto \\sqrt{{τd}/{{n}\\prime}} . However, it is still an open question to what extent the scintillation rise time ({τr} ) and other fast or prompt photons, e.g. Cherenkov photons, at the beginning of the scintillation process influence the CTR. This paper presents measurements of the scintillation emission rate for different LSO type crystals, i.e. LSO:Ce, LYSO:Ce, LSO:Ce codoped Ca and LGSO:Ce. For the various LSO-type samples measured we find an average value of 70 ps for the scintillation rise time, although some crystals like LSO:Ce codoped Ca seem to have a much faster rise time in the order of 20 ps. Additional measurements for LuAG:Ce and LuAG:Pr show a rise time of 535 ps and 251 ps, respectively. For these crystals, prompt photons (Cherenkov) can be observed at the beginning of the scintillation event. Furthermore a significantly lower rise time value is observed when codoping with calcium. To quantitatively investigate the influence of the rise time to the time resolution we measured the CTR with the same L(Y)SO samples and compared the values to Monte Carlo simulations. Using the measured relative light yields, rise- and decay times of the scintillators we are able to quantitatively understand the measured CTRs in our simulations. Although the rise time is important to fully explain the CTR variation for the different samples tested we determined its influence on the CTR to be in the order of a few percent only. This result is surprising because, if only photonstatistics of the scintillation process is considered, the CTR would be proportional to the square root of the rise time. The unexpected small rise time influence on the CTR can be explained by the convolution of the scintillation rate with the single photon time resolution (SPTR) of the photodetector and the photon travel spread (PTS) in the crystal. The timing benefits of prompt photons at the beginning of the scintillation process (Cherenkov etc) are further studied, which leads to the conclusion that the scintillation rise time, SPTR and PTS have to be lowered simultaneously to fully profit from these fast photons in order to improve the CTR significantly.

Performance evaluation of a high-resolution brain PET scanner using four-layer MPPC DOI detectors.

PubMed

Watanabe, Mitsuo; Saito, Akinori; Isobe, Takashi; Ote, Kibo; Yamada, Ryoko; Moriya, Takahiro; Omura, Tomohide

2017-08-18

A high-resolution positron emission tomography (PET) scanner, dedicated to brain studies, was developed and its performance was evaluated. A four-layer depth of interaction detector was designed containing five detector units axially lined up per layer board. Each of the detector units consists of a finely segmented (1.2 mm) LYSO scintillator array and an 8  ×  8 array of multi-pixel photon counters. Each detector layer has independent front-end and signal processing circuits, and the four detector layers are assembled as a detector module. The new scanner was designed to form a detector ring of 430 mm diameter with 32 detector modules and 168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm, respectively, which are sufficient to measure a whole human brain. The single-event data generated at each detector module were transferred to the data acquisition servers through optical fiber cables. The single-event data from all detector modules were merged and processed to create coincidence event data in on-the-fly software in the data acquisition servers. For image reconstruction, the high-resolution mode (HR-mode) used a 1.2 mm 2 crystal segment size and the high-speed mode (HS-mode) used a 4.8 mm 2 size by collecting 16 crystal segments of 1.2 mm each to reduce the computational cost. The performance of the brain PET scanner was evaluated. For the intrinsic spatial resolution of the detector module, coincidence response functions of the detector module pair, which faced each other at various angles, were measured by scanning a 0.25 mm diameter 22 Na point source. The intrinsic resolutions were obtained with 1.08 mm full width at half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the first layer pair, respectively. The system spatial resolutions were less than 1.0 mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The system sensitivity was 21.4 cps kBq -1 as measured using an 18 F line source aligned with the center of the transaxial FOV. High count rate capability was evaluated using a cylindrical phantom (20 cm diameter  ×  70 cm length), resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml -1 at the peak count in a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the-fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps for single and coincidence count rates, respectively. Using phantom studies, we also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom and an ultra-micro hot-spot phantom. The images obtained were of acceptable quality for high-resolution determination. As clinical and pre-clinical studies, we imaged brains of a human and of small animals.

Performance evaluation of a high-resolution brain PET scanner using four-layer MPPC DOI detectors

NASA Astrophysics Data System (ADS)

Watanabe, Mitsuo; Saito, Akinori; Isobe, Takashi; Ote, Kibo; Yamada, Ryoko; Moriya, Takahiro; Omura, Tomohide

2017-09-01

A high-resolution positron emission tomography (PET) scanner, dedicated to brain studies, was developed and its performance was evaluated. A four-layer depth of interaction detector was designed containing five detector units axially lined up per layer board. Each of the detector units consists of a finely segmented (1.2 mm) LYSO scintillator array and an 8  ×  8 array of multi-pixel photon counters. Each detector layer has independent front-end and signal processing circuits, and the four detector layers are assembled as a detector module. The new scanner was designed to form a detector ring of 430 mm diameter with 32 detector modules and 168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm, respectively, which are sufficient to measure a whole human brain. The single-event data generated at each detector module were transferred to the data acquisition servers through optical fiber cables. The single-event data from all detector modules were merged and processed to create coincidence event data in on-the-fly software in the data acquisition servers. For image reconstruction, the high-resolution mode (HR-mode) used a 1.2 mm2 crystal segment size and the high-speed mode (HS-mode) used a 4.8 mm2 size by collecting 16 crystal segments of 1.2 mm each to reduce the computational cost. The performance of the brain PET scanner was evaluated. For the intrinsic spatial resolution of the detector module, coincidence response functions of the detector module pair, which faced each other at various angles, were measured by scanning a 0.25 mm diameter 22Na point source. The intrinsic resolutions were obtained with 1.08 mm full width at half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the first layer pair, respectively. The system spatial resolutions were less than 1.0 mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The system sensitivity was 21.4 cps kBq-1 as measured using an 18F line source aligned with the center of the transaxial FOV. High count rate capability was evaluated using a cylindrical phantom (20 cm diameter  ×  70 cm length), resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml-1 at the peak count in a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the-fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps for single and coincidence count rates, respectively. Using phantom studies, we also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom and an ultra-micro hot-spot phantom. The images obtained were of acceptable quality for high-resolution determination. As clinical and pre-clinical studies, we imaged brains of a human and of small animals.

Design and Performance of a 1 mm3 Resolution Clinical PET System Comprising 3-D Position Sensitive Scintillation Detectors.

PubMed

Hsu, David F C; Freese, David L; Reynolds, Paul D; Innes, Derek R; Levin, Craig S

2018-04-01

We are developing a 1-mm 3 resolution, high-sensitivity positron emission tomography (PET) system for loco-regional cancer imaging. The completed system will comprise two cm detector panels and contain 4 608 position sensitive avalanche photodiodes (PSAPDs) coupled to arrays of mm 3 LYSO crystal elements for a total of 294 912 crystal elements. For the first time, this paper summarizes the design and reports the performance of a significant portion of the final clinical PET system, comprising 1 536 PSAPDs, 98 304 crystal elements, and an active field-of-view (FOV) of cm. The sub-system performance parameters, such as energy, time, and spatial resolutions are predictive of the performance of the final system due to the modular design. Analysis of the multiplexed crystal flood histograms shows 84% of the crystal elements have>99% crystal identification accuracy. The 511 keV photopeak energy resolution was 11.34±0.06% full-width half maximum (FWHM), and coincidence timing resolution was 13.92 ± 0.01 ns FWHM at 511 keV. The spatial resolution was measured using maximum likelihood expectation maximization reconstruction of a grid of point sources suspended in warm background. The averaged resolution over the central 6 cm of the FOV is 1.01 ± 0.13 mm in the X-direction, 1.84 ± 0.20 mm in the Y-direction, and 0.84 ± 0.11 mm in the Z-direction. Quantitative analysis of acquired micro-Derenzo phantom images shows better than 1.2 mm resolution at the center of the FOV, with subsequent resolution degradation in the y-direction toward the edge of the FOV caused by limited angle tomography effects.

A front-end readout mixed chip for high-efficiency small animal PET imaging

NASA Astrophysics Data System (ADS)

Ollivier-Henry, N.; Berst, J. D.; Colledani, C.; Hu-Guo, Ch.; Mbow, N. A.; Staub, D.; Guyonnet, J. L.; Hu, Y.

2007-02-01

Today, the main challenge of Positron Emission Tomography (PET) systems dedicated to small animal imaging is to obtain high detection efficiency and a highly accurate localization of radioisotopes. If we focus only on the PET characteristics such as the spatial resolution, its accuracy depends on the design of detector and on the electronics readout system as well. In this paper, we present a new design of such readout system with full custom submicrometer CMOS implementation. The front end chip consists of two main blocks from which the energy information and the time stamp with subnanosecond resolution can be obtained. In our A Multi-Modality Imaging System for Small Animal (AMISSA) PET system design, a matrix of LYSO crystals has to be read at each end by a 64 channels multianode photomultiplier tube. A specific readout electronic has been developed at the Hubert Curien Multidisciplinary Institute (IPHC, France). The architecture of this readout for the energy information detection is composed of a low-noise preamplifier, a CR-RC shaper and an analogue memory. In order to obtain the required dynamic range from 15 to 650 photoelectrons with good linearity, a current mode approach has been chosen for the preamplifier. To detect the signal with a temporal resolution of 1 ns, a comparator with a very low threshold (˜0.3 photoelectron) has been implemented. It gives the time reference of arrival signal coming from the detector. In order to obtain the time coincidence with a temporal resolution of 1 ns, a Time-to-Digital Converter (TDC) based on a Delay-Locked-Loop (DLL) has been designed. The chip is fabricated with AMS 0.35 μm process. The ASIC architecture and some simulation results will be presented in the paper.

Characterization of Sensitivity Encoded Silicon Photomultiplier (SeSP) with 1-Dimensional and 2-Dimensional Encoding for High Resolution PET/MR

NASA Astrophysics Data System (ADS)

Omidvari, Negar; Schulz, Volkmar

2015-06-01

This paper evaluates the performance of a new type of PET detectors called sensitivity encoded silicon photomultiplier (SeSP), which allows a direct coupling of small-pitch crystal arrays to the detector with a reduction in the number of readout channels. Four SeSP devices with two separate encoding schemes of 1D and 2D were investigated in this study. Furthermore, both encoding schemes were manufactured in two different sizes of 4 ×4 mm2 and 7. 73 ×7. 9 mm2, in order to investigate the effect of size on detector parameters. All devices were coupled to LYSO crystal arrays with 1 mm pitch size and 10 mm height, with optical isolation between crystals. The characterization was done for the key parameters of crystal-identification, energy resolution, and time resolution as a function of triggering threshold and over-voltage (OV). Position information was archived using the center of gravity (CoG) algorithm and a least squares approach (LSQA) in combination with a mean light matrix around the photo-peak. The positioning results proved the capability of all four SeSP devices in precisely identifying all crystals coupled to the sensors. Energy resolution was measured at different bias voltages, varying from 12% to 18% (FWHM) and paired coincidence time resolution (pCTR) of 384 ps to 1.1 ns was obtained for different SeSP devices at about 18 °C room temperature. However, the best time resolution was achieved at the highest over-voltage, resulting in a noise ratio of 99.08%.

A simulation study of a dual-plate in-room PET system for dose verification in carbon ion therapy

NASA Astrophysics Data System (ADS)

Chen, Ze; Hu, Zheng-Guo; Chen, Jin-Da; Zhang, Xiu-Ling; Guo, Zhong-Yan; Xiao, Guo-Qing; Sun, Zhi-Yu; Huang, Wen-Xue; Wang, Jian-Song

2014-08-01

During carbon ion therapy, lots of positron emitters such as 11C, 15O, 10C are generated in irradiated tissues by nuclear reactions, and can be used to track the carbon beam in the tissue by a positron emission tomography (PET) scanner. In this study, an dual-plate in-room PET scanner has been designed and evaluated based on the GATE simulation platform to monitor patient dose in carbon ion therapy. The dual-plate PET is designed to avoid interference with the carbon beamline and with patient positioning. Its performance was compared with that of four-head and full-ring PET scanners. The dual-plate, four-head and full-ring PET scanners consisted of 30, 60, 60 detector modules, respectively, with a 36 cm distance between directly opposite detector modules for dose deposition measurements. Each detector module consisted of a 24×24 array of 2 mm×2 mm×18 mm LYSO pixels coupled to a Hamamatsu H8500 PMT. To estimate the production yield of positron emitters, a 10 cm×15 cm×15 cm cuboid PMMA phantom was irradiated with 172, 200, 250 MeV/u 12C beams. 3D images of the activity distribution measured by the three types of scanner are produced by an iterative reconstruction algorithm. By comparing the longitudinal profile of positron emitters along the carbon beam path, it is indicated that use of the dual-plate PET scanner is feasible for monitoring the dose distribution in carbon ion therapy.

Timing capabilities of garnet crystals for detection of high energy charged particles

NASA Astrophysics Data System (ADS)

Lucchini, M. T.; Gundacker, S.; Lecoq, P.; Benaglia, A.; Nikl, M.; Kamada, K.; Yoshikawa, A.; Auffray, E.

2017-04-01

Particle detectors at future collider experiments will operate at high collision rates and thus will have to face high pile up and a harsh radiation environment. Precision timing capabilities can help in the reconstruction of physics events by mitigating pile up effects. In this context, radiation tolerant, scintillating crystals coupled to silicon photomultipliers (SiPMs) can provide a flexible and compact option for the implementation of a precision timing layer inside large particle detectors. In this paper, we compare the timing performance of aluminum garnet crystals (YAG: Ce, LuAG: Ce, GAGG: Ce) and the improvements of their time resolution by means of codoping with Mg2+ ions. The crystals were read out using SiPMs from Hamamatsu glued to the rear end of the scintillator and their timing performance was evaluated by measuring the coincidence time resolution (CTR) of 150 GeV charged pions traversing a pair of crystals. The influence of crystal properties, such as density, light yield and decay kinetics on the timing performance is discussed. The best single detector time resolutions are in the range of 23-30 ps (sigma) and only achieved by codoping the garnet crystals with divalent ions, such as Mg2+. The much faster scintillation decay in the co-doped samples as compared to non co-doped garnets explains the higher timing performance. Samples of LSO: Ce, Ca and LYSO:Ce crystals have also been used as reference time device and showed a time resolution at the level of 17 ps, in agreement with previous results.

Impact of detector design on imaging performance of a long axial field-of-view, whole-body PET scanner

NASA Astrophysics Data System (ADS)

Surti, S.; Karp, J. S.

2015-07-01

Current generation of commercial time-of-flight (TOF) PET scanners utilize 20-25 mm thick LSO or LYSO crystals and have an axial FOV (AFOV) in the range of 16-22 mm. Longer AFOV scanners would provide increased intrinsic sensitivity and require fewer bed positions for whole-body imaging. Recent simulation work has investigated the sensitivity gains that can be achieved with these long AFOV scanners, and has motivated new areas of investigation such as imaging with a very low dose of injected activity as well as providing whole-body dynamic imaging capability in one bed position. In this simulation work we model a 72 cm long scanner and prioritize the detector design choices in terms of timing resolution, crystal size (spatial resolution), crystal thickness (detector sensitivity), and depth-of-interaction (DOI) measurement capability. The generated list data are reconstructed with a list-mode OSEM algorithm using a Gaussian TOF kernel that depends on the timing resolution and blob basis functions for regularization. We use lesion phantoms and clinically relevant metrics for lesion detectability and contrast measurement. The scan time was fixed at 10 min for imaging a 100 cm long object assuming a 50% overlap between adjacent bed positions. Results show that a 72 cm long scanner can provide a factor of ten reduction in injected activity compared to an identical 18 cm long scanner to get equivalent lesion detectability. While improved timing resolution leads to further gains, using 3 mm (as opposed to 4 mm) wide crystals does not show any significant benefits for lesion detectability. A detector providing 2-level DOI information with equal crystal thickness also does not show significant gains. Finally, a 15 mm thick crystal leads to lower lesion detectability than a 20 mm thick crystal when keeping all other detector parameters (crystal width, timing resolution, and DOI capability) the same. However, improved timing performance with 15 mm thick crystals can provide similar or better performance than that achieved by a detector using 20 mm thick crystals.

Use of LysoTracker to detect programmed cell death in embryos and differentiating embryonic stem cells.

PubMed

Fogel, Jennifer L; Thein, Thu Zan Tun; Mariani, Francesca V

2012-10-11

Programmed cell death (PCD) occurs in adults to maintain normal tissue homeostasis and during embryological development to shape tissues and organs(1,2,6,7). During development, toxic chemicals or genetic alterations can cause an increase in PCD or change PCD patterns resulting in developmental abnormalities and birth defects(3-5). To understand the etiology of these defects, the study of embryos can be complemented with in vitro assays that use differentiating embryonic stem (ES) cells. Apoptosis is a well-studied form of PCD that involves both intrinsic and extrinsic signaling to activate the caspase enzyme cascade. Characteristic cell changes include membrane blebbing, nuclear shrinking, and DNA fragmentation. Other forms of PCD do not involve caspase activation and may be the end-result of prolonged autophagy. Regardless of the PCD pathway, dying cells need to be removed. In adults, the immune cells perform this function, while in embryos, where the immune system has not yet developed, removal occurs by an alternative mechanism. This mechanism involves neighboring cells (called "non-professional phagocytes") taking on a phagocytic role-they recognize the 'eat me' signal on the surface of the dying cell and engulf it(8-10). After engulfment, the debris is brought to the lysosome for degradation. Thus regardless of PCD mechanism, an increase in lysosomal activity can be correlated with increased cell death. To study PCD, a simple assay to visualize lysosomes in thick tissues and multilayer differentiating cultures can be useful. LysoTracker dye is a highly soluble small molecule that is retained in acidic subcellular compartments such as the lysosome(11-13). The dye is taken up by diffusion and through the circulation. Since penetration is not a hindrance, visualization of PCD in thick tissues and multi-layer cultures is possible(12,13). In contrast, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) analysis(14), is limited to small samples, histological sections, and monolayer cultures because the procedure requires the entry/permeability of a terminal transferase. In contrast to Aniline blue, which diffuses and is dissolved by solvents, LysoTracker Red DND-99 is fixable, bright, and stable. Staining can be visualized with standard fluorescent or confocal microscopy in whole-mount or section using aqueous or solvent-based mounting media(12,13). Here we describe protocols using this dye to look at PCD in normal and sonic hedgehog null mouse embryos. In addition, we demonstrate analysis of PCD in differentiating ES cell cultures and present a simple quantification method. In summary, LysoTracker staining can be a great complement to other methods of detecting PCD.

Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

PubMed

Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

2015-01-01

Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

Study of nsLTPs in Lotus japonicus genome reveal a specific epidermal cell member (LjLTP10) regulated by drought stress in aerial organs with a putative role in cutin formation.

PubMed

Tapia, G; Morales-Quintana, L; Parra, C; Berbel, A; Alcorta, M

2013-07-01

The cuticle is the first defense against pathogens and the second way water is lost in plants. Hydrophobic layers covering aerial plant organs from primary stages of development form cuticle, including major classes of aliphatic wax components and cutin. Extensive research has been conducted to understand cuticle formation mechanisms in plants. However, many questions remain unresolved in the transport of lipid components to form cuticle. Database studies of the Lotus japonicus genome have revealed the presence of 24 sequences classified as putative non-specific lipid transfer proteins (nsLTPs), which were classified in seven groups; four groups were selected because of their expression in aerial organs. LjLTP8 forms a cluster with DIR1 in Arabidopsis thaliana while LjLTP6, LjLTP9, and LjLTP10 were grouped as type I LTPs. In silico studies showed a high level of structural conservation, and substrate affinity studies revealed palmitoyl-CoA as the most likely ligand for these LTPs, although the Lyso-Myristoyl Phosphatidyl Choline, Lyso-myristoyl phosphatidyl glycerol, and Lyso-stearyl phosphatidyl choline ligands also showed a high affinity with the proteins. The LjLTP6 and LjLTP10 genes were expressed in both the stems and the leaves under normal conditions and were highly induced during drought stress. LjLTP10 was the most induced gene in shoots during drought. The gene was only expressed in the epidermal cells of stems, primordial leaves, and young leaflets. LjLTP10 was positively regulated by MeJA but repressed by abscisic acid (ABA), ethylene, and H2O2, while LjLTP6 was weakly induced by MeJA, repressed by H2O2, and not affected by ABA and ethylene. We suggest that LjLTP10 is involved in plant development of stem and leaf cuticle, but also in acclimation to tolerate drought stress in L. japonicus.

Readout Strategy of an Electro-optical Coupled PET Detector for Time-of-Flight PET/MRI

PubMed Central

Bieniosek, M F; Olcott, P D; Levin, C S

2013-01-01

Combining PET with MRI in a single system provides clinicians with complementary molecular and anatomical information. However, existing integrated PET/MRI systems do not have time-of-flight PET capabilities. This work describes an MRI-compatible front-end electronic system with ToF capabilities. The approach employs a fast arrival-time pickoff comparator to digitize the timing information, and a laser diode to drive a 10m fiber-optic cable to optically transmit asynchronous timing information to a photodiode receiver readout system. The comparator and this electo-optical link show a combined 11.5ps fwhm jitter in response to a fast digital pulse. When configured with LYSO scintillation crystals and Hamamatsu MPPC silicon photo-multipliers the comparator and electro-optical link achieved a 511keV coincidence time resolution of 254.7ps +/− 8.0ps fwhm with 3×3×20mm crystals and 166.5 +/− 2.5ps fwhm with 3×3×5mm crystals. PMID:24061218

Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum.

PubMed

Brancucci, Nicolas M B; Gerdt, Joseph P; Wang, ChengQi; De Niz, Mariana; Philip, Nisha; Adapa, Swamy R; Zhang, Min; Hitz, Eva; Niederwieser, Igor; Boltryk, Sylwia D; Laffitte, Marie-Claude; Clark, Martha A; Grüring, Christof; Ravel, Deepali; Blancke Soares, Alexandra; Demas, Allison; Bopp, Selina; Rubio-Ruiz, Belén; Conejo-Garcia, Ana; Wirth, Dyann F; Gendaszewska-Darmach, Edyta; Duraisingh, Manoj T; Adams, John H; Voss, Till S; Waters, Andrew P; Jiang, Rays H Y; Clardy, Jon; Marti, Matthias

2017-12-14

Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

High-speed digitization readout of silicon photomultipliers for time of flight positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ronzhin, A.; Los, S.; Martens, M.

2011-02-01

We report on work to develop a system with about 100 picoseconds (ps) time resolution for time of flight positron emission tomography [TOF-PET]. The chosen photo detectors for the study were Silicon Photomultipliers (SiPM's). This study was based on extensive experience in studying timing properties of SiPM's. The readout of these devices used the commercial high speed digitizer DRS4. We applied different algorithms to get the best time resolution of 155 ps Guassian (sigma) for a LYSO crystal coupled to a SiPM. We consider the work as a first step in building a prototype TOF-PET module. The field of positron-emission-tomographymore » (PET) has been rapidly developing. But there are significant limitations in how well current PET scanners can reconstruct images, related to how fast data can be acquired, how much volume they can image, and the spatial and temporal resolution of the generated photons. Typical modern scanners now include multiple rings of detectors, which can image a large volume of the patient. In this type of scanner, one can treat each ring as a separate detector and require coincidences only within the ring, or treat the entire region viewed by the scanner as a single 3 dimensional volume. This 3d technique has significantly better sensitivity since more photon pair trajectories are accepted. However, the scattering of photons within the volume of the patient, and the effect of random coincidences limits the technique. The advent of sub-nanosecond timing resolution detectors means that there is potentially much better rejection of scattered photon events and random coincidence events in the 3D technique. In addition, if the timing is good enough, then the origin of photons pairs can be determined better, resulting in improved spatial resolution - so called 'Time-of-Flight' PET, or TOF-PET. Currently a lot of activity has occurred in applications of SiPMs for TOF-PET. This is due to the devices very good time resolution, low profile, lack of high voltage needed, and their non-sensitivity to magnetic fields. While investigations into this technique have begun elsewhere, we feel that the extensive SiPM characterization and data acquisition expertise of Fermilab, and the historical in-depth research of PET imaging at University of Chicago will combine to make significant strides in this field. We also benefit by a working relationship with the SiPM producer STMicroelectronics (STM).« less

Highly efficient and high-power diode-pumped femtosecond Yb:LYSO laser

NASA Astrophysics Data System (ADS)

Tian, Wenlong; Wang, Zhaohua; Zhu, Jiangfeng; Zheng, Lihe; Xu, Jun; Wei, Zhiyi

2017-04-01

A diode-pumped high-power femtosecond Yb:LYSO laser with high efficiency is demonstrated. With a semiconductor saturable absorber mirror for passive mode-locking and a Gires-Tournois interferometer mirror for intracavity dispersion compensation, stable mode-locking pulses of 297 fs duration at 1042 nm were obtained. The maximum average power of 3.07 W was realized under 5.17 W absorbed pump power, corresponding to as high as 59.4% opt-opt efficiency. The single pulse energy and peak power are about 35.5 nJ and 119.5 kW, respectively.

Lipidomics and H218O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos

PubMed Central

McDougall, Melissa Q.; Choi, Jaewoo; Stevens, Jan F.; Truong, Lisa; Tanguay, Robert L.; Traber, Maret G.

2016-01-01

We hypothesized that vitamin E (α-tocopherol) is required by the developing embryonic brain to prevent depletion of highly polyunsaturated fatty acids, especially docosahexaenoic acid (DHA, 22:6), the loss of which we predicted would underlie abnormal morphological and behavioral outcomes. Therefore, we fed adult 5D zebrafish (Danio rerio) defined diets without (E−) or with added α-tocopherol (E+, 500 mg RRR-α-tocopheryl acetate/kg diet) for a minimum of 80 days, and then spawned them to obtain E− and E+ embryos. The E− compared with E+ embryos were 82% less responsive (p<0.01) to a light/dark stimulus at 96 h post-fertilization (hpf), demonstrating impaired locomotor behavior, even in the absence of gross morphological defects. Evaluation of phospholipid (PL) and lysophospholipid (lyso-PL) composition using untargeted lipidomics in E− compared with E+ embryos at 24, 48, 72, and 120 hpf showed that four PLs and three lyso-PLs containing docosahexaenoic acid (DHA), including lysophosphatidylcholine (LPC 22:6, required for transport of DHA into the brain, p<0.001), were at lower concentrations in E− at all time-points. Additionally, H218O labeling experiments revealed enhanced turnover of LPC 22:6 (p<0.001) and three other DHA-containing PLs in the E− compared with the E+ embryos, suggesting that increased membrane remodeling is a result of PL depletion. Together, these data indicate that α-tocopherol deficiency in the zebrafish embryo causes the specific depletion and increased turnover of DHA-containing PL and lyso-PLs, which may compromise DHA delivery to the brain and thereby contribute to the functional impairments observed in E− embryos. PMID:26774753

A novel intra-operative positron imager for rapid localization of tumor margins

NASA Astrophysics Data System (ADS)

Sabet, Hamid; Stack, Brendan C.; Nagarkar, Vivek V.

2014-03-01

We have developed an intra-operative and compact imaging tool for surgeons to detect PET- positive lesions. Currently, most such probes on the market are non-imaging, and provide no ancillary information of surveyed areas, such as clear delineations of malignant tissues. Our probe consists of a novel hybrid scintillator coupled to a compact silicon photomultiplier (SiPM) array with associated front-end electronics encapsulated in an ergonomic housing. Pulse shape discrimination electronics has been implemented and integrated into the downstream data acquisition system. The hybrid scintillator consists of a 0.4 mm thick layer of CsI:Tl scintillator coupled to a 1 mm thick LYSO crystal. To achieve high spatial resolution, CsI:Tl is pixelated to 0.5×0.5 mm2 pixels using laser ablation technique. While CsI:Tl act as beta-sensitive scintillator, LYSO senses the gamma radiation and can be used to navigate the probe to the locations of interest. The gamma response is also subtracted from the beta image for improved SNR and contrast. To achieve accurate centroid position estimation and uniform beta sensitivity over the entire imaging area, the LYSO thickness is optimized such that it acts as scintillation light diffuser by spreading CsI:Tl light over multiple SiPM pixels. The results show that the response of the two scintillators exposed to radiation could be easily distinguished based on their pulse shapes. The probe's spatial resolution is <1.5 mm FWHM in its 10×10 mm2 effective imaging area. The probe can rapidly detect and localize nCi levels of F-18 beta radiation even in presence of strong gamma background.

Sex differences in the association of phospholipids with components of the metabolic syndrome in young adults.

PubMed

Rauschert, Sebastian; Uhl, Olaf; Koletzko, Berthold; Mori, Trevor A; Beilin, Lawrence J; Oddy, Wendy H; Hellmuth, Christian

2017-01-01

There are differences in the prevalence and severity of diseases between males, females not taking hormonal contraceptives (non-HC females) and females taking hormonal contraceptives (HC females). The aim of this study was to identify sex-specific differences in the metabolome and its relation to components of the metabolic syndrome in a young adult population. The subjects analysed are from the 20-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study. Two hundred fifteen plasma metabolites were analysed in 1021 fasted plasma samples by a targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) metabolomics approach. Principal component analysis between males ( n  = 550), non-HC females ( n  = 199) and HC females ( n  = 269) was applied. Regression analysis with a sex × metabolite concentration interaction was performed on components of the MetS, namely waist circumference, systolic blood pressure, and plasma HDL-C, triglycerides and glucose concentration, as outcome to select the significant metabolites of the interaction. Those selected metabolites were used as predictors in a sex group stratified analysis to compare the different β coefficients and therefore the sex group-dependent associations. Principal component analysis between males, non-HC females, and HC females showed a general discriminating trend between males and HC females. One hundred twenty-seven metabolites were significantly different between males and non-HC females, whereas 97 differed between non-HC females and HC females. Males and non-HC females mainly differed in sphingomyelin, lyso-phosphatidylcholine, acyl-carnitine and amino acid species, whilst non-HC females and HC females mainly differed in phosphatidylcholine, lyso-phosphatidylcholine and acyl-carnitine concentrations. Forty-one metabolites (phosphatidylcholines, sphingomyelines, lyso-phosphatidylcholine) were significantly differently associated with the MetS factors in the different groups. We have shown clear differences between plasma metabolite concentrations in males, and HC or non-HC females, especially in lyso-phosphatidylcholine, sphingomyelin and phosphatidylcholine, which have been shown to associate with obesity in other studies. The association of these metabolites differed between sexes with components of the metabolic syndrome, which means that development of diseases like obesity and diabetes may differ between the sexes. Our findings highlight the importance of considering sex differences when conducting a metabolomics study and the need to account for the effect of HC usage in females in future studies.

Simulation study of a D-shape PET scanner for improved sensitivity and reduced cost in whole-body imaging

NASA Astrophysics Data System (ADS)

Ahmed, Abdella M.; Tashima, Hideaki; Yamaya, Taiga

2017-05-01

Much research effort is being made to increase the sensitivity and improve the imaging performance of positron emission tomography (PET) scanners. Conventionally, sensitivity can be increased by increasing the number of detector rings in the axial direction (but at high cost) or reducing the diameter of the scanner (with the disadvantages of reducing the space for patients and degrading the spatial resolution due to the parallax error). In this study, we proposed a PET scanner with a truncated ring and an array of detectors that can be arranged in a straight line below the bed. We called this system ‘D-PET’ as it resembles the letter ‘D’ when it is rotated by 90° in the counterclockwise direction. The basic design idea was to cut the unused space under the patient’s bed; this area is usually not in use in clinical diagnosis. We conducted Monte Carlo simulations of the D-PET scanner and compared its performance with a cylindrical PET scanner. The scanners were constructed from 4-layer depth-of-interaction detectors which consisted of a 16  ×  16  ×  4 LYSO crystal array with dimensions of 2.85  ×  2.85  ×  5 mm3. The results showed that the D-PET had an increase in sensitivity and peak-NECR of 30% and 18%, respectively. The D-PET had low noise in the reconstructed images throughout the field-of-view compared to the cylindrical PET. These were achieved while keeping sufficient space for the patient, and also without a severe effect on the spatial resolution. Furthermore, the number of detectors (and hence the cost) of the D-PET scanner was reduced by 12% compared to the cylindrical PET scanner.

Quantitative PET and SPECT performance characteristics of the Albira Trimodal pre-clinical tomograph

NASA Astrophysics Data System (ADS)

Spinks, T. J.; Karia, D.; Leach, M. O.; Flux, G.

2014-02-01

The Albira Trimodal pre-clinical scanner comprises PET, SPECT and CT sub-systems and thus provides a range of pre-clinical imaging options. The PET component consists of three rings of single-crystal LYSO detectors with axial/transverse fields-of-view (FOVs) of 148/80 mm. The SPECT component has two opposing CsI detectors (100 × 100 mm2) with single-pinhole (SPH) or multi(9)-pinhole (MPH) collimators; the detectors rotate in 6° increments and their spacing can be adjusted to provide different FOVs (25 to 120 mm). The CT sub-system provides ‘low’ (200 µA, 35 kVp) or ‘high’ (400 µA, 45 kVp) power x-rays onto a flat-panel CsI detector. This study examines the performance characteristics and quantitative accuracy of the PET and SPECT components. Using the NEMA NU 4-2008 specifications (22Na point source), the PET spatial resolution is 1.5 + 0.1 mm on axis and sensitivity 6.3% (axial centre) and 4.6% (central 70 mm). The usable activity range is ≤ 10 MBq (18F) over which good linearity (within 5%) is obtained for a uniform cylinder spanning the axial FOV; increasing deviation from linearity with activity is, however, observed for the NEMA (mouse) line source phantom. Image uniformity axially is within 5%. Spatial resolution (SPH/MPH) for the minimum SPECT FOV used for mouse imaging (50 mm) is 1.5/1.7 mm and point source sensitivity 69/750 cps MBq-1. Axial uniformity of SPECT images (%CV of regions-of-interest counts along the axis) is mostly within 8% although there is a range of 30-40% for the largest FOV. The variation is significantly smaller within the central 40 mm. Instances of count rate nonlinearity (PET) and axial non-uniformity (SPECT) were found to be reproducible and thus amenable to empirical correction.

Metabolomics Profiles of Hepatocellular Carcinoma in a Korean Prospective Cohort: The Korean Cancer Prevention Study-II.

PubMed

Jee, Sun Ha; Kim, Minjoo; Kim, Minkyung; Yoo, Hye Jin; Kim, Hyungyoon; Jung, Keum Ji; Hong, Seri; Lee, Jong Ho

2018-05-01

In the prospective Korean Cancer Prevention Study-II (KCPS-II), we investigated the application of metabolomics to differentiate subjects with incident hepatocellular carcinoma (HCC group) from subjects who remained free of cancer (control group) during a mean follow-up period of 7 years with the aim of identifying valuable metabolic biomarkers for HCC. We used baseline serum samples from 75 subjects with incident HCC and 134 age- and gender-matched cancer-free subjects. Serum metabolic profiles associated with HCC incidence were investigated via metabolomics analysis. Compared with the control group, the HCC group showed significantly higher serum levels of aspartate aminotransferase (AST), alanine aminotransferase, and γ-glutamyl transpeptidase. At baseline, compared with the control group, the HCC group showed significantly higher levels of 9 metabolites, including leucine, 5-hydroxyhexanoic acid, phenylalanine, tyrosine, arachidonic acid, and tauroursodeoxycholic acid (TUDCA), but lower levels of 28 metabolites, including oleamide, androsterone sulfate, L-palmitoylcarnitine, lysophosphatidic acid (LPA) 16:0, LPA 18:1, and lysophosphatidylcholines (lysoPC). Multiple linear regression revealed that the incidence of HCC was associated with the levels of tyrosine, AST, lysoPCs (16:1, 20:3), oleamide, 5-hydroxyhexanoic acid, androsterone sulfate, and TUDCA (adjusted R 2 = 0.514, P = 0.036). This study showed the clinical relevance of the dysregulation of not only branched amino acids, aromatic amino acids, and lysoPCs but also bile acid biosynthesis and linoleic acid, arachidonic acid, and fatty acid metabolism. In addition, tyrosine, AST, lysoPCs (16:1, 20:3), oleamide, 5-hydroxyhexanoic acid, androsterone sulfate, and TUDCA were identified as independent variables associated with the incidence of HCC. Cancer Prev Res; 11(5); 303-12. ©2018 AACR . ©2018 American Association for Cancer Research.

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD

PubMed Central

Naz, Shama; Kolmert, Johan; Yang, Mingxing; Reinke, Stacey N.; Kamleh, Muhammad Anas; Snowden, Stuart; Heyder, Tina; Levänen, Bettina; Erle, David J.; Sköld, C. Magnus; Wheelock, Åsa M.; Wheelock, Craig E.

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD. Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform. Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung. These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence. PMID:28642310

Description and properties of a resistive network applied to emission tomography detector readouts

NASA Astrophysics Data System (ADS)

Boisson, F.; Bekaert, V.; Sahr, J.; Brasse, D.

2017-11-01

Over the last twenty years, PET systems have used discrete crystal detector modules coupled to multi-channel photodetectors, mostly to improve the spatial resolution. Although reading each readout channels individually would be of great interest, costs associated with the electronics would, in most cases, be too expensive. It is therefore essential to propose lower-cost solutions that do not degrade the overall system's performance. One possible solution to reduce the development costs of a PET system without degrading performance is the use of a resistive network which reduces the total number of readout channels. In this study, we present a symmetric charge division resistive network and associated software methods to assess the performance of a PET detector. Our approach consists in keeping the n lines and n columns information provided by a symmetric charge division circuit (SCD). We provided equations relative to output currents of the network, which enable estimation of the charge. We propose a novel approach to reconstruct the charge distribution from the lines and columns projection using a maximum likelihood expectation maximization (MLEM) approach which takes the non-uniformity of the photodetector channel gains into account. We also introduce a mathematical proof of the relation between the sigma of the reconstructed charge distribution and the Ratio between the line of interest (maximum value) and the background signal charges. To the best of our knowledge, this is the first study reporting these equations. Preliminary results obtained with a resistive network used in readout of a monolithic 50 × 50 × 8mm3 LYSO crystal coupled to a H9500 PMT validated the effectiveness of the reconstructed charge distribution to optimize both the x and y spatial resolution and the energy resolution. We obtained a mean x and y spatial resolution of 1.10 mm FWHM and a 14.7% energy resolution by calculating the integral of the reconstructed charge distribution. Finally, the relation between the ratio and the sigma of the reconstructed charge distribution may provide new opportunities in terms of Depth-of-Interaction estimation when using a monolithic crystal coupled to a multi-channel photodetector.

Design and performance evaluation of a high resolution IRI-microPET preclinical scanner

NASA Astrophysics Data System (ADS)

Islami rad, S. Z.; Peyvandi, R. Gholipour; lehdarboni, M. Askari; Ghafari, A. A.

2015-05-01

PET for small animal, IRI-microPET, was designed and built at the NSTRI. The scanner is made of four detectors positioned on a rotating gantry at a distance 50 mm from the center. Each detector consists of a 10×10 crystal matrix of 2×2×10 mm3 directly coupled to a PS-PMT. A position encoding circuit for specific PS-PMT has been designed, built and tested with a PD-MFS-2MS/s-8/14 data acquisition board. After implementing reconstruction algorithms (FBP, MLEM and SART) on sinograms, images quality and system performance were evaluated by energy resolution, timing resolution, spatial resolution, scatter fraction, sensitivity, RMS contrast and SNR parameters. The energy spectra were obtained for the crystals with an energy window of 300-700 keV. The energy resolution in 511 keV averaged over all modules, detectors, and crystals, was 23.5%. A timing resolution of 2.4 ns FWHM obtained by coincidence timing spectrum was measured with crystal LYSO. The radial and tangential resolutions for 18F (1.15-mm inner diameter) at the center of the field of view were 1.81 mm and 1.90 mm, respectively. At a radial offset of 5 mm, the FWHM values were 1.96 and 2.06 mm. The system scatter fraction was 7.1% for the mouse phantom. The sensitivity was measured for different energy windows, leading to a sensitivity of 1.74% at the center of FOV. Also, images quality was evaluated by RMS contrast and SNR factors, and the results show that the reconstructed images by MLEM algorithm have the best RMS contrast, and SNR. The IRI-microPET presents high image resolution, low scatter fraction values and improved SNR for animal studies.

Scintillation properties of selected oxide monocrystals activated with Ce and Pr

NASA Astrophysics Data System (ADS)

Wojtowicz, Andrzej J.; Drozdowski, Winicjusz; Wisniewski, Dariusz; Lefaucheur, Jean-Luc; Galazka, Zbigniew; Gou, Zhenhui; Lukasiewicz, Tadeusz; Kisielewski, Jaroslaw

2006-01-01

In the last 10-15 years there has been a significant effort toward development of new, more efficient and faster materials for detection of ionizing radiation. A growing demand for better scintillator crystals for detection of 511 keV gamma particles has been due mostly to recent advances in modern imaging systems employing positron emitting radionuclides for medical diagnostics in neurology, oncology and cardiology. While older imaging systems were almost exclusively based on BGO and NaI:Tl crystals the new systems, e.g., ECAT Accel, developed by Siemens/CTI, are based on recently discovered and developed LSO (Lu 2SiO 5:Ce, Ce-activated lutetium oxyorthosilicate) crystals. Interestingly, despite very good properties of LSO, there still is a strong drive toward development of new scintillator crystals that would show even better performance and characteristics. In this presentation we shall review spectroscopic and scintillator characterization of new complex oxide crystals, namely LSO, LYSO, YAG, LuAP (LuAlO 3, lutetium aluminate perovskite) and LuYAP activated with Ce and Pr. The LSO:Ce crystals have been grown by CTI Inc (USA), LYSO:Ce, LuAP:Ce and LuYAP:Ce crystals have been grown by Photonic Materials Ltd., Scotland (PML is the only company providing large LuAP:Ce crystals on a commercial scale), while YAG:Pr and LuAP:Pr crystals have been grown by Institute of Electronic Materials Technology (Poland). All these crystals have been characterized at Institute of Physics, N. Copernicus University (Poland). We will review and compare results of measurements of radioluminescence, VUV spectroscopy, scintillation light yields, scintillation time profiles and low temperature thermoluminescence performed on these crystals. We will demonstrate that all experiments clearly indicate that there is a significant room for improvement of LuAP, LuYAP and YAG. While both Ce-activated LSO and LYSO perform very well, we also note that LuYAP:Ce, LuAP:Ce and YAG:Pr offer some advantages and, after a likely improvement of some parameters, may also present a viable and desired alternative in applications that require high counting rates or better time resolution. Unfortunately, LuAP:Pr, although the fastest among all the materials studied, may be seriously limited in its achievable light yield by inherent physical processes that are responsible for nonradiative quenching of scintillation light in this material.

Development of a High Precision Axial 3-D PET for Brain Imaging

NASA Astrophysics Data System (ADS)

Bolle, E.; Braem, A.; Casella, C.; Chesi, E.; Clinthorne, N.; Cochran, E.; De Leo, R.; Dissertori, G.; Djambazov, L.; Honscheid, K.; Huh, S.; Johnson, I.; Joram, C.; Kagan, H.; Lacasta, C.; Lustermann, W.; Meddi, F.; Nappi, E.; Nessi-Tedaldi, F.; Oliver, J. F.; Pauss, F.; Rafecas, M.; Renker, D.; Rudge, A.; Schinzel, D.; Schneider, T.; Séguinot, J.; Smith, S.; Solevi, P.; Stapnes, S.; Vilardi, I.; Weilhammer, P.

2009-12-01

We describe a PET device based on a novel method to extract the coordinates of the interaction point of the 511keV γ rays from 100 mm long and thin LYSO (Lutetium Yttrium OxyorthoSilicate) scintillator bars, positioned axially in the tomograph. The coordinate along the hit crystal is measured by using a hodoscope of Wave Length Shifting (WLS) plastic strips mounted perpendicularly to each plane of scintillators. As photodetectors, new Geiger mode Avalanche PhotoDetectors (G-APDs) with integrated electronics are being used to detect both the hit crystal in a block (x and y coordinates) and the interaction point in the crystal (z coordinate) through the light escaping from the crystal and transmitted to the WLS strips. In this way, the γ interaction point can be determined with a spatial resolution of few cubic millimeters down to a minimum deposited energy of about 50 keV, resulting in a volumetric precision very close to the limits imposed by the physics of the positron annihilation. The method allows to increase the detection efficiency without affecting the spatial resolution by adding scintillator planes in the radial direction. A demonstrator scanner, based on two matrices of 8 × 6 LYS crystals and 312 WLS strips, slotted in between the crystals, is under construction. Preliminary results from the feasibility studies of the various components will be presented.

Validation of a highly integrated SiPM readout system with a TOF-PET demonstrator

NASA Astrophysics Data System (ADS)

Niknejad, T.; Setayeshi, S.; Tavernier, S.; Bugalho, R.; Ferramacho, L.; Di Francesco, A.; Leong, C.; Rolo, M. D.; Shamshirsaz, M.; Silva, J. C.; Silva, R.; Silveira, M.; Zorraquino, C.; Varela, J.

2016-12-01

We have developed a highly integrated, fast and compact readout electronics for Silicon Photomultiplier (SiPM) based Time of Flight Positron Emission Tomography (TOF-PET) scanners. The readout is based on the use of TOP-PET Application Specific Integrated Circuit (PETsys TOFPET1 ASIC) with 64 channels, each with its amplifier, discriminator, Time to Digital Converter (TDC) and amplitude determination using Time Over Threshold (TOT). The ASIC has 25 ps r.m.s. intrinsic time resolution and fully digital output. The system is optimised for high rates, good timing, low power consumption and low cost. For validating the readout electronics, we have built a technical PET scanner, hereafter called ``demonstrator'', with 2'048 SiPM channels. The PET demonstrator has 16 compact Detector Modules (DM). Each DM has two ASICs reading 128 SiPM pixels in one-to-one coupling to 128 Lutetium Yttrium Orthosilicate (LYSO) crystals measuring 3.1 × 3.1 × 15 mm3 each. The data acquisition system for the demonstrator has two Front End Boards type D (FEB/D), each collecting the data of 1'024 channels (8 DMs), and transmitting assembled data frames through a serial link (4.8 Gbps), to a single Data Acquisition (DAQ) board plugged into the Peripheral Component Interconnect Express (PCIe) bus of the data acquisition PC. Results obtained with this PET demonstrator are presented.

Evaluating scintillator performance in time-resolved hard X-ray studies at synchrotron light sources.

PubMed

Rutherford, Michael E; Chapman, David J; White, Thomas G; Drakopoulos, Michael; Rack, Alexander; Eakins, Daniel E

2016-05-01

The short pulse duration, small effective source size and high flux of synchrotron radiation is ideally suited for probing a wide range of transient deformation processes in materials under extreme conditions. In this paper, the challenges of high-resolution time-resolved indirect X-ray detection are reviewed in the context of dynamic synchrotron experiments. In particular, the discussion is targeted at two-dimensional integrating detector methods, such as those focused on dynamic radiography and diffraction experiments. The response of a scintillator to periodic synchrotron X-ray excitation is modelled and validated against experimental data collected at the Diamond Light Source (DLS) and European Synchrotron Radiation Facility (ESRF). An upper bound on the dynamic range accessible in a time-resolved experiment for a given bunch separation is calculated for a range of scintillators. New bunch structures are suggested for DLS and ESRF using the highest-performing commercially available crystal LYSO:Ce, allowing time-resolved experiments with an interframe time of 189 ns and a maximum dynamic range of 98 (6.6 bits).

Evaluating scintillator performance in time-resolved hard X-ray studies at synchrotron light sources

PubMed Central

Rutherford, Michael E.; Chapman, David J.; White, Thomas G.; Drakopoulos, Michael; Rack, Alexander; Eakins, Daniel E.

2016-01-01

The short pulse duration, small effective source size and high flux of synchrotron radiation is ideally suited for probing a wide range of transient deformation processes in materials under extreme conditions. In this paper, the challenges of high-resolution time-resolved indirect X-ray detection are reviewed in the context of dynamic synchrotron experiments. In particular, the discussion is targeted at two-dimensional integrating detector methods, such as those focused on dynamic radiography and diffraction experiments. The response of a scintillator to periodic synchrotron X-ray excitation is modelled and validated against experimental data collected at the Diamond Light Source (DLS) and European Synchrotron Radiation Facility (ESRF). An upper bound on the dynamic range accessible in a time-resolved experiment for a given bunch separation is calculated for a range of scintillators. New bunch structures are suggested for DLS and ESRF using the highest-performing commercially available crystal LYSO:Ce, allowing time-resolved experiments with an interframe time of 189 ns and a maximum dynamic range of 98 (6.6 bits). PMID:27140147

High resolution gamma detector for small-animal positron emission tomography

NASA Astrophysics Data System (ADS)

Ling, Tao

In this study, the performance of continuous miniature crystal element (cMiCE) detectors with LYSO crystals of different thickness were investigated. Potential designs of a cMiCE small animal positron emission tomography scanner were also evaluated by an analytical simulation approach. The cMiCE detector was proposed as a high sensitivity, low cost alternative to the prevailing discrete crystal detectors. A statistics based positioning (SBP) algorithm was developed to solve the scintillation position estimation problem and proved to be successful on a cMiCE detector with a 4 mm thick crystal. By assuming a Gaussian distribution, the distributions of the photomultiplier signals could be characterized by mean and variance, which are functions of scintillation position. After calibrating the detector on a grid of locations, a 2D table of the mean and variance can be built. The SBP algorithm searches the tables to find the location that maximizes the likelihood between the mean and variance of known positions and the incoming scintillation event. In this work, the performance of the SBP algorithm on cMiCE detectors with thicker crystals (6 and 8 mm) was studied. The stopping power of a cMiCE detector is 40% and 49% for 6 and 8 mm thick crystals respectively. The intrinsic spatial resolution is 1.2 mm and 1.4 mm FWHM for the center and corner sections of a 6 mm thick crystal detector, and 1.3 mm and 1.6 mm for center and corner of an 8 mm thick crystal detector. These results demonstrate that the cMiCE detector is a promising candidate for high resolution, high sensitivity PET applications. A maximum-likelihood (ML) clustering method was developed to empirically separate the experimental data set into two to four subgroups according to the depth-of-interaction of the detected photons. This method enabled us to build 2-DOI lookup tables (LUT) (mean and variance lookup tables for front group and back group). Using the 2-DOI SBP LUTs, the scintillation position and DOI could be estimated at the same time. The experimental measured misclassification rate for the 8 mm thick crystal detector is approximately 25%. The ML clustering method also provided a better fit to the distributions of the experimental signals, especially for the skewed ones. It therefore led to a significant improvement in the intrinsic spatial resolution in the corner region of the detector. In order to eliminate the effort in calibrating a cMiCE detector, a parametric positioning method was studied. Gaussian, Cauchy, and parametric models for the light distribution inside the crystal were tested. From the diagnosis of the sum of squared residues and the goodness of fit to the experimental data, the parametric model was found to be the best fit to the light distribution. It was also the best performer in terms of intrinsic spatial resolution and DOI resolution. Using the parametric model, the intrinsic spatial resolution is 1.1 mm and 1.3 mm FWHM for the center and corner regions of the 8 mm thick crystal detector respectively. The DOI resolution is 3.2 mm FWHM. Another variation of the SBP algorithm was tried to reduce the number of readouts need to be digitized. Several themes of different trade-offs between the readout number and spatial resolution were tested. The results show that excluding the PMT channels with less 1% of the total signal or digitizing only the nearest 21 channels around the channel with the maximum signal are the best choices, while the intrinsic spatial resolution is not compromised. An analytical simulation approach was developed to investigate how the choice of cMiCE detectors affect image figures of merit for mouse-imaging cMICE PET scanners. For a high resolution imaging system, important physical effects that impact image quality are positron range, detector point-spread function and coincident photon count levels (i.e., statistical noise). Modeling of these effects was included in an analytical simulation that generated multiple realizations of sinograms with varying levels of each effect. To evaluate image quality with respect to quantitation and detection task performance, four different figures of merit were measured: (1) root mean square error; (2) a region of interest SNR (SNRROI); (3) non-prewhitening matched filter SNR (SNRNPW); and (4) recovery coefficient. The results indicate that positron range and non-stationary detector point-spread response effects cause significant reductions of quantitation (SNRROI) and detection (SNRNPW) accuracy for small regions, e.g., a 0.01 cc sphere. A cMiCE detector with 6 mm thick crystal is better for quantitation, while the one with 8 mm thick crystal is better for detection. DOI capability makes a major impact on the FOMs. cMiCE detector with 8 mm thick crystal + 2-DOI capability proved to be the best candidate for both quantitation and detection.

Live Imaging of LysoTracker-Labelled Phagolysosomes Tracks Diurnal Phagocytosis of Photoreceptor Outer Segment Fragments in Rat RPE Tissue Ex Vivo.

PubMed

Mao, Yingyu; Finnemann, Silvia C

2016-01-01

Renewal of rod photoreceptor outer segments in the mammalian eye involves synchronized diurnal shedding after light onset of spent distal outer segment fragments (POS) linked to swift clearance of shed POS from the subretinal space by the adjacent retinal pigment epithelium (RPE). Engulfed POS phagosomes in RPE cells mature to acidified phagolysosomes, which accomplish enzymatic degradation of POS macromolecules. Here, we used an acidophilic fluorophore LysoTracker to label acidic organelles in freshly dissected, live rat RPE tissue flat mounts. We observed that all RPE cells imaged contained numerous acidified POS phagolysosomes whose abundance per cell was dramatically increased 2 h after light onset as compared to either 1 h before or 4 h after light onset. Lack of organelles of similar diameter (of 1-2 μm) in phagocytosis-defective mutant RCS rat RPE confirmed that LysoTracker live imaging detected POS phagolysosomes. Lack of increase in lysosomal membrane protein LAMP-1 in RPE/choroid during the diurnal phagocytic burst suggests that formation of POS phagolysosomes in RPE in situ may not involve extra lysosome membrane biogenesis. Taken together, we report a new imaging approach that directly detects POS phagosome acidification and allows rapid tracking and quantification of POS phagocytosis by live RPE -tissue ex situ.

Evaluation of acridine orange, LysoTracker Red, and quinacrine as fluorescent probes for long-term tracking of acidic vesicles.

PubMed

Pierzyńska-Mach, Agnieszka; Janowski, Paweł A; Dobrucki, Jurek W

2014-08-01

Acidic vesicles can be imaged and tracked in live cells after staining with several low molecular weight fluorescent probes, or with fluorescently labeled proteins. Three fluorescent dyes, acridine orange, LysoTracker Red DND-99, and quinacrine, were evaluated as acidic vesicle tracers for confocal fluorescence imaging and quantitative analysis. The stability of fluorescent signals, achievable image contrast, and phototoxicity were taken into consideration. The three tested tracers exhibit different advantages and pose different problems in imaging experiments. Acridine orange makes it possible to distinguish acidic vesicles with different internal pH but is fairly phototoxic and can cause spectacular bursts of the dye-loaded vesicles. LysoTracker Red is less phototoxic but its rapid photobleaching limits the range of useful applications considerably. We demonstrate that quinacrine is most suitable for long-term imaging when a high number of frames is required. This capacity made it possible to trace acidic vesicles for several hours, during a process of drug-induced apoptosis. An ability to record the behavior of acidic vesicles over such long periods opens a possibility to study processes like autophagy or long-term effects of drugs on endocytosis and exocytosis. © 2014 International Society for Advancement of Cytometry.

First full-beam PET acquisitions in proton therapy with a modular dual-head dedicated system

NASA Astrophysics Data System (ADS)

Sportelli, G.; Belcari, N.; Camarlinghi, N.; Cirrone, G. A. P.; Cuttone, G.; Ferretti, S.; Kraan, A.; Ortuño, J. E.; Romano, F.; Santos, A.; Straub, K.; Tramontana, A.; Del Guerra, A.; Rosso, V.

2014-01-01

During particle therapy irradiation, positron emitters with half-lives ranging from 2 to 20 min are generated from nuclear processes. The half-lives are such that it is possible either to detect the positron signal in the treatment room using an in-beam positron emission tomography (PET) system, right after the irradiation, or to quickly transfer the patient to a close PET/CT scanner. Since the activity distribution is spatially correlated with the dose, it is possible to use PET imaging as an indirect method to assure the quality of the dose delivery. In this work, we present a new dedicated PET system able to operate in-beam. The PET apparatus consists in two 10 cm × 10 cm detector heads. Each detector is composed of four scintillating matrices of 23 × 23 LYSO crystals. The crystal size is 1.9 mm × 1.9 mm × 16 mm. Each scintillation matrix is read out independently with a modularized acquisition system. The distance between the two opposing detector heads was set to 20 cm. The system has very low dead time per detector area and a 3 ns coincidence window, which is capable to sustain high single count rates and to keep the random counts relatively low. This allows a new full-beam monitoring modality that includes data acquisition also while the beam is on. The PET system was tested during the irradiation at the CATANA (INFN, Catania, Italy) cyclotron-based proton therapy facility. Four acquisitions with different doses and dose rates were analysed. In all cases the random to total coincidences ratio was equal or less than 25%. For each measurement we estimated the accuracy and precision of the activity range on a set of voxel lines within an irradiated PMMA phantom. Results show that the inclusion of data acquired during the irradiation, referred to as beam-on data, improves both the precision and accuracy of the range measurement with respect to data acquired only after irradiation. Beam-on data alone are enough to give precisions better than 1 mm when at least 5 Gy are delivered.

Hybrid charge division multiplexing method for silicon photomultiplier based PET detectors

NASA Astrophysics Data System (ADS)

Park, Haewook; Ko, Guen Bae; Lee, Jae Sung

2017-06-01

Silicon photomultiplier (SiPM) is widely utilized in various positron emission tomography (PET) detectors and systems. However, the individual recording of SiPM output signals is still challenging owing to the high granularity of the SiPM; thus, charge division multiplexing is commonly used in PET detectors. Resistive charge division method is well established for reducing the number of output channels in conventional multi-channel photosensors, but it degrades the timing performance of SiPM-based PET detectors by yielding a large resistor-capacitor (RC) constant. Capacitive charge division method, on the other hand, yields a small RC constant and provides a faster timing response than the resistive method, but it suffers from an output signal undershoot. Therefore, in this study, we propose a hybrid charge division method which can be implemented by cascading the parallel combination of a resistor and a capacitor throughout the multiplexing network. In order to compare the performance of the proposed method with the conventional methods, a 16-channel Hamamatsu SiPM (S11064-050P) was coupled with a 4  ×  4 LGSO crystal block (3  ×  3  ×  20 mm3) and a 9  ×  9 LYSO crystal block (1.2  ×  1.2  ×  10 mm3). In addition, we tested a time-over-threshold (TOT) readout using the digitized position signals to further demonstrate the feasibility of the time-based readout of multiplexed signals based on the proposed method. The results indicated that the proposed method exhibited good energy and timing performance, thus inheriting only the advantages of conventional resistive and capacitive methods. Moreover, the proposed method showed excellent pulse shape uniformity that does not depend on the position of the interacted crystal. Accordingly, we can conclude that the hybrid charge division method is useful for effectively reducing the number of output channels of the SiPM array.

Fluorescence studies on the interaction of choline-binding domain B of the major bovine seminal plasma protein, PDC-109 with phospholipid membranes.

PubMed

Damai, Rajani S; Anbazhagan, V; Rao, K Babu; Swamy, Musti J

2009-12-01

The microenvironment and accessibility of the tryptophan residues in domain B of PDC-109 (PDC-109/B) in the native state and upon ligand binding have been investigated by fluorescence quenching, time-resolved fluorescence and red-edge excitation shift (REES) studies. The increase in the intrinsic fluorescence emission intensity of PDC-109/B upon binding to lysophosphatidylcholine (Lyso-PC) micelles and dimyristoylphosphatidylcholine (DMPC) membranes was considerably less as compared to that observed with the whole PDC-109 protein. The degree of quenching achieved by different quenchers with PDC-109/B bound to Lyso-PC and DMPC membranes was significantly higher as compared to the full PDC-109 protein, indicating that membrane binding afforded considerably lesser protection to the tryptophan residues of domain B as compared to those in the full PDC-109 protein. Finally, changes in red-edge excitation shift (REES) seen with PDC-109/B upon binding to DMPC membranes and Lyso-PC micelles were smaller that the corresponding changes in the REES values observed for the full PDC-109. These results, taken together suggest that intact PDC-109 penetrates deeper into the hydrophobic parts of the membrane as compared to domain B alone, which could be the reason for the inability of PDC-109/B to induce cholesterol efflux, despite its ability to recognize choline phospholipids at the membrane surface.

ATP-containing vesicles in stria vascular marginal cell cytoplasms in neonatal rat cochlea are lysosomes.

PubMed

Liu, Jun; Liu, Wenjing; Yang, Jun

2016-02-11

We confirmed that ATP is released from cochlear marginal cells in the stria vascular but the cell organelle in which ATP stores was not identified until now. Thus, we studied the ATP-containing cell organelles and suggest that these are lysosomes. Primary cultures of marginal cells of Sprague-Dawley rats aged 1-3 days was established. Vesicles within marginal cells stained with markers were identified under confocal laser scanning microscope and transmission electron microscope (TEM). Then ATP release from marginal cells was measured after glycyl-L-phenylalanine-ß- naphthylamide (GPN) treatment using a bioluminescent assay. Quinacrine-stained granules within marginal cells were labeled with LysoTracker, a lysosome tracer, and lysosomal-associated membrane protein 1(LAMP1), but not labeled with the mitochondrial tracer MitoTracker. Furthermore, LysoTracker-labelled puncta showed accumulation of Mant-ATP, an ATP analog. Treatment with 200 μM GPN quenched fluorescently labeled puncta after incubation with LysoTracker or quinacrine, but not MitoTracker. Quinacrine-labeled organelles observed by TEM were lysosomes, and an average 27.7 percent increase in ATP luminescence was observed in marginal cells extracellular fluid after GPN treatment. ATP-containing vesicles in cochlear marginal cells of the stria vascular from neonatal rats are likely lysosomes. ATP release from marginal cells may be via Ca(2+)-dependent lysosomal exocytosis.

ATP-containing vesicles in stria vascular marginal cell cytoplasms in neonatal rat cochlea are lysosomes

PubMed Central

Liu, Jun; Liu, Wenjing; Yang, Jun

2016-01-01

We confirmed that ATP is released from cochlear marginal cells in the stria vascular but the cell organelle in which ATP stores was not identified until now. Thus, we studied the ATP-containing cell organelles and suggest that these are lysosomes. Primary cultures of marginal cells of Sprague-Dawley rats aged 1–3 days was established. Vesicles within marginal cells stained with markers were identified under confocal laser scanning microscope and transmission electron microscope (TEM). Then ATP release from marginal cells was measured after glycyl-L-phenylalanine-ß- naphthylamide (GPN) treatment using a bioluminescent assay. Quinacrine-stained granules within marginal cells were labeled with LysoTracker, a lysosome tracer, and lysosomal-associated membrane protein 1(LAMP1), but not labeled with the mitochondrial tracer MitoTracker. Furthermore, LysoTracker-labelled puncta showed accumulation of Mant-ATP, an ATP analog. Treatment with 200 μM GPN quenched fluorescently labeled puncta after incubation with LysoTracker or quinacrine, but not MitoTracker. Quinacrine-labeled organelles observed by TEM were lysosomes, and an average 27.7 percent increase in ATP luminescence was observed in marginal cells extracellular fluid after GPN treatment. ATP-containing vesicles in cochlear marginal cells of the stria vascular from neonatal rats are likely lysosomes. ATP release from marginal cells may be via Ca2+-dependent lysosomal exocytosis. PMID:26864824

In-treatment tests for the monitoring of proton and carbon-ion therapy with a large area PET system at CNAO

NASA Astrophysics Data System (ADS)

Rosso, V.; Battistoni, G.; Belcari, N.; Camarlinghi, N.; Ciocca, M.; Collini, F.; Ferretti, S.; Kraan, A. C.; Lucenò, S.; Molinelli, S.; Pullia, M.; Sportelli, G.; Zaccaro, E.; Del Guerra, A.

2016-07-01

One of the most promising new radiotherapy techniques makes use of charged particles like protons and carbon ions, rather than photons. At present, there are more than 50 particle therapy centers operating worldwide, and many new centers are being constructed. Positron Emission Tomography (PET) is considered a well-established non-invasive technique to monitor range and delivered dose in patients treated with particle therapy. Nuclear interactions of the charged hadrons with the patient tissue lead to the production of β+ emitting isotopes (mainly 15O and 11C), that decay with a short lifetime producing a positron. The two 511 keV annihilation photons can be detected with a PET detector. In-beam PET is particularly interesting because it could allow monitoring the ions range also during dose delivery. A large area dual head PET prototype was built and tested. The system is based on an upgraded version of the previously developed DoPET prototype. Each head covers now 15×15 cm2 and is composed by 9 (3×3) independent modules. Each module consists of a 23×23 LYSO crystal matrix (2 mm pitch) coupled to H8500 PMT and is readout by custom front-end and a FPGA based data acquisition electronics. Data taken at the CNAO treatment facility in Pavia with proton and carbon beams impinging on heterogeneous phantoms demonstrate the DoPET capability to detect the presence of a small air cavity in the phantom.

Evaluation of Matrix9 silicon photomultiplier array for small-animal PET.

PubMed

Du, Junwei; Schmall, Jeffrey P; Yang, Yongfeng; Di, Kun; Roncali, Emilie; Mitchell, Gregory S; Buckley, Steve; Jackson, Carl; Cherry, Simon R

2015-02-01

The MatrixSL-9-30035-OEM (Matrix9) from SensL is a large-area silicon photomultiplier (SiPM) photodetector module consisting of a 3 × 3 array of 4 × 4 element SiPM arrays (total of 144 SiPM pixels) and incorporates SensL's front-end electronics board and coincidence board. Each SiPM pixel measures 3.16 × 3.16 mm(2) and the total size of the detector head is 47.8 × 46.3 mm(2). Using 8 × 8 polished LSO/LYSO arrays (pitch 1.5 mm) the performance of this detector system (SiPM array and readout electronics) was evaluated with a view for its eventual use in small-animal positron emission tomography (PET). Measurements of noise, signal, signal-to-noise ratio, energy resolution, flood histogram quality, timing resolution, and array trigger error were obtained at different bias voltages (28.0-32.5 V in 0.5 V intervals) and at different temperatures (5 °C-25 °C in 5 °C degree steps) to find the optimal operating conditions. The best measured signal-to-noise ratio and flood histogram quality for 511 keV gamma photons were obtained at a bias voltage of 30.0 V and a temperature of 5 °C. The energy resolution and timing resolution under these conditions were 14.2% ± 0.1% and 4.2 ± 0.1 ns, respectively. The flood histograms show that all the crystals in the 1.5 mm pitch LSO array can be clearly identified and that smaller crystal pitches can also be resolved. Flood histogram quality was also calculated using different center of gravity based positioning algorithms. Improved and more robust results were achieved using the local 9 pixels for positioning along with an energy offset calibration. To evaluate the front-end detector readout, and multiplexing efficiency, an array trigger error metric is introduced and measured at different lower energy thresholds. Using a lower energy threshold greater than 150 keV effectively eliminates any mispositioning between SiPM arrays. In summary, the Matrix9 detector system can resolve high-resolution scintillator arrays common in small-animal PET with adequate energy resolution and timing resolution over a large detector area. The modular design of the Matrix9 detector allows it to be used as a building block for simple, low channel-count, yet high performance, small animal PET or PET/MRI systems.

Evaluation of Matrix9 silicon photomultiplier array for small-animal PET

PubMed Central

Du, Junwei; Schmall, Jeffrey P.; Yang, Yongfeng; Di, Kun; Roncali, Emilie; Mitchell, Gregory S.; Buckley, Steve; Jackson, Carl; Cherry, Simon R.

2015-01-01

Purpose: The MatrixSL-9-30035-OEM (Matrix9) from SensL is a large-area silicon photomultiplier (SiPM) photodetector module consisting of a 3 × 3 array of 4 × 4 element SiPM arrays (total of 144 SiPM pixels) and incorporates SensL’s front-end electronics board and coincidence board. Each SiPM pixel measures 3.16 × 3.16 mm2 and the total size of the detector head is 47.8 × 46.3 mm2. Using 8 × 8 polished LSO/LYSO arrays (pitch 1.5 mm) the performance of this detector system (SiPM array and readout electronics) was evaluated with a view for its eventual use in small-animal positron emission tomography (PET). Methods: Measurements of noise, signal, signal-to-noise ratio, energy resolution, flood histogram quality, timing resolution, and array trigger error were obtained at different bias voltages (28.0–32.5 V in 0.5 V intervals) and at different temperatures (5 °C–25 °C in 5 °C degree steps) to find the optimal operating conditions. Results: The best measured signal-to-noise ratio and flood histogram quality for 511 keV gamma photons were obtained at a bias voltage of 30.0 V and a temperature of 5 °C. The energy resolution and timing resolution under these conditions were 14.2% ± 0.1% and 4.2 ± 0.1 ns, respectively. The flood histograms show that all the crystals in the 1.5 mm pitch LSO array can be clearly identified and that smaller crystal pitches can also be resolved. Flood histogram quality was also calculated using different center of gravity based positioning algorithms. Improved and more robust results were achieved using the local 9 pixels for positioning along with an energy offset calibration. To evaluate the front-end detector readout, and multiplexing efficiency, an array trigger error metric is introduced and measured at different lower energy thresholds. Using a lower energy threshold greater than 150 keV effectively eliminates any mispositioning between SiPM arrays. Conclusions: In summary, the Matrix9 detector system can resolve high-resolution scintillator arrays common in small-animal PET with adequate energy resolution and timing resolution over a large detector area. The modular design of the Matrix9 detector allows it to be used as a building block for simple, low channel-count, yet high performance, small animal PET or PET/MRI systems. PMID:25652479

Evaluation of Matrix9 silicon photomultiplier array for small-animal PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Junwei, E-mail: jwdu@ucdavis.edu; Schmall, Jeffrey P.; Yang, Yongfeng

Purpose: The MatrixSL-9-30035-OEM (Matrix9) from SensL is a large-area silicon photomultiplier (SiPM) photodetector module consisting of a 3 × 3 array of 4 × 4 element SiPM arrays (total of 144 SiPM pixels) and incorporates SensL’s front-end electronics board and coincidence board. Each SiPM pixel measures 3.16 × 3.16 mm{sup 2} and the total size of the detector head is 47.8 × 46.3 mm{sup 2}. Using 8 × 8 polished LSO/LYSO arrays (pitch 1.5 mm) the performance of this detector system (SiPM array and readout electronics) was evaluated with a view for its eventual use in small-animal positron emission tomographymore » (PET). Methods: Measurements of noise, signal, signal-to-noise ratio, energy resolution, flood histogram quality, timing resolution, and array trigger error were obtained at different bias voltages (28.0–32.5 V in 0.5 V intervals) and at different temperatures (5 °C–25 °C in 5 °C degree steps) to find the optimal operating conditions. Results: The best measured signal-to-noise ratio and flood histogram quality for 511 keV gamma photons were obtained at a bias voltage of 30.0 V and a temperature of 5 °C. The energy resolution and timing resolution under these conditions were 14.2% ± 0.1% and 4.2 ± 0.1 ns, respectively. The flood histograms show that all the crystals in the 1.5 mm pitch LSO array can be clearly identified and that smaller crystal pitches can also be resolved. Flood histogram quality was also calculated using different center of gravity based positioning algorithms. Improved and more robust results were achieved using the local 9 pixels for positioning along with an energy offset calibration. To evaluate the front-end detector readout, and multiplexing efficiency, an array trigger error metric is introduced and measured at different lower energy thresholds. Using a lower energy threshold greater than 150 keV effectively eliminates any mispositioning between SiPM arrays. Conclusions: In summary, the Matrix9 detector system can resolve high-resolution scintillator arrays common in small-animal PET with adequate energy resolution and timing resolution over a large detector area. The modular design of the Matrix9 detector allows it to be used as a building block for simple, low channel-count, yet high performance, small animal PET or PET/MRI systems.« less

A sub-millimeter resolution detector module for small-animal PET applications

NASA Astrophysics Data System (ADS)

Sacco, I.; Dohle, R.; Fischer, P.; Gola, A.; Piemonte, C.; Ritzert, M.

2017-01-01

We present a gamma detection module optimized for very high resolution PET applications, able to resolve arrays of scintillating crystals with sub-millimeter pitch. The detector is composed of a single ceramic substrate (LTCC): it hosts four flip-chip mounted PETA5 ASICs on the bottom side and an array of SiPM sensors on the top surface, fabricated in HD-RGB technology by FBK. Each chip has 36 channels, for a maximum of 144 readout channels on a sensitive area of about 32 mm × 32 mm. The module is MR-compatible. The thermal decoupling of the readout electronics from the photon sensors is obtained with an efficient internal liquid channel, integrated within the ceramic substrate. Two modules have been designed, based on different SiPM topologies: • Light spreader-based: an array of 12 × 12 SiPMs, with an overall pitch of 2.5 mm, is coupled with a scintillators array using a 1 mm thick glass plate. The light from one crystal is spread over a group of SiPMs, which are read out in parallel using PETA5 internal neighbor logic. • Interpolating SiPM-based: ISiPMs are intrinsic position-sensitive sensors. The photon diodes in the array are connected to one of the four available outputs so that the center of gravity of any bunch of detected photons can be reconstructed using a proper weight function of the read out amplitudes. An array of ISiPMs, each 7.5 mm× 5 mm sized, is directly coupled with the scintillating crystals. Both modules can clearly resolve LYSO arrays with a pitch of only 0.833 mm. The detector can be adjusted for clinical PET, where it has already shown ToF resolution of about 230 ps CRT at FWHM. The module designs, their features and results are described.

DOI Determination by Rise Time Discrimination in Single-Ended Readout for TOF PET Imaging

PubMed Central

Wiener, R.I.; Surti, S.; Karp, J.S.

2013-01-01

Clinical TOF PET systems achieve detection efficiency using thick crystals, typically of thickness 2–3cm. The resulting dispersion in interaction depths degrades spatial resolution for increasing radial positions due to parallax error. Furthermore, interaction depth dispersion results in time pickoff dispersion and thus in degraded timing resolution, and is therefore of added concern in TOF scanners. Using fast signal digitization, we characterize the timing performance, pulse shape and light output of LaBr3:Ce, CeBr3 and LYSO. Coincidence timing resolution is shown to degrade by ~50ps/cm for scintillator pixels of constant cross section and increasing length. By controlling irradiation depth in a scintillator pixel, we show that DOI-dependence of time pickoff is a significant factor in the loss of timing performance in thick detectors. Using the correlated DOI-dependence of time pickoff and charge collection, we apply a charge-based correction to the time pickoff, obtaining improved coincidence timing resolution of <200ps for a uniform 4×4×30mm3 LaBr3 pixel. In order to obtain both DOI identification and improved timing resolution, we design a two layer LaBr3[5%Ce]/LaBr3[30%Ce] detector of total size 4×4×30mm3, exploiting the dependence of scintillator rise time on [Ce] in LaBr3:Ce. Using signal rise time to determine interaction layer, excellent interaction layer discrimination is achieved, while maintaining coincidence timing resolution of <250ps and energy resolution <7% using a R4998 PMT. Excellent layer separation and timing performance is measured with several other commercially-available TOF photodetectors, demonstrating the practicality of this design. These results indicate the feasibility of rise time discrimination as a technique for measuring event DOI while maintaining sensitivity, timing and energy performance, in a well-known detector architecture. PMID:24403611

DOI Determination by Rise Time Discrimination in Single-Ended Readout for TOF PET Imaging.

PubMed

Wiener, R I; Surti, S; Karp, J S

2013-06-01

Clinical TOF PET systems achieve detection efficiency using thick crystals, typically of thickness 2-3cm. The resulting dispersion in interaction depths degrades spatial resolution for increasing radial positions due to parallax error. Furthermore, interaction depth dispersion results in time pickoff dispersion and thus in degraded timing resolution, and is therefore of added concern in TOF scanners. Using fast signal digitization, we characterize the timing performance, pulse shape and light output of LaBr 3 :Ce, CeBr 3 and LYSO. Coincidence timing resolution is shown to degrade by ~50ps/cm for scintillator pixels of constant cross section and increasing length. By controlling irradiation depth in a scintillator pixel, we show that DOI-dependence of time pickoff is a significant factor in the loss of timing performance in thick detectors. Using the correlated DOI-dependence of time pickoff and charge collection, we apply a charge-based correction to the time pickoff, obtaining improved coincidence timing resolution of <200ps for a uniform 4×4×30mm 3 LaBr 3 pixel. In order to obtain both DOI identification and improved timing resolution, we design a two layer LaBr 3 [5%Ce]/LaBr 3 [30%Ce] detector of total size 4×4×30mm 3 , exploiting the dependence of scintillator rise time on [Ce] in LaBr 3 :Ce. Using signal rise time to determine interaction layer, excellent interaction layer discrimination is achieved, while maintaining coincidence timing resolution of <250ps and energy resolution <7% using a R4998 PMT. Excellent layer separation and timing performance is measured with several other commercially-available TOF photodetectors, demonstrating the practicality of this design. These results indicate the feasibility of rise time discrimination as a technique for measuring event DOI while maintaining sensitivity, timing and energy performance, in a well-known detector architecture.

LysoPC-acyl C16:0 is associated with brown adipose tissue activity in men.

PubMed

Boon, Mariëtte R; Bakker, Leontine E H; Prehn, Cornelia; Adamski, Jerzy; Vosselman, Maarten J; Jazet, Ingrid M; Arias-Bouda, Lenka M Pereira; van Lichtenbelt, Wouter D Marken; van Dijk, Ko Willems; Rensen, Patrick C N; Mook-Kanamori, Dennis O

2017-01-01

Brown adipose tissue (BAT) recently emerged as a potential therapeutic target in the treatment of obesity and associated disorders due to its fat-burning capacity. The current gold standard in assessing BAT activity is [ 18 F]FDG PET-CT scan, which has severe limitations including radiation exposure, being expensive, and being labor-intensive. Therefore, indirect markers are needed of human BAT activity and volume. We aimed to identify metabolites in serum that are associated with BAT volume and activity in men. We assessed 163 metabolites in fasted serum of a cohort of twenty-two healthy lean men (age 24.1 (21.7-26.6) years, BMI 22.1 (20.5-23.4) kg/m 2 ) who subsequently underwent a cold-induced [ 18 F]FDG PET-CT scan to assess BAT volume and activity. In addition, we included three replication cohorts consisting of in total thirty-seven healthy lean men that were similar with respect to age and BMI compared to the discovery cohort. After correction for multiple testing, fasting concentrations of lysophosphatidylcholine-acyl (LysoPC-acyl) C16:1, LysoPC-acyl C16:0 and phosphatidylcholine-diacyl C32:1 showed strong positive correlations with BAT volume (β= 116 (85-148) mL, R 2  = 0.81, p = 4.6 × 10 -7 ; β = 79 (93-119) mL, R 2  = 0.57, p = 5.9 × 10 -4 and β= 91 (40-141) mL, R 2  = 0.52, p = 1.0 × 10 -3 , respectively) as well as with BAT activity (β= 0.20 (0.11-0.29) g/mL, R 2  = 0.59, p = 1.9 × 10 -4 ; β = 0.15 (0.06-0.23) g/mL, R 2  = 0.47, p = 2.0 × 10 -3 and β= 0.13 (0.01-0.25) g/mL, R 2  = 0.28, p = 0.04, respectively). When tested in three independent replication cohorts (total n = 37), the association remained significant between LysoPC-acyl C16:0 and BAT activity in a pooled analysis (β= 0.15 (0.07-0.23) g/mL, R 2  = 0.08, p = 4.2 × 10 -4 ). LysoPC-acyl C16:0 is associated with BAT activity in men. Since BAT is regarded as a promising tool in the battle against obesity and related disorders, the identification of such a noninvasive marker is highly relevant.

Development of a Small-Sized, Flexible, and Insertable Fiber-Optic Radiation Sensor for Gamma-Ray Spectroscopy

PubMed Central

Yoo, Wook Jae; Shin, Sang Hun; Lee, Dong Eun; Jang, Kyoung Won; Cho, Seunghyun; Lee, Bongsoo

2015-01-01

We fabricated a small-sized, flexible, and insertable fiber-optic radiation sensor (FORS) that is composed of a sensing probe, a plastic optical fiber (POF), a photomultiplier tube (PMT)-amplifier system, and a multichannel analyzer (MCA) to obtain the energy spectra of radioactive isotopes. As an inorganic scintillator for gamma-ray spectroscopy, a cerium-doped lutetium yttrium orthosilicate (LYSO:Ce) crystal was used and two solid-disc type radioactive isotopes with the same dimensions, cesium-137 (Cs-137) and cobalt-60 (Co-60), were used as gamma-ray emitters. We first determined the length of the LYSO:Ce crystal considering the absorption of charged particle energy and measured the gamma-ray energy spectra using the FORS. The experimental results demonstrated that the proposed FORS can be used to discriminate species of radioactive isotopes by measuring their inherent energy spectra, even when gamma-ray emitters are mixed. The relationship between the measured photon counts of the FORS and the radioactivity of Cs-137 was subsequently obtained. The amount of scintillating light generated from the FORS increased by increasing the radioactivity of Cs-137. Finally, the performance of the fabricated FORS according to the length and diameter of the POF was also evaluated. Based on the results of this study, it is anticipated that a novel FORS can be developed to accurately measure the gamma-ray energy spectrum in inaccessible locations such as narrow areas and holes. PMID:26343667

Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease

PubMed Central

Ashe, Karen M; Budman, Eva; Bangari, Dinesh S; Siegel, Craig S; Nietupski, Jennifer B; Wang, Bing; Desnick, Robert J; Scheule, Ronald K; Leonard, John P; Cheng, Seng H; Marshall, John

2015-01-01

Fabry disease, an X-linked glycosphingolipid storage disorder, is caused by the deficient activity of α-galactosidase A (α-Gal A). This results in the lysosomal accumulation in various cell types of its glycolipid substrates, including globotriaosylceramide (GL-3) and lysoglobotriaosylceramide (globotriaosyl lysosphingolipid, lyso-GL-3), leading to kidney, heart, and cerebrovascular disease. To complement and potentially augment the current standard of care, biweekly infusions of recombinant α-Gal A, the merits of substrate reduction therapy (SRT) by selectively inhibiting glucosylceramide synthase (GCS) were examined. Here, we report the development of a novel, orally available GCS inhibitor (Genz-682452) with pharmacological and safety profiles that have potential for treating Fabry disease. Treating Fabry mice with Genz-682452 resulted in reduced tissue levels of GL-3 and lyso-GL-3 and a delayed loss of the thermal nociceptive response. Greatest improvements were realized when the therapeutic intervention was administered to younger mice before they developed overt pathology. Importantly, as the pharmacologic profiles of α-Gal A and Genz-682452 are different, treating animals with both drugs conferred the greatest efficacy. For example, because Genz-682452, but not α-Gal A, can traverse the blood–brain barrier, levels of accumulated glycosphingolipids were reduced in the brain of Genz-682452–treated but not α-Gal A–treated mice. These results suggest that combining substrate reduction and enzyme replacement may confer both complementary and additive therapeutic benefits in Fabry disease. PMID:25938659

Structural, mechanical and light yield characterisation of heat treated LYSO:Ce single crystals for medical imaging applications

NASA Astrophysics Data System (ADS)

Mengucci, P.; André, G.; Auffray, E.; Barucca, G.; Cecchi, C.; Chipaux, R.; Cousson, A.; Davì, F.; Di Vara, N.; Rinaldi, D.; Santecchia, E.

2015-06-01

Five single crystals of cerium-doped lutetium yttrium oxyorthosilicate (LYSO:Ce) grown by the Czochralski method were submitted to structural characterisation by X-ray (XRD) and neutron (ND) diffraction, scanning (SEM) and transmission (TEM) electron microscopy and energy dispersive microanalysis (EDS). The Ultimate Tensile Strength (UTS), the Young Modulus (YM) and the Light Yield (LY) of the samples were also measured in order to correlate the mechanical and the optical behaviour of the crystals with the characteristics of their microstructure. Two of the samples analysed were also heat treated at 300 °C for 10 h to evidence possible variations induced by the temperature in the optical and mechanical response of the crystals. Results showed that the mean compositional variations evidenced by the structural analyses do not affect the mechanical and optical behaviour of the samples. On the contrary, the thermal treatment could induce the formation of coherent spherical particles (size 10 to 15 nm), not uniformly distributed inside the sample, that strongly reduce the UTS and YM values, but it does not affect the optical response of the crystal. This latter result was attributed to the low value of the heating temperature (300 °C) that is not sufficiently high to induce annealing of the oxygen vacancies traps that are responsible of the deterioration of the scintillation properties of the LYSO:Ce crystals. This study was carried out in the framework of the Crystal Clear Collaboration (CCC).

Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis.

PubMed

Zeng, Chunwei; Wen, Bo; Hou, Guixue; Lei, Li; Mei, Zhanlong; Jia, Xuekun; Chen, Xiaomin; Zhu, Wu; Li, Jie; Kuang, Yehong; Zeng, Weiqi; Su, Juan; Liu, Siqi; Peng, Cong; Chen, Xiang

2017-10-01

Psoriasis is a common and chronic inflammatory skin disease that is complicated by gene-environment interactions. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes such as cell proliferation, apoptosis, immunity, angiogenesis, and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and to identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and analyzed. Statistical analysis was applied to find different metabolites between the disease and healthy groups. In addition, enzyme-linked immunosorbent assay was performed to validate differentially expressed lipids in psoriatic patient plasma. Finally, we identified differential expression of several lipids including lysophosphatidic acid (LPA), lysophosphatidylcholine (LysoPC), phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidic acid (PA); among these metabolites, LPA, LysoPC, and PA were significantly increased, while PC and PI were down-regulated in psoriasis patients. We found that elements of glycerophospholipid metabolism such as LPA, LysoPC, PA, PI, and PC were significantly altered in the plasma of psoriatic patients; this study characterizes the circulating lipids in psoriatic patients and provides novel insight into the role of lipids in psoriasis. © The Author 2017. Published by Oxford University Press.

Lysophosphatidylcholine and amide as metabolites for detecting alzheimer disease using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabonomics.

PubMed

Cui, Yu; Liu, Xiuqin; Wang, Maoqing; Liu, Liyan; Sun, Xiaohong; Ma, Lan; Xie, Wei; Wang, Chao; Tang, Sisi; Wang, Decai; Wu, Qunhong

2014-10-01

Alzheimer disease (AD) can be diagnosed by clinical and neuropsychologic tests and at autopsy, but there are no simple effective diagnostic methods for detecting biomarkers in patients at early stages of cognitive impairment. Early metabolic alterations that may facilitate AD diagnosis have not been thoroughly explored. We applied a nontargeted metabonomic approach using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry to analyze serum and urine samples from 46 patients with AD and 36 healthy controls. Metabolite profiles were processed using multivariate analysis to identify potential metabolites, which were further confirmed using tandem mass spectrometry. Ultrahigh-performance liquid chromatography mass spectrometry methods were additionally used to quantify potentially important biomarkers. Independent samples were then selected to validate the identified biomarkers. There was a clear separation between healthy controls and AD patients; AD patient samples had disordered amino acid and phospholipid metabolism and dysregulated palmitic amide. Receiver operator characteristic curve and quantification suggested that palmitic amide, lysophosphatidylcholine (LysoPC, 18:0), LysoPC(18:2), L-glutamine, and 5-L-glutamylglycine were the optimal metabolites. In addition, areas under the curve from the palmitic amide, LysoPC(18:2), and 5-L-glutamylglycine in the validation study were 0.714, 0.996, and 0.734, respectively. These data elucidate the metabolic alterations associated with AD and suggest new biomarkers for AD diagnosis, thereby permitting early intervention designed to prevent disease progression.

Precision Crystal Calorimeters in High Energy Physics

ScienceCinema

Ren-Yuan Zhu

2017-12-09

Precision crystal calorimeters traditionally play an important role in high energy physics experiments. In the last two decades, it faces a challenge to maintain its precision in a hostile radiation environment. This paper reviews the performance of crystal calorimeters constructed for high energy physics experiments and the progress achieved in understanding crystal’s radiation damage as well as in developing high quality scintillating crystals for particle physics. Potential applications of new generation scintillating crystals of high density and high light yield, such as LSO and LYSO, in particle physics experiments is also discussed.

Proof of concept of an imaging system demonstrator for PET applications with SiPM

NASA Astrophysics Data System (ADS)

Morrocchi, Matteo; Marcatili, Sara; Belcari, Nicola; Giuseppina Bisogni, Maria; Collazuol, Gianmaria; Ambrosi, Giovanni; Santoni, Cristiano; Corsi, Francesco; Foresta, Maurizio; Marzocca, Cristoforo; Matarrese, Gianvito; Sportelli, Giancarlo; Guerra, Pedro; Santos, Andres; Del Guerra, Alberto

2013-08-01

A PET imaging system demonstrator based on LYSO crystal arrays coupled to SiPM matrices is under construction at the University and INFN of Pisa. Two SiPM matrices, composed of 8×8 SiPM pixels, and 1,5 mm pitch, have been coupled one to one to a LYSO crystals array and read out by a custom electronics system. front-end ASICs were used to read 8 channels of each matrix. Data from each front-end were multiplexed and sent to a DAQ board for the digital conversion; a motherboard collects the data and communicates with a host computer through a USB port for the storage and off-line data processing. In this paper we show the first preliminary tomographic image of a point-like radioactive source acquired with part of the two detection heads in time coincidence.

Mechanism of Fructus Aurantii Flavonoids Promoting Gastrointestinal Motility: From Organic and Inorganic Endogenous Substances Combination Point of View.

PubMed

Wang, Shuai; Bao, Yong-Rui; Li, Tian-Jiao; Yu, Ting; Chang, Xin; Yang, Guan-Lin; Meng, Xian-Sheng

2017-01-01

Fructus Aurantii (FA) derived from the dried, and unripe fruit of Citrus aurantium L. is one of the commonly used traditional Chinese medicines to treat gastrointestinal motility dysfunction diseases. According to the literature research, FA flavonoids (FAF) are important active ingredients of FA promoting gastrointestinal motility, but the exact material basis and mechanism of action are still not very clear. This experiment was designed to illustrate the material basis of FAF promoting gastrointestinal motility and explore the mechanism of action from an organic and inorganic combination point of view. In this experiment, high-performance liquid chromatography (HPLC) method was used to analyze the composition and content of FAF. Based on the prominent prokinetic effect of FAF on mice, the mechanism of action was speculated through a combination of HPLC coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). With the method of HPLC, ten dominating components of FAF including neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletin accounting for more than 86% of FAF were identified. Combined HPLC-QTOF-MS with ICP-MS, the endogenous substances with difference in the blood of mice were analyzed, in which 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC(18:2 (9Z, 12Z)), and Ca 2+ , Mg 2+ , Zn 2+ metal ions had significant changes, involving tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways. The results preliminarily elaborated the mechanism of FAF promoting gastrointestinal motility from an organic and inorganic point of view, which provide valuable information for researching and developing new multi-component Chinese medicine curing gastrointestinal underpower associated diseases. Fructus Aurantii flavonoids are one of the main components of Fructus Aurantii that possess prominent gastrointestinal motility promoting efficacyThe mainly material basis of Fructus Aurantii flavonoids promoting gastrointestinal motility were neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletinFructus Aurantii flavonoids can regulate the content of 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC.(18:2(9Z, 12Z)) and Ca 2+ , Mg 2+ , Zn 2+ -metal ions, through tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways to present its gastrointestinal motility promoting efficacy. Abbreviations used: FA: Fructus Aurantii; FAF: Fructus Aurantii flavonoids; HPLC: High performance liquid chromatography; HPLC-QTOF-MS: High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry; ICP-MS: Inductively coupled plasma mass spectrometry; PCA: Principal components analysis; CG: Control group; FAFLG: Low-dosage group of Fructus Aurantii flavonoids; FAFMG: Middle-dosage group of Fructus Aurantii flavonoids; FAFHG: High-dosage group of Fructus Aurantii flavonoids; DPG: Domperidone group.

Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos.

PubMed

Fisher, M C; Zeisel, S H; Mar, M H; Sadler, T W

2001-08-01

Choline is an essential nutrient in methylation, acetylcholine and phospholipid biosynthesis, and in cell signaling. The demand by an embryo or fetus for choline may place a pregnant woman and, subsequently, the developing conceptus at risk for choline deficiency. To determine whether a disruption in choline uptake and metabolism results in developmental abnormalities, early somite staged mouse embryos were exposed in vitro to either an inhibitor of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), or an inhibitor of phosphatidylcholine synthesis, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH(3)). Cell death following inhibitor exposure was investigated with LysoTracker Red and histology. Embryos exposed to 250-750 microM DMAE for 26 hr developed craniofacial hypoplasia and open neural tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed to 125-275 microM ET-18-OCH(3) exhibited similar defects or expansion of the brain vesicles. ET-18-OCH(3)-affected embryos also had a distended neural tube at the posterior neuropore. Embryonic growth was reduced in embryos treated with either DMAE (375, 500, and 750 microM) or ET-18-OCH(3) (200 and 275 microM). Whole mount staining with LysoTracker Red and histological sections showed increased areas of cell death in embryos treated with 275 microM ET-18-OCH(3) for 6 hr, but there was no evidence of cell death in DMAE-exposed embryos. Inhibition of choline uptake and metabolism during neurulation results in growth retardation and developmental defects that affect the neural tube and face. Copyright 2001 Wiley-Liss, Inc.

Intrinsic spatial resolution evaluation of the X'tal cube PET detector based on a 3D crystal block segmented by laser processing.

PubMed

Yoshida, Eiji; Tashima, Hideaki; Inadama, Naoko; Nishikido, Fumihiko; Moriya, Takahiro; Omura, Tomohide; Watanabe, Mitsuo; Murayama, Hideo; Yamaya, Taiga

2013-01-01

The X'tal cube is a depth-of-interaction (DOI)-PET detector which is aimed at obtaining isotropic resolution by effective readout of scintillation photons from the six sides of a crystal block. The X'tal cube is composed of the 3D crystal block with isotropic resolution and arrays of multi-pixel photon counters (MPPCs). In this study, to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving (SSLE) technique to a monolithic crystal block instead of gluing segmented small crystals. The SSLE technique provided micro-crack walls which carve a groove into a monolithic scintillator block. Using the fabricated X'tal cube, we evaluated its intrinsic spatial resolution to show a proof of concept of isotropic resolution. The 3D grids of 2 mm pitch were fabricated into an 18 × 18 × 18 mm(3) monolithic lutetium yttrium orthosilicate (LYSO) crystal by the SSLE technique. 4 × 4 MPPCs were optically coupled to each surface of the crystal block. The X'tal cube was uniformly irradiated by (22)Na gamma rays, and all of the 3D grids on the 3D position histogram were separated clearly by an Anger-type calculation from the 96-channel MPPC signals. Response functions of the X'tal cube were measured by scanning with a (22)Na point source. The gamma-ray beam with a 1.0 mm slit was scanned in 0.25 mm steps by positioning of the X'tal cube at vertical and 45° incident angles. The average FWHM resolution at both incident angles was 2.1 mm. Therefore, we confirmed the isotropic spatial resolution performance of the X'tal cube.

Targeted metabolomics: new insights into pathobiology of retained placenta in dairy cows and potential risk biomarkers.

PubMed

Dervishi, E; Zhang, G; Mandal, R; Wishart, D S; Ametaj, B N

2018-05-01

A targeted quantitative metabolomics approach was used to study temporal changes of serum metabolites in cows that normally released their fetal membranes and those that retained the placenta. We identified and measured serum concentrations of 128 metabolites including amino acids, acylcarnitines, biogenic amines, glycerophospholipids, sphingolipids and hexose at -8 and -4 weeks before parturition, during the week of retained placenta (RP) diagnosis, and at +4 and +8 weeks after parturition. In addition, we aimed at identifying metabolite signatures of pre-RP in the serum that might be used as predictive biomarkers for risk of developing RP in dairy cows. Results revealed major alterations in the metabolite fingerprints of pre-RP cows starting as early as -8 weeks before parturition and continuing as far as +8 weeks after calving. Biomarker candidates found in this study are mainly biomarkers of inflammation which might not be specific to RP. Therefore, the relevance of serum Lys, Orn, acetylornithine, lysophophatidylcholine LysoPC a C28:0, Asp, Leu and Ile as potential serum biomarkers for prediction of risk of RP in dairy cows will have to be tested in the future. In addition, lower concentrations of LysoPCs, Trp, and higher kynurenine in the serum during prepartum and the week of occurrence of RP suggest involvement of inflammation in the pathobiology of RP.

Neural stem cells for disease modeling of Wolman disease and evaluation of therapeutics.

PubMed

Aguisanda, Francis; Yeh, Charles D; Chen, Catherine Z; Li, Rong; Beers, Jeanette; Zou, Jizhong; Thorne, Natasha; Zheng, Wei

2017-06-28

Wolman disease (WD) is a rare lysosomal storage disorder that is caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL). Deficiency in LAL function causes accumulation of cholesteryl esters and triglycerides in lysosomes. Fatality usually occurs within the first year of life. While an enzyme replacement therapy has recently become available, there is currently no small-molecule drug treatment for WD. We have generated induced pluripotent stem cells (iPSCs) from two WD patient dermal fibroblast lines and subsequently differentiated them into neural stem cells (NSCs). The WD NSCs exhibited the hallmark disease phenotypes of neutral lipid accumulation, severely deficient LAL activity, and increased LysoTracker dye staining. Enzyme replacement treatment dramatically reduced the WD phenotype in these cells. In addition, δ-tocopherol (DT) and hydroxypropyl-beta-cyclodextrin (HPBCD) significantly reduced lysosomal size in WD NSCs, and an enhanced effect was observed in DT/HPBCD combination therapy. The results demonstrate that these WD NSCs are valid cell-based disease models with characteristic disease phenotypes that can be used to evaluate drug efficacy and screen compounds. DT and HPBCD both reduce LysoTracker dye staining in WD cells. The cells may be used to further dissect the pathology of WD, evaluate compound efficacy, and serve as a platform for high-throughput drug screening to identify new compounds for therapeutic development.

STIC3 - Silicon Photomultiplier Timing Chip with picosecond resolution

NASA Astrophysics Data System (ADS)

Stankova, Vera; Shen, Wei; Briggl, Konrad; Chen, Huangshan; Fischer, Peter; Gil, Alejandro; Harion, Tobias; Kiworra, Volker; Munwes, Yonathan; Ritzert, Michael; Schultz-Coulon, Hans-Christian

2015-07-01

The diagnostic of pancreas and prostate cancer is a challenging task due to the background noise coming from the closer organs. The EndoToFPET-US project aims to combine the synergy between metabolic and anatomical (ultrasound) image in order to improve the precision in the tumor localization. The goal of the project is to develop a Positron Emission Tomography (PET) system that provides a time-of-flight resolution of 200 ps FWHM for improving the signal to noise ratio and further to improve the medical image quality. In order to achieve this purpose an ASIC has been designed for very high timing resolution in time-of-flight (ToF) applications. In this paper we present the ASIC performance and the first characterization measurements with the 64-channels prototype version (STiC3). Measurements are performed with LYSO scintillator crystal and a Multi Pixel Photon Counter (MPPC). Measurements with the chip show an analog-front-end stage jitter of 35 ps for the first photo-electron equivalent charge and reach 18 ps for the third photo-electron. Coincidence time resolution (CTR) of 240 ps FWHM is measured with 3.1×3.1×15 mm3 LYSO crystal and 50 μm pixel pitch MPPC. Further optimization including the Time-to-Digital Converter (TDC) non-linearity corrections and setup fine tuning are ongoing for achieving the desired CTR of 200 ps FWHM.

Biomarkers and Imaging Findings of Anderson–Fabry Disease—What We Know Now

PubMed Central

Beirão, Idalina; Cabrita, Ana; Torres, Márcia; Silva, Fernando; Aguiar, Patrício; Laranjeira, Francisco; Gomes, Ana Marta

2017-01-01

Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients. An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients. PMID:28933368

Data Processing for a High Resolution Preclinical PET Detector Based on Philips DPC Digital SiPMs

NASA Astrophysics Data System (ADS)

Schug, David; Wehner, Jakob; Goldschmidt, Benjamin; Lerche, Christoph; Dueppenbecker, Peter Michael; Hallen, Patrick; Weissler, Bjoern; Gebhardt, Pierre; Kiessling, Fabian; Schulz, Volkmar

2015-06-01

In positron emission tomography (PET) systems, light sharing techniques are commonly used to readout scintillator arrays consisting of scintillation elements, which are smaller than the optical sensors. The scintillating element is then identified evaluating the signal heights in the readout channels using statistical algorithms, the center of gravity (COG) algorithm being the simplest and mostly used one. We propose a COG algorithm with a fixed number of input channels in order to guarantee a stable calculation of the position. The algorithm is implemented and tested with the raw detector data obtained with the Hyperion-II D preclinical PET insert which uses Philips Digital Photon Counting's (PDPC) digitial SiPMs. The gamma detectors use LYSO scintillator arrays with 30 ×30 crystals of 1 ×1 ×12 mm3 in size coupled to 4 ×4 PDPC DPC 3200-22 sensors (DPC) via a 2-mm-thick light guide. These self-triggering sensors are made up of 2 ×2 pixels resulting in a total of 64 readout channels. We restrict the COG calculation to a main pixel, which captures most of the scintillation light from a crystal, and its (direct and diagonal) neighboring pixels and reject single events in which this data is not fully available. This results in stable COG positions for a crystal element and enables high spatial image resolution. Due to the sensor layout, for some crystals it is very likely that a single diagonal neighbor pixel is missing as a result of the low light level on the corresponding DPC. This leads to a loss of sensitivity, if these events are rejected. An enhancement of the COG algorithm is proposed which handles the potentially missing pixel separately both for the crystal identification and the energy calculation. Using this advancement, we show that the sensitivity of the Hyperion-II D insert using the described scintillator configuration can be improved by 20-100% for practical useful readout thresholds of a single DPC pixel ranging from 17-52 photons. Furthermore, we show that the energy resolution of the scanner is superior for all readout thresholds if singles with a single missing pixel are accepted and correctly handled compared to the COG method only accepting singles with all neighbors present by 0-1.6% (relative difference). The presented methods can not only be applied to gamma detectors employing DPC sensors, but can be generalized to other similarly structured and self-triggering detectors, using light sharing techniques, as well.

PKU-PET-II: A novel SiPM-based PET imaging system for small animals

NASA Astrophysics Data System (ADS)

Xie, Zhaoheng; Li, Suying; Zhou, Kun; Vuletic, Ivan; Meng, Xiangxi; Zhu, Sihao; Xu, Huan; Yang, Kun; Xu, Baixuan; Zhang, Jinming; Ren, Qiushi

2018-01-01

The objective of this study was to introduce, describe, and validate the performance of a novel preclinical silicon photomultiplier (SiPM)-based PET system (PKU-PET-II). Briefly, the detector assembly consisted of cerium-doped lutetium-yttrium oxyorthosilicate (LYSO) crystals, with dimensions of 2 ×2 ×15 mm3, that offered a 60 mm transaxial field of view (FOV) and 32 mm axial FOV, respectively. The compact front-end electronics readout and digital controller implemented architecture in the FPGA were noteworthy improvements in PKU-PET-II over its predecessor (PKU-PET-I). Based on the National Electrical Manufacturers Association (NEMA) NU 04-2008 standards, the design of the PKU-PET-II system was validated by a phantom experiment. The results presented spatial resolution (evaluated as full width at half maximum) with a system range from 1.68 ±0.07 to 2.31 ±0.03 mm at the FOV center and from 1.43 ±0.02 to 2.10 ±0.10 mm at the 1/4th axial FOV, respectively. The system's absolute sensitivity at the center position was 1.35% with the coincidence window of 6 ns and energy window of 300-700 keV. In addition, the NEMA image quality phantom and an animal study results validated the system imaging performance in preclinical imaging application. In conclusion, this SiPM-based, small-animal PET system (PKU-PET-II) provided higher-resolution, adequate sensitivity, and excellent image quality and has potential as a useful tool for real-time imaging of disease progression and development in vivo.

Characterisation of crystal matrices and single pixels for nuclear medicine applications

NASA Astrophysics Data System (ADS)

Herbert, D. J.; Belcari, N.; Camarda, M.; Guerra, A. Del; Vaiano, A.

2005-01-01

Commercially constructed crystal matrices are characterised for use with PSPMT detectors for PET system developments and other nuclear medicine applications. The matrices of different scintillation materials were specified with pixel dimensions of 1.5×1.5 mm2 in cross-section and a length corresponding to one gamma ray interaction length at 511 keV. The materials used in this study were BGO, LSO, LYSO, YSO and CsI(Na). Each matrix was constructed using a white TiO loaded epoxy that forms a 0.2 mm septa between each pixel. The white epoxy is not the optimum choice in terms of the reflective properties, but represents a good compromise between cost and the need for optical isolation between pixels. We also tested a YAP matrix that consisted of pixels of the same size specification but was manufactured by a different company, who instead of white epoxy, used a thin aluminium reflective layer for optical isolation that resulted in a septal thickness of just 0.01 mm, resulting in a much higher packing fraction. The characteristics of the scintillation materials, such as the light output and energy resolution, were first studied in the form of individual crystal elements by using a single pixel HPD. A comparison of individual pixels with and without the epoxy/dielectric coatings was also performed. Then the matrices themselves were coupled to a PSPMT in order to study the imaging performance. In particular, the system pixel resolution and the peak to valley ratio were measured at 511 and 122 keV.

Time resolution deterioration with increasing crystal length in a TOF-PET system

NASA Astrophysics Data System (ADS)

Gundacker, S.; Knapitsch, A.; Auffray, E.; Jarron, P.; Meyer, T.; Lecoq, P.

2014-02-01

Highest time resolution in scintillator based detectors is becoming more and more important. In medical detector physics L(Y)SO scintillators are commonly used for time of flight positron emission tomography (TOF-PET). Coincidence time resolutions (CTRs) smaller than 100 ps FWHM are desirable in order to improve the image signal to noise ratio and thus give benefit to the patient by shorter scanning times. Also in high energy physics there is the demand to improve the timing capabilities of calorimeters down to 10 ps. To achieve these goals it is important to study the whole chain, i.e. the high energy particle interaction in the crystal, the scintillation process itself, the scintillation light transfer in the crystal, the photodetector and the electronics. Time resolution measurements for a PET like system are performed with the time-over-threshold method in a coincidence setup utilizing the ultra-fast amplifier-discriminator NINO. With 2×2×3 mm3 LSO:Ce codoped 0.4%Ca crystals coupled to commercially available SiPMs (Hamamatsu S10931-050P MPPC) we achieve a CTR of 108±5 ps FWHM at an energy of 511 keV. Under the same experimental conditions an increase in crystal length to 5 mm deteriorates the CTR to 123±7 ps FWHM, 10 mm to 143±7 ps FWHM and 20 mm to 176±7 ps FWHM. This degradation in CTR is caused by the light transfer efficiency (LTE) and light transfer time spread (LTTS) in the crystal. To quantitatively understand the measured values, we developed a Monte Carlo simulation tool in MATLAB incorporating the timing properties of the photodetector and electronics, the scintillation properties of the crystal and the light transfer within the crystal simulated by SLITRANI. In this work, we show that the predictions of the simulation are in good agreement with the experimental data. We conclude that for longer crystals the deterioration in CTR is mainly caused by the LTE, i.e. the ratio of photons reaching the photodetector to the total amount of photons generated by the scintillation whereas the LTTS influence is partly offset by the gamma absorption in the crystal.

Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics

PubMed Central

Choi, Jaewoo; Leonard, Scott W.; Kasper, Katherine; McDougall, Melissa; Stevens, Jan F.; Tanguay, Robert L.; Traber, Maret G.

2015-01-01

We hypothesized that brains from vitamin E-deficient (E−) zebrafish (Danio rerio) would undergo increased lipid peroxidation because they contain highly polyunsaturated fatty acids, thus susceptible lipids could be identified. Brains from zebrafish fed for 9 months defined diets without (E−) or with (E+) added vitamin E (500 mg RRR-α-tocopheryl acetate per kilogram diet) were studied. Using an untargeted approach, 1-hexadecanoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine [DHA-PC 38:6, PC 16:0/22:6]was the lipid that showed the most significant and greatest fold-differences between groups. DHA-PC concentrations were approximately 1/3 lower in E− (4.3 ± 0.6 mg/g) compared with E+ brains (6.5 ± 0.9 mg/g, mean ± SEM, n = 10 per group, P = 0.04). Using lipidomics, 155 lipids in brain extracts were identified. Only four phospholipids (PLs) were different (P < 0.05) between groups; they were lower in E− brains and contained DHA with DHA-PC 38:6 at the highest abundances. Moreover, hydroxy-DHA-PC 38:6 was increased in E− brains (P = 0.0341) supporting the hypothesis of DHA peroxidation. More striking was the depletion in E− brains of nearly 60% of 19 different lysophospholipids (lysoPLs) (combined P = 0.0003), which are critical for membrane PL remodeling. Thus, E− brains contained fewer DHA-PLs, more hydroxy-DHA-PCs, and fewer lysoPLs, suggesting that lipid peroxidation depletes membrane DHA-PC and homeostatic mechanisms to repair the damage resulting in lysoPL depletion. PMID:25855633

TDC Array Tradeoffs in Current and Upcoming Digital SiPM Detectors for Time-of-Flight PET

NASA Astrophysics Data System (ADS)

Tétrault, Marc-André; Therrien, Audrey Corbeil; Lemaire, William; Fontaine, Réjean; Pratte, Jean-François

2017-03-01

Radiation detection used in positron emission tomography (PET) exploits the timing information to remove background noise and refine position measurement through time-of-flight information. Fine time resolution in the order of 10 ps full-width at half-maximum (FWHM) would not only improve contrast in the image, but would also enable direct image reconstruction without iterative or back-projected algorithms. Currently, PET experimental setups based on silicon photomultipliers (SiPMs) reach 73 ps FWHM, where the scintillation process plays the larger role in spreading the timing resolution. This will change with the optimization of faster light emission mechanisms (prompt photons), where readout optoelectronics will once more have a noticeable contribution to the timing resolution limit. In addition to reducing electronic jitter as much as possible, other aspects of the design space must also explored, especially for digital SiPMs. Unlike traditional SiPMs, digital SiPMs can integrate circuits like time-to-digital converters (TDCs) directly with individual or groups of light sensing cells. Designers should consider the number of TDCs to integrate, the area they occupy, their power consumption, their resolution, and the impact of signal processing algorithms and find a compromise with the figure of merit and the coincidence timing resolution (CTR). This paper presents a parametric simulation flow for digital SiPM microsystems that evaluates CTR based on these aspects and on the best linear unbiased estimator (BLUE) in order to guide their design for present and future PET systems. For a small 1.1 × 1.1 × 3.0 mm3 LYSO crystal, the simulations indicate that for a low jitter digital SiPM microsystem with 18.2% photon detection efficiency, fewer than four timestamps with any multi-TDC configuration scheme nearly obtain the optimal CTR with BLUE (just below 100 ps FWHM), but with limited 5% improvement over only using the first observed photon. On the other hand, if a similar crystal but with 2.5% prompt photon fraction is considered, BLUE provides an improvement between 80% and 200% (depending on electronic jitter) over using only the first observed photon. In this case, a few tens of timestamps are required, yielding very different design guidelines than for standard LYSO scintillators.

Compact pulse width modulation circuitry for silicon photomultiplier readout.

PubMed

Bieniosek, M F; Olcott, P D; Levin, C S

2013-08-07

The adoption of solid-state photodetectors for positron emission tomography (PET) system design and the interest in 3D interaction information from PET detectors has lead to an increasing number of readout channels in PET systems. To handle these additional readout channels, PET readout electronics should be simplified to reduce the power consumption, cost, and size of the electronics for a single channel. Pulse-width modulation (PWM), where detector pulses are converted to digital pulses with width proportional to the detected photon energy, promises to simplify PET readout by converting the signals to digital form at the beginning of the processing chain, and allowing a single time-to-digital converter to perform the data acquisition for many channels rather than routing many analogue channels and digitizing in the back end. Integrator based PWM systems, also known as charge-to-time converters (QTCs), are especially compact, reducing the front-end electronics to an op-amp integrator with a resistor discharge, and a comparator. QTCs, however, have a long dead-time during which dark count noise is integrated, reducing the output signal-to-noise ratio. This work presents a QTC based PWM circuit with a gated integrator that shows performance improvements over existing QTC based PWM. By opening and closing an analogue switch on the input of the integrator, the circuit can be controlled to integrate only the portions of the signal with a high signal-to-noise ratio. It also allows for multiplexing different detectors into the same PWM circuit while avoiding uncorrelated noise propagation between photodetector channels. Four gated integrator PWM circuits were built to readout the spatial channels of two position sensitive solid-state photomultiplier (PS-SSPM). Results show a 4 × 4 array 0.9 mm × 0.9 mm × 15 mm of LYSO crystals being identified on the 5 mm × 5 mm PS-SSPM at room temperature with no degradation for twofold multiplexing. In principle, much larger multiplexing ratios are possible, limited only by count rate issues.

Optimization of an ultralow-dose high-resolution pediatric PET scanner design based on monolithic scintillators with dual-sided digital SiPM readout: a simulation study

NASA Astrophysics Data System (ADS)

Mikhaylova, Ekaterina; Tabacchini, Valerio; Borghi, Giacomo; Mollet, Pieter; D'Hoe, Ester; Schaart, Dennis R.; Vandenberghe, Stefaan

2017-11-01

The goal of this simulation study is the performance evaluation and comparison of six potential designs for a time-of-flight PET scanner for pediatric patients of up to about 12 years of age. It is designed to have a high sensitivity and provide high-contrast and high-resolution images. The simulated pediatric PET is a full ring scanner, consisting of 32  ×  32 mm2 monolithic LYSO:Ce crystals coupled to digital silicon photomultiplier arrays. The six considered designs differ in axial lengths (27.2 cm, 54.4 cm and 102 cm) and crystal thicknesses (22 mm and 11 mm). The simulations are based on measured detector response data. We study two possible detector arrangements: 22 mm-thick crystals with dual-sided readout and 11 mm-thick crystals with back-sided readout. The six designs are simulated by means of the GEANT4 application for tomographic emission software, using the measured spatial, energy and time response of the monolithic scintillator detectors as input. The performance of the six designs is compared on the basis of four studies: (1) spatial resolution; (2) NEMA NU2-2012 sensitivity and scatter fraction (SF) tests; (3) non-prewhitening signal-to-noise ratio observer study; and (4) receiver operating characteristics analysis. Based on the results, two designs are identified as cost-effective solutions for fast and efficient imaging of children: one with 54.4 cm axial field-of-view (FOV) and 22 mm-thick crystals, and another one with 102 cm axial FOV and 11 cm-thick crystals. The first one has a higher center point sensitivity than the second one, but requires dual-sided readout. The second design has the advantage of allowing a whole-body scan in a single bed position acquisition. Both designs have the potential to provide an excellent spatial resolution (˜2 mm) and an ultra-high sensitivity (>100 cps kBq-1 ).

WHOLE INSECT AND MAMMALIAN EMBRYO IMAGING WITH CONFOCAL MICROSCOPY: MORPHOLOGY AND APOPTOSIS

EPA Science Inventory

Background: After fluorochromes are incorporated into cells, tissues, and organisms, confocal microscopy can be used to observe three-dimensional structures. LysoTracker Red (LT) is a paraformaldehyde fixable probe that concentrates into acidic compartments of cells and indicates...

Interaction of the major protein from bovine seminal plasma, PDC-109 with phospholipid membranes and soluble ligands investigated by fluorescence approaches.

PubMed

Anbazhagan, V; Damai, Rajani S; Paul, Aniruddha; Swamy, Musti J

2008-06-01

The major protein from bovine seminal plasma, PDC-109 binds selectively to choline phospholipids on the sperm plasma membrane and plays a crucial role in priming spermatozoa for fertilization. The microenvironment and accessibility of tryptophans of PDC-109 in the native state, in the presence of phosphorylcholine (PrC) and phospholipid membranes as well as upon denaturation have been investigated by fluorescence approaches. Quenching of the protein intrinsic fluorescence by different quenchers decreased in the order: acrylamide>succinimide>Cs(+)>I(-). Ligand binding afforded considerable protection from quenching, with shielding efficiencies following the order: dimyristoylphosphatidylcholine (DMPC)>lysophosphatidylcholine (Lyso-PC)>PrC. This has been attributed to a partial penetration of the protein into the DMPC membranes and Lyso-PC micelles, as well as a further stabilization of the binding due to the interaction of PDC-109 with lipid acyl chains and the resulting tightening of the protein structure, leading to a decreased accessibility of the tryptophan residues. Red-edge excitation shift (REES) studies yielded REES values of 4 nm for both native and denatured PDC-109, whereas reduced and denatured protein gave a REES of only 0.5 nm, clearly indicating that the structural and dynamic features of the microenvironment around the tryptophan residues are retained even after denaturation, presumably due to the constraints imposed on the protein structure by disulfide bonds. Upon binding of PDC-109 to DMPC membranes and Lyso-PC micelles the REES values were reduced to 2.5 and 1.0 nm, respectively, which could be due to the penetration of some parts of the protein, especially the segment containing Trp-90 into the membrane interior, where the red-edge effects are considerably reduced.

Altered Plasma Lysophosphatidylcholines and Amides in Non-Obese and Non-Diabetic Subjects with Borderline-To-Moderate Hypertriglyceridemia: A Case-Control Study

PubMed Central

Jung, Saem; Lee, Sang-Hyun; Lee, Jong Ho

2015-01-01

Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease (CVD). We investigated alterations in plasma metabolites associated with borderline-to-moderate HTG (triglycerides (TG) 150-500 mg/dL). Using UPLC-LTQ-Orbitrap mass spectrometry analysis, the metabolomics profiles of 111 non-diabetic and non-obese individuals with borderline-to-moderate HTG were compared with those of 111 age- and sex-matched controls with normotriglyceridemia (NTG, TG <150 mg/dL). When compared to the NTG control group, the HTG group exhibited higher plasma levels of lysophosphatidylcholines (lysoPCs), including C14:0 (q = 0.001) and C16:0 (q = 1.8E-05), and several amides, including N-ethyldodecanamide (q = 2.9E-05), N-propyldodecanamide (q = 3.5E-05), palmitoleamide (q = 2.9E-06), and palmitic amide (q = 0.019). The metabolomic profiles of the HTG group also exhibited lower plasma levels of cis-4-octenedioic acid (q<1.0E-9) and docosanamide (q = 0.002) compared with those of the NTG controls. LysoPC 16:0 and palmitoleamide emerged as the primary metabolites able to discriminate the HTG group from the NTG group in a partial least-squares discriminant analysis and were positively associated with the fasting triglyceride levels. We identified alterations in lysoPCs, amides, and cis-4-octenedioic acid among non-diabetic and non-obese individuals with borderline-to-moderate HTG. These results provide novel insights into the metabolic alterations that occur in the early metabolic stages of HTG. This information may facilitate the design of early interventions to prevent disease progression. PMID:25856314

Role of lecithin-cholesterol acyltransferase in the metabolism of oxidized phospholipids in plasma: studies with platelet-activating factor-acetyl hydrolase-deficient plasma.

PubMed

Subramanian, V S; Goyal, J; Miwa, M; Sugatami, J; Akiyama, M; Liu, M; Subbaiah, P V

1999-07-09

To determine the relative importance of platelet-activating factor-acetylhydrolase (PAF-AH) and lecithin-cholesterol acyltransferase (LCAT) in the hydrolysis of oxidized phosphatidylcholines (OXPCs) to lyso-phosphatidylcholine (lyso-PC), we studied the formation and metabolism of OXPCs in the plasma of normal and PAF-AH-deficient subjects. Whereas the loss of PC following oxidation was similar in the deficient and normal plasmas, the formation of lyso-PC was significantly lower, and the accumulation of OXPC was higher in the deficient plasma. Isolated LDL from the PAF-AH-deficient subjects was more susceptible to oxidation, and stimulated adhesion molecule synthesis in endothelial cells, more than the normal LDL. Oxidation of 16:0-[1-14C]-18:2 PC, equilibrated with plasma PC, resulted in the accumulation of labeled short- and long-chain OXPCs, in addition to the labeled aqueous products. The formation of the aqueous products decreased by 80%, and the accumulation of short-chain OXPC increased by 110% in the deficient plasma, compared to the normal plasma, showing that PAF-AH is predominantly involved in the hydrolysis of the truncated OXPCs. Labeled sn-2-acyl group from the long-chain OXPC was not only hydrolyzed to free fatty acid, but was preferentially transferred to diacylglycerol, in both the normal and deficient plasmas. In contrast, the acyl group from unoxidized PC was transferred only to cholesterol, showing that the specificity of LCAT is altered by OXPC. It is concluded that, while PAF-AH carries out the hydrolysis of mainly truncated OXPCs, LCAT hydrolyzes and transesterifies the long-chain OXPCs.

Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation.

PubMed

Goyal, J; Wang, K; Liu, M; Subbaiah, P V

1997-06-27

Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.

Involvement of lysosomal dysfunction in silver nanoparticle-induced cellular damage in A549 human lung alveolar epithelial cells.

PubMed

Miyayama, Takamitsu; Matsuoka, Masato

2016-01-01

While silver nanoparticles (AgNPs) are widely used in consumer and medical products, the mechanism by which AgNPs cause pulmonary cytotoxicity is not clear. AgNP agglomerates are found in endo-lysosomal structures within the cytoplasm of treated cells. In this study, the functional role of lysosomes in AgNP-induced cellular damage was examined in A549 human lung alveolar epithelial cells. We evaluated the intracellular distribution of AgNPs, lysosomal pH, cellular viability, Ag dissolution, and metallothionein (MT) mRNA levels in AgNP-exposed A549 cells that were treated with bafilomycin A1, the lysosomal acidification inhibitor. Exposure of A549 cells to citrate-coated AgNPs (20 nm diameter) for 24 h induced cellular damage and cell death at 100 and 200 μg Ag/ml, respectively. Confocal laser microscopic examination of LysoTracker-stained cells showed that AgNPs colocalized with lysosomes and their agglomeration increased in a dose-dependent manner (50-200 μg Ag/ml). In addition, the fluorescence signals of LysoTracker were reduced following exposure to AgNPs, suggesting the elevation of lysosomal pH. Treatment of A549 cells with 200 nM bafilomycin A1 and AgNPs (50 μg Ag/ml) further reduced the fluorescence signals of LysoTracker. AgNP-induced cell death was also increased by bafilomycin A1 treatment. Finally, treatment with bafilomycin A1 suppressed the dissolution of Ag and decreased the mRNA expression levels of MT-I and MT-II following exposure to AgNPs. The perturbation of lysosomal pH by AgNP exposure may play a role in AgNP agglomeration and subsequent cellular damage in A549 cells.

LPCAT1 controls phosphate homeostasis in a zinc-dependent manner

PubMed Central

Kisko, Mushtak; Bouain, Nadia; Safi, Alaeddine; Medici, Anna; Akkers, Robert C; Secco, David; Fouret, Gilles; Krouk, Gabriel; Aarts, Mark GM; Busch, Wolfgang

2018-01-01

All living organisms require a variety of essential elements for their basic biological functions. While the homeostasis of nutrients is highly intertwined, the molecular and genetic mechanisms of these dependencies remain poorly understood. Here, we report a discovery of a molecular pathway that controls phosphate (Pi) accumulation in plants under Zn deficiency. Using genome-wide association studies, we first identified allelic variation of the Lyso-PhosphatidylCholine (PC) AcylTransferase 1 (LPCAT1) gene as the key determinant of shoot Pi accumulation under Zn deficiency. We then show that regulatory variation at the LPCAT1 locus contributes significantly to this natural variation and we further demonstrate that the regulation of LPCAT1 expression involves bZIP23 TF, for which we identified a new binding site sequence. Finally, we show that in Zn deficient conditions loss of function of LPCAT1 increases the phospholipid Lyso-PhosphatidylCholine/PhosphatidylCholine ratio, the expression of the Pi transporter PHT1;1, and that this leads to shoot Pi accumulation. PMID:29453864

mTor Regulates Lysosomal ATP-sensitive Two-Pore Na+ Channel to Adapt to Metabolic State

PubMed Central

Navarro, Betsy; Seo, Young-jun; Aranda, Kimberly; Shi, Lucy; Battaglia-Hsu, Shyuefang; Nissim, Itzhak; Clapham, David E.; Ren, Dejian

2014-01-01

SUMMARY Survival in the wild requires organismal adaptations to the availability of nutrients. Endosomes and lysosomes are key intracellular organelles that couple nutrition and metabolic status to cellular responses, but how they detect cytosolic ATP levels is not well understood. Here we identify an endolysosomal ATP-sensitive Na+ channel (lysoNaATP). The channel is a complex formed by Two-Pore Channels (TPC1 and TPC2), ion channels previously thought to be gated by nicotinic acid adenine dinucleotide phosphate (NAADP), and the mammalian target of rapamycin (mTOR). The channel complex detects nutrient status, becomes constitutively open upon nutrient removal and mTOR translocation off the lysosomal membrane, and controls the lysosome's membrane potential, pH stability, and the amino acid homeostasis. Mutant mice lacking lysoNaATP have much reduced exercise endurance after fasting. Thus, TPCs are a new ion channel family that couple the cell's metabolic state to endolysosomal function and are crucial for physical endurance during food restriction. PMID:23394946

Cloning and expression of a novel lysophospholipase which structurally resembles lecithin cholesterol acyltransferase.

PubMed

Taniyama, Y; Shibata, S; Kita, S; Horikoshi, K; Fuse, H; Shirafuji, H; Sumino, Y; Fujino, M

1999-04-02

Lecithin cholesterol acyltransferase (LCAT) is the key enzyme in the esterification of plasma cholesterol and in the reverse cholesterol transport on high-density lipoprotein (HDL). We have found a novel LCAT-related gene among differentially expressed cDNA fragments between two types of foam cells derived from THP-1 cells, which are different in cholesterol efflux ability, using a subtractive PCR technique. The deduced 412-amino-acid sequence has 49% amino acid sequence similarity with human LCAT. In contrast to the liver-specific expression of LCAT, mRNA expression of the gene was observed mainly in peripheral tissues including kidney, placenta, pancreas, testis, spleen, heart, and skeletal muscle. The protein exists in human plasma and is probably associated with HDL. Moreover, we discovered that the recombinant protein hydrolyzed lysophosphatidylcholine (lysoPC), a proatherogenic lipid, to glycerophosphorylcholine and a free fatty acid. We have therefore named this novel enzyme LCAT-like lysophospholipase (LLPL), through which a new catabolic pathway for lysoPC on lipoproteins could be elucidated. Copyright 1999 Academic Press.

Effects of garlic extract on platelet aggregation: a randomized placebo-controlled double-blind study.

PubMed

Morris, J; Burke, V; Mori, T A; Vandongen, R; Beilin, L J

1995-01-01

1. Studies of the effects of garlic on platelet aggregation have produced inconsistent results possibly related to variations in study design and in the garlic preparations used. 2. The present study examined the effects on platelet aggregation and serum thromboxane and lyso-platelet activating factor, of feeding garlic extract to healthy men using a placebo-controlled, double-blind design. The effects of the same garlic preparation on platelet aggregation in vitro were also investigated. 3. There were no significant differences in platelet aggregation with adenosine diphosphate, platelet activating factor (PAF) or collagen according to treatment group. Serum thromboxane and lysoPAF also showed no change related to garlic supplements. 4. In vitro aggregation with collagen decreased linearly with increasing amounts of garlic extract, but concentrations were higher than those attainable in vivo. Gastrointestinal side effects prevented the use of higher doses of garlic which must be considered to be pharmacological as they exceed changes achievable by dietary modification.

RED BLOOD CELL STORAGE LESION

PubMed Central

Kor, Daryl J.; Van Buskirk, Camille M; Gajic, Ognjen

2009-01-01

The past two decades have witnessed increased scrutiny regarding efficacy and risk of the once unquestioned therapy of red blood cell (RBC) transfusion. Simultaneously, a variety of changes have been identified within the RBC and storage media during RBC preservation that are correlated with reduced tissue oxygenation and transfusion-associated adverse effects. These alterations are collectively termed the storage lesion and include extensive biochemical, biomechanical, and immunologic changes involving cells of diverse origin. Time-dependent falls is 2,3-diphosphoglycerate, intracellular RBC adenosine triphosphate, and nitric oxide have been shown to impact RBC deformability and delivery of oxygen to the end-organ. The accumulation of biologic response modifiers such as soluble CD40 ligand (sCD40L), lyso-phosphatidylcholine (lyso-PC), and Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) have been associated with altered recipient immune function as well. This review will address the alterations occurring within the RBC and storage media during RBC preservation and will address the potential clinical consequence thereof.

PROGRAMMED CELL DEATH IN EXTRAOCULAR MUSCLE TENDON/SCLERA PRECURSORS

EPA Science Inventory

Abstract

Purpose: This study was designed to examine the occurrence of natural cell death in the periocular mesenchyme of mouse embryos.

Methods: Vital staining with LysoTracker Red and Nile blue sulphate as well as terminal nick end labeling (TUNEL) were utiliz...

Spatial resolution properties of digital autoradiography systems for pre-clinical alpha particle imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tanguay, Jesse; Benard, Francois; Celler, Anna; Ruth, Thomas; Schaffer, Paul

2017-03-01

Attaching alpha-emitting radionuclides to cancer-targeting agents increases the anti-tumor effects of targeted cancer therapies. The success of alpha therapy for treating bone metastases has increased interest in using targeted alpha therapy (TAT) to treat a broad spectrum of metastatic cancers. Estimating radiation doses to targeted tumors, including small (<250 μm) clusters of cancer cells, and to non-targeted tissues is critical in the pre-clinical development of TATs. However, accurate quantification of heterogeneous distributions of alpha-emitters in small metastases is not possible with existing pre-clinical in-vivo imaging systems. Ex-vivo digital autoradiography using a scintillator in combination with an image intensifier and a charged coupled device (CCD) has gained interest for pre-clinical ex-vivo alpha particle imaging. We present a simulation-based analysis of the fundamental spatial resolution limits of digital autoradiography systems. Spatial resolution was quantified in terms of the modulation transfer function (MTF) and Wagner's equivalent aperture. We modeled systems operating in either particle-counting (PC) or energy-integrating (EI) mode using a cascaded systems approach that accounts for: 1) the stopping power of alpha particles; 2) the distance alpha particles travel within the scintillator; 3) optical blur, and; 4) binning in detector elements. We applied our analysis to imaging of astatine-211 using an LYSO scintillator with thickness ranging from 10 μm to 20 μm. Our analysis demonstrates that when these systems are operated in particle-counting mode with a centroid-calculation algorithm, the effective apertures of 35 μm can be achieved, which suggests that digital autoradiography may enable quantifying the uptake of alpha emitters in tumors consisting of a few cancer cells. Future work will investigate the image noise and energy-resolution properties of digital autoradiography systems.

QUANTITATIVE FLUORESCENCE OF 5-FU-TREATED FETAL RAT LIMBS USING CONFOCAL LASER SCANNING MICROSCOPY AND LYSOTRACKER RED

EPA Science Inventory

Background: LysoTracker Red (LT) is a paraformaldehyde fixable probe that concentrates into acidic compartments of cells and tissues. After cell death a high level of lysosomal activity (acidic enzyme) is expressed resulting from phagocytosis of apoptotic bodies by neighboring ce...

Evaluation of a lysostaphin-fusion protein as a dry-cow therapy for Staphylococcus aureus mastitis in dairy cattle

USDA-ARS?s Scientific Manuscript database

This study evaluated the efficacy of a lysostaphin-fusion protein (Lyso-PTD) as a dry-cow therapy for the treatment of experimentally-induced chronic, subclinical Staphylococcus aureus mastitis. Twenty-two Holstein dairy cows were experimentally infected with Staph. aureus in a single pair of diago...

Lipid oxidation in base algae oil and water-in-algae oil emulsion: Impact of natural antioxidants and emulsifiers.

PubMed

Chen, Bingcan; Rao, Jiajia; Ding, Yangping; McClements, David Julian; Decker, Eric Andrew

2016-07-01

The impact of natural hydrophilic antioxidants, metal chelators, and hydrophilic antioxidant/metal chelator mixture on the oxidative stability of base algae oil and water-in-algae oil emulsion was investigated. The results showed that green tea extract and ascorbic acid had greatest protective effect against algae oil oxidation and generated four day lag phase, whereas rosmarinic acid, grape seed extract, grape seed extract polymer, deferoxamine (DFO), and ethylenediaminetetraacetic acid (EDTA) had no significant protective effect. Besides, there was no synergistic effect observed between natural antioxidants and ascorbic acid. The emulsifiers are critical to the physicochemical stability of water-in-algae oil emulsions. Polyglycerol polyricinoleate (PGPR) promoted the oxidation of emulsion. Conversely, the protective effect on algae oil oxidation was appreciated when defatted soybean lecithin (PC 75) or defatted lyso-lecithin (Lyso-PC) was added. The role of hydrophilic antioxidants in emulsion was similar to that in algae oil except EDTA which demonstrated strong antioxidative effect in emulsion. The results could provide information to build up stable food products containing polyunsaturated fatty acids (PUFA). Copyright © 2016 Elsevier Ltd. All rights reserved.

High-energy radiographic imaging performance of LYSO

DOE PAGES

Smalley, Duane; Duke, Dana; Webb, Timothy; ...

2018-05-23

Here, a comprehensive comparison of the dominant sources of radiation-induced blur for radiographic imaging system performance is made. End-point energies of 6, 10, 15, and 20 MeV bremsstrahlung photon radiation produced at the Los Alamos National Laboratory Microtron facility were used to examine the performance of large-panel cerium-doped lutetium yttrium silicon oxide (LYSO:Ce) scintillators 3, 5 and 10 mm thick. The system resolution was measured and compared between the various end-point energies and scintillator thicknesses. Contrary to expectations, it is found that there was only a minor dependence of system resolution on scintillator thickness or beam end-point energy. This indicatesmore » that increased scintillator thickness does not have a dramatic effect on system performance. The data are then compared to Geant4 simulations to assess contributions to the system performance through the examination of modulation transfer functions. It was determined that the low-frequency response of the system is dominated by the radiation-induced signal, while the higher-frequency response of the system is dominated by the optical imaging of the scintillation emission.« less

Improvement of light extraction of LYSO scintillator by using a combination of self-assembly of nanospheres and atomic layer deposition.

PubMed

Zhu, Zhichao; Liu, Bo; Zhang, Haifeng; Ren, Weina; Cheng, Chuanwei; Wu, Shuang; Gu, Mu; Chen, Hong

2015-03-23

The self-assembled monolayer periodic array of polystyrene spheres conformally coated with TiO₂ layer using atomic layer deposition is designed to obtain a further enhancement of light extraction for LYSO scintillator. The maximum enhancement is 149% for the sample with polystyrene spheres conformally coated with TiO₂ layer, while the enhancement is only 76% for the sample with only polystyrene spheres. Such further enhancement could be contributed from the additional modes forming by TiO₂ layer due to its high refractive index, which can be approved by the simulation of electric field distribution. The experimental results are agreement with the simulated results. Furthermore, the prepared structured layer exhibits an excellent combination with the surface of scintillator, which is in favor of the practical application. Therefore, it is safely concluded that the combination of self-assembly method and atomic layer deposition is a promising approach to obtain a significant enhancement of light extraction for a large area. This method can be extended to many other luminescent materials and devices.

The loss of plasma membrane lysopip and an increase of PIP sub 2 result from treatment of carrot cells with fungal enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Q.; Boss, W.F.

1989-04-01

The plasma membranes of carrot cells grown in suspension culture are enriched with PIP, lysoPIP, and PIP{sub 2}. To determine whether or not these lipids are involved in signal transduction, we have challenged the cells with a mixture of fungal cellulases, Driselase, and monitored the changes in the phosphoinositides and in the phosphoinositide kinase activity. With cell prelabeled with ({sup 3}H)inositol, two major changes are observed: (1) lysoPIP decreases 30% compared to the sorbitol control and (2) PIP{sub 2} doubles. There is no increase in IP, IP{sub 2}, or IP{sub 3}. In vitro phosphorylation studies using ({gamma}-{sup 32}P)ATP indicate thatmore » the increase in PIP{sub 2} is due in part to activation of the PIP kinase. These data suggest that the role of the polyphosphoinositides in signal transduction in plants may involve activation of the PIP kinase and/or activation of A type phospholipases rather than C type phospholipases.« less

Circulating Hemocytes from Larvae of the Japanese Rhinoceros Beetle Allomyrina dichotoma (Linnaeus) (Coleoptera: Scarabaeidae) and the Cellular Immune Response to Microorganisms.

PubMed

Hwang, Sejung; Bang, Kyeongrin; Lee, Jiae; Cho, Saeyoull

2015-01-01

Hemocytes of the last larva of the Japanese rhinoceros beetle A. dichotoma (Linnaeus) (Coleoptera: Scarabaeidae) were classified as granulocytes, plasmatocytes, oenocytoids, spherulocytes, prohemocytes, and adipohemocytes. Among these cell types, only the granulocytes became immunologically activated with obvious morphological changes, displaying large amoeba-like, lobopodia-like, and fan-like structures. In addition, their cytoplasmic granules became larger and greatly increased in number. To explore whether these granules could be immunologically generated as phagosomes, total hemocytes were stained with LysoTracker. Greater than 90% of the granulocytes retained the LysoTracker dye at 4 h post-bacterial infection. In flow cytometry analysis, the red fluorescent signal was highly increased at 4 h post-bacterial infection (60.36%) compared to controls (5.08%), as was confirmed by fluorescent microscopy. After 12 h post-infection, these signals returned to basal levels. The uptake of pathogens by granulocytes rapidly triggered the translocation of the microtubule-associated protein 1 light chain 3 alpha (LC3) to the phagosome, which may result in enhanced pathogen killing.

Circulating Hemocytes from Larvae of the Japanese Rhinoceros Beetle Allomyrina dichotoma (Linnaeus) (Coleoptera: Scarabaeidae) and the Cellular Immune Response to Microorganisms

PubMed Central

Hwang, Sejung; Bang, Kyeongrin; Lee, Jiae; Cho, Saeyoull

2015-01-01

Hemocytes of the last larva of the Japanese rhinoceros beetle A. dichotoma (Linnaeus) (Coleoptera: Scarabaeidae) were classified as granulocytes, plasmatocytes, oenocytoids, spherulocytes, prohemocytes, and adipohemocytes. Among these cell types, only the granulocytes became immunologically activated with obvious morphological changes, displaying large amoeba-like, lobopodia-like, and fan-like structures. In addition, their cytoplasmic granules became larger and greatly increased in number. To explore whether these granules could be immunologically generated as phagosomes, total hemocytes were stained with LysoTracker. Greater than 90% of the granulocytes retained the LysoTracker dye at 4 h post-bacterial infection. In flow cytometry analysis, the red fluorescent signal was highly increased at 4 h post-bacterial infection (60.36%) compared to controls (5.08%), as was confirmed by fluorescent microscopy. After 12 h post-infection, these signals returned to basal levels. The uptake of pathogens by granulocytes rapidly triggered the translocation of the microtubule-associated protein 1 light chain 3 alpha (LC3) to the phagosome, which may result in enhanced pathogen killing. PMID:26030396

High-energy radiographic imaging performance of LYSO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smalley, Duane; Duke, Dana; Webb, Timothy

Here, a comprehensive comparison of the dominant sources of radiation-induced blur for radiographic imaging system performance is made. End-point energies of 6, 10, 15, and 20 MeV bremsstrahlung photon radiation produced at the Los Alamos National Laboratory Microtron facility were used to examine the performance of large-panel cerium-doped lutetium yttrium silicon oxide (LYSO:Ce) scintillators 3, 5 and 10 mm thick. The system resolution was measured and compared between the various end-point energies and scintillator thicknesses. Contrary to expectations, it is found that there was only a minor dependence of system resolution on scintillator thickness or beam end-point energy. This indicatesmore » that increased scintillator thickness does not have a dramatic effect on system performance. The data are then compared to Geant4 simulations to assess contributions to the system performance through the examination of modulation transfer functions. It was determined that the low-frequency response of the system is dominated by the radiation-induced signal, while the higher-frequency response of the system is dominated by the optical imaging of the scintillation emission.« less

Highly improved operation of monolithic BGO-PET blocks

NASA Astrophysics Data System (ADS)

Gonzalez-Montoro, A.; Sanchez, F.; Majewski, S.; Zanettini, S.; Benlloch, J. M.; Gonzalez, A. J.

2017-11-01

In PET scanners both scintillation crystals and photosensors are key components defining the system's performance and cost. Original PET systems used BGO or NaI(Tl) scintillators but achieved limited performance due to its slow decay and relatively low light output. Moreover, NaI(Tl) has low stopping power for 511 keV annihilation photons. In this study we report the possibility to reintroduce BGO crystals, and in particular in the form of monolithic blocks, especially suitable for low-dose large-size PET scanners, offering significantly improved sensitivity at a highly reduced cost compared to LYSO type fast scintillators. We have studied the performance of a monolithic BGO block as large as 50 × 50 × 15 mm3 with black-painted lateral walls to reduce lights spread, enabling accurate photon depth of interaction (DOI) measurements. A directional optical layer, called retro-reflector, was coupled to the entrance face bouncing back the scintillation light in the direction of the emission source and, therefore, adding to the light signal while preserving the narrow light cone distribution. Four configurations namely 12 × 12 and 16 × 16 SiPM arrays (3 mm × 3 mm each) as photosensors, with or without a nanopattern treatment at the crystal exit face, have been studied. This structure consisted of a thin layer of a specific high refractive index material shaped with a periodic nanopattern, increasing the scintillation light extraction. The readout returned information for each SiPM row and column, characterizing the X-Y light distribution projections. We have studied the detector spatial resolution using collimated 22Na sources at normal incidence. The DOI resolution was evaluated using collimated gamma beams with lateral incidence. The overall best detector performance was obtained for the 16× 16 SiPM array offering higher readout granularity. We have determined the spatial resolution for 3 separated DOI layers, obtaining the best results for the DOI region near to the photosensor.

Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards.

PubMed

Sato, K; Shidahara, M; Watabe, H; Watanuki, S; Ishikawa, Y; Arakawa, Y; Nai, Y H; Furumoto, S; Tashiro, M; Shoji, T; Yanai, K; Gonda, K

2016-01-21

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards

NASA Astrophysics Data System (ADS)

Sato, K.; Shidahara, M.; Watabe, H.; Watanuki, S.; Ishikawa, Y.; Arakawa, Y.; Nai, YH; Furumoto, S.; Tashiro, M.; Shoji, T.; Yanai, K.; Gonda, K.

2016-01-01

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10min after intravenous injection of 18F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415kcps at 14.6MBq ml-1. The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

Nicotiana benthamiana α-galactosidase A1.1 can functionally complement human α-galactosidase A deficiency associated with Fabry disease.

PubMed

Kytidou, Kassiani; Beekwilder, Jules; Artola, Marta; van Meel, Eline; Wilbers, Ruud H P; Moolenaar, Geri F; Goosen, Nora; Ferraz, Maria J; Katzy, Rebecca; Voskamp, Patrick; Florea, Bogdan I; Hokke, Cornelis H; Overkleeft, Herman S; Schots, Arjen; Bosch, Dirk; Pannu, Navraj; Aerts, Johannes M F G

2018-04-19

α-Galactosidases (EC 3.2.1.22) are retaining glycosidases that cleave terminal α-linked galactose residues from glycoconjugate substrates. α-Galactosidases take part in the turnover of cell wall-associated galactomannans in plants and in the lysosomal degradation of glycosphingolipids in animals. Deficiency of human α-galactosidase A (α-Gal A) causes Fabry disease (FD), a heritable, X-linked lysosomal storage disorder, characterized by accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3). Current management of FD involves enzyme-replacement therapy (ERT). An activity-based probe (ABP) covalently labeling the catalytic nucleophile of α-Gal A has been previously designed to study α-galactosidases for use in FD therapy. Here, we report that this ABP labels proteins in Nicotiana benthamiana leaf extracts, enabling the identification and biochemical characterization of an N. benthamiana α-galactosidase we name here A1.1 (gene accession GJZM-1660). The transiently overexpressed and purified enzyme was a monomer lacking N-glycans and was active toward 4-methylumbelliferyl-α-D-galactopyranoside substrate (Km = 0.17 mM) over a broad pH range. A1.1 structural analysis by X-ray crystallography revealed marked similarities with human α-Gal A, even including A1.1's ability to hydrolyze Gb3 and lysoGb3, which are not endogenous in plants. Of note, A1.1 uptake into FD fibroblasts reduced the elevated lysoGb3 levels in these cells, consistent with A1.1 delivery to lysosomes as revealed by confocal microscopy. The ease of production and the features of A1.1, such as stability over a broad pH range, combined with its capacity to degrade glycosphingolipid substrates, warrant further examination of its value as a potential therapeutic agent for ERT-based FD management. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Revealing anti-inflammation mechanism of water-extract and oil of forsythiae fructus on carrageenan-Induced edema rats by serum metabolomics.

PubMed

Yuan, An; Gong, Lihong; Luo, Lin; Dang, Jue; Gong, Xiaohong; Zhao, Mengjie; Li, Yan; Li, Yunxia; Peng, Cheng

2017-11-01

Forsythiae Fructus is an important Chinese medicine which shows a significant effect against inflammation. This study aimed to investigate the preventive anti-inflammation mechanism of Forsythiae Fructus by serum metabolomics strategy and compare the difference of the metabolism pathways between Forsythia extract and Forsythia oil in rat. Four groups (control group, model group, Forsythia extract group and Forsythia oil group) were orally administered 10mL/kg 0.5% Tween 80 solution, 10mL/kg 0.5% Tween 80 solution, 5g/kg Forsythia extract and 0.48mL/kg Forsythia oil respectively. 30min after drug administration, rat acute inflammation was induced by subcutaneous injection of carrageenan in the right paw in model group, Forsythia extract group and Forsythia oil group. After being administered Forsythia extract and Forsythia oil, the percentage of rat paw edema was significantly decreased (P<0.05) compared with model group. Metabolomics based on UPLC-Q-TOF-MS/MS was used to analyze the collected serum sample. Multivariate analysis was established for metabolomics analysis. According to Principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) results, four groups were clearly separated. And thirteen alterative biomarkers were identified in the serum, namely PC (19:0/0:0), LysoPC (20:0), LysoPC (20:1), LysoPC (17:0), Sphingosine, Linoleic acid, 3R-hydroxy-butanoic acid (3-HB), 2-hydroxyhexadecanoic acid, Lactic acid, L-Threonine, L-Leucine, Maleic acid, Adipic acid. The change of biomarkers suggested that Forsythia extract affected Linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, Sphingolipid metabolism and Glycerophospholipid metabolism. Forsythia oil affected Sphingolipid metabolism and Glycerophospholipid metabolism. It indicated that Forsythia extract and Forsythia oil both showed significant preventive anti-inflammatory effect through acting on different metabolism pathways. Moreover, efficacy mechanism of Forsythiae Fructus could recover metabolites disturb in the body through affecting particular drug targets associated with the inflammatory pathway. Copyright © 2017. Published by Elsevier Masson SAS.

Increased resting cerebral blood flow in adult Fabry disease: MRI arterial spin labeling study.

PubMed

Phyu, Po; Merwick, Aine; Davagnanam, Indran; Bolsover, Fay; Jichi, Fatima; Wheeler-Kingshott, Claudia; Golay, Xavier; Hughes, Deralynn; Cipolotti, Lisa; Murphy, Elaine; Lachmann, Robin H; Werring, David John

2018-04-17

To assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3. This cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using semiautomated software. We measured CBF in regions of interest in whole-brain, WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3. The mean age (% male) for FD and healthy controls was 42.2 years (44%) and 37.1 years (50%). Mean whole-brain CBF was 27.56 mL/100 mL/min (95% confidence interval [CI] 23.78-31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08-24.70) for healthy controls, p = 0.03. In WM, CBF was higher in FD (22.42 mL/100 mL/min [95% CI 17.72-27.12] vs 16.25 mL/100 mL/min [95% CI 14.03-18.48], p = 0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI 36.85-43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57-42.35], p = 0.38). In patients with FD with WMH (n = 20), whole-brain CBF correlated with WMH volume ( r = 0.59, p = 0.006), not with plasma lyso-Gb3. In FD, resting CBF is increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that cerebral perfusion changes might contribute to, or result from, WM injury. © 2018 American Academy of Neurology.

The triglyceride-lowering effect of supplementation with dual probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032: Reduction of fasting plasma lysophosphatidylcholines in nondiabetic and hypertriglyceridemic subjects.

PubMed

Ahn, H Y; Kim, M; Ahn, Y-T; Sim, J-H; Choi, I-D; Lee, S-H; Lee, J H

2015-08-01

This study evaluated the triglyceride (TG)-lowering effects of consuming dual probiotic strains of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 on the fasting plasma metabolome. A randomized, double-blind, placebo-controlled study was conducted on 92 participants with hypertriglyceridemia but without diabetes. Over a 12-week testing period, the probiotic group consumed 2 g of powder containing 5 × 10(9) colony-forming units (cfu) of L. curvatus HY7601 and 5 × 10(9) cfu of L. plantarum KY1032 each day, whereas the placebo group consumed the same product without probiotics. Fasting plasma metabolomes were profiled using UPLC-LTQ-Orbitrap MS. After 12 weeks of treatment, the probiotic group displayed a 20% reduction (p = 0.001) in serum TGs and 25% increases (p=0.001) in apolipoprotein A-V (apoA-V). At the 12-week follow-up assessment, the following 11 plasma metabolites were significantly reduced in the probiotic group than the placebo group: palmitoleamide, palmitic amide, oleamide, and lysophosphatidyl choline (lysoPC) containing C14:0, C16:1, C16:0, C17:0, C18:3, C18:2, C18:1, and C20:3. In the probiotic group, changes (▵) in TG were negatively correlated with ▵ apoA-V, which was positively correlated with ▵ FFA. In addition, ▵ FFA was strongly and positively correlated with ▵ lysoPCs in the probiotic group but not the placebo group. The triglyceride-lowering effects of probiotic supplementation, partly through elevated apoA-V, in borderline to moderate hypertriglyceridemic subjects showed reductions in plasma metabolites, fatty acid primary amides and lysoPCs (NCT02215694; http://www.clinicaltrials.gov). Clinical trials: NCT02215694; http://www.clinicaltrials.gov. Copyright © 2015 Elsevier B.V. All rights reserved.

Global and targeted metabolomics of esophageal squamous cell carcinoma discovers potential diagnostic and therapeutic biomarkers.

PubMed

Xu, Jing; Chen, Yanhua; Zhang, Ruiping; Song, Yongmei; Cao, Jianzhong; Bi, Nan; Wang, Jingbo; He, Jiuming; Bai, Jinfa; Dong, Lijia; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

2013-05-01

Diagnostic and therapeutic biomarkers useful for esophageal squamous cell carcinoma (ESCC) have the ability to increase the long term survival of cancer patients. A metabolomics study, using plasma from four groups including ESCC patients before, during, and after chemoradiotherapy (CRT) and healthy controls, was originally carried out by LC-MS to determine global alterations in the metabolic profiles and find biomarkers potentially applicable to diagnosis and monitoring treatment effects. It is worth pointing out that a clear clustering and separation of metabolic data from the four groups was observed, which indicated that disease status and treatment intervention resulted in specific metabolic perturbations in the patients. A series of metabolites were found to be significantly altered in ESCC patients versus healthy controls and in pre- versus post-treatment patients based on multivariate statistical data analysis (MVDA). To further validate the reliability of these potential biomarkers, an independent validation was performed by using the selected reaction monitoring (SRM) based targeted approach. Finally, 18 most significantly altered plasma metabolites in ESCC patients, relative to healthy controls, were tentatively identified as lysophosphatidylcholines (lysoPCs), fatty acids, l-carnitine, acylcarnitines, organic acids, and a sterol metabolite. The classification performance of these metabolites were analyzed by receiver operating characteristic (ROC)(1) analysis and a biomarker panel was generated. Together, biological significance of these metabolites was discussed. Comparison between pre- and post-treatment patients generated 11 metabolites as potential therapeutic biomarkers that were tentatively identified as amino acids, acylcarnitines, and lysoPCs. Levels of three of these (octanoylcarnitine, lysoPC(16:1), and decanoylcarnitine) were closely correlated with treatment effect. Moreover, variation of these three potential biomarkers was investigated over the treatment course. The results suggest that these biomarkers may be useful in diagnosis, as well as in monitoring therapeutic responses and predicting outcomes of the ESCC.

Profiling membrane glycerolipids during γ-ray-induced membrane injury.

PubMed

Zheng, Guowei; Li, Weiqi

2017-11-15

γ-rays are high-energy radiation that cause a range of random injuries to plant cells. Most studies on this issue have focused on γ-ray-induced nucleotide damage and the production of reactive oxygen species in cells, so little is known about the glycerolipid metabolism during γ-rays induced membrane injury. Using an ESI-MS/MS-based lipidomic method, we analysed the lipidome changes in wild-type and phospholipase D (PLD)δ- and α1-deficient Arabidopsis after γ-ray treatment. The aim of this study was to investigate the role of PLD-mediated glycerolipid metabolism in γ-ray-induced membrane injury. The ion leakage of Arabidopsis leaves after 2885-Gy γ-ray treatment was less than 10%. High does γ-ray treatment could induce the accumulation of intracellular reactive oxygen species (ROS). Inhibition of PLDα1 caused severe lipid degradation under γ-ray treatment. γ-ray-induced glycerolipid degradation mostly happened in chloroplastidic lipids, rather than extraplastidic ones. The levels of lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) were maintained in the WS ecotypes during γ-ray treatments, while increased significantly in the Col ecotype treated with 1100 Gy. After 210- and 1100-Gy γ-ray treatments, the level of lysophosphatidylglycerol (lysoPG) decreased significantly in the four genotypes of Arabidopsis. γ-ray-induced membrane injury may occur via an indirect mechanism. The degradation of distinct lipids is not synchronous, and that interconversions among lipids can occur. During γ-ray-induced membrane injury, the degradation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) may be mediated by PLDζ1 or phospholipase A1. The degradation of phosphatidylglycerol was not mediated by PLA, PLDδ or PLDα1, but by phospholipase C or other PLDs. γ-rays can decrease the double-bond index and increase the acyl chain length in membrane lipids, which may make membranes more rigid and further cause injury in membranes.

Characterization of blue sensitive 3 × 3 mm2 SiPMs and their use in PET

NASA Astrophysics Data System (ADS)

Schneider, F. R.; Ganka, T. R.; Şeker, G.; Engelmann, E.; Renker, D.; Paul, S.; Hansch, W.; Ziegler, S. I.

2014-07-01

Three types of SiPMs (Silicon Photomultiplier) with an active area of 3 × 3 mm2 manufactured by KETEK with cell sizes of 50 μm (PM3350), 60 μm (PM3360) and 75 μm (PM3375) have been investigated. All devices have optical trenches in between the cells to suppress direct crosstalk. Their breakdown voltage at room temperature is about 23 V and the gain at an overvoltage Uover = 3.4 V is > 6·106. The temperature variation of the breakdown voltage is < 16 mV/K and the gain coefficient with temperature is < 1% for overvoltages Uover > 1.7 V. The photodetection efficiency (PDE) at 420 nm and Uover = 3.4 V is 51% for PM3350, 55% for PM3360 and 58% for PM3375. At Uover = 3.4 V, the dark count rates are < 470 kHz/mm2 at 20°C and the afterpulse probability is < 9% at -20°C. Single photon timing of 230 ps FWHM for PM3350, 320 ps for PM3360 and 375 ps for PM3375 have been achieved. To test their performance in PET (Positron Emission Tomography), energy spectra of 22Na with LYSO (Lutetium Yttrium Oxyorthosilicate, Lu1.8Y.2SiO5:Ce) and GAGG (Gadolinium Aluminum Gallium Garnet, Gd3(Ga,Al)5O15:Ce) scintillators with a size of 2 × 2×6 mm3 have been acquired. The saturation corrected energy resolution (FHWM) at 511 keV was with LYSO 12.3% for PM3350, 13.4% for PM3360, 12.4% for PM3375 and with GAGG 10.8% for PM3350. Coincidence timing (FWHM) at Uover = 3.4 V was with LYSO 174 ps for PM3350, 178 ps for PM3360, 157 ps for PM3375 and with GAGG 430 ps for PM3350.

Investigation of the imaging characteristics of the ALBIRA II small animal PET system for 18F, 68Ga and 64Cu.

PubMed

Attarwala, Ali Asgar; Karanja, Yvonne Wanjiku; Hardiansyah, Deni; Romanó, Chiara; Roscher, Mareike; Wängler, Björn; Glatting, Gerhard

2017-06-01

In this study the performance characteristics of the Albira II PET sub-system and the response of the system for the following radionuclides 18 F, 68 Ga and 64 Cu was analyzed. The Albira II tri-modal system (Bruker BioSpin MRI GmbH, Ettlingen, Germany) is a pre-clinical device for PET, SPECT and CT. The PET sub-system uses single continuous crystal detectors of lutetium yttrium orthosilicate (LYSO). The detector assembly consists of three rings of 8 detector modules. The transaxial field of view (FOV) has a diameter of 80mm and the axial FOV is 148mm. A NEMA NU-4 image quality phantom (Data Spectrum Corporation, Durham, USA) having five rods with diameters of 1, 2, 3, 4 and 5mm and a uniform central region was used. Measurements with 18 F, 68 Ga and 64 Cu were performed in list mode acquisition over 10h. Data were reconstructed using a maximum-likelihood expectation-maximization (MLEM) algorithm with iteration numbers between 5 and 50. System sensitivity, count rate linearity, convergence and recovery coefficients were analyzed. The sensitivities for the entire FOV (non-NEMA method) for 18 F, 68 Ga and 64 Cu were (3.78±0.05)%, (3.97±0.18)% and (3.79±0.37)%, respectively. The sensitivity based on the NEMA protocol using the 22 Na point source yielded (5.53±0.06)%. Dead-time corrected true counts were linear for activities ≤7MBq ( 18 F and 68 Ga) and ≤17MBq ( 64 Cu) in the phantom. The radial, tangential and axial full widths at half maximum (FWHMs) were 1.52, 1.47 and 1.48mm. Recovery coefficients for the uniform region with a total activity of 8MBq in the phantom were (0.97±0.05), (0.98±0.06), (0.98±0.06) for 18 F, 68 Ga and 64 Cu, respectively. The Albira II pre-clinical PET system has an adequate sensitivity range and the system linearity is suitable for the range of activities used for pre-clinical imaging. Overall, the system showed a favorable image quality for pre-clinical applications. Copyright © 2017. Published by Elsevier GmbH.

Neural Responses to Injury: Prevention, Protection, and Repair. Neurochemical Protection of the Brain, Neural Plasticity and Repair

DTIC Science & Technology

1998-10-01

can be displaced by BN-52021, a terpenoid extracted from the leaf of the Ginkgo biloba tree, which binds preferentially to the synaptosomal site...lyso PAF (22-24). Presynaptic membranes display PAF binding that can be displaced by BN 52021, a terpenoid extracted from the leaf of the Ginkgo

Screening of phospholipase A activity and its production by new actinomycete strains cultivated by solid-state fermentation.

PubMed

Sutto-Ortiz, Priscila; Camacho-Ruiz, María de Los Angeles; Kirchmayr, Manuel R; Camacho-Ruiz, Rosa María; Mateos-Díaz, Juan Carlos; Noiriel, Alexandre; Carrière, Frédéric; Abousalham, Abdelkarim; Rodríguez, Jorge A

2017-01-01

Novel microbial phospholipases A (PLAs) can be found in actinomycetes which have been poorly explored as producers of this activity. To investigate microbial PLA production, efficient methods are necessary such as high-throughput screening (HTS) assays for direct search of PLAs in microbial cultures and cultivation conditions to promote this activity. About 200 strains isolated with selected media for actinomycetes and mostly belonging to Streptomyces (73%) and Micromonospora (10%) genus were first screened on agar-plates containing the fluorophore rhodamine 6G and egg yolk phosphatidylcholine (PC) to detect strains producing phospholipase activity. Then, a colorimetric HTS assay for general PLA activity detection (cHTS-PLA) using enriched PC (≈60%) as substrate and cresol red as indicator was developed and applied; this cHTS-PLA assay was validated with known PLAs. For the first time, actinomycete strains were cultivated by solid-state fermentation (SSF) using PC as inductor and sugar-cane bagasse as support to produce high PLA activity (from 207 to 2,591 mU/g of support). Phospholipase activity of the enzymatic extracts from SSF was determined using the implemented cHTS-PLA assay and the PC hydrolysis products obtained, were analyzed by TLC showing the presence of lyso-PC. Three actinomycete strains of the Streptomyces genus that stood out for high accumulation of lyso-PC, were selected and analyzed with the specific substrate 1,2-α-eleostearoyl- sn -glycero-3-phosphocholine (EEPC) in order to confirm the presence of PLA activity in their enzymatic extracts. Overall, the results obtained pave the way toward the HTS of PLA activity in crude microbial enzymatic extracts at a larger scale. The cHTS-PLA assay developed here can be also proposed as a routine assay for PLA activity determination during enzyme purification,directed evolution or mutagenesis approaches. In addition, the production of PLA activity by actinomycetes using SSF allow find and produce novel PLAs with potential applications in biotechnology.

Screening of phospholipase A activity and its production by new actinomycete strains cultivated by solid-state fermentation

PubMed Central

Sutto-Ortiz, Priscila; Camacho-Ruiz, María de los Angeles; Kirchmayr, Manuel R.; Camacho-Ruiz, Rosa María; Mateos-Díaz, Juan Carlos; Noiriel, Alexandre; Carrière, Frédéric; Abousalham, Abdelkarim

2017-01-01

Novel microbial phospholipases A (PLAs) can be found in actinomycetes which have been poorly explored as producers of this activity. To investigate microbial PLA production, efficient methods are necessary such as high-throughput screening (HTS) assays for direct search of PLAs in microbial cultures and cultivation conditions to promote this activity. About 200 strains isolated with selected media for actinomycetes and mostly belonging to Streptomyces (73%) and Micromonospora (10%) genus were first screened on agar-plates containing the fluorophore rhodamine 6G and egg yolk phosphatidylcholine (PC) to detect strains producing phospholipase activity. Then, a colorimetric HTS assay for general PLA activity detection (cHTS-PLA) using enriched PC (≈60%) as substrate and cresol red as indicator was developed and applied; this cHTS-PLA assay was validated with known PLAs. For the first time, actinomycete strains were cultivated by solid-state fermentation (SSF) using PC as inductor and sugar-cane bagasse as support to produce high PLA activity (from 207 to 2,591 mU/g of support). Phospholipase activity of the enzymatic extracts from SSF was determined using the implemented cHTS-PLA assay and the PC hydrolysis products obtained, were analyzed by TLC showing the presence of lyso-PC. Three actinomycete strains of the Streptomyces genus that stood out for high accumulation of lyso-PC, were selected and analyzed with the specific substrate 1,2-α-eleostearoyl-sn-glycero-3-phosphocholine (EEPC) in order to confirm the presence of PLA activity in their enzymatic extracts. Overall, the results obtained pave the way toward the HTS of PLA activity in crude microbial enzymatic extracts at a larger scale. The cHTS-PLA assay developed here can be also proposed as a routine assay for PLA activity determination during enzyme purification,directed evolution or mutagenesis approaches. In addition, the production of PLA activity by actinomycetes using SSF allow find and produce novel PLAs with potential applications in biotechnology. PMID:28695068

Plasma Metabolomics Reveal Alterations of Sphingo- and Glycerophospholipid Levels in Non-Diabetic Carriers of the Transcription Factor 7-Like 2 Polymorphism rs7903146

PubMed Central

Kirchhofer, Anna; Grallert, Harald; Krug, Susanne; Kastenmüller, Gabi; Römisch-Margl, Werner; Claussnitzer, Melina; Illig, Thomas; Heier, Margit; Meisinger, Christa; Adamski, Jerzy; Thorand, Barbara; Huth, Cornelia; Peters, Annette; Prehn, Cornelia; Heukamp, Ina; Laumen, Helmut; Lechner, Andreas; Hauner, Hans; Seissler, Jochen

2013-01-01

Aims/Hypothesis Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant. Methods Seventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subjects carrying no risk allele were submitted to intravenous glucose tolerance test and euglycemic-hyperinsulinemic clamp. Plasma samples were analysed for concentrations of 163 metabolites through targeted mass spectrometry. Results TCF7L2 risk allele carriers had a reduced first-phase insulin response and normal insulin sensitivity. Under fasting conditions, carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins (SMs), phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) species. A significant genotype effect was detected in response to challenge tests in 6 SMs (C16:0, C16:1, C18:0, C18:1, C24:0, C24:1), 5 hydroxy-SMs (C14:1, C16:1, C22:1, C22:2, C24:1), 4 lysoPCs (C14:0, C16:0, C16:1, C17:0), 3 diacyl-PCs (C28:1, C36:6, C40:4) and 4 long-chain acyl-alkyl-PCs (C40:2, C40:5, C44:5, C44:6). Discussion Plasma metabolomic profiling identified alterations of phospholipid metabolism in response to challenge tests in subjects with TCF7L2 rs7903146 genotype. This may reflect a genotype-mediated link to early metabolic abnormalities prior to the development of disturbed glucose tolerance. PMID:24205231

Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.

PubMed

Then, Cornelia; Wahl, Simone; Kirchhofer, Anna; Grallert, Harald; Krug, Susanne; Kastenmüller, Gabi; Römisch-Margl, Werner; Claussnitzer, Melina; Illig, Thomas; Heier, Margit; Meisinger, Christa; Adamski, Jerzy; Thorand, Barbara; Huth, Cornelia; Peters, Annette; Prehn, Cornelia; Heukamp, Ina; Laumen, Helmut; Lechner, Andreas; Hauner, Hans; Seissler, Jochen

2013-01-01

Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant. Seventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subjects carrying no risk allele were submitted to intravenous glucose tolerance test and euglycemic-hyperinsulinemic clamp. Plasma samples were analysed for concentrations of 163 metabolites through targeted mass spectrometry. TCF7L2 risk allele carriers had a reduced first-phase insulin response and normal insulin sensitivity. Under fasting conditions, carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins (SMs), phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) species. A significant genotype effect was detected in response to challenge tests in 6 SMs (C16:0, C16:1, C18:0, C18:1, C24:0, C24:1), 5 hydroxy-SMs (C14:1, C16:1, C22:1, C22:2, C24:1), 4 lysoPCs (C14:0, C16:0, C16:1, C17:0), 3 diacyl-PCs (C28:1, C36:6, C40:4) and 4 long-chain acyl-alkyl-PCs (C40:2, C40:5, C44:5, C44:6). Plasma metabolomic profiling identified alterations of phospholipid metabolism in response to challenge tests in subjects with TCF7L2 rs7903146 genotype. This may reflect a genotype-mediated link to early metabolic abnormalities prior to the development of disturbed glucose tolerance.

Profiling and relative quantification of phosphatidylethanolamine based on acetone stable isotope derivatization.

PubMed

Wang, Xiang; Wei, Fang; Xu, Ji-Qu; Lv, Xin; Dong, Xu-Yan; Han, Xianlin; Quek, Siew-Young; Huang, Feng-Hong; Chen, Hong

2016-01-01

Phosphatidylethanolamine (PE) is considered to be one of the pivotal lipids for normal cellular function as well as disease initiation and progression. In this study, a simple, efficient, reliable, and inexpensive method for the qualitative analysis and relative quantification of PE, based on acetone stable isotope derivatization combined with double neutral loss scan-shotgun electrospray ionization tandem-quadrupole mass spectrometry analysis (ASID-DNLS-Shotgun ESI-MS/MS), was developed. The ASID method led to alkylation of the primary amino groups of PE with an isopropyl moiety. The use of acetone (d0-acetone) and deuterium-labeled acetone (d6-acetone) introduced a 6 Da mass shift that was ideally suited for relative quantitative analysis, and enhanced sensitivity for mass analysis. The DNLS model was introduced to simultaneously analyze the differential derivatized PEs by shotgun ESI-MS/MS with high selectivity and accuracy. The reaction specificity, labeling efficiency, and linearity of the ASID method were thoroughly evaluated in this study. Its excellent applicability was validated by qualitative and relative quantitative analysis of PE species presented in liver samples from rats fed different diets. Using the ASID-DNLS-Shotgun ESI-MS/MS method, 45 PE species from rat livers have been identified and quantified in an efficient manner. The level of total PEs tended to decrease in the livers of rats on high fat diets compared with controls. The levels of PE 32:1, 34:3, 34:2, 36:3, 36:2, 42:10, plasmalogen PE 36:1 and lyso PE 22:6 were significantly reduced, while levels of PE 36:1 and lyso PE 16:0 increased. Copyright © 2015 Elsevier B.V. All rights reserved.

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study

PubMed Central

Biegstraaten, Marieke; Wanner, Christoph; Sirrs, Sandra; Mehta, Atul; Elliott, Perry M; Oder, Daniel; Watkinson, Oliver T; Bichet, Daniel G; Khan, Aneal; Iwanochko, Mark; Vaz, Frédéric M; van Kuilenburg, André B P; West, Michael L; Hughes, Derralynn A; Hollak, Carla E M

2018-01-01

Background Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes. Methods In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex. Results 387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: −18 nmol/L, P<0.001), persisting in the presence of antibodies. The risk to develop antibodies was higher for patients treated with agalsidase beta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar. Conclusions Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta. PMID:29437868

Hydrophilic interaction liquid chromatography-mass spectrometry of (lyso)phosphatidic acids, (lyso)phosphatidylserines and other lipid classes.

PubMed

Cífková, Eva; Hájek, Roman; Lísa, Miroslav; HolĿapek, Michal

2016-03-25

The goal of this work is a systematic optimization of hydrophilic interaction liquid chromatography (HILIC) separation of acidic lipid classes (namely phosphatidic acids-PA, lysophosphatidic acids-LPA, phosphatidylserines-PS and lysophosphatidylserines-LPS) and other lipid classes under mass spectrometry (MS) compatible conditions. The main parameters included in this optimization are the type of stationary phases used in HILIC, pH of the mobile phase, the type and concentration of mobile phase additives. Nine HILIC columns with different chemistries (unmodified silica, modified silica using diol, 2-picolylamine, diethylamine and 1-aminoanthracene and hydride silica) are compared with the emphasis on peak shapes of acidic lipid classes. The optimization of pH is correlated with the theoretical calculation of acidobasic equilibria of studied lipid classes. The final method using the hydride column, pH 4 adjusted by formic acid and the gradient of acetonitrile and 40 mmol/L of aqueous ammonium formate provides good peak shapes for all analyzed lipid classes including acidic lipids. This method is applied for the identification of lipids in real samples of porcine brain and kidney extracts. Copyright © 2016 Elsevier B.V. All rights reserved.

Characteristics of weak base-induced vacuoles formed around individual acidic organelles.

PubMed

Hiruma, Hiromi; Kawakami, Tadashi

2011-01-01

We have previously found that the weak base 4-aminopyridine induces Brownian motion of acidic organelles around which vacuoles are formed, causing organelle traffic disorder in neurons. Our present study investigated the characteristics of vacuoles induced by weak bases (NH(4)Cl, aminopyridines, and chloroquine) using mouse cells. Individual vacuoles included acidic organelles identified by fluorescent protein expression. Mitochondria and actin filaments were extruded outside the vacuoles, composing the vacuole rim. Staining with amine-reactive fluorescence showed no protein/amino acid content in vacuoles. Thus, serous vacuolar contents are probably partitioned by viscous cytosol, other organelles, and cytoskeletons, but not membrane. The weak base (chloroquine) was immunochemically detected in intravacuolar organelles, but not in vacuoles. Early vacuolization was reversible, but long-term vacuolization caused cell death. The vacuolization and cell death were blocked by the vacuolar H(+)-ATPase inhibitor and Cl--free medium. Staining with LysoTracker or LysoSensor indicated that intravacuolar organelles were strongly acidic and vacuoles were slightly acidic. This suggests that vacuolization is caused by accumulation of weak base and H(+) in acidic organelles, driven by vacuolar H(+)-ATPase associated with Cl(-) entering, and probably by subsequent extrusion of H(+) and water from organelles to the surrounding cytoplasm.

Performance evaluation of a LYSO-based PET scanner for monitoring of dose delivery in hadrontherapy

NASA Astrophysics Data System (ADS)

Fabbiani, E.; Belcari, N.; Camarlinghi, N.; Del Guerra, A.; Ferretti, S.; Kraan, A.; Panetta, D.; Sportelli, G.; Rosso, V.

2015-12-01

The DoPET scanner is a compact positron emission tomography (PET) device. It has been developed for monitoring the range of charged particles during therapy with hadron beams. Previous works have focused on the development and upgrade of the device and on data analysis. In this paper, a full performance characterization of the DoPET system in terms of the energy resolution, spatial resolution, sensitivity, uniformity, and noise equivalent count rate is reported. All measurements refer to an adapted version of the National Electrical Manufacturers Association (NEMA) NU 4 - 2008 protocol, which was written originally for small animal PET systems. Since DoPET is a dual head planar system, it requires a modified characterisation procedure with respect to those described for ring geometries as in the NEMA NU 4 - 2008 protocol. The presented procedure may be of interest for any other PET system with a similar geometry as DoPET.

Analog electro-optical readout of SiPMs achieves fast timing required for time-of-flight PET/MR

PubMed Central

Bieniosek, MF

2015-01-01

The design of combined positron emission tomography/magnetic resonance (PET/MR) systems presents a number of challenges to engineers, as it forces the PET system to acquire data in space constrained environment that is sensitive to electro-magnetic interference and contains high static, radio frequency (RF) and gradient fields. In this work we validate fast timing performance of a PET scintillation detector using a potentially very compact, very low power, and MR compatible readout method in which analog silicon photomultipliers (SiPM) signals are transmitted optically away from the MR bore with little or even no additional readout electronics. This analog ‘electro-optial’ method could reduce the entire PET readout in the MR bore to two compact, low power components (SiPMs and lasers). Our experiments show fast timing performance from analog electro-optical readout with and without pre-amplification. With 3mm × 3mm × 20mm lutetium-yttrium oxyorthosilicate (LYSO) crystals and Excelitas SiPMs the best two-sided fwhm coincident timing resolution achieved was 220 +/- 3ps in electrical mode, 230 +/- 2ps in electro-optical with preamp mode, and 253 +/- 2ps in electro-optical without preamp mode. Timing measurements were also performed with Hamamatsu SiPMs and 3mm × 3mm × 5mm crystals. In the future the timing degradation seen can be further reduced with lower laser noise or improvements SiPM rise time or gain. PMID:25905626

Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease.

PubMed

Goker-Alpan, Ozlem; Gambello, Michael J; Maegawa, Gustavo H B; Nedd, Khan J; Gruskin, Daniel J; Blankstein, Larry; Weinreb, Neal J

2016-01-01

Agalsidase alfa and agalsidase beta, recombinant enzyme preparations for treatment of Fabry disease (FD), have different approved dosing schedules: 0.2 mg/kg and 1.0 mg/kg every other week (EOW), respectively. This open-label, multicenter, exploratory phase 4 study evaluated plasma globotriaosylsphingosine (lyso-GL-3) and plasma and urine globotriaosylceramide (GL-3) levels at baseline and 2, 4, and 6 months after the switch from agalsidase alfa (0.2 mg/kg EOW for ≥12 months) to agalsidase beta (1.0 mg/kg EOW) in 15 male patients with FD. Immunoglobulin (Ig)G antidrug antibody titers were assessed, and safety was monitored throughout the study. Plasma lyso-GL-3 concentrations decreased significantly within 2 months after switch and reductions continued through month 6 (mean absolute changes, -12.8, -16.1, and -16.7 ng/mL at 2, 4, and 6 months, respectively; all P < 0.001). The mean percentage reduction from baseline was 39.5% (P < 0.001) at month 6. For plasma GL-3, the mean absolute change from baseline (-0.9 μg/mL) and percentage reduction (17.9%) at month 6 were both significant (P < 0.05). Urine GL-3 measurements showed intra-patient variability and changes from baseline were not significant. No clinical outcomes were assessed in this 6-month study, and, therefore, no conclusions can be drawn regarding the correlation of observed reductions in glycosphingolipid concentrations with clinically relevant outcomes. There were no differences in IgG antidrug antibody titers between the two enzymes. The switch from agalsidase alfa to agalsidase beta was well tolerated. Plasma lyso-GL-3 and GL-3 levels reduced after switching from agalsidase alfa to agalsidase beta, indicating that agalsidase beta has a greater pharmacodynamic effect on these markers at the recommended dose. These data further support the use of agalsidase beta 1.0 mg/kg EOW as enzyme replacement therapy in FD.

Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A)

PubMed Central

Lin, Hsiang-Yu; Liu, Hao-Chuan; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Ching-Yuang; Lin, Shuan-Pei; Niu, Dau-Ming

2013-01-01

Objective Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). Design Retrospective cohort study. Setting Tertiary medical centre. Participants 21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase β (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months. Outcome measures These data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index. Results After 6–39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (p<0.05) between the data at baseline and those after ERT for values of plasma lyso-Gb3, LVMI, IVS, LPW and Mainz Severity Score Index. No severe clinical events were reported during the treatment. Conclusions ERT is beneficial and appears to be safe for Taiwanese patients with cardiac-type Fabry disease, as well as for those with the classic type. PMID:23864212

De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy.

PubMed

Fassio, Anna; Esposito, Alessandro; Kato, Mitsuhiro; Saitsu, Hirotomo; Mei, Davide; Marini, Carla; Conti, Valerio; Nakashima, Mitsuko; Okamoto, Nobuhiko; Olmez Turker, Akgun; Albuz, Burcu; Semerci Gündüz, C Nur; Yanagihara, Keiko; Belmonte, Elisa; Maragliano, Luca; Ramsey, Keri; Balak, Chris; Siniard, Ashley; Narayanan, Vinodh; Ohba, Chihiro; Shiina, Masaaki; Ogata, Kazuhiro; Matsumoto, Naomichi; Benfenati, Fabio; Guerrini, Renzo

2018-06-01

V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p.Pro27Arg, p.Asp100Tyr), and to moderate delay with milder epilepsy in the other two (p.Asp349Asn, p.Asp371Gly). Modelling performed on the available prokaryotic and eukaryotic structures of v-ATPase predicted p.Pro27Arg to perturb subunit interaction, p.Asp100Tyr to cause steric hindrance and destabilize protein folding, p.Asp349Asn to affect the catalytic function and p.Asp371Gly to impair the rotation process, necessary for proton transport. We addressed the impact of p.Asp349Asn and p.Asp100Tyr mutations on ATP6V1A expression and function by analysing ATP6V1A-overexpressing HEK293T cells and patients' lymphoblasts. The p.Asp100Tyr mutant was characterized by reduced expression due to increased degradation. Conversely, no decrease in expression and clearance was observed for p.Asp349Asn. In HEK293T cells overexpressing either pathogenic or control variants, p.Asp349Asn significantly increased LysoTracker® fluorescence with no effects on EEA1 and LAMP1 expression. Conversely, p.Asp100Tyr decreased both LysoTracker® fluorescence and LAMP1 levels, leaving EEA1 expression unaffected. Both mutations decreased v-ATPase recruitment to autophagosomes, with no major impact on autophagy. Experiments performed on patients' lymphoblasts using the LysoSensor™ probe revealed lower pH of endocytic organelles for p.Asp349Asn and a reduced expression of LAMP1 with no effect on the pH for p.Asp100Tyr. These data demonstrate gain of function for p.Asp349Asn characterized by an increased proton pumping in intracellular organelles, and loss of function for p.Asp100Tyr with decreased expression of ATP6V1A and reduced levels of lysosomal markers. We expressed p.Asp349Asn and p.Asp100Tyr in rat hippocampal neurons and confirmed significant and opposite effects in lysosomal labelling. However, both mutations caused a similar defect in neurite elongation accompanied by loss of excitatory inputs, revealing that altered lysosomal homeostasis markedly affects neurite development and synaptic connectivity. This study provides evidence that de novo heterozygous ATP6V1A mutations cause a developmental encephalopathy with a pathomechanism that involves perturbations of lysosomal homeostasis and neuronal connectivity, uncovering a novel role for v-ATPase in neuronal development.

Effect of surfactants and natural detergents on phosphatidylcholine synthesis in photoreceptor membranes.

PubMed

Roque, M E; Castagnet, P I; Giusto, N M

2001-07-01

The synthesis of phosphatidylcholine (PC) in rod outer segments (ROS) catalysed by lysophosphatidylcholine acyltransferase and phosphatidylethanolamine N-methyltransferase (PE N-MTase) was studied and the effects of natural (FA and lysophospholipids) and synthetic (Triton X-100, deoxycholate and CHAPS) surfactants was evaluated. In all experimental conditions used, incorporation of labelled oleate into lysophosphatidylcholine (lysoPC) was at least 40 times greater than oleate incorporation into any other lysophospholipid. Acylation of lysoPC was slightly affected by Triton X-100 and was totally inhibited in the presence of 10 mM sodium deoxycholate (NaDOC) or CHAPS. Below their critical micelle concentration (cmc) Triton X-100 and NaDOC stimulated acylation of all ROS lysophospholipids analysed. The activity of PE N-MTase was stimulated at detergent concentrations below the cmc and inhibited at concentrations above the cmc for all three detergents tested. The effect of FA with differing degree of unsaturation on PC synthesis was evaluated. Oleic acid (10 microM) inhibited methyl group incorporation into total PC, whereas from 100 microM onward, the methylating activity increased with preferential synthesis of PC. Docosahexaenoic acid, in turn, inhibited PE N-MTase activity at every concentration tested. These results suggest that PC synthesis in ROS membranes is modified by bioregulators and surfactants altering the physico-chemical state of the membrane.

Trophosome of the Deep-Sea Tubeworm Riftia pachyptila Inhibits Bacterial Growth.

PubMed

Klose, Julia; Aistleitner, Karin; Horn, Matthias; Krenn, Liselotte; Dirsch, Verena; Zehl, Martin; Bright, Monika

2016-01-01

The giant tubeworm Riftia pachyptila lives in symbiosis with the chemoautotrophic gammaproteobacterium Cand. Endoriftia persephone. Symbionts are released back into the environment upon host death in high-pressure experiments, while microbial fouling is not involved in trophosome degradation. Therefore, we examined the antimicrobial effect of the tubeworm's trophosome and skin. The growth of all four tested Gram-positive, but only of one of the tested Gram-negative bacterial strains was inhibited by freshly fixed and degrading trophosome (incubated up to ten days at either warm or cold temperature), while no effect on Saccharomyces cerevisiae was observed. The skin did not show antimicrobial effects. A liquid chromatography-mass spectrometric analysis of the ethanol supernatant of fixed trophosomes lead to the tentative identification of the phospholipids 1-palmitoleyl-2-lyso-phosphatidylethanolamine, 2-palmitoleyl-1-lyso-phosphatidylethanolamine and the free fatty acids palmitoleic, palmitic and oleic acid, which are known to have an antimicrobial effect. As a result of tissue autolysis, the abundance of the free fatty acids increased with longer incubation time of trophosome samples. This correlated with an increasing growth inhibition of Bacillus subtilis and Listeria welshimeri, but not of the other bacterial strains. Therefore, the free fatty acids produced upon host degradation could be the cause of inhibition of at least these two bacterial strains.

Analysis of plasma membrane phosphoinositides from fusogenic carrot cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wheeler, J.J.; Boss, W.F.

1987-04-01

Phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP/sub 2/) were found to be associated with the plasma membrane-rich fractions isolated by aqueous polymer two-phase partitioning from fusogenic cells. They represented at least 5% and 0.7% of the total inositol-labeled lipids in the plasma membrane-rich fractions, respectively, and were present in a ratio of about 7:1 (PIP:PIP/sub 2/). In addition, two unidentified inositol-labeled compounds, which together were approximately 3% of the inositol-labeled lipids, were found predominantly in the plasma membrane-rich fractions and migrated between PIP/sub 2/ and PIP. The R/sub f/s of these compounds were approximately 0.31 and 0.34 in the solventmore » system CHCl/sub 3/:MeOH:15N NH/sub 4/OH:H/sub 2/O (90:90:7:22) using LK5 plates presoaked in 1% potassium oxalate. These compounds incorporated /sup 32/P/sub i/, (/sup 3/H)inositol and were hydrolyzed in mild base. These data suggested that they were glycero-phospholipids. Although the compounds did not comigrate with lysoPIP obtained from bovine brain (R/sub f/ approx. 0.35), when endogenous PIP was hydrolyzed to lysoPIP, the breakdown product migrated in the region of the unidentified inositol lipids.« less

Influence of yttrium content on the location of rare earth ions in LYSO:Ce crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Dongzhou, E-mail: dongzhou_ding@mail.sic.ac.cn; R and D Center of Shanghai Institute of Ceramics, No. 588 Heshuo Road, Shanghai 201899; Weng, Linhong

2014-01-15

Single-crystal X-ray diffraction (SCD), X-ray fluorescence (XRF), inductively coupled plasma optical emission spectroscopy (ICP-OES) and X-ray excited luminescence (XEL) measurements were performed to investigate structure details and segregation coefficients of (Lu{sub 1−x}Y{sub x}){sub 2}SiO{sub 5}:Ce (x=0 at%, 8.7 at%, 25.7 at%, 44.7 at%, 65.7 at%, 87.9 at% and 100 at%). Y{sup 3+} cations were found to have a preferential occupation for RE1 site (7-oxygen-coordinated) over RE2 site (6-oxygen-coordinated), which results in a greater increase of cell parameter c than that of a with increase in Y content due to LYSO's microstructure characteristics. Results presented here revealed that the less themore » difference in electronegativity and effective ionic radius between the two ions, the easier substitution of one ion by the other, and hence the higher segregation coefficients. Besides, the contribution of luminescence of Ce1 and Ce2 in the whole XEL was evaluated, and the location of Ce{sup 3+} ion was discussed. - Graphical abstract: Segregation coefficients of (Lu{sub 1−x}Y{sub x}){sub 2}SiO{sub 5}:Cce:italic> at RT/ce:italic>. Display Omitted.« less

Metabolic profiling of the hepatotoxicity and nephrotoxicity of Ginkgolic acids in rats using ultra-performance liquid chromatography-high-definition mass spectrometry.

PubMed

Qian, Yiyun; Peng, Yunru; Shang, Erxin; Zhao, Ming; Yan, Liang; Zhu, Zhenhua; Tao, Jinhua; Su, Shulan; Guo, Sheng; Duan, Jin-Ao

2017-08-01

Ginkgolic acids (GAs) are thought to be the potentially hazardous constituents corresponding to the toxic side effects of Ginkgo products. In this study, toxicological and metabolomics studies of GAs were carried out by ultra-performance liquid chromatography-high-definition mass spectrometry (UPLC-HDMS). Significant changes in serum clinical chemistry were observed in the both low (100 mg/kg) and high (900 mg/kg) doses. Especially the serum enzyme of ALT, AST, LDH, and CK decreased in treated groups. The histopathological observation demonstrated hepatic steatosis in liver and tubular vacuolar degeneration in kidney. These results demonstrated the hepatotoxicity and nephrotoxicity of GAs. Functional disorders are more likely to be toxic induced by GAs. Metabolic profiling within seven days revealed the change of the body status after oral administration. The results indicated the body function was significantly influenced at the 3rd day and could recover in seven days. Metabolomic analysis showed alterations in 14 metabolites from plasma such as LysoPC(18:0), LysoPC(18:2) and other lipids. The results suggested that exposure to GAs could cause disturbances in liver and kidney function associated with the metabolisms of lipids, glucose and the enzyme activity. Copyright © 2017. Published by Elsevier B.V.

Metabotypes of response to bariatric surgery independent of the magnitude of weight loss

PubMed Central

Tulipani, Sara; Marco-Ramell, Anna; Miñarro, Antonio; Jáuregui, Olga; Sanchez-Pla, Alex; Ramos-Molina, Bruno; Tinahones, Francisco J.; Andres-Lacueva, Cristina

2018-01-01

Objective Bariatric surgery is considered the most efficient treatment for morbid obesity and its related diseases. However, its role as a metabolic modifier is not well understood. We aimed to determine biosignatures of response to bariatric surgery and elucidate short-term metabolic adaptations. Methods We used a LC- and FIA-ESI-MS/MS approach to quantify acylcarnitines, (lyso)phosphatidylcholines, sphingomyelins, amino acids, biogenic amines and hexoses in serum samples of subjects with morbid obesity (n = 39) before and 1, 3 and 6 months after bariatric surgery. K-means cluster analysis allowed to distinguish metabotypes of response to bariatric surgery. Results For the first time, global metabolic changes following bariatric surgery independent of the baseline health status of the subjects have been revealed. We identify two metabolic phenotypes (metabotypes) at the interval 6 months-baseline after surgery, which presented differences in the levels of compounds of urea metabolism, gluconeogenic precursors and (lyso)phospholipid particles. Clinically, metabotypes were different in terms of the degree of improvement in insulin resistance, cholesterol, low-density lipoproteins and uric acid independent of the magnitude of weight loss. Conclusions This study opens new perspectives and new hypotheses on the metabolic benefits of bariatric surgery and understanding of the biology of obesity and its associated diseases. PMID:29856816

Metabotypes of response to bariatric surgery independent of the magnitude of weight loss.

PubMed

Palau-Rodriguez, Magali; Tulipani, Sara; Marco-Ramell, Anna; Miñarro, Antonio; Jáuregui, Olga; Sanchez-Pla, Alex; Ramos-Molina, Bruno; Tinahones, Francisco J; Andres-Lacueva, Cristina

2018-01-01

Bariatric surgery is considered the most efficient treatment for morbid obesity and its related diseases. However, its role as a metabolic modifier is not well understood. We aimed to determine biosignatures of response to bariatric surgery and elucidate short-term metabolic adaptations. We used a LC- and FIA-ESI-MS/MS approach to quantify acylcarnitines, (lyso)phosphatidylcholines, sphingomyelins, amino acids, biogenic amines and hexoses in serum samples of subjects with morbid obesity (n = 39) before and 1, 3 and 6 months after bariatric surgery. K-means cluster analysis allowed to distinguish metabotypes of response to bariatric surgery. For the first time, global metabolic changes following bariatric surgery independent of the baseline health status of the subjects have been revealed. We identify two metabolic phenotypes (metabotypes) at the interval 6 months-baseline after surgery, which presented differences in the levels of compounds of urea metabolism, gluconeogenic precursors and (lyso)phospholipid particles. Clinically, metabotypes were different in terms of the degree of improvement in insulin resistance, cholesterol, low-density lipoproteins and uric acid independent of the magnitude of weight loss. This study opens new perspectives and new hypotheses on the metabolic benefits of bariatric surgery and understanding of the biology of obesity and its associated diseases.

A review of the developments of radioxenon detectors for nuclear explosion monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sivels, Ciara B.; McIntyre, Justin I.; Bowyer, Theodore W.

Developments in radioxenon monitoring since the implementation of the International Monitoring System are reviewed with emphasis on the most current technologies to improve detector sensitivity and resolution. The nuclear detectors reviewed include combinations of plastic and NaI(Tl) detectors, high purity germanium detectors, silicon detectors, and phoswich detectors. The minimum detectable activity and calibration methods for the various detectors are also discussed.

Detection of long wavelength infrared at moderate temperatures

NASA Technical Reports Server (NTRS)

Tredwell, T. J.

1977-01-01

Technical approaches for the advanced development of 8-12 micrometer detectors operating at elevated temperatures were defined. The theoretical limits to performance of 8-12 micrometer quantum detectors (photoconductive and photovoltaic) and thermal detectors (pyroelectrics, bolometers etc). An analytic model of signal and noise in both quantum detectors and pyroelectric detectors was developed and candidate materials for both detector types were identified and examined. The present status of both quantum and thermal detectors was assessed as well as the parameters limiting operating temperature and detectivity. The areas of research and development likely to lead to detector performance near the theoretical limit are identified.

Advanced Space Radiation Detector Technology Development

NASA Technical Reports Server (NTRS)

Wrbanek, John D.; Wrbanek, Susan Y.; Fralick, Gustave C.

2013-01-01

The advanced space radiation detector development team at the NASA Glenn Research Center (GRC) has the goal of developing unique, more compact radiation detectors that provide improved real-time data on space radiation. The team has performed studies of different detector designs using a variety of combinations of solid-state detectors, which allow higher sensitivity to radiation in a smaller package and operate at lower voltage than traditional detectors. Integration of multiple solid-state detectors will result in an improved detector system in comparison to existing state-of-the-art instruments for the detection and monitoring of the space radiation field for deep space and aerospace applications.

Advanced Space Radiation Detector Technology Development

NASA Technical Reports Server (NTRS)

Wrbanek, John D.; Wrbanek, Susan Y.; Fralick, Gustave C.

2013-01-01

The advanced space radiation detector development team at NASA Glenn Research Center (GRC) has the goal of developing unique, more compact radiation detectors that provide improved real-time data on space radiation. The team has performed studies of different detector designs using a variety of combinations of solid-state detectors, which allow higher sensitivity to radiation in a smaller package and operate at lower voltage than traditional detectors. Integration of multiple solid-state detectors will result in an improved detector system in comparison to existing state-of-the-art instruments for the detection and monitoring of the space radiation field for deep space and aerospace applications.

Advanced Space Radiation Detector Technology Development

NASA Technical Reports Server (NTRS)

Wrbanek, John D.; Wrbanek, Susan Y.; Fralick, Gustave C.

2013-01-01

The advanced space radiation detector development team at NASA Glenn Research Center (GRC) has the goal of developing unique, more compact radiation detectors that provide improved real-time data on space radiation. The team has performed studies of different detector designs using a variety of combinations of solid-state detectors, which allow higher sensitivity to radiation in a smaller package and operate at lower voltage than traditional detectors. Integration of multiple solid-state detectors will result in an improved detector system in comparison to existing state-of-the-art (SOA) instruments for the detection and monitoring of the space radiation field for deep space and aerospace applications.

Transport and release of colloidal 3-mercaptopropionic acid-coated CdSe–CdS/ZnS core-multishell quantum dots in human umbilical vein endothelial cells

PubMed Central

Fontana, Jacopo M; Yin, Huijuan; Chen, Yun; Florez, Ricardo; Brismar, Hjalmar; Fu, Ying

2017-01-01

Colloidal semiconductor quantum dots (QDs) have been extensively researched and developed for biomedical applications, including drug delivery and biosensing assays. Hence, it is pivotal to understand their behavior in terms of intracellular transport and toxicological effects. In this study, we focused on 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots (3MPA-QDs) converted from the as-grown octadecylamine-coated quantum dots (ODA-QDs) and their direct and dynamic interactions with human umbilical vein endothelial cells (HUVECs). Live cell imaging using confocal fluorescence microscopy showed that 3MPA-QDs first attached to and subsequently aggregated on HUVEC plasma membrane ~25 min after QD deposition. The aggregated QDs started being internalized at ~2 h and reached their highest internalization degree at ~24 h. They were released from HUVECs after ~48 h. During the 48 h period, the HUVECs responded normally to external stimulations, grew, proliferated and wound healed without any perceptible apoptosis. Furthermore, 1) 3MPA-QDs were internalized in newly formed LysoTracker-stained early endosomes; 2) adenosine 5′-triphosphate-induced [Ca2+]i modulation caused a transient decrease in the fluorescence of 3MPA-QDs that were attached to the plasma membrane but a transient increase in the internalized 3MPA-QDs; and 3) fluorescence signal modulations of co-stained LysoTracker and QDs induced by the lysosomotropic agent Gly-Phe-β-naphthylamide were spatially co-localized and temporally synchronized. Our findings suggest that 3MPA-QDs converted from ODA-QDs are a potential nontoxic fluorescent probe for future use in clinical applications. Moreover, the photophysical strategy and techniques reported in this work are easily applicable to study of direct interactions between other nanoparticles and live cells; contributing to awareness and implementation of the safe applications of nanoparticles. PMID:29270011

Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

1998-06-01

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.

Transport and release of colloidal 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots in human umbilical vein endothelial cells.

PubMed

Fontana, Jacopo M; Yin, Huijuan; Chen, Yun; Florez, Ricardo; Brismar, Hjalmar; Fu, Ying

2017-01-01

Colloidal semiconductor quantum dots (QDs) have been extensively researched and developed for biomedical applications, including drug delivery and biosensing assays. Hence, it is pivotal to understand their behavior in terms of intracellular transport and toxicological effects. In this study, we focused on 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots (3MPA-QDs) converted from the as-grown octadecylamine-coated quantum dots (ODA-QDs) and their direct and dynamic interactions with human umbilical vein endothelial cells (HUVECs). Live cell imaging using confocal fluorescence microscopy showed that 3MPA-QDs first attached to and subsequently aggregated on HUVEC plasma membrane ~25 min after QD deposition. The aggregated QDs started being internalized at ~2 h and reached their highest internalization degree at ~24 h. They were released from HUVECs after ~48 h. During the 48 h period, the HUVECs responded normally to external stimulations, grew, proliferated and wound healed without any perceptible apoptosis. Furthermore, 1) 3MPA-QDs were internalized in newly formed LysoTracker-stained early endosomes; 2) adenosine 5'-triphosphate-induced [Ca 2+ ] i modulation caused a transient decrease in the fluorescence of 3MPA-QDs that were attached to the plasma membrane but a transient increase in the internalized 3MPA-QDs; and 3) fluorescence signal modulations of co-stained LysoTracker and QDs induced by the lysosomotropic agent Gly-Phe-β-naphthylamide were spatially co-localized and temporally synchronized. Our findings suggest that 3MPA-QDs converted from ODA-QDs are a potential nontoxic fluorescent probe for future use in clinical applications. Moreover, the photophysical strategy and techniques reported in this work are easily applicable to study of direct interactions between other nanoparticles and live cells; contributing to awareness and implementation of the safe applications of nanoparticles.

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

PubMed

Arends, Maarten; Biegstraaten, Marieke; Wanner, Christoph; Sirrs, Sandra; Mehta, Atul; Elliott, Perry M; Oder, Daniel; Watkinson, Oliver T; Bichet, Daniel G; Khan, Aneal; Iwanochko, Mark; Vaz, Frédéric M; van Kuilenburg, André B P; West, Michael L; Hughes, Derralynn A; Hollak, Carla E M

2018-05-01

Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes. In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex. 387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: -18 nmol/L, P<0.001), persisting in the presence of antibodies. The risk to develop antibodies was higher for patients treated with agalsidase beta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar. Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

24 CFR 200.76 - Smoke detectors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Smoke detectors. 200.76 Section 200.76 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Eligibility Requirements for Existing Projects Property Requirements § 200.76 Smoke detectors. Smoke detectors...

24 CFR 200.76 - Smoke detectors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Smoke detectors. 200.76 Section 200.76 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Eligibility Requirements for Existing Projects Property Requirements § 200.76 Smoke detectors. Smoke detectors...

24 CFR 200.76 - Smoke detectors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Smoke detectors. 200.76 Section 200.76 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Eligibility Requirements for Existing Projects Property Requirements § 200.76 Smoke detectors. Smoke detectors...

24 CFR 200.76 - Smoke detectors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Smoke detectors. 200.76 Section 200.76 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Eligibility Requirements for Existing Projects Property Requirements § 200.76 Smoke detectors. Smoke detectors...

24 CFR 200.76 - Smoke detectors.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Smoke detectors. 200.76 Section 200.76 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Eligibility Requirements for Existing Projects Property Requirements § 200.76 Smoke detectors. Smoke detectors...

Development of a mercuric iodide solid state spectrometer for X-ray astronomy

NASA Technical Reports Server (NTRS)

Vallerga, J.

1983-01-01

Mercuric iodide detectors, experimental development for astronomical use, X ray observations of the 1980 Cygnus X-1 High State, astronomical had X ray detectors in current use, detector development, balloon flight of large area (1500 sq cm) Phoswich detectors, had X ray telescope design, shielded mercuric iodide background measurement, Monte Carlo analysis, measurements with a shielded mercuric iodide detector are discussed.

Far-Infrared Blocked Impurity Band Detector Development

NASA Technical Reports Server (NTRS)

Hogue, H. H.; Guptill, M. T.; Monson, J. C.; Stewart, J. W.; Huffman, J. E.; Mlynczak, M. G.; Abedin, M. N.

2007-01-01

DRS Sensors & Targeting Systems, supported by detector materials supplier Lawrence Semiconductor Research Laboratory, is developing far-infrared detectors jointly with NASA Langley under the Far-IR Detector Technology Advancement Partnership (FIDTAP). The detectors are intended for spectral characterization of the Earth's energy budget from space. During the first year of this effort we have designed, fabricated, and evaluated pilot Blocked Impurity Band (BIB) detectors in both silicon and germanium, utilizing pre-existing customized detector materials and photolithographic masks. A second-year effort has prepared improved silicon materials, fabricated custom photolithographic masks for detector process, and begun detector processing. We report the characterization results from the pilot detectors and other progress.

High performance visual display for HENP detectors

NASA Astrophysics Data System (ADS)

McGuigan, Michael; Smith, Gordon; Spiletic, John; Fine, Valeri; Nevski, Pavel

2001-08-01

A high end visual display for High Energy Nuclear Physics (HENP) detectors is necessary because of the sheer size and complexity of the detector. For BNL this display will be of special interest because of STAR and ATLAS. To load, rotate, query, and debug simulation code with a modern detector simply takes too long even on a powerful work station. To visualize the HENP detectors with maximal performance we have developed software with the following characteristics. We develop a visual display of HENP detectors on BNL multiprocessor visualization server at multiple level of detail. We work with general and generic detector framework consistent with ROOT, GAUDI etc, to avoid conflicting with the many graphic development groups associated with specific detectors like STAR and ATLAS. We develop advanced OpenGL features such as transparency and polarized stereoscopy. We enable collaborative viewing of detector and events by directly running the analysis in BNL stereoscopic theatre. We construct enhanced interactive control, including the ability to slice, search and mark areas of the detector. We incorporate the ability to make a high quality still image of a view of the detector and the ability to generate animations and a fly through of the detector and output these to MPEG or VRML models. We develop data compression hardware and software so that remote interactive visualization will be possible among dispersed collaborators. We obtain real time visual display for events accumulated during simulations.

Measurement of LYSO Intrinsic Light Yield Using Electron Excitation

NASA Astrophysics Data System (ADS)

Turtos, Rosana Martinez; Gundacker, Stefan; Pizzichemi, Marco; Ghezzi, Alessio; Pauwels, Kristof; Auffray, Etiennette; Lecoq, Paul; Paganoni, Marco

2016-04-01

The determination of the intrinsic light yield (LYint) of scintillating crystals, i.e. number of optical photons created per amount of energy deposited, constitutes a key factor in order to characterize and optimize their energy and time resolution. However, until now measurements of this quantity are affected by large uncertainties and often rely on corrections for bulk absorption and surface/edge state. The novel idea presented in this contribution is based on the confinement of the scintillation emission in the central upper part of a 10 mm cubic crystal using a 1.5 MeV electron beam with diameter of 1 mm. A black non-reflective pinhole aligned with the excitation point is used to fix the light extraction solid angle (narrower than total reflection angle), which then sets a light cone travel path through the crystal. The final number of photoelectrons detected using a Hamamatsu R2059 photomultiplier tube (PMT) was corrected for the extraction solid angle, the Fresnel reflection coefficient and quantum efficiency (QE) of the PMT. The total number of optical photons produced per energy deposited was found to be 40000 ph/MeV ± 9% (syst) ±3% (stat) for LYSO. Simulations using Geant4 were successfully compared to light output measurements of 2 × 2 mm2 section crystals with lengths of 5-30 mm, in order to validate the light transport model and set a limit on Light Transfer Efficiency estimations.

Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

PubMed Central

Bao, Jiaolin; Liu, Fang; Zhang, Chao; Wang, Kai; Jia, Xuejing; Wang, Xiaotong; Chen, Meiwan; Li, Peng; Su, Huanxing; Wang, Yitao; Wan, Jian-Bo; He, Chengwei

2016-01-01

Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors. PMID:27991567

UPLC-QTOFMS-based metabolomic analysis of the serum of hypoxic preconditioning mice

PubMed Central

Liu, Jie; Zhang, Gang; Chen, Dewei; Chen, Jian; Yuan, Zhi-Bin; Zhang, Er-Long; Gao, Yi-Xing; Xu, Gang; Sun, Bing-Da; Liao, Wenting; Gao, Yu-Qi

2017-01-01

Hypoxic preconditioning (HPC) is well-known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC. PMID:28901489

Curcumin prevents the oxidation and lipid modification of LDL and its inhibition of prostacyclin generation by endothelial cells in culture.

PubMed

Mahfouz, Mohamedain M; Zhou, Sherry Q; Kummerow, Fred A

2009-11-01

Low-density lipoprotein (LDL) was isolated from human plasma and oxidized by 5microM copper sulfate for 4h at 37 degrees C in the absence and presence of 1, 3, 5, 10, or 20microM of curcumin. LDL oxidized in the absence of curcumin (oxLDL) showed an increased levels of conjugated dienes, lipid peroxides (TBARS) and lysolecithin (lysoPC) and a significant loss of polyunsaturated fatty acids (PUFA). LDL oxidized with 5microM copper sulfate in the presence of curcumin caused a significant decrease of conjugated diene, lipid peroxides, lysoPC and significant increase of PUFA compared to oxLDL. These changes were dose dependent and reached a maximum at 5microM curcumin. Incubation of human endothelial cells (EC) with 200microg protein/ml of oxLDL caused a significant decrease of prostacyclin (PGI(2)) generation. LDL oxidized in presence of 5microM curcumin did not show any inhibition of PGI(2) generation compared to the control cells. These results indicate that curcumin is an effective chain-breaking antioxidant which prevents oxidation and lipid modification of LDL. The inhibition of oxLDL on PGI(2) is considered a contributing factor in the pathogenesis of thrombosis and atherosclerosis. Curcumin supplementation could be an effective strategy in preventing LDL oxidation and its impact on atherosclerosis and lesion formation.

The value of grip test, lysophosphatidlycholines, glycerophosphocholine, ornithine, glucuronic acid decrement in assessment of nutritional and metabolic characteristics in hepatitis B cirrhosis

PubMed Central

Zhang, Lei; Xiao, Huijuan; Qi, Yumei; Liu, Shuye; Qian, Baoxin; Wang, Fengmei; Han, Tao

2017-01-01

The liver is essential for the regulation of energy, protein and amino acids, as well as in other aspects of metabolism. To identify efficient indexes for evaluation of nutritional status and metabolic characteristics during different Child-Pugh stages of hepatitis B cirrhosis, 83 patients and 35 healthy individuals were enrolled in our study. We found that grip strength, triceps skinfold thickness (TSF), body fat and skeletal muscle of the patients were reduced compared to the control group (P<0.05). Ultra-high-performance liquid chromatography data combined with mass spectrometry (UPLC-MS) showed that levels of a variety of metabolites, including lysophosphatidylcholines (LysoPCs), glycerophosphocholine, ornithine and glucuronic acid were reduced in the serum of patients with hepatitis B cirrhosis (P<0.001). However, glycerophosphoserine and taurocholic acid levels were higher than in the control group (P<0.001). Moreover, grip strength was correlated with the Child-Pugh score (P<0.05). Serum albumin, total cholesterol, LDL, LysoPCs, glycerophosphocholine, ornithine, glucuronic acid, glycerophosphoserine and taurocholic acid were correlated with the Child-Pugh score (P<0.01). These findings suggested that grip strength and the above small molecular substances might be considered as sensitive and important indexes for evaluating nutritional status and metabolic characteristics of patients with hepatitis B cirrhosis, which may help assess prognosis and adjust nutritional treatment. PMID:28384211

Detectors for Linear Colliders: Detector design for a Future Electron-Positron Collider (4/4)

ScienceCinema

Thomson, Mark

2018-05-21

In this lecture I will discuss the issues related to the overall design and optimization of a detector for ILC and CLIC energies. I will concentrate on the two main detector concepts which are being developed in the context of the ILC. Here there has been much recent progress in developing realistic detector models and in understanding the physics performance of the overall detector concept. In addition, I will discuss the how the differences in the detector requirements for the ILC and CLIC impact the overall detector design.

Cherenkov Water Detectors in Particle Physics and Cosmic Rays

NASA Astrophysics Data System (ADS)

Petrukhin, A. A.; Yashin, I. I.

2017-12-01

Among various types of Cherenkov detectors (solid, liquid and gaseous) created for different studies, the most impressive development was gained by water detectors: from the first detector with a volume of several liters in which the Cherenkov radiation was discovered, to the IceCube detector with a volume of one cubic kilometer. The review of the development of Cherenkov water detectors for various purposes and having different locations - ground-based, underground and underwater-is presented in the paper. The prospects of their further development are also discussed.

Polarimetric subspace target detector for SAR data based on the Huynen dihedral model

NASA Astrophysics Data System (ADS)

Larson, Victor J.; Novak, Leslie M.

1995-06-01

Two new polarimetric subspace target detectors are developed based on a dihedral signal model for bright peaks within a spatially extended target signature. The first is a coherent dihedral target detector based on the exact Huynen model for a dihedral. The second is a noncoherent dihedral target detector based on the Huynen model with an extra unknown phase term. Expressions for these polarimetric subspace target detectors are developed for both additive Gaussian clutter and more general additive spherically invariant random vector clutter including the K-distribution. For the case of Gaussian clutter with unknown clutter parameters, constant false alarm rate implementations of these polarimetric subspace target detectors are developed. The performance of these dihedral detectors is demonstrated with real millimeter-wave fully polarimetric SAR data. The coherent dihedral detector which is developed with a more accurate description of a dihedral offers no performance advantage over the noncoherent dihedral detector which is computationally more attractive. The dihedral detectors do a better job of separating a set of tactical military targets from natural clutter compared to a detector that assumes no knowledge about the polarimetric structure of the target signal.

Technology of silicon charged-particle detectors developed at the Institute of Electron Technology (ITE)

NASA Astrophysics Data System (ADS)

Wegrzecka, Iwona; Panas, Andrzej; Bar, Jan; Budzyński, Tadeusz; Grabiec, Piotr; Kozłowski, Roman; Sarnecki, Jerzy; Słysz, Wojciech; Szmigiel, Dariusz; Wegrzecki, Maciej; Zaborowski, Michał

2013-07-01

The paper discusses the technology of silicon charged-particle detectors developed at the Institute of Electron Technology (ITE). The developed technology enables the fabrication of both planar and epiplanar p+-ν-n+ detector structures with an active area of up to 50 cm2. The starting material for epiplanar structures are silicon wafers with a high-resistivity n-type epitaxial layer ( ν layer - ρ < 3 kΩcm) deposited on a highly doped n+-type substrate (ρ< 0,02Ωcm) developed and fabricated at the Institute of Electronic Materials Technology. Active layer thickness of the epiplanar detectors (νlayer) may range from 10 μm to 150 μm. Imported silicon with min. 5 kΩcm resistivity is used to fabricate planar detectors. Active layer thickness of the planar detectors (ν) layer) may range from 200 μm to 1 mm. This technology enables the fabrication of both discrete and multi-junction detectors (monolithic detector arrays), such as single-sided strip detectors (epiplanar and planar) and double-sided strip detectors (planar). Examples of process diagrams for fabrication of the epiplanar and planar detectors are presented in the paper, and selected technological processes are discussed.

Advances in TlBr detector development

NASA Astrophysics Data System (ADS)

Hitomi, Keitaro; Shoji, Tadayoshi; Ishii, Keizo

2013-09-01

Thallium bromide (TlBr) is a promising compound semiconductor for fabrication of gamma-ray detectors. The attractive physical properties of TlBr lie in its high photon stopping power, high resistivity and good charge transport properties. Gamma-ray detectors fabricated from TlBr crystals have exhibited excellent spectroscopic performance. In this paper, advances in TlBr radiation detector development are reviewed with emphasis on crystal growth, detector fabrication, physical properties and detector performance.

Low-Power Multi-Aspect Space Radiation Detector System

NASA Technical Reports Server (NTRS)

Wrbanek, John D.; Wrbanek, Susan Y.; Fralick, Gustave; Freeman, Jon C.; Burkebile, Stephen P.

2012-01-01

The advanced space radiation detector development team at NASA Glenn Research Center (GRC) has the goal of developing unique, more compact radiation detectors that provide improved real-time data on space radiation. The team has performed studies of different detector designs using a variety of combinations of solid-state detectors, which allow higher sensitivity to radiation in a smaller package and operate at lower voltage than traditional detectors. Integration of all of these detector technologies will result in an improved detector system in comparison to existing state-of-the-art (SOA) instruments for the detection and monitoring of the deep space radiation field.

X-ray imaging detectors for synchrotron and XFEL sources

PubMed Central

Hatsui, Takaki; Graafsma, Heinz

2015-01-01

Current trends for X-ray imaging detectors based on hybrid and monolithic detector technologies are reviewed. Hybrid detectors with photon-counting pixels have proven to be very powerful tools at synchrotrons. Recent developments continue to improve their performance, especially for higher spatial resolution at higher count rates with higher frame rates. Recent developments for X-ray free-electron laser (XFEL) experiments provide high-frame-rate integrating detectors with both high sensitivity and high peak signal. Similar performance improvements are sought in monolithic detectors. The monolithic approach also offers a lower noise floor, which is required for the detection of soft X-ray photons. The link between technology development and detector performance is described briefly in the context of potential future capabilities for X-ray imaging detectors. PMID:25995846

Development of the MAMA Detectors for the Hubble Space Telescope Imaging Spectrograph

NASA Technical Reports Server (NTRS)

Timothy, J. Gethyn

1997-01-01

The development of the Multi-Anode Microchannel Array (MAMA) detector systems started in the early 1970's in order to produce multi-element detector arrays for use in spectrographs for solar studies from the Skylab-B mission. Development of the MAMA detectors for spectrographs on the Hubble Space Telescope (HST) began in the late 1970's, and reached its culmination with the successful installation of the Space Telescope Imaging Spectrograph (STIS) on the second HST servicing mission (STS-82 launched 11 February 1997). Under NASA Contract NAS5-29389 from December 1986 through June 1994 we supported the development of the MAMA detectors for STIS, including complementary sounding rocket and ground-based research programs. This final report describes the results of the MAMA detector development program for STIS.

History of infrared detectors

NASA Astrophysics Data System (ADS)

Rogalski, A.

2012-09-01

This paper overviews the history of infrared detector materials starting with Herschel's experiment with thermometer on February 11th, 1800. Infrared detectors are in general used to detect, image, and measure patterns of the thermal heat radiation which all objects emit. At the beginning, their development was connected with thermal detectors, such as thermocouples and bolometers, which are still used today and which are generally sensitive to all infrared wavelengths and operate at room temperature. The second kind of detectors, called the photon detectors, was mainly developed during the 20th Century to improve sensitivity and response time. These detectors have been extensively developed since the 1940's. Lead sulphide (PbS) was the first practical IR detector with sensitivity to infrared wavelengths up to ˜3 μm. After World War II infrared detector technology development was and continues to be primarily driven by military applications. Discovery of variable band gap HgCdTe ternary alloy by Lawson and co-workers in 1959 opened a new area in IR detector technology and has provided an unprecedented degree of freedom in infrared detector design. Many of these advances were transferred to IR astronomy from Departments of Defence research. Later on civilian applications of infrared technology are frequently called "dual-use technology applications." One should point out the growing utilisation of IR technologies in the civilian sphere based on the use of new materials and technologies, as well as the noticeable price decrease in these high cost technologies. In the last four decades different types of detectors are combined with electronic readouts to make detector focal plane arrays (FPAs). Development in FPA technology has revolutionized infrared imaging. Progress in integrated circuit design and fabrication techniques has resulted in continued rapid growth in the size and performance of these solid state arrays.

Workshop on detectors for third-generation synchrotron sources: Proceedings

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1994-12-01

The aims of the workshop were (1) to acquaint APS users with current R and D being carried out on detectors, (2) to identify new detector systems possible during the next five years, (3) to identify new detectors theoretically possible in the future, (4) to stimulate interactions between user groups and detector developers, and (5) to obtain recommendations from expert panels on technical issues needing resolution. Development of detectors at ESRF, Spring-8, BNL, CERN and LBL are included.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolotnikov, Aleksey; Cui, Yonggang; Vernon, Emerson

This document presents motivations, goals and the current status of this project; development (fabrication, performance) of position-sensitive virtual Frisch-grid detectors proposed for nanoRaider, an instrument commonly used by nuclear inspectors; ASIC developments for CZT detectors; and the electronics development for the detector prototype..

A multi-channel photometric detector for multi-component analysis in flow injection analysis

PubMed Central

Tan, Aimin; Huang, Jialin; Geng, Liudi; Xu, Jinhua; Zhao, Xinna

1994-01-01

The detector, a multi-channel photometric detector, described in this paper was developed using multi-wavelength LEDs (light emitting diode) and phototransistors for absorbance measurement controlled by an Intel 8031 8-bit single chip microcomputer. Up to four flow cells can be attached to the detector. The LEDs and phototransistors are both inexpensive, and reliable. The results given by the detector for simultaneous determination of trace amounts of cobalt and cadmium in zinc sulphate electrolyte are reported. Because of the newly developed detector, this approach employs much less hardware apparatus than by employing conventional photometric detectors. PMID:18924688

A multi-channel photometric detector for multi-component analysis in flow injection analysis.

PubMed

Tan, A; Huang, J; Geng, L; Xu, J; Zhao, X

1994-01-01

The detector, a multi-channel photometric detector, described in this paper was developed using multi-wavelength LEDs (light emitting diode) and phototransistors for absorbance measurement controlled by an Intel 8031 8-bit single chip microcomputer. Up to four flow cells can be attached to the detector. The LEDs and phototransistors are both inexpensive, and reliable. The results given by the detector for simultaneous determination of trace amounts of cobalt and cadmium in zinc sulphate electrolyte are reported. Because of the newly developed detector, this approach employs much less hardware apparatus than by employing conventional photometric detectors.

Recent developments in PET detector technology

PubMed Central

Lewellen, Tom K

2010-01-01

Positron emission tomography (PET) is a tool for metabolic imaging that has been utilized since the earliest days of nuclear medicine. A key component of such imaging systems is the detector modules—an area of research and development with a long, rich history. Development of detectors for PET has often seen the migration of technologies, originally developed for high energy physics experiments, into prototype PET detectors. Of the many areas explored, some detector designs go on to be incorporated into prototype scanner systems and a few of these may go on to be seen in commercial scanners. There has been a steady, often very diverse development of prototype detectors, and the pace has accelerated with the increased use of PET in clinical studies (currently driven by PET/CT scanners) and the rapid proliferation of pre-clinical PET scanners for academic and commercial research applications. Most of these efforts are focused on scintillator-based detectors, although various alternatives continue to be considered. For example, wire chambers have been investigated many times over the years and more recently various solid-state devices have appeared in PET detector designs for very high spatial resolution applications. But even with scintillators, there have been a wide variety of designs and solutions investigated as developers search for solutions that offer very high spatial resolution, fast timing, high sensitivity and are yet cost effective. In this review, we will explore some of the recent developments in the quest for better PET detector technology. PMID:18695301

Analyzing Noise for the Muon Silicon Scanner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchan, Miguelangel; Utes, Michael

2017-01-01

The development of a silicon muon tomography detector is a joint project between Fermilab and National Security Technologies, LLC. The goal of this detector is to detect nuclear materials better than technology in the past. Using silicon strip detectors and readout chips used by experiments at CERN we have been developing the detector. This summer we have been testing components of the detector and have been analyzing noise characteristics.

Progress in the Development of CdZnTe Unipolar Detectors for Different Anode Geometries and Data Corrections

PubMed Central

Zhang, Qiushi; Zhang, Congzhe; Lu, Yanye; Yang, Kun; Ren, Qiushi

2013-01-01

CdZnTe detectors have been under development for the past two decades, providing good stopping power for gamma rays, lightweight camera heads and improved energy resolution. However, the performance of this type of detector is limited primarily by incomplete charge collection problems resulting from charge carriers trapping. This paper is a review of the progress in the development of CdZnTe unipolar detectors with some data correction techniques for improving performance of the detectors. We will first briefly review the relevant theories. Thereafter, two aspects of the techniques for overcoming the hole trapping issue are summarized, including irradiation direction configuration and pulse shape correction methods. CdZnTe detectors of different geometries are discussed in detail, covering the principal of the electrode geometry design, the design and performance characteristics, some detector prototypes development and special correction techniques to improve the energy resolution. Finally, the state of art development of 3-D position sensing and Compton imaging technique are also discussed. Spectroscopic performance of CdZnTe semiconductor detector will be greatly improved even to approach the statistical limit on energy resolution with the combination of some of these techniques. PMID:23429509

Development of a circular shape Si-PM-based detector ring for breast-dedicated PET system

NASA Astrophysics Data System (ADS)

Nakanishi, Kouhei; Yamamoto, Seiichi; Watabe, Hiroshi; Abe, Shinji; Fujita, Naotoshi; Kato, Katsuhiko

2018-02-01

In clinical situations, various breast-dedicated positron emission tomography (PET) systems have been used. However, clinical breast-dedicated PET systems have polygonal detector ring. Polygonal detector ring sometimes causes image artifact, so complicated reconstruction algorithm is needed to reduce artifact. Consequently, we developed a circular detector ring for breast-dedicated PET to obtain images without artifact using a simple reconstruction algorithm. We used Lu1.9Gd0.1SiO5 (LGSO) scintillator block which was made of 1.5 x 1.9 x 15 mm pixels that were arranged in an 8 x 24 matrix. As photodetectors, we used silicon photomultiplier (Si-PM) arrays whose channel size was 3 x 3 mm. A detector unit was composed of four scintillator blocks, 16 Si-PM arrays and a light guide. The developed detector unit had angled configuration since the light guide was bending. A detector unit had three gaps with an angle of 5.625° between scintillator blocks. With these configurations, we could arrange 64 scintillator blocks in nearly circular shape (regular 64-sided polygon) using 16 detector units. The use of the smaller number of detector units could reduce the size of the front-end electronics circuits. The inner diameter of the developed detector ring was 260 mm. This size was similar to those of brain PET systems, so our breast-dedicated PET detector ring can measure not only breast but also brain. Measured radial, tangential and axial spatial resolution of the detector ring reconstructed by the filtered back-projection (FBP) algorithm were 2.1 mm FWHM, 2.0 mm FWHM and 1.7 mm FWHM at center of field of view (FOV), respectively. The sensitivity was 2.0% at center of the axial FOV. With the developed detector ring, we could obtain high resolution image of the breast phantom and the brain phantom. We conclude that our developed Si-PM-based detector ring is promising for a high resolution breast-dedicated PET system that can also be used for brain PET system.

Development of a fast multi-line x-ray CT detector for NDT

NASA Astrophysics Data System (ADS)

Hofmann, T.; Nachtrab, F.; Schlechter, T.; Neubauer, H.; Mühlbauer, J.; Schröpfer, S.; Ernst, J.; Firsching, M.; Schweiger, T.; Oberst, M.; Meyer, A.; Uhlmann, N.

2015-04-01

Typical X-ray detectors for non-destructive testing (NDT) are line detectors or area detectors, like e.g. flat panel detectors. Multi-line detectors are currently only available in medical Computed Tomography (CT) scanners. Compared to flat panel detectors, line and multi-line detectors can achieve much higher frame rates. This allows time-resolved 3D CT scans of an object under investigation. Also, an improved image quality can be achieved due to reduced scattered radiation from object and detector themselves. Another benefit of line and multi-line detectors is that very wide detectors can be assembled easily, while flat panel detectors are usually limited to an imaging field with a size of approx. 40 × 40 cm2 at maximum. The big disadvantage of line detectors is the limited number of object slices that can be scanned simultaneously. This leads to long scan times for large objects. Volume scans with a multi-line detector are much faster, but with almost similar image quality. Due to the promising properties of multi-line detectors their application outside of medical CT would also be very interesting for NDT. However, medical CT multi-line detectors are optimized for the scanning of human bodies. Many non-medical applications require higher spatial resolutions and/or higher X-ray energies. For those non-medical applications we are developing a fast multi-line X-ray detector.In the scope of this work, we present the current state of the development of the novel detector, which includes several outstanding properties like an adjustable curved design for variable focus-detector-distances, conserving nearly uniform perpendicular irradiation over the entire detector width. Basis of the detector is a specifically designed, radiation hard CMOS imaging sensor with a pixel pitch of 200 μ m. Each pixel has an automatic in-pixel gain adjustment, which allows for both: a very high sensitivity and a wide dynamic range. The final detector is planned to have 256 lines of pixels. By using a modular assembly of the detector, the width can be chosen as multiples of 512 pixels. With a frame rate of up to 300 frames/s (full resolution) or 1200 frame/s (analog binning to 400 μ m pixel pitch) time-resolved 3D CT applications become possible. Two versions of the detector are in development, one with a high resolution scintillator and one with a thick, structured and very efficient scintillator (pitch 400 μ m). This way the detector can even work with X-ray energies up to 450 kVp.

Functional Involvement of Carbonic Anhydrase in the Lysosomal Response to Cadmium Exposure in Mytilus galloprovincialis Digestive Gland

PubMed Central

Caricato, Roberto; Giordano, M. Elena; Schettino, Trifone; Lionetto, M. Giulia

2018-01-01

Carbonic anhydrase (CA) is a ubiquitous metalloenzyme, whose functions in animals span from respiration to pH homeostasis, electrolyte transport, calcification, and biosynthetic reactions. CA is sensitive to trace metals in a number of species. In mussels, a previous study demonstrated CA activity and protein expression to be enhanced in digestive gland by cadmium exposure. The aim of the present work was to investigate the functional meaning, if any, of this response. To this end the study addressed the possible involvement of CA in the lysosomal system response of digestive gland cells to metal exposure. The in vivo exposure to acetazolamide, specific CA inhibitor, significantly inhibited the acidification of the lysosomal compartment in the digestive gland cells charged with the acidotropic probe LysoSensor Green D-189, demonstrating in vivo the physiological contribution of CA to the acidification of the lysosomes. Under CdCl2 exposure, CA activity significantly increased in parallel to the increase of the fluorescence of LysoSensor Green charged cells, which is in turn indicative of proliferation and/or increase in size of lysosomes. Acetazolamide exposure was able to completely inhibit the cadmium induced Lysosensor fluorescence increase in digestive gland cells. In conclusion, our results demonstrated the functional role of CA in the lysosomal acidification of Mytilus galloprovincialis digestive gland and its involvement in the lysosomal activation following cadmium exposure. CA induction could physiologically respond to a prolonged increased requirement of H+ for supporting lysosomal acidification during lysosomal activation. PMID:29670538

Isothermal titration calorimetric studies on the interaction of the major bovine seminal plasma protein, PDC-109 with phospholipid membranes.

PubMed

Anbazhagan, V; Sankhala, Rajeshwer S; Singh, Bhanu Pratap; Swamy, Musti J

2011-01-01

The interaction of the major bovine seminal plasma protein, PDC-109 with lipid membranes was investigated by isothermal titration calorimetry. Binding of the protein to model membranes made up of diacyl phospholipids was found to be endothermic, with positive values of binding enthalpy and entropy, and could be analyzed in terms of a single type of binding sites on the protein. Enthalpies and entropies for binding to diacylphosphatidylcholine membranes increased with increase in temperature, although a clear-cut linear dependence was not observed. The entropically driven binding process indicates that hydrophobic interactions play a major role in the overall binding process. Binding of PDC-109 with dimyristoylphosphatidylcholine membranes containing 25 mol% cholesterol showed an initial increase in the association constant as well as enthalpy and entropy of binding with increase in temperature, whereas the values decreased with further increase in temperature. The affinity of PDC-109 for phosphatidylcholine increased at higher pH, which is physiologically relevant in view of the basic nature of the seminal plasma. Binding of PDC-109 to Lyso-PC could be best analysed in terms of two types of binding interactions, a high affinity interaction with Lyso-PC micelles and a low-affinity interaction with the monomeric lipid. Enthalpy-entropy compensation was observed for the interaction of PDC-109 with phospholipid membranes, suggesting that water structure plays an important role in the binding process.

Isothermal Titration Calorimetric Studies on the Interaction of the Major Bovine Seminal Plasma Protein, PDC-109 with Phospholipid Membranes

PubMed Central

Anbazhagan, V.; Sankhala, Rajeshwer S.; Singh, Bhanu Pratap; Swamy, Musti J.

2011-01-01

The interaction of the major bovine seminal plasma protein, PDC-109 with lipid membranes was investigated by isothermal titration calorimetry. Binding of the protein to model membranes made up of diacyl phospholipids was found to be endothermic, with positive values of binding enthalpy and entropy, and could be analyzed in terms of a single type of binding sites on the protein. Enthalpies and entropies for binding to diacylphosphatidylcholine membranes increased with increase in temperature, although a clear-cut linear dependence was not observed. The entropically driven binding process indicates that hydrophobic interactions play a major role in the overall binding process. Binding of PDC-109 with dimyristoylphosphatidylcholine membranes containing 25 mol% cholesterol showed an initial increase in the association constant as well as enthalpy and entropy of binding with increase in temperature, whereas the values decreased with further increase in temperature. The affinity of PDC-109 for phosphatidylcholine increased at higher pH, which is physiologically relevant in view of the basic nature of the seminal plasma. Binding of PDC-109 to Lyso-PC could be best analysed in terms of two types of binding interactions, a high affinity interaction with Lyso-PC micelles and a low-affinity interaction with the monomeric lipid. Enthalpy-entropy compensation was observed for the interaction of PDC-109 with phospholipid membranes, suggesting that water structure plays an important role in the binding process. PMID:22022488

Clinical observations on enzyme replacement therapy in patients with Fabry disease and the switch from agalsidase beta to agalsidase alfa.

PubMed

Lin, Hsiang-Yu; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Liu, Hao-Chuan; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Shuan-Pei; Niu, Dau-Ming

2014-04-01

Fabry disease is an X-linked inherited lysosomal storage disease that can be treated with the enzymes of agalsidase beta (Fabrazyme) and agalsidase alfa (Replagal). Since June 2009, viral contamination of Genzyme's production facility has resulted in a worldwide shortage of agalsidase beta, leading to the switch to agalsidase alfa for patients with Fabry disease in Taiwan. The medical records were retrospectively reviewed for nine male patients with Fabry disease from the start of agalsidase beta treatment until the switch to agalsidase alfa for at least 1 year. After 12-112 months of enzyme replacement therapy (ERT), decreased plasma globotriaosylsphingosine (lyso-Gb3) was found in five out of seven patients, indicating improvement in disease severity. Among the six patients with available echocardiographic data at baseline and after ERT, all six experienced reductions of left ventricular mass index. Renal function, including microalbuminuria and estimated glomerular filtration rate, showed stability after ERT. Mainz Severity Score Index scores revealed that all nine patients remained stable at 12 months after switching to agalsidase alfa. ERT improved or stabilized cardiac status and stabilized renal function, while reducing plasma lyso-Gb3. ERT was well tolerated, even among the three patients who had hypersensitivity reactions. The switch of ERT from agalsidase beta to agalsidase alfa appears to be safe after 1 year of follow-up for Taiwanese patients with Fabry disease. Copyright © 2013. Published by Elsevier B.V.

Primary Metabolism and Medium-Chain Fatty Acid Alterations Precede Long-Chain Fatty Acid Changes Impacting Neutral Lipid Metabolism in Response to an Anticancer Lysophosphatidylcholine Analogue in Yeast.

PubMed

Tambellini, Nicolas P; Zaremberg, Vanina; Krishnaiah, Saikumari; Turner, Raymond J; Weljie, Aalim M

2017-10-06

The nonmetabolizable lysophosphatidylcholine (LysoPC) analogue edelfosine is the prototype of a class of compounds being investigated for their potential as selective chemotherapeutic agents. Edelfosine targets membranes, disturbing cellular homeostasis. Is not clear at this point how membrane alterations are communicated between intracellular compartments leading to growth inhibition and eventual cell death. In the present study, a combined metabolomics/lipidomics approach for the unbiased identification of metabolic pathways altered in yeast treated with sublethal concentrations of the LysoPC analogue was employed. Mass spectrometry of polar metabolites, fatty acids, and lipidomic profiling was used to study the effects of edelfosine on yeast metabolism. Amino acid and sugar metabolism, the Krebs cycle, and fatty acid profiles were most disrupted, with polar metabolites and short-medium chain fatty acid changes preceding long and very long-chain fatty acid variations. Initial increases in metabolites such as trehalose, proline, and γ-amino butyric acid with a concomitant decrease in metabolites of the Krebs cycle, citrate and fumarate, are interpreted as a cellular attempt to offset oxidative stress in response to mitochondrial dysfunction induced by the treatment. Notably, alanine, inositol, and myristoleic acid showed a steady increase during the period analyzed (2, 4, and 6 h after treatment). Of importance was the finding that edelfosine induced significant alterations in neutral glycerolipid metabolism resulting in a significant increase in the signaling lipid diacylglycerol.

Inhibition of Autophagy Potentiates Atorvastatin-Induced Apoptotic Cell Death in Human Bladder Cancer Cells in Vitro

PubMed Central

Kang, Minyong; Jeong, Chang Wook; Ku, Ja Hyeon; Kwak, Cheol; Kim, Hyeon Hoe

2014-01-01

Statins are cholesterol reduction agents that exhibit anti-cancer activity in several human cancers. Because autophagy is a crucial survival mechanism for cancer cells under stress conditions, cooperative inhibition of autophagy acts synergistically with other anti-cancer drugs. Thus, this study investigates whether combined treatment of atorvastatin and autophagy inhibitors results in enhancing the cytotoxic effects of atorvastatin, upon human bladder cancer cells, T24 and J82, in vitro. To measure cell viability, we performed the EZ-Cytox cell viability assay. We examined apoptosis by flow cytometry using annexin-V/propidium iodide (PI and western blot using procaspase-3 and poly (ADP-ribose) polymerase (PARP) antibodies. To examine autophagy activation, we evaluated the co-localization of LC3 and LysoTracker by immunocytochemistry, as well as the expression of LC3 and p62/sequestosome-1 (SQSTM1) by western blot. In addition, we assessed the survival and proliferation of T24 and J82 cells by a clonogenic assay. We found that atorvastatin reduced the cell viability of T24 and J82 cells via apoptotic cell death and induced autophagy activation, shown by the co-localization of LC3 and LysoTracker. Moreover, pharmacologic inhibition of autophagy significantly enhanced atorvastatin-induced apoptosis in T24 and J82 cells. In sum, inhibition of autophagy potentiates atorvastatin-induced apoptotic cell death in human bladder cancer cells in vitro, providing a potential therapeutic approach to treat bladder cancer. PMID:24815071

Collimator design for a multipinhole brain SPECT insert for MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Audenhaege, Karen; Van Holen, Roel; Vanhove, Christian

Purpose: Brain single photon emission computed tomography (SPECT) imaging is an important clinical tool, with unique tracers for studying neurological diseases. Nowadays, most commercial SPECT systems are combined with x-ray computed tomography (CT) in so-called SPECT/CT systems to obtain an anatomical background for the functional information. However, while CT images have a high spatial resolution, they have a low soft-tissue contrast, which is an important disadvantage for brain imaging. Magnetic resonance imaging (MRI), on the other hand, has a very high soft-tissue contrast and does not involve extra ionizing radiation. Therefore, the authors designed a brain SPECT insert that canmore » operate inside a clinical MRI. Methods: The authors designed and simulated a compact stationary multipinhole SPECT insert based on digital silicon photomultiplier detector modules, which have shown to be MR-compatible and have an excellent intrinsic resolution (0.5 mm) when combined with a monolithic 2 mm thick LYSO crystal. First, the authors optimized the different parameters of the SPECT system to maximize sensitivity for a given target resolution of 7.2 mm in the center of the field-of-view, given the spatial constraints of the MR system. Second, the authors performed noiseless simulations of two multipinhole configurations to evaluate sampling and reconstructed resolution. Finally, the authors performed Monte Carlo simulations and compared the SPECT insert with a clinical system with ultrahigh-resolution (UHR) fan beam collimators, based on contrast-to-noise ratio and a visual comparison of a Hoffman phantom with a 9 mm cold lesion. Results: The optimization resulted in a stationary multipinhole system with a collimator radius of 150.2 mm and a detector radius of 172.67 mm, which corresponds to four rings of 34 diSPM detector modules. This allows the authors to include eight rings of 24 pinholes, which results in a system volume sensitivity of 395 cps/MBq. Noiseless simulations show sufficient axial sampling (in a Defrise phantom) and a reconstructed resolution of 5.0 mm (in a cold-rod phantom). The authors compared the 24-pinhole setup with a 34-pinhole system (with the same detector radius but a collimator radius of 156.63 mm) and found that 34 pinholes result in better uniformity but a worse reconstruction of the cold-rod phantom. The authors also compared the 24-pinhole system with a clinical triple-head UHR fan beam system based on contrast-to-noise ratio and found that the 24-pinhole setup performs better for the 6 mm hot and the 16 mm cold lesions and worse for the 8 and 10 mm hot lesions. Finally, the authors reconstructed noisy projection data of a Hoffman phantom with a 9 mm cold lesion and found that the lesion was slightly better visible on the multipinhole image compared to the fan beam image. Conclusions: The authors have optimized a stationary multipinhole SPECT insert for MRI and showed the feasibility of doing brain SPECT imaging inside a MRI with an image quality similar to the best clinical SPECT systems available.« less

Initial performance evaluation of a preclinical PET scanner available as a clip-on assembly in a sequential PET/MRI system.

PubMed

Vrigneaud, Jean-Marc; McGrath, John; Courteau, Alan; Pegg, Rosie; Sanchez-Pastor Gomis, Alberto; Camacho, Angela; Martin, Gary; Schramm, Nils; Brunotte, François

2018-05-15

We evaluated the performance characteristics of a prototype preclinical PET scanner available as an easy clippable assembly that can dock to an MRI system. The single ring version of the PET system consists of 8 detectors, each of which comprises a 12 × 12 silicon photomultipliers (SiPMs) array coupled with a dual layer of offset scintillation crystals to measure depth of interaction. The crystal arrays have 29 × 29 (30 × 30 for the outer layer) 4 mm long LYSO crystals (6 mm for the outer layer). The ring diameter is 119.2 mm and the axial field of view is 50.4 mm. The NEMA NU-4-2008 protocol was followed for studying the PET performance. Temperature stability of SiPMs was also investigated. The peak system absolute sensitivity was 4.70% with an energy window of 250-750 keV. The spatial resolution was 1.28/1.88/1.85 mm FWHM (radial/tangential/axial) at a distance of 5 mm from the center. Peak noise equivalent counting rate (NECR) and scatter fraction for mouse phantom were 61.9 kcps at 14.9 MBq and 21.0%, respectively. The uniformity was 6.3% and the spill-over ratios in the images of the water- and air-filled chambers were 0.07 and 0.17, respectively. Recovery coefficients ranged from 0.13 to 0.96. Change in sensitivity as a function of ambient temperature was 0.3%/°C. These first results indicate excellent spatial resolution performance for use with animal studies. Moreover, the clippable assembly can be upgraded to accept a second ring of SiPMs modules, leading to improved sensitivity and axial coverage. © 2018 Institute of Physics and Engineering in Medicine.

Phase contrast in high resolution electron microscopy

DOEpatents

Rose, H.H.

1975-09-23

This patent relates to a device for developing a phase contrast signal for a scanning transmission electron microscope. The lens system of the microscope is operated in a condition of defocus so that predictable alternate concentric regions of high and low electron density exist in the cone of illumination. Two phase detectors are placed beneath the object inside the cone of illumination, with the first detector having the form of a zone plate, each of its rings covering alternate regions of either higher or lower electron density. The second detector is so configured that it covers the regions of electron density not covered by the first detector. Each detector measures the number of electrons incident thereon and the signal developed by the first detector is subtracted from the signal developed by the record detector to provide a phase contrast signal. (auth)

Development of FARICH detector for particle identification system at accelerators

NASA Astrophysics Data System (ADS)

Finogeev, D. A.; Kurepin, A. B.; Razin, V. I.; Reshetin, A. I.; Usenko, E. A.; Barnyakov, A. Yu.; Barnyakov, M. Yu.; Bobrovnikov, V. S.; Buzykaev, A. R.; Kasyanenko, P. V.; Kononov, S. A.; Kravchenko, E. A.; Kuyanov, I. A.; Onuchin, A. P.; Ovtin, I. V.; Podgornov, N. A.; Talyshev, A. A.; Danilyuk, A. F.

2018-01-01

Aerogel has been successfully used as a radiator in Cherenkov detectors. In 2004, a multilayer aerogel providing Cherenkov ring focusing was proposed and produced. FARICH (Focusing Aerogel Rich Imaging CHerenkov) detectors such as ARICH for Belle-II (KEK, Japan), Forward RICH for PANDA detector (FAIR, Germany), and FARICH for the Super Charm-Tau factory project (BINP, Novosibirsk) have been developed based on this aerogel. Prototypes of FARICH detector based on MRS APD and Philips DPC photosensors were developed and tested in the framework of this project. An angular resolution for Cherenkov rings of 3.6 mrad was achieved.

Secondary radiation measurements for particle therapy applications: prompt photons produced by 4He, 12C and 16O ion beams in a PMMA target.

PubMed

Mattei, I; Bini, F; Collamati, F; De Lucia, E; Frallicciardi, P M; Iarocci, E; Mancini-Terracciano, C; Marafini, M; Muraro, S; Paramatti, R; Patera, V; Piersanti, L; Pinci, D; Rucinski, A; Russomando, A; Sarti, A; Sciubba, A; Solfaroli Camillocci, E; Toppi, M; Traini, G; Voena, C; Battistoni, G

2017-02-21

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z  >  1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at [Formula: see text] and [Formula: see text] with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

Secondary radiation measurements for particle therapy applications: prompt photons produced by 4He, 12C and 16O ion beams in a PMMA target

NASA Astrophysics Data System (ADS)

Mattei, I.; Bini, F.; Collamati, F.; De Lucia, E.; Frallicciardi, P. M.; Iarocci, E.; Mancini-Terracciano, C.; Marafini, M.; Muraro, S.; Paramatti, R.; Patera, V.; Piersanti, L.; Pinci, D.; Rucinski, A.; Russomando, A.; Sarti, A.; Sciubba, A.; Solfaroli Camillocci, E.; Toppi, M.; Traini, G.; Voena, C.; Battistoni, G.

2017-02-01

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z  >  1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at {{60}\\circ} and {{90}\\circ} with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

In-core flux sensor evaluations at the ATR critical facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Troy Unruh; Benjamin Chase; Joy Rempe

2014-09-01

Flux detector evaluations were completed as part of a joint Idaho State University (ISU) / Idaho National Laboratory (INL) / French Atomic Energy commission (CEA) ATR National Scientific User Facility (ATR NSUF) project to compare the accuracy, response time, and long duration performance of several flux detectors. Special fixturing developed by INL allows real-time flux detectors to be inserted into various ATRC core positions and perform lobe power measurements, axial flux profile measurements, and detector cross-calibrations. Detectors initially evaluated in this program include the French Atomic Energy Commission (CEA)-developed miniature fission chambers; specialized self-powered neutron detectors (SPNDs) developed by themore » Argentinean National Energy Commission (CNEA); specially developed commercial SPNDs from Argonne National Laboratory. As shown in this article, data obtained from this program provides important insights related to flux detector accuracy and resolution for subsequent ATR and CEA experiments and flux data required for bench-marking models in the ATR V&V Upgrade Initiative.« less

Semiconductor Radiation Detectors: Basic principles and some uses of a recent tool that has revolutionized nuclear physics are described.

PubMed

Goulding, F S; Stone, Y

1970-10-16

The past decade has seen the rapid development and exploitation of one of the most significant tools of nuclear physics, the semiconductor radiation detector. Applications of the device to the analysis of materials promises to be one of the major contributions of nuclear research to technology, and may even assist in some aspects of our environmental problems. In parallel with the development of these applications, further developments in detectors for nuclear research are taking place: the use of very thin detectors for heavyion identification, position-sensitive detectors for nuclear-reaction studies, and very pure germanium for making more satisfactory detectors for many applications suggest major future contributions to physics.

Expanding the detection efficiency of silicon drift detectors

NASA Astrophysics Data System (ADS)

Schlosser, D. M.; Lechner, P.; Lutz, G.; Niculae, A.; Soltau, H.; Strüder, L.; Eckhardt, R.; Hermenau, K.; Schaller, G.; Schopper, F.; Jaritschin, O.; Liebel, A.; Simsek, A.; Fiorini, C.; Longoni, A.

2010-12-01

To expand the detection efficiency Silicon Drift Detectors (SDDs) with various customized radiation entrance windows, optimized detector areas and geometries have been developed. Optimum values for energy resolution, peak to background ratio (P/B) and high count rate capability support the development. Detailed results on sensors optimized for light element detection down to Boron or even lower will be reported. New developments for detecting medium and high X-ray energies by increasing the effective detector thickness will be presented. Gamma-ray detectors consisting of a SDD coupled to scintillators like CsI(Tl) and LaBr 3(Ce) have been examined. Results of the energy resolution for the 137Cs 662 keV line and the light yield (LY) of such detector systems will be reported.

Design and properties of silicon charged-particle detectors developed at the Institute of Electron Technology (ITE)

NASA Astrophysics Data System (ADS)

Wegrzecki, Maciej; Bar, Jan; Budzyński, Tadeusz; CieŻ, Michal; Grabiec, Piotr; Kozłowski, Roman; Kulawik, Jan; Panas, Andrzej; Sarnecki, Jerzy; Słysz, Wojciech; Szmigiel, Dariusz; Wegrzecka, Iwona; Wielunski, Marek; Witek, Krzysztof; Yakushev, Alexander; Zaborowski, Michał

2013-07-01

The paper discusses the design of charged-particle detectors commissioned and developed at the Institute of Electron Technology (ITE) in collaboration with foreign partners, used in international research on transactinide elements and to build personal radiation protection devices in Germany. Properties of these detectors and the results obtained using the devices are also presented. The design of the following epiplanar detector structures is discussed: ♢ 64-element chromatographic arrays for the COMPACT (Cryo On-line Multidetector for Physics And Chemistry of Transactinides) detection system used at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt (GSI) for research on Hassium, Copernicium and Flerovium, as well as elements 119 and 120, ♢ 2-element flow detectors for the COLD (Cryo On-Line Detector) system used for research on Copernicium and Flerovium at the Joint Institute for Nuclear Research, Dubna, ♢ detectors for a radon exposimeter and sensors for a neutron dosimeter developed at the Institut für Strahlenschutz, Helmholtz Zentrum München. The design of planar detectors - single-sided and double-sided strip detectors for the Focal Plane Detector Box used at GSI for research on Flerovium and elements 119 and 120 is also discussed.

AO WFS detector developments at ESO to prepare for the E-ELT

NASA Astrophysics Data System (ADS)

Downing, Mark; Casali, Mark; Finger, Gert; Lewis, Steffan; Marchetti, Enrico; Mehrgan, Leander; Ramsay, Suzanne; Reyes, Javier

2016-07-01

ESO has a very active on-going AO WFS detector development program to not only meet the needs of the current crop of instruments for the VLT, but also has been actively involved in gathering requirements, planning, and developing detectors and controllers/cameras for the instruments in design and being proposed for the E-ELT. This paper provides an overall summary of the AO WFS Detector requirements of the E-ELT instruments currently in design and telescope focal units. This is followed by a description of the many interesting detector, controller, and camera developments underway at ESO to meet these needs; a) the rationale behind and plan to upgrade the 240x240 pixels, 2000fps, "zero noise", L3Vision CCD220 sensor based AONGC camera; b) status of the LGSD/NGSD High QE, 3e- RoN, fast 700fps, 1760x1680 pixels, Visible CMOS Imager and camera development; c) status of and development plans for the Selex SAPHIRA NIR eAPD and controller. Most of the instruments and detector/camera developments are described in more detail in other papers at this conference.

Continued development of room temperature semiconductor nuclear detectors

NASA Astrophysics Data System (ADS)

Kim, Hadong; Cirignano, Leonard; Churilov, Alexei; Ciampi, Guido; Kargar, Alireza; Higgins, William; O'Dougherty, Patrick; Kim, Suyoung; Squillante, Michael R.; Shah, Kanai

2010-08-01

Thallium bromide (TlBr) and related ternary compounds, TlBrI and TlBrCl, have been under development for room temperature gamma ray spectroscopy due to several promising properties. Due to recent advances in material processing, electron mobility-lifetime product of TlBr is close to Cd(Zn)Te's value which allowed us to fabricate large working detectors. We were also able to fabricate and obtain spectroscopic results from TlBr Capacitive Frisch Grid detector and orthogonal strip detectors. In this paper we report on our recent TlBr and related ternary detector results and preliminary results from Cinnabar (HgS) detectors.

Progress in the Development of CdTe and CdZnTe Semiconductor Radiation Detectors for Astrophysical and Medical Applications

PubMed Central

Sordo, Stefano Del; Abbene, Leonardo; Caroli, Ezio; Mancini, Anna Maria; Zappettini, Andrea; Ubertini, Pietro

2009-01-01

Over the last decade, cadmium telluride (CdTe) and cadmium zinc telluride (CdZnTe) wide band gap semiconductors have attracted increasing interest as X-ray and gamma ray detectors. Among the traditional high performance spectrometers based on silicon (Si) and germanium (Ge), CdTe and CdZnTe detectors show high detection efficiency and good room temperature performance and are well suited for the development of compact and reliable detection systems. In this paper, we review the current status of research in the development of CdTe and CdZnTe detectors by a comprehensive survey on the material properties, the device characteristics, the different techniques for improving the overall detector performance and some major applications. Astrophysical and medical applications are discussed, pointing out the ongoing Italian research activities on the development of these detectors. PMID:22412323

MCP detector development for UV space missions

NASA Astrophysics Data System (ADS)

Conti, Lauro; Barnstedt, Jürgen; Hanke, Lars; Kalkuhl, Christoph; Kappelmann, Norbert; Rauch, Thomas; Stelzer, Beate; Werner, Klaus; Elsener, Hans-Rudolf; Schaadt, Daniel M.

2018-04-01

We are developing imaging and photon counting UV-MCP detectors, which are sensitive in the wavelength range from far ultraviolet to near ultraviolet. A good quantum efficiency, solar blindness and high spatial resolution is the aim of our development. The sealed detector has a Cs-activated photoactive layer of GaN (or similarly advanced photocathode), which is operated in semitransparent mode on (001)-MgF2. The detector comprises a stack of two long-life MCPs and a coplanar cross strip anode with advanced readout electronics. The main challenge is the flawless growth of the GaN photocathode layer as well as the requirements for the sealing of the detector, to prevent a degradation of the photocathode. We present here the detector concept and the experimental setup, examine in detail the status in the production and describe the current status of the readout electronics development.

Sofradir latest developments for infrared space detectors

NASA Astrophysics Data System (ADS)

Chorier, Philippe; Delannoy, Anne

2011-06-01

Sofradir is one of the leading companies that develop and produce infrared detectors. Space applications have become a significant activity and Sofradir relies now on 20 years of experience in development and production of MCT infrared detectors of 2nd and 3rd generation for space applications. Thanks to its capabilities and experience, Sofradir is now able to offer high reliability infrared detectors for space applications. These detectors cover various kinds of applications like hyperspectral observation, earth observations for meteorological or scientific purpose and science experiments. In this paper, we present a review of latest Sofradir's development for infrared space applications. A presentation of Sofradir infrared detectors answering hyperspectral needs from visible up to VLWIR waveband will be made. In addition a particular emphasis will be placed on the different programs currently running, with a presentation of the associated results as they relate to performances and qualifications for space use.

Variable-Temperature Cryostat For Radiation-Damage Testing Of Germanium Detectors

NASA Technical Reports Server (NTRS)

Floyd, Samuel R.; Puc, Bernard P.

1992-01-01

Variable-temperature cryostats developed to study radiation damage to, and annealing of, germanium gamma-ray detectors. Two styles: one accommodates large single detector and one accommodates two medium-sized detectors. New cryostats allow complete testing of large-volume germanium gamma-ray detectors without breaking cryostat vacuum and removing detectors for annealing.

Development and calibration of a new gamma camera detector using large square Photomultiplier Tubes

NASA Astrophysics Data System (ADS)

Zeraatkar, N.; Sajedi, S.; Teimourian Fard, B.; Kaviani, S.; Akbarzadeh, A.; Farahani, M. H.; Sarkar, S.; Ay, M. R.

2017-09-01

Large area scintillation detectors applied in gamma cameras as well as Single Photon Computed Tomography (SPECT) systems, have a major role in in-vivo functional imaging. Most of the gamma detectors utilize hexagonal arrangement of Photomultiplier Tubes (PMTs). In this work we applied large square-shaped PMTs with row/column arrangement and positioning. The Use of large square PMTs reduces dead zones in the detector surface. However, the conventional center of gravity method for positioning may not introduce an acceptable result. Hence, the digital correlated signal enhancement (CSE) algorithm was optimized to obtain better linearity and spatial resolution in the developed detector. The performance of the developed detector was evaluated based on NEMA-NU1-2007 standard. The acquired images using this method showed acceptable uniformity and linearity comparing to three commercial gamma cameras. Also the intrinsic and extrinsic spatial resolutions with low-energy high-resolution (LEHR) collimator at 10 cm from surface of the detector were 3.7 mm and 7.5 mm, respectively. The energy resolution of the camera was measured 9.5%. The performance evaluation demonstrated that the developed detector maintains image quality with a reduced number of used PMTs relative to the detection area.

Using a flat-panel detector in high resolution cone beam CT for dental imaging.

PubMed

Baba, R; Ueda, K; Okabe, M

2004-09-01

Cone beam CT (CBCT) requires a two-dimensional X-ray detector. In the several CBCT systems developed for dental imaging, detection has been by the combination of an X-ray image intensifier and charge-coupled device (CCD) camera. In this paper, we propose a new CBCT system in which the detector is of the flat-panel type and evaluate its performance in dental imaging. We developed a prototype CBCT that has a flat-panel-type detector. The detector consists of a CsI scintillator screen and a photosensor array. First, the flat panel detector and image intensifier detector were compared in terms of the signal-to-noise ratio (SNR) of projected images. We then used these data and a theoretical formula to evaluate noise in reconstructed images. Second, reconstructed images of a bar pattern phantom were obtained as a way of evaluating the spatial resolution. Then, reconstructed images of a skull phantom were obtained. The SNR of the developed system was 1.6 times as high as that of a system with an image intensifier detector of equal detector pitch. The system was capable of resolving a 0.35 mm pattern and its field of view almost completely encompassed that of an image intensifier detector which is used in dentomaxillofacial imaging. The fine spatial resolution of the detector led to images in which the structural details of a skull phantom were clearly visible. The system's isotropically fine resolution will lead to improved precision in dental diagnosis and surgery. The next stage of our research will be the development of a flat panel detector system with a high frame acquisition rate.

Development of ultrahigh resolution alpha particle imaging detector using 1 mm channel size Si-PM array

NASA Astrophysics Data System (ADS)

Yamamoto, Seiichi; Kawaguchi, Wataru

2018-06-01

For precise distribution measurements of alpha particles, a high-resolution alpha particle imaging detector is required. Although combining a thin scintillator with a silicon photomultiplier (Si-PM) array is a promising method for achieving high resolution, the spatial resolution is limited. Reducing the size of the Si-PM array is a possible approach to improving the spatial resolution of the alpha particle imaging detector. Consequently, we employed a 1 mm channel size Si-PM array combined with a thin ZnS(Ag) sheet to form an alpha particle imaging detector and evaluated the performance. For the developed alpha particle imaging detector, an Si-PM array with 1 mm x 1 mm channel size arranged 8 x 8 was optically coupled to a ZnS(Ag) sheet with a 1-mm-thick light guide between them. The size of the alpha particle imaging detector was 9.5 mm x 9.5 mm. The spatial resolution of the developed alpha particle imaging detector was 0.14 mm FWHM, and the energy resolution was 74% FWHM for 5.5 MeV alpha particles. The uniformity of the imaging detector at the central part of the field of view (FOV) was ±4.7%. The background count rate was 0.06 counts/min. We obtained various high-resolution phantom images for alpha particles with the developed system. We conclude that the developed imaging detector is promising for high-resolution distribution measurements of alpha particles.

Radioembolization and the Dynamic Role of 90Y PET/CT

PubMed Central

Pasciak, Alexander S.; Bourgeois, Austin C.; McKinney, J. Mark; Chang, Ted T.; Osborne, Dustin R.; Acuff, Shelley N.; Bradley, Yong C.

2014-01-01

Before the advent of tomographic imaging, it was postulated that decay of 90 Y to the 0+ excited state of 90Zr may result in emission of a positron–electron pair. While the branching ratio for pair-production is small (~32 × 10−6), PET has been successfully used to image 90 Y in numerous recent patients and phantom studies. 90 Y PET imaging has been performed on a variety of PET/CT systems, with and without time-of-flight (TOF) and/or resolution recovery capabilities as well as on both bismuth-germanate and lutetium yttrium orthosilicate (LYSO)-based scanners. On all systems, resolution and contrast superior to bremsstrahlung SPECT has been reported. The intrinsic radioactivity present in LYSO-based PET scanners is a potential limitation associated with accurate quantification of 90 Y. However, intrinsic radioactivity has been shown to have a negligible effect at the high activity concentrations common in 90 Y radioembolization. Accurate quantification is possible on a variety of PET scanner models, with or without TOF, although TOF improves accuracy at lower activity concentrations. Quantitative 90 Y PET images can be transformed into 3-dimensional (3D) maps of absorbed dose based on the premise that the 90 Y activity distribution does not change after infusion. This transformation has been accomplished in several ways, although the most common is with the use of 3D dose-point-kernel convolution. From a clinical standpoint, 90 Y PET provides a superior post-infusion evaluation of treatment technical success owing to its improved resolution. Absorbed dose maps generated from quantitative PET data can be used to predict treatment efficacy and manage patient follow-up. For patients who receive multiple treatments, this information can also be used to provide patient-specific treatment-planning for successive therapies, potentially improving response. The broad utilization of 90 Y PET has the potential to provide a wealth of dose–response information, which may lead to development of improved radioembolization treatment-planning models in the future. PMID:24579065

Differential release of cell-signaling metabolites by male and female bovine embryos cultured in vitro.

PubMed

Gómez, E; Carrocera, S; Martin, D; Herrero, P; Canela, N; Muñoz, M

2018-07-01

Male and female early bovine embryos show dimorphic transcription that impacts metabolism. Individual release of metabolites was examined in a 24h single culture medium from Day-6 male and female morulae that developed to Day-7 expanded blastocysts. Embryos were produced in vitro, fertilized with a single bull and cultured in SOFaaci+6  g/L BSA. The embryonic sex was identified (amelogenin gene amplification). Embryos (N = 10 males and N = 10 females) and N = 6 blank samples (i.e. SOFaaci+6  g/L BSA incubated with no embryos) were collected from 3 replicates. Metabolome was analyzed by UHPLC-TOF-MS in spent culture medium. After tentative identification, N = 13 metabolites significantly (P < 0.05; ANOVA) differed in their concentrations between male and female embryos, although N = 10 of these metabolites showed heterogeneity (Levene's test; P > 0.05). LysoPC(15:0) was the only metabolite found at higher concentration in females (fold change [FC] male to female = 0.766). FC of metabolites more abundant in male culture medium (N = 12) varied from 1.069 to 1.604. Chemical taxonomy grouped metabolites as amino-acids and related compounds (DL-2 aminooctanoic acid, arginine, 5-hydroxy-l-tryptophan, and palmitoylglycine); lipids (2-hexenoylcarnitine; Lauroyl diethanolamide; 5,6 dihydroxyprostaglandin F1a; LysoPC(15:0); DG(14:0/14:1(9Z)/0:0) and triterpenoid); endogenous amine ((S)-N-Methylsalsolinol/(R)-N-Methylsalsolinol); n-acyl-alpha-hexosamine (N-acetyl-alpha-d-galactosamine 1-phosphate); and dUMP, a product of pyrimidine metabolism. Among the compounds originally contained in CM, female embryos significantly depleted more arginine than males and blank controls (P < 0.001). Male and female embryos induce different concentrations of metabolites with potential signaling effects. The increased abundance of metabolites released from males is consistent with the higher metabolic activity attributed to such blastocysts. Copyright © 2018 Elsevier Inc. All rights reserved.

Intravenous infusion of PAF affects ovulation, fertilization and preimplantation embryonic development in NZB x NZW F1 hybrid mice.

PubMed

Sakellariou, Maria; Drakakis, Peter; Antonopoulou, Smaragdi; Anagnostou, Elli; Loutradis, Dimitris; Patargias, Theoxaris

2008-03-01

Platelet Activating Factor (PAF) is a bioactive phospholipid, which exhibits a variety of biological activities and plays a significant role in all aspects of reproduction. In this work, a single intravenous injection of various concentrations of PAF shortly after Human Chorionic Gonadotropin (HCG) administration as well as 24 and 48 h before HCG administration was studied in NZB x NZW F1 hybrid mice. Optimum results were observed when PAF was injected just after the administration of HCG. In this protocol, the concentrations of PAF exhibited bell-shaped response to every stage of development. Any concentration of PAF between 5.5 x 10(-11) and 5.5 x 10(-15)g/g b.w., caused an improved ovulation rate, an increased fertilization rate, an increased rate of cell cycle and an enhanced hatching blastocyst rate (P<0.05 for all stages). Injection of lyso-PAF had no effect in any stage. Our data show that the effect of PAF on early stages of embryo development in vitro is dependent on its way of administration, on the concentrations used as well as on the time PAF is injected.

Development of a Coded Aperture X-Ray Backscatter Imager for Explosive Device Detection

NASA Astrophysics Data System (ADS)

Faust, Anthony A.; Rothschild, Richard E.; Leblanc, Philippe; McFee, John Elton

2009-02-01

Defence R&D Canada has an active research and development program on detection of explosive devices using nuclear methods. One system under development is a coded aperture-based X-ray backscatter imaging detector designed to provide sufficient speed, contrast and spatial resolution to detect antipersonnel landmines and improvised explosive devices. The successful development of a hand-held imaging detector requires, among other things, a light-weight, ruggedized detector with low power requirements, supplying high spatial resolution. The University of California, San Diego-designed HEXIS detector provides a modern, large area, high-temperature CZT imaging surface, robustly packaged in a light-weight housing with sound mechanical properties. Based on the potential for the HEXIS detector to be incorporated as the detection element of a hand-held imaging detector, the authors initiated a collaborative effort to demonstrate the capability of a coded aperture-based X-ray backscatter imaging detector. This paper will discuss the landmine and IED detection problem and review the coded aperture technique. Results from initial proof-of-principle experiments will then be reported.

Design philosophy of the Jet Propulsion Laboratory infrared detector test facility

NASA Technical Reports Server (NTRS)

Burns, R.; Blessinger, M. A.

1983-01-01

To support the development of advanced infrared remote sensing instrumentation using line and area arrays, a test facility has been developed to characterize the detectors. The necessary performance characteristics of the facility were defined by considering current and projected requirements for detector testing. The completed facility provides the desired level of detector testing capability as well as providing ease of human interaction.

MCT (HgCdTe) IR detectors: latest developments in France

NASA Astrophysics Data System (ADS)

Reibel, Yann; Rubaldo, Laurent; Vaz, Cedric; Tribolet, Philippe; Baier, Nicolas; Destefanis, Gérard

2010-10-01

This paper presents an overview of the very recent developments of the MCT infrared detector technology developed by CEA-LETI and Sofradir in France. New applications require high sensitivity, higher operating temperature and dual band detectors. The standard n on p technology in production at Sofradir for 25 years is well mastered with an extremely robust and reliable process. Sofradir's interest in p on n technology opens the perspective of reducing dark current of diodes so detectors could operate in lower flux or higher operating temperature. In parallel, MCT Avalanche Photo Diodes (APD) have demonstrated ideal performances for low flux and high speed application like laser gated imaging during the last few years. This technology also opens new prospects on next generation of imaging detectors for compact, low flux and low power applications. Regarding 3rd Gen IR detectors, the development of dual-band infrared detectors has been the core of intense research and technological improvements for the last ten years. New TV (640 x 512 pixels) format MWIR/LWIR detectors on 20μm pixel pitch, made from Molecular Beam Epitaxy, has been developed with dedicated Read-Out Integrated Circuit (ROIC) for real simultaneous detection and maximum SNR. Technological and products achievements, as well as latest results and performances are presented outlining the availability of p/n, avalanche photodiodes and dual band technologies for new applications at system level.

The Future of Single- to Multi-band Detector Technologies: Review

NASA Technical Reports Server (NTRS)

Abedin, M. Nurul; Bhat, Ishwara; Gunapala, Sarath D.; Bandara, Sumith V.; Refaat, Tamer F.; Sandford, Stephen P.; Singh, Upendra N.

2006-01-01

Using classical optical components such as filters, prisms and gratings to separate the desired wavelengths before they reach the detectors results in complex optical systems composed of heavy components. A simpler system will result by utilizing a single optical system and a detector that responds separately to each wavelength band. Therefore, a continuous endeavors to develop the capability to reliably fabricate detector arrays that respond to multiple wavelength regions. In this article, we will review the state-of-the-art single and multicolor detector technologies over a wide spectral-range, for use in space-based and airborne remote sensing applications. Discussions will be focused on current and the most recently developed focal plane arrays (FPA) in addition to emphasizing future development in UV-to-Far infrared multicolor FPA detectors for next generation space-based instruments to measure water vapor and greenhouse gases. This novel detector component will make instruments designed for these critical measurements more efficient while reducing complexity and associated electronics and weight. Finally, we will discuss the ongoing multicolor detector technology efforts at NASA Langley Research Center, Jet Propulsion Laboratory, Rensselaer Polytechnic Institute, and others.

Quantum Well and Quantum Dot Modeling for Advanced Infrared Detectors and Focal Plane Arrays

NASA Technical Reports Server (NTRS)

Ting, David; Gunapala, S. D.; Bandara, S. V.; Hill, C. J.

2006-01-01

This viewgraph presentation reviews the modeling of Quantum Well Infrared Detectors (QWIP) and Quantum Dot Infrared Detectors (QDIP) in the development of Focal Plane Arrays (FPA). The QWIP Detector being developed is a dual band detector. It is capable of running on two bands Long-Wave Infrared (LWIR) and Medium Wavelength Infrared (MWIR). The same large-format dual-band FPA technology can be applied to Quantum Dot Infrared Photodetector (QDIP) with no modification, once QDIP exceeds QWIP in single device performance. Details of the devices are reviewed.

LANL receiver system development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laubscher, B.; Cooke, B.; Cafferty, M.

1997-08-01

The CALIOPE receiver system development at LANL is the story of two technologies. The first of these technologies consists of off-the-shelf mercury-cadmium-telluride (MCT) detectors and amplifiers. The vendor for this system is Kolmar Technologies. This system was fielded in the Tan Trailer I (TTI) in 1995 and will be referred to in this paper as GEN I. The second system consists of a MCT detector procured from Santa Barbara Research Center (SBRC) and an amplifier designed and built by LANL. This system was fielded in the Tan Trailer II (TTII) system at the NTS tests in 1996 and will bemore » referred to as GEN II. The LANL CALIOPE experimental plan for 1996 was to improve the lidar system by progressing to a higher rep rate laser to perform many shots in a much shorter period of time. In keeping with this plan, the receiver team set a goal of developing a detector system that was background limited for the projected 100 nanosecond (ns) laser pulse. A set of detailed simulations of the DIAL lidar experiment was performed. From these runs, parameters such as optimal detector size, field of view of the receiver system, nominal laser return power, etc. were extracted. With this information, detector physics and amplifier electronic models were developed to obtain the required specifications for each of these components. These derived specs indicated that a substantial improvement over commercially available, off-the-shelf, amplifier and detector technologies would be needed to obtain the goals. To determine if the original GEN I detector was usable, the authors performed tests on a 100 micron square detector at cryogenic temperatures. The results of this test and others convinced them that an advanced detector was required. Eventually, a suitable detector was identified and a number of these single element detectors were procured from SBRC. These single element detectors were witness for the detector arrays built for another DOE project.« less

New installation for inclined EAS investigations

NASA Astrophysics Data System (ADS)

Zadeba, E. A.; Ampilogov, N. V.; Barbashina, N. S.; Bogdanov, A. G.; Borisov, A. A.; Chernov, D. V.; Dushkin, L. I.; Fakhrutdinov, R. M.; Kokoulin, R. P.; Kompaniets, K. G.; Kozhin, A. S.; Ovchinnikov, V. V.; Ovechkin, A. S.; Petrukhin, A. A.; Shutenko, V. V.; Volkov, N. S.; Vorobjev, V. S.; Yashin, I. I.

2017-06-01

The large-scale coordinate-tracking detector TREK for registration of inclined EAS is being developed in MEPhI. The detector is based on multiwire drift chambers from the neutrino experiment at the IHEP U-70 accelerator. Their key advantages are a large effective area (1.85 m2), a good coordinate and angular resolution with a small number of measuring channels. The detector will be operated as part of the experimental complex NEVOD, in particular, jointly with a Cherenkov water detector (CWD) with a volume of 2000 cubic meters and the coordinate detector DECOR. The first part of the detector named Coordinate-Tracking Unit based on the Drift Chambers (CTUDC), representing two coordinate planes of 8 drift chambers in each, has been developed and mounted on opposite sides of the CWD. It has the same principle of joint operation with the NEVOD-DECOR triggering system and the same drift chambers alignment, so the main features of the TREK detector will be examined. Results of the CTUDC development and a joint operation with NEVOD-DECOR complex are presented.

The high energy cosmic-radiation detection (HERD) facility onboard China's Space Station

NASA Astrophysics Data System (ADS)

Zhang, S. N.; Adriani, O.; Albergo, S.; Ambrosi, G.; An, Q.; Bao, T. W.; Battiston, R.; Bi, X. J.; Cao, Z.; Chai, J. Y.; Chang, J.; Chen, G. M.; Chen, Y.; Cui, X. H.; Dai, Z. G.; D'Alessandro, R.; Dong, Y. W.; Fan, Y. Z.; Feng, C. Q.; Feng, H.; Feng, Z. Y.; Gao, X. H.; Gargano, F.; Giglietto, N.; Gou, Q. B.; Guo, Y. Q.; Hu, B. L.; Hu, H. B.; He, H. H.; Huang, G. S.; Huang, J.; Huang, Y. F.; Li, H.; Li, L.; Li, Y. G.; Li, Z.; Liang, E. W.; Liu, H.; Liu, J. B.; Liu, J. T.; Liu, S. B.; Liu, S. M.; Liu, X.; Lu, J. G.; Mazziotta, M. N.; Mori, N.; Orsi, S.; Pearce, M.; Pohl, M.; Quan, Z.; Ryde, F.; Shi, H. L.; Spillantini, P.; Su, M.; Sun, J. C.; Sun, X. L.; Tang, Z. C.; Walter, R.; Wang, J. C.; Wang, J. M.; Wang, L.; Wang, R. J.; Wang, X. L.; Wang, X. Y.; Wang, Z. G.; Wei, D. M.; Wu, B. B.; Wu, J.; Wu, X.; Wu, X. F.; Xia, J. Q.; Xiao, H. L.; Xu, H. H.; Xu, M.; Xu, Z. Z.; Yan, H. R.; Yin, P. F.; Yu, Y. W.; Yuan, Q.; Zha, M.; Zhang, L.; Zhang, L.; Zhang, L. Y.; Zhang, Y.; Zhang, Y. J.; Zhang, Y. L.; Zhao, Z. G.

2014-07-01

The High Energy cosmic-Radiation Detection (HERD) facility is one of several space astronomy payloads of the cosmic lighthouse program onboard China's Space Station, which is planned for operation starting around 2020 for about 10 years. The main scientific objectives of HERD are indirect dark matter search, precise cosmic ray spectrum and composition measurements up to the knee energy, and high energy gamma-ray monitoring and survey. HERD is composed of a 3-D cubic calorimeter (CALO) surrounded by microstrip silicon trackers (STKs) from five sides except the bottom. CALO is made of about 104 cubes of LYSO crystals, corresponding to about 55 radiation lengths and 3 nuclear interaction lengths, respectively. The top STK microstrips of seven X-Y layers are sandwiched with tungsten converters to make precise directional measurements of incoming electrons and gamma-rays. In the baseline design, each of the four side SKTs is made of only three layers microstrips. All STKs will also be used for measuring the charge and incoming directions of cosmic rays, as well as identifying back scattered tracks. With this design, HERD can achieve the following performance: energy resolution of 1% for electrons and gamma-rays beyond 100 GeV, 20% for protons from 100 GeV to 1 PeV; electron/proton separation power better than 10-5; effective geometrical factors of >3 m2sr for electron and diffuse gamma-rays, >2 m2sr for cosmic ray nuclei. R and D is under way for reading out the LYSO signals with optical fiber coupled to image intensified CCD and the prototype of one layer of CALO.

Mass Spectrometry Analysis of Wild-Type and Knock-in Q140/Q140 Huntington's Disease Mouse Brains Reveals Changes in Glycerophospholipids Including Alterations in Phosphatidic Acid and Lyso-Phosphatidic Acid.

PubMed

Vodicka, Petr; Mo, Shunyan; Tousley, Adelaide; Green, Karin M; Sapp, Ellen; Iuliano, Maria; Sadri-Vakili, Ghazaleh; Shaffer, Scott A; Aronin, Neil; DiFiglia, Marian; Kegel-Gleason, Kimberly B

2015-01-01

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG expansion in the HD gene, which encodes the protein Huntingtin. Huntingtin associates with membranes and can interact directly with glycerophospholipids in membranes. We analyzed glycerophospholipid profiles from brains of 11 month old wild-type (WT) and Q140/Q140 HD knock-in mice to assess potential changes in glycerophospholipid metabolism. Polar lipids from cerebellum, cortex, and striatum were extracted and analyzed by liquid chromatography and negative ion electrospray tandem mass spectrometry analysis (LC-MS/MS). Gene products involved in polar lipid metabolism were studied using western blotting, immuno-electron microscopy and qPCR. Significant changes in numerous species of glycerophosphate (phosphatidic acid, PA) were found in striatum, cerebellum and cortex from Q140/Q140 HD mice compared to WT mice at 11 months. Changes in specific species could also be detected for other glycerophospholipids. Increases in species of lyso-PA (LPA) were measured in striatum of Q140/Q140 HD mice compared to WT. Protein levels for c-terminal binding protein 1 (CtBP1), a regulator of PA biosynthesis, were reduced in striatal synaptosomes from HD mice compared to wild-type at 6 and 12 months. Immunoreactivity for CtBP1 was detected on membranes of synaptic vesicles in striatal axon terminals in the globus pallidus. These novel results identify a potential site of molecular pathology caused by mutant Huntingtin that may impart early changes in HD.

Antibiotic susceptibility and intracellular localization of Diplorickettsia massiliensis.

PubMed

Subramanian, Geetha; Barry, Abdoulaye O; Ghigo, Eric; Raoult, Didier; Mediannikov, Oleg

2012-02-01

Diplorickettsia massiliensis is an obligate intracellular bacterium from the Coxiellaceae family recently isolated from Ixodes ricinus ticks. The inhibitory effects of antimicrobial agents were assessed by two different methods, immunofluorescence and Gimenez staining assay. Different markers (EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99) were used to reveal the nature of the vacuole containing the bacterium. Ciprofloxacin, levofloxacin, and rifampin had MIC values of 2 lg mL(-1). We found that 4 lg mL(-1) of Doxycycline inhibited the growth of D. massiliensis strain. Surprisingly, D. massiliensis was resistant to chloramphenicol up to the concentration of 64 lg mL(-1). We found that penicillin G, ammonium chloride, gentamycin, omeprazole, bafilomycin A1, and chloroquine were not active against D. massiliensis. Studies performed with markers EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99 showed that D. massiliensis is localized within an acidic compartment that is not an early phagosome, but a late phagosome or a phagolysosome. Gimenez staining stays a good method that will work with a very low number of bacteria and can be used to determine the MICs of new therapeutic antibiotics precisely. The resistance profile of D. massiliensis was found to be quite unusual for intracellular Gram-negative bacterium with marked resistance to chloramphenicol. Despite of localization in acidic compartment, pH-neutralizing agents do not significantly inhibit intracellular growth of bacterium. The results of these studies prove that antibiotic resistance does not depend on pH of vacuole. This pH-related mechanism seems not to play a contributing role in the overall resistance of D. massiliensis.

Angiotensin peptides attenuate platelet-activating factor-induced inflammatory activity in rats.

PubMed

Sato, Akira; Yokoyama, Izumi; Ebina, Keiichi

2015-11-01

Angiotensin (Ang)--a peptide that is part of the renin-angiotensin system-induces vasoconstriction and a subsequent increase in blood pressure; Ang peptides, especially AngII, can also act as potent pro-inflammatory mediators. Platelet-activating factor (PAF) is a potent phospholipid mediator that is implicated in many inflammatory diseases. In this study, we investigated the effects of Ang peptides (AngII, AngIII, and AngIV) on PAF-induced inflammatory activity. In experiments using a rat hind-paw oedema model, AngII markedly and dose-dependently attenuated the paw oedema induced by PAF. The inhibitory effects of AngIII and AngIV on PAF-induced paw oedema were lower than that of AngII. Two Ang receptors, the AT1 and AT2 receptors, did not affect the AngII-mediated attenuation of PAF-induced paw oedema. Moreover, intrinsic tyrosine fluorescence studies demonstrated that AngII, AngIII, and AngIV interact with PAF, and that their affinities were closely correlated with their inhibitory effects on PAF-induced rat paw oedema. Also, AngII interacted with metabolite/precursor of PAF (lyso-PAF), and an oxidized phospholipid, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), which bears a marked structural resemblance to PAF. Furthermore, POVPC dose-dependently inhibited AngII-mediated attenuation of PAF-induced paw oedema. These results suggest that Ang peptides can attenuate PAF-induced inflammatory activity through binding to PAF and lyso-PAF in rats. Therefore, Ang peptides may be closely involved in the regulation of many inflammatory diseases caused by PAF. Copyright © 2015 Elsevier Inc. All rights reserved.

Operation and performance of new NIR detectors from SELEX

NASA Astrophysics Data System (ADS)

Atkinson, D.; Bezawada, N.; Hipwood, L. G.; Shorrocks, N.; Milne, H.

2012-07-01

The European Space Agency (ESA) has funded SELEX Galileo, Southampton, UK to develop large format near infrared (NIR) detectors for its future space and ground based programmes. The UKATC has worked in collaboration with SELEX Galileo to test and characterise the new detectors produced during phase-1 of the development. In order to demonstrate the detector material performance, the HgCdTe (MCT) detector diodes (grown on GaAs substrate through MOVPE process in small 320×256, 24μm pixel format) are hybridised to the existing SELEX Galileo SWALLOW CMOS readout chip. The substrate removed and MCT thinned detector arrays were then tested and evaluated at the UKATC following screening tests at SELEX. This paper briefly describes the test setup, the operational aspects of the readout multiplexer and presents the performance parameters of the detector arrays including: conversion gain, detector dark current, read noise, linearity, quantum efficiency and persistence for various detector temperatures between 80K and 140K.

Simulation of the MoEDAL experiment

NASA Astrophysics Data System (ADS)

King, Matthew; MoEDAL Collaboration

2016-04-01

The MoEDAL experiment (Monopole and Exotics Detector at the LHC) is designed to directly search for magnetic monopoles and other highly ionising stable or meta-stable particles at the LHC. The MoEDAL detector comprises an array of plastic track detectors and aluminium trapping volumes around the P8 intersection region, opposite from the LHCb detector. TimePix devices are also installed for monitoring of the experiment. As MoEDAL mostly employs passive detectors the software development focusses on particle simulation, rather than digitisation or reconstruction. Here, we present the current status of the MoEDAL simulation software. Specifically, the development of a material description of the detector and simulations of monopole production and propagation at MoEDAL.

CCD detector development projects by the Beamline Technical Support Group at the Advanced Photon Source

NASA Astrophysics Data System (ADS)

Lee, John H.; Fernandez, Patricia; Madden, Tim; Molitsky, Michael; Weizeorick, John

2007-11-01

This paper will describe two ongoing detector projects being developed by the Beamline Technical Support Group at the Advanced Photon Source (APS) at Argonne National Laboratory (ANL). The first project is the design and construction of two detectors: a single-CCD system and a two-by-two Mosaic CCD camera for Small-Angle X-ray Scattering (SAXS). Both of these systems utilize the Kodak KAF-4320E CCD coupled to fiber optic tapers, custom mechanical hardware, electronics, and software developed at ANL. The second project is a Fast-CCD (FCCD) detector being developed in a collaboration between ANL and Lawrence Berkeley National Laboratory (LBNL). This detector will use ANL-designed readout electronics and a custom LBNL-designed CCD, with 480×480 pixels and 96 outputs, giving very fast readout.

Cherenkov water detector NEVOD

NASA Astrophysics Data System (ADS)

Petrukhin, A. A.

2015-05-01

A unique multipurpose Cherenkov water detector, the NEVOD facility, uses quasispherical measuring modules to explore all the basic components of cosmic rays on Earth's surface, including neutrinos. Currently, the experimental complex includes the Cherenkov water detector, a calibration telescope system, and a coordinate detector. This paper traces the basic development stages of NEVOD, examines research directions, presents the results obtained, including the search for the solution to the 'muon puzzle', and discusses possible future development prospects.

Development of 1.45-mm resolution four-layer DOI-PET detector for simultaneous measurement in 3T MRI.

PubMed

Nishikido, Fumihiko; Tachibana, Atsushi; Obata, Takayuki; Inadama, Naoko; Yoshida, Eiji; Suga, Mikio; Murayama, Hideo; Yamaya, Taiga

2015-01-01

Recently, various types of PET-MRI systems have been developed by a number of research groups. However, almost all of the PET detectors used in these PET-MRI systems have no depth-of-interaction (DOI) capability. The DOI detector can reduce the parallax error and lead to improvement of the performance. We are developing a new PET-MRI system which consists of four-layer DOI detectors positioned close to the measured object to achieve high spatial resolution and high scanner sensitivity. As a first step, we are investigating influences the PET detector and the MRI system have on each other using a prototype four-layer DOI-PET detector. This prototype detector consists of a lutetium yttrium orthosilicate crystal block and a 4 × 4 multi-pixel photon counter array. The size of each crystal element is 1.45 mm × 1.45 mm × 4.5 mm, and the crystals are arranged in 6 × 6 elements × 4 layers with reflectors. The detector and some electric components are packaged in an aluminum shielding box. Experiments were carried out with 3.0 T MRI (GE, Signa HDx) and a birdcage-type RF coil. We demonstrated that the DOI-PET detector was normally operated in simultaneous measurements with no influence of the MRI measurement. A slight influence of the PET detector on the static magnetic field of the MRI was observed near the PET detector. The signal-to-noise ratio was decreased by presence of the PET detector due to environmental noise entering the MRI room through the cables, even though the PET detector was not powered up. On the other hand, no influence of electric noise from the PET detector in the simultaneous measurement on the MRI images was observed, even though the PET detector was positioned near the RF coil.

24 CFR 242.74 - Smoke detectors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Smoke detectors. 242.74 Section 242... INSURANCE FOR HOSPITALS Miscellaneous Requirements § 242.74 Smoke detectors. Each occupied room must include such smoke detectors as are required by law. ...

24 CFR 242.74 - Smoke detectors.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Smoke detectors. 242.74 Section 242... INSURANCE FOR HOSPITALS Miscellaneous Requirements § 242.74 Smoke detectors. Each occupied room must include such smoke detectors as are required by law. ...

24 CFR 242.74 - Smoke detectors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Smoke detectors. 242.74 Section 242... INSURANCE FOR HOSPITALS Miscellaneous Requirements § 242.74 Smoke detectors. Each occupied room must include such smoke detectors as are required by law. ...

24 CFR 242.74 - Smoke detectors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Smoke detectors. 242.74 Section 242... INSURANCE FOR HOSPITALS Miscellaneous Requirements § 242.74 Smoke detectors. Each occupied room must include such smoke detectors as are required by law. ...

24 CFR 242.74 - Smoke detectors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Smoke detectors. 242.74 Section 242... INSURANCE FOR HOSPITALS Miscellaneous Requirements § 242.74 Smoke detectors. Each occupied room must include such smoke detectors as are required by law. ...

Highly efficient preparation of sphingoid bases from glucosylceramides by chemoenzymatic method[S

PubMed Central

Gowda, Siddabasave Gowda B.; Usuki, Seigo; Hammam, Mostafa A. S.; Murai, Yuta; Igarashi, Yasuyuki; Monde, Kenji

2016-01-01

Sphingoid base derivatives have attracted increasing attention as promising chemotherapeutic candidates against lifestyle diseases such as diabetes and cancer. Natural sphingoid bases can be a potential resource instead of those derived by time-consuming total organic synthesis. In particular, glucosylceramides (GlcCers) in food plants are enriched sources of sphingoid bases, differing from those of animals. Several chemical methodologies to transform GlcCers to sphingoid bases have already investigated; however, these conventional methods using acid or alkaline hydrolysis are not efficient due to poor reaction yield, producing complex by-products and resulting in separation problems. In this study, an extremely efficient and practical chemoenzymatic transformation method has been developed using microwave-enhanced butanolysis of GlcCers and a large amount of readily available almond β-glucosidase for its deglycosylation reaction of lysoGlcCers. The method is superior to conventional acid/base hydrolysis methods in its rapidity and its reaction cleanness (no isomerization, no rearrangement) with excellent overall yield. PMID:26667669

Characterizing X-ray detectors for prototype digital breast tomosynthesis systems

NASA Astrophysics Data System (ADS)

Kim, Y.-s.; Park, H.-s.; Park, S.-J.; Choi, S.; Lee, H.; Lee, D.; Choi, Y.-W.; Kim, H.-J.

2016-03-01

The digital breast tomosynthesis (DBT) system is a newly developed 3-D imaging technique that overcomes the tissue superposition problems of conventional mammography. Therefore, it produces fewer false positives. In DBT system, several parameters are involved in image acquisition, including geometric components. A series of projections should be acquired at low exposure. This makes the system strongly dependent on the detector's characteristic performance. This study compares two types of x-ray detectors developed by the Korea Electrotechnology Research Institute (KERI). The first prototype DBT system has a CsI (Tl) scintillator/CMOS based flat panel digital detector (2923 MAM, Dexela Ltd.), with a pixel size of 0.0748 mm. The second uses a-Se based direct conversion full field detector (AXS 2430, analogic) with a pixel size of 0.085 mm. The geometry of both systems is same, with a focal spot 665.8 mm from the detector, and a center of rotation 33 mm above the detector surface. The systems were compared with regard to modulation transfer function (MTF), normalized noise power spectrum (NNPS), detective quantum efficiency (DQE) and a new metric, the relative object detectability (ROD). The ROD quantifies the relative performance of each detector at detecting specified objects. The system response function demonstrated excellent linearity (R2>0.99). The CMOS-based detector had a high sensitivity, while the Anrad detector had a large dynamic range. The higher MTF and noise power spectrum (NPS) values were measured using an Anrad detector. The maximum DQE value of the Dexela detector was higher than that of the Anrad detector with a low exposure level, considering one projection exposure for tomosynthesis. Overall, the Dexela detector performed better than did the Anrad detector with regard to the simulated Al wires, spheres, test objects of ROD with low exposure level. In this study, we compared the newly developed prototype DBT system with two different types of x-ray detectors for commercial DBT systems. Our findings suggest that the Dexela detector can be applied to the DBT system with regard to its high imaging performance.

Infrared Detector Activities at NASA Langley Research Center

NASA Technical Reports Server (NTRS)

Abedin, M. N.; Refaat, T. F.; Sulima, O. V.; Amzajerdian, F.

2008-01-01

Infrared detector development and characterization at NASA Langley Research Center will be reviewed. These detectors were intended for ground, airborne, and space borne remote sensing applications. Discussion will be focused on recently developed single-element infrared detector and future development of near-infrared focal plane arrays (FPA). The FPA will be applied to next generation space-based instruments. These activities are based on phototransistor and avalanche photodiode technologies, which offer high internal gain and relatively low noise-equivalent-power. These novel devices will improve the sensitivity of active remote sensing instruments while eliminating the need for a high power laser transmitter.

A Test Stand to Characterize and Contribute to the Development of DEPFET X-ray Detectors

NASA Astrophysics Data System (ADS)

Falcone, Abe

The field of X-ray astronomy is currently looking forward to several new missions (e.g Athena, BeppiColumbo, and IXPE which is a new SMEX polarimeter), and there is the possibility of a flag-ship mission (e.g. the Lynx X-ray Surveyor) and/or other SMEX through probe class missions in the long-term future with many mission concepts being developed (e.g. ARCUS). The X-ray detec-tors for these future missions must be developed to suitable maturity to be proposed for flight, and expertise operating the newest versions of the detectors must be acquired by potential mis-sion designers and proposers. There are several silicon X-ray imaging active pixel sensor (APS) detectors being developed at this time (hybrid CMOS, monolithic CMOS, and DEPFETs), and each of these have their own advantages and levels of maturity, while they all provide enhanced radia-tion hardness, lower power operation, and versatile readout modes. Of the new APS X-ray detec-tors being developed, the DEPleted p-channel Field Effect Transistors (DEPFETs) have exhibited the best noise performance to-date. While they do require larger pixel structures than their com-petitors, the low noise performance of these detectors makes them an excellent choice for many mission applications (e.g. they will be launched on 2 ESA missions, Athena & BepiColumbo), and their further development could benefit other missions, particularly future missions that might be led by NASA and US scientists. Up until now, the development of these detectors has been lim-ited to only two groups located in Germany; one group is at Max Planck Institute and the other is PNSensors which is comprised of engineers and scientists that previously led the DEPFET design work at Max Planck. We propose to engage one of these groups in order to: (a) acquire newly de-signed test DEPFET detectors built by PNSensor, through a very-low-cost arrangement, (b) build a test stand that can operate these detectors and gain valuable experience running them in vari-ous modes with variations on the detector settings, (c) characterize the DEPFETs independently of the manufacturer and in modes that are relevant to our x-ray applications, and (d) use this new operation experience and characterization data to inform the next design iterations and the op-timization of DEPFET detectors for future X-ray missions.

Discourse for slide presentation: An overview of chemical detection systems

NASA Technical Reports Server (NTRS)

Peters, Randy Alan; Galen, Theodore J.; Pierson, Duane L.

1990-01-01

A brief overview of some of the analytical techniques currently used in monitoring and analyzing permanent gases and selected volatile organic compound in air are presented. Some of the analytical considerations in developing a specific method are discussed. Four broad groups of hardware are discussed: compound class specific personal monitors, gas chromatographic systems, infrared spectroscopic systems, and mass spectrometric residual gas analyzer systems. Three types of detectors are also discussed: catalytic sensor based systems, photoionization detectors, and wet or dry chemical reagent systems. Under gas chromatograph based systems five detector systems used in combination with a GC are covered: thermal conductivity detectors, photoionization detectors, Fourier transform infrared spectrophotometric systems, quadrapole mass spectrometric systems, and a relatively recent development, a surface acoustic wave vapor detector.

Recent developments in photodetection for medical applications

NASA Astrophysics Data System (ADS)

Llosá, Gabriela

2015-07-01

The use of the most advanced technology in medical imaging results in the development of high performance detectors that can significantly improve the performance of the medical devices employed in hospitals. Scintillator crystals coupled to photodetectors remain to be essential detectors in terms of performance and cost for medical imaging applications in different imaging modalities. Recent advances in photodetectors result in an increase of the performance of the medical scanners. Solid state detectors can provide substantial performance improvement, but are more complex to integrate into clinical detectors due mainly to their higher cost. Solid state photodetectors (APDs, SiPMs) have made new detector concepts possible and have led to improvements in different imaging modalities. Recent advances in detectors for medical imaging are revised.

Design and fabrication of a novel self-powered solid-state neutron detector

NASA Astrophysics Data System (ADS)

LiCausi, Nicholas

There is a strong interest in intercepting special nuclear materials (SNM) at national and international borders and ports for homeland security applications. Detection of SNM such as U and Pu is often accomplished by sensing their natural or induced neutron emission. Such detector systems typically use thermal neutron detectors inside a plastic moderator. In order to achieve high detection efficiency gas filled detectors are often used; these detectors require high voltage bias for operation, which complicates the system when tens or hundreds of detectors are deployed. A better type of detector would be an inexpensive solid-state detector that can be mass-produced like any other computer chip. Research surrounding solid-state detectors has been underway since the late 1990's. A simple solid-state detector employs a planar solar-cell type p-n junction and a thin conversion material that converts incident thermal neutrons into detectable alpha-particles and 7Li ions. Existing work has typically used 6LiF or 10B as this conversion layer. Although a simple planar detector can act as a highly portable, low cost detector, it is limited to relatively low detection efficiency (˜10%). To increase the efficiency, 3D perforated p-i-n silicon devices were proposed. To get high efficiency, these detectors need to be biased, resulting in increased leakage current and hence detector noise. In this research, a new type of detector structure was proposed, designed and fabricated. Among several detector structures evaluated, a honeycomb-like silicon p-n structure was selected, which is filled with natural boron as the neutron converter. A silicon p+-n diode formed on the thin silicon wall of the honeycomb structure detects the energetic alpha-particles emitted from the boron conversion layer. The silicon detection layer is fabricated to be fully depleted with an integral step during the boron filling process. This novel feature results in a simplified fabrication process. Three key advantages of the novel devices are theoretical neutron detection efficiency of ˜48%, a self-passivating structure that reduces leakage current and detector operation with no bias resulting in extremely low device noise. Processes required to fabricate the 3D type detector were explored and developed in this thesis. The detector capacitance and processing steps have been simulated with MEDICI and TSuprem-4, respectively. Lithography masks were then designed using Cadence. The fabrication process development was conducted in line with standard CMOS grade integrated circuit processing to allow for simple integration with existing fabrication facilities. A number of new processes were developed including the low pressure chemical vapor deposition of conformal boron films using diborane on very high aspect-ratio trenches and holes. Development also included methods for "wet" chemical etching and "dry" reactive ion etching of the deposited boron films. Fabricated detectors were characterized with the transmission line method, 4-point probe, I-V measurements and C-V measurements. Finally the detector response to thermal neutrons was studied. Characterization has shown significant reduction in reverse leakage current density to ˜8x10-8 A/cm2 (nearly 4 orders of magnitude over the previously published data). Results show that the fabrication process developed is capable of producing efficient (˜22.5%) solid-state thermal neutron detectors.

Comparison of CdZnTe neutron detector models using MCNP6 and Geant4

NASA Astrophysics Data System (ADS)

Wilson, Emma; Anderson, Mike; Prendergasty, David; Cheneler, David

2018-01-01

The production of accurate detector models is of high importance in the development and use of detectors. Initially, MCNP and Geant were developed to specialise in neutral particle models and accelerator models, respectively; there is now a greater overlap of the capabilities of both, and it is therefore useful to produce comparative models to evaluate detector characteristics. In a collaboration between Lancaster University, UK, and Innovative Physics Ltd., UK, models have been developed in both MCNP6 and Geant4 of Cadmium Zinc Telluride (CdZnTe) detectors developed by Innovative Physics Ltd. Herein, a comparison is made of the relative strengths of MCNP6 and Geant4 for modelling neutron flux and secondary γ-ray emission. Given the increasing overlap of the modelling capabilities of MCNP6 and Geant4, it is worthwhile to comment on differences in results for simulations which have similarities in terms of geometries and source configurations.

A semiconductor radiation imaging pixel detector for space radiation dosimetry

NASA Astrophysics Data System (ADS)

Kroupa, Martin; Bahadori, Amir; Campbell-Ricketts, Thomas; Empl, Anton; Hoang, Son Minh; Idarraga-Munoz, John; Rios, Ryan; Semones, Edward; Stoffle, Nicholas; Tlustos, Lukas; Turecek, Daniel; Pinsky, Lawrence

2015-07-01

Progress in the development of high-performance semiconductor radiation imaging pixel detectors based on technologies developed for use in high-energy physics applications has enabled the development of a completely new generation of compact low-power active dosimeters and area monitors for use in space radiation environments. Such detectors can provide real-time information concerning radiation exposure, along with detailed analysis of the individual particles incident on the active medium. Recent results from the deployment of detectors based on the Timepix from the CERN-based Medipix2 Collaboration on the International Space Station (ISS) are reviewed, along with a glimpse of developments to come. Preliminary results from Orion MPCV Exploration Flight Test 1 are also presented.

Detector arrays for low-background space infrared astronomy

NASA Technical Reports Server (NTRS)

Mccreight, C. R.; Mckelvey, M. E.; Goebel, J. H.; Anderson, G. M.; Lee, J. H.

1986-01-01

The status of development and characterization tests of integrated infrared detector array technology for astronomy applications is described. The devices under development include intrinsic, extrinsic silicon, and extrinsic germanium detectors, with hybrid silicon multiplexers. Laboratory test results and successful astronomy imagery have established the usefulness of integrated arrays in low-background astronomy applications.

Detector arrays for low-background space infrared astronomy

NASA Technical Reports Server (NTRS)

Mccreight, C. R.; Mckelvey, M. E.; Goebel, J. H.; Anderson, G. M.; Lee, J. H.

1986-01-01

The status of development and characterization tests of integrated infrared detector array technology for astronomy applications is described. The devices under development include intrinsic, extrinsic silicon, and extrinsic germanium detectors, with hybrid silicon multiplexers. Laboratary test results and successful astronomy imagery have established the usefulness of integrated arrays in low-background astronomy applications.

Variables affecting resolution of lung phospholipids in one-dimensional thin-layer chromatography.

PubMed

Krahn, J

1987-01-01

Resolution of the confusion in the literature about the separation of lung phospholipids in thin-layer chromatographic systems has awaited a systematic study of the variables that potentially affect this separation. In this study I show that: incorporation of ammonium sulfate into silica gel "GHL" has a dramatic effect on separation of lung phospholipids; this effect is equally dramatic but different in activated and nonactivated gels; when it picks up moisture, ammonium sulfate-activated gel very rapidly loses its ability to resolve lecithin from phosphatidylinositol; in gel containing ammonium sulfate, small amounts of phosphatidylethanolamine are hydrolyzed to lyso-phosphatidylethanolamine.

Development of a front-end analog circuit for multi-channel SiPM readout and performance verification for various PET detector designs

NASA Astrophysics Data System (ADS)

Ko, Guen Bae; Yoon, Hyun Suk; Kwon, Sun Il; Lee, Chan Mi; Ito, Mikiko; Hong, Seong Jong; Lee, Dong Soo; Lee, Jae Sung

2013-03-01

Silicon photomultipliers (SiPMs) are outstanding photosensors for the development of compact imaging devices and hybrid imaging systems such as positron emission tomography (PET)/ magnetic resonance (MR) scanners because of their small size and MR compatibility. The wide use of this sensor for various types of scintillation detector modules is being accelerated by recent developments in tileable multichannel SiPM arrays. In this work, we present the development of a front-end readout module for multi-channel SiPMs. This readout module is easily extendable to yield a wider detection area by the use of a resistive charge division network (RCN). We applied this readout module to various PET detectors designed for use in small animal PET/MR, optical fiber PET/MR, and double layer depth of interaction (DOI) PET. The basic characteristics of these detector modules were also investigated. The results demonstrate that the PET block detectors developed using the readout module and tileable multi-channel SiPMs had reasonable performance.

Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior and Metabolite Levels in 129Sv and Bl6 Mouse Strains.

PubMed

Vanaveski, Taavi; Narvik, Jane; Innos, Jürgen; Philips, Mari-Anne; Ottas, Aigar; Plaas, Mario; Haring, Liina; Zilmer, Mihkel; Vasar, Eero

2018-01-01

The main goal of the study was to characterize the behavioral and metabolomic profiles of repeated administration (for 11 days) of d-amphetamine (AMPH, 3 mg/kg i. p.), indirect agonist of dopamine (DA), in widely used 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6) mouse strains. Acute administration of AMPH (acute AMPH) induced significantly stronger motor stimulation in Bl6. However, repeated administration of AMPH (repeated AMPH) caused stronger motor sensitization in 129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH induced an elevation of isoleucine and leucine, branched chain amino acids (BCAA), whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines [asymmetric dimethylarginine (ADMA), alpha-aminoadipic acid (alpha-AAA), kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in 129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:2, lysoPC a C20:4), phosphatidylcholine (PC) diacyls (PC aa C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4) and alkyl-acyls (PC ae C38:4, PC ae C40:4). However, repeated AMPH increased the levels of valine and isoleucine, long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1), PC diacyls (PC aa C38:4, PC aa C38:6, PC aa C42:6), PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:3) and sphingolipids [SM(OH)C22:1, SM C24:0] compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after repeated AMPH compared to saline in 129Sv. The established changes probably reflect a shift in energy metabolism toward lipid molecules in 129Sv because of reduced level of hexoses. Pooled data from both strains showed that the elevation of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral sensitization. Simultaneously a significant decline of hexoses, citrulline, ADMA, and kynurenine occurred. The reduced levels of kynurenine, ADMA, and citrulline likely reflect altered function of N-methyl-D-aspartate (NMDA) and NO systems caused by repeated AMPH. Altogether, 129Sv strain displays stronger sensitization toward AMPH and larger variance in metabolite levels than Bl6.

Optimization of ultra-high pressure liquid chromatography - tandem mass spectrometry determination in plasma and red blood cells of four sphingolipids and their evaluation as biomarker candidates of Gaucher's disease.

PubMed

Chipeaux, Caroline; de Person, Marine; Burguet, Nathalie; Billette de Villemeur, Thierry; Rose, Christian; Belmatoug, Nadia; Héron, Sylvie; Le Van Kim, Caroline; Franco, Mélanie; Moussa, Fathi

2017-11-24

While important advances have been recently achieved in the optimization of lipid classes' separation, information on the specific determination of medium polarity lipids such as sphingolipids (SLs) in highly complex matrices remains fragmentary. In human, disorders of SL metabolism known as sphingolipidoses are a heterogeneous group of inherited disorders affecting primarily the central nervous. Early diagnosis of these conditions is of importance notably when a corrective therapy is available. The diagnosis is generally based on the determination of specific SLs in plasma and red blood cells (RBCs). For instance, glucosylceramide (GL1), glucosylsphingosine (Lyso-GL1), sphingosine (Sph), and sphingosine-1-phosphate (S1P) are proposed as relevant biomarkers for Gaucher disease (GD). Our main objective was to evaluate these biomarker candidates in a cohort of GD patients. However, most of current methods of GL1, Lyso-GL1, Sph, and S1P determination in plasma of GD patients require at least two liquid chromatographic runs. On the other hand, except for GL1 nothing is known concerning the RBC sphingolipid content. Yet, several reversed phase LC-MS methods of SLs separation and/or determination in various media with different sample preparation approaches have been proposed since 2010. Here we focused on stationary phase selection and mobile phase composition as well as on the sample preparation step to optimize and validate an UHPLC-MS/MS method for the simultaneous quantification of the four sphingolipids in both plasma and RBCs. A comparison between seven stationary phases including two RP18, two polar embedded RP18, and three HILIC phases shows that under our conditions polar embedded RP18 phases are the most appropriate for the separation of the four SLs, in terms of efficiency, peak symmetry, and separation time. In the same way, a comparison between a single step extraction with methanol and a liquid-liquid extraction with a mixture of methanol/methyl tert-butyl ether, shows that the latter mixture is the most appropriate for the extraction of SLs in terms of recovery and absence of matrix effect. After validation, this method was applied to the evaluation of the targeted SLs in a cohort of 15 known GD patients. The obtained results show that Lyso-GL1 is the only relevant biomarker in both plasma and RBCs for GD diagnosis. As the proposed method is applicable to the determination in such a highly complex matrices of four SLs with a large difference in polarity, and as the sample preparation procedure is freedom of matrix effects, this method can be easily adapted to a large diversity of samples. Copyright © 2017 Elsevier B.V. All rights reserved.

AO wavefront sensing detector developments at ESO

NASA Astrophysics Data System (ADS)

Downing, Mark; Kolb, Johann; Baade, Dietrich; Iwert, Olaf; Hubin, Norbert; Reyes, Javier; Feautrier, Philippe; Gach, Jean-Luc; Balard, Philippe; Guillaume, Christian; Stadler, Eric; Magnard, Yves

2010-07-01

The detector is a critical component of any Adaptive Optics WaveFront Sensing (AO WFS) system. The required combination of fast frame rate, high quantum efficiency, low noise, large number and size of pixels, and low image lag can often only be met by specialized custom developments. ESO's very active WFS detector development program is described. Key test results are presented for newly developed detectors: a) the e2v L3Vision CCD220 (the fastest/lowest noise AO detector to date) to be deployed soon on 2nd Generation VLT instruments, and b) the MPI-HLL pnCCD with its superb high "red" response. The development of still more advanced laser/natural guide-star WFS detectors is critical for the feasibility of ESO's EELT. The paper outlines: a) the multi-phased development plan that will ensure detectors are available on-time for EELT first-light AO systems, b) results of design studies performed by industry during 2007 including a comparison of the most promising technologies, c) results from CMOS technology demonstrators that were built and tested over the past two years to assess and validate various technologies at the pixel level, their fulfillment of critical requirements (especially read noise and speed), and scalability to full-size. The next step will be towards Scaled-Down Demonstrators (SDD) to retire architecture and process risks. The SDD will be large enough to be used for E-ELT first-light AO WFS systems. For full operability, 30-50 full-scale devices will be needed.

Space activity and programs at SOFRADIR

NASA Astrophysics Data System (ADS)

Bouakka-Manesse, A.; Jamin, N.; Delannoy, A.; Fieque, B.; Leroy, C.; Pidancier, P.; Vial, L.; Chorier, P.; Péré-Laperne, N.

2016-09-01

SOFRADIR is one of the leading companies involved in the development and manufacturing of infrared detectors for space applications. As a matter of fact, SOFRADIR is involved in many space programs from visible up to VLWIR spectral ranges. These programs concern operational missions for earth imagery, meteorology and also scientific missions for universe exploration. One of the last space detectors available at SOFRADIR is a visible - SWIR detector named Next Generation Panchromatic Detector (NGP) which is well adapted for hyperspectral, imagery and spectroscopy applications. In parallel of this new space detector, numerous programs are currently running for different kind of missions: meteorology (MTG), Copernicus with the Sentinel detectors series, Metop-SG system (3MI), Mars exploration (Mamiss, etc.). In this paper, we present the last developments made for space activity and in particular the NGP detector. We will also present the space applications using this detector and show appropriateness of its use to answer space programs specifications, as for example those of Sentinel-5.

Space activity and programs at Sofradir

NASA Astrophysics Data System (ADS)

Bouakka-Manesse, A.; Jamin, N.; Delannoy, A.; Fièque, B.; Leroy, C.; Pidancier, P.; Vial, L.; Chorier, P.; Péré Laperne, N.

2016-10-01

SOFRADIR is one of the leading companies involved in the development and manufacturing of infrared detectors for space applications. As a matter of fact, SOFRADIR is involved in many space programs from visible up to VLWIR spectral ranges. These programs concern operational missions for earth imagery, meteorology and also scientific missions for universe exploration. One of the last space detectors available at SOFRADIR is a visible - SWIR detector named Next Generation Panchromatic Detector (NGP) which is well adapted for hyperspectral, imagery and spectroscopy applications. In parallel of this new space detector, numerous programs are currently running for different kind of missions: meteorology (MTG), Copernicus with the Sentinel detectors series, Metop-SG system (3MI), Mars exploration (Mamiss, etc….)… In this paper, we present the last developments made for space activity and in particular the NGP detector. We will also present the space applications using this detector and show appropriateness of its use to answer space programs specifications, as for example those of Sentinel-5.

Development of a Bolometer Detector System for the NIST High Accuracy Infrared Spectrophotometer

PubMed Central

Zong, Y.; Datla, R. U.

1998-01-01

A bolometer detector system was developed for the high accuracy infrared spectrophotometer at the National Institute of Standards and Technology to provide maximum sensitivity, spatial uniformity, and linearity of response covering the entire infrared spectral range. The spatial response variation was measured to be within 0.1 %. The linearity of the detector output was measured over three decades of input power. After applying a simple correction procedure, the detector output was found to deviate less than 0.2 % from linear behavior over this range. The noise equivalent power (NEP) of the bolometer system was 6 × 10−12 W/Hz at the frequency of 80 Hz. The detector output 3 dB roll-off frequency was 200 Hz. The detector output was stable to within ± 0.05 % over a 15 min period. These results demonstrate that the bolometer detector system will serve as an excellent detector for the high accuracy infrared spectrophotometer. PMID:28009364

Development of real-time thermal neutron monitor using boron-loaded plastic scintillator with optical fiber for boron neutron capture therapy.

PubMed

Ishikawa, M; Ono, K; Sakurai, Y; Unesaki, H; Uritani, A; Bengua, G; Kobayashi, T; Tanaka, K; Kosako, T

2004-11-01

A new thermal neutron monitor for boron neutron capture therapy was developed in this study. We called this monitor equipped boron-loaded plastic scintillator that uses optical fiber for signal transmission as an [scintillator with optical fiber] SOF detector. A water phantom experiment was performed to verify how the SOF detector compared with conventional method of measuring thermal neutron fluence. Measurements with a single SOF detector yielded indistinguishable signals for thermal neutrons and gamma rays. To account for the gamma ray contribution in the signal recorded by the SOF detector, a paired SOF detector system was employed. This was composed of an SOF detector with boron-loaded scintillator and an SOF detector with a boron-free scintillator. The difference between the recorded counts of these paired SOF detectors was used as the measure of the gamma ray contribution in the measured neutron fluence. The paired SOF detectors were ascertained to be effective in measuring thermal neutron flux in the range above 10(6)(n/cm(2)/s). Clinical trials using paired SOF to measure thermal neutron flux during therapy confirmed that paired SOF detectors were effective as a real-time thermal neutron flux monitor.

TES-Based Light Detectors for the CRESST Direct Dark Matter Search

NASA Astrophysics Data System (ADS)

Rothe, J.; Angloher, G.; Bauer, P.; Bento, A.; Bucci, C.; Canonica, L.; D'Addabbo, A.; Defay, X.; Erb, A.; Feilitzsch, F. v.; Ferreiro Iachellini, N.; Gorla, P.; Gütlein, A.; Hauff, D.; Jochum, J.; Kiefer, M.; Kluck, H.; Kraus, H.; Lanfranchi, J.-C.; Langenkämper, A.; Loebell, J.; Mancuso, M.; Mondragon, E.; Münster, A.; Pagliarone, C.; Petricca, F.; Potzel, W.; Pröbst, F.; Puig, R.; Reindl, F.; Schäffner, K.; Schieck, J.; Schipperges, V.; Schönert, S.; Seidel, W.; Stahlberg, M.; Stodolsky, L.; Strandhagen, C.; Strauss, R.; Tanzke, A.; Trinh Thi, H. H.; Türkoğlu, C.; Ulrich, A.; Usherov, I.; Wawoczny, S.; Willers, M.; Wüstrich, M.

2018-05-01

The CRESST experiment uses cryogenic detectors based on transition-edge sensors to search for dark matter interactions. Each detector module consists of a scintillating CaWO_4 crystal and a silicon-on-sapphire (SOS) light detector which operate in coincidence (phonon-light technique). The 40-mm-diameter SOS disks (2 g mass) used in the data taking campaign of CRESST-II Phase 2 (2014-2016) reached absolute baseline resolutions of σ = 4-7 eV. This is the best performance reported for cryogenic light detectors of this size. Newly developed silicon beaker light detectors (4 cm height, 4 cm diameter, 6 g mass), which cover a large fraction of the target crystal surface, have achieved a baseline resolution of σ = 5.8 eV. First results of further improved light detectors developed for the ongoing low-threshold CRESST-III experiment are presented.

Introduction to lead salt infrared detectors

NASA Astrophysics Data System (ADS)

Kondas, David A.

1993-02-01

This technical report establishes the background necessary to understand how lead sulfide (PbS) and lead selenide (PbSe) infrared detectors operate. Both detectors, which are members of the lead salt family of infrared detectors, use the photoconductive effect to detect energy residing within the infrared region of the electromagnetic spectrum. PbS detectors are useful for detecting energies in the 1 to 3 micrometer region, while PbSe detectors can detect energies in the 1 to 7 micrometer region. They are essentially polycrystalline thin films which are fabricated by chemical deposition techniques in either single element or multi-element array configurations. The significance of the electronic structure of these crystalline films and the effects of temperature on their operation and performance are discussed. The history of the development of lead salt detectors from the early years before World War I to the more recent developments is detailed. In addition, an overview of a typical infrared system is also presented.

Direct imaging detectors for electron microscopy

NASA Astrophysics Data System (ADS)

Faruqi, A. R.; McMullan, G.

2018-01-01

Electronic detectors used for imaging in electron microscopy are reviewed in this paper. Much of the detector technology is based on the developments in microelectronics, which have allowed the design of direct detectors with fine pixels, fast readout and which are sufficiently radiation hard for practical use. Detectors included in this review are hybrid pixel detectors, monolithic active pixel sensors based on CMOS technology and pnCCDs, which share one important feature: they are all direct imaging detectors, relying on directly converting energy in a semiconductor. Traditional methods of recording images in the electron microscope such as film and CCDs, are mentioned briefly along with a more detailed description of direct electronic detectors. Many applications benefit from the use of direct electron detectors and a few examples are mentioned in the text. In recent years one of the most dramatic advances in structural biology has been in the deployment of the new backthinned CMOS direct detectors to attain near-atomic resolution molecular structures with electron cryo-microscopy (cryo-EM). The development of direct detectors, along with a number of other parallel advances, has seen a very significant amount of new information being recorded in the images, which was not previously possible-and this forms the main emphasis of the review.

Characterization of a Commercial Silicon Beta Cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foxe, Michael P.; Hayes, James C.; Mayer, Michael F.

Silicon detectors are of interest for the verification of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) due to their enhanced energy resolution compared to plastic scintillators beta cells. Previous work developing a figure-of-merit (FOM) for comparison of beta cells suggests that the minimum detectable activity (MDA) could be reduced by a factor of two to three with the use of silicon detectors. Silicon beta cells have been developed by CEA (France) and Lares Ltd. (Russia), with the PIPSBox developed by CEA being commercially available from Canberra for approximately $35k, but there is still uncertainty about the reproducibility of the capabilities in themore » field. PNNL is developing a high-resolution beta-gamma detector system in the shallow underground laboratory, which will utilize and characterize the operation of the PIPSBox detector. Throughout this report, we examine the capabilities of the PIPSBox as developed by CEA. The lessons learned through the testing and use of the PIPSBox will allow PNNL to strategically develop a silicon detector optimized to better suit the communities needs in the future.« less

Distributed state machine supervision for long-baseline gravitational-wave detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rollins, Jameson Graef, E-mail: jameson.rollins@ligo.org

The Laser Interferometer Gravitational-wave Observatory (LIGO) consists of two identical yet independent, widely separated, long-baseline gravitational-wave detectors. Each Advanced LIGO detector consists of complex optical-mechanical systems isolated from the ground by multiple layers of active seismic isolation, all controlled by hundreds of fast, digital, feedback control systems. This article describes a novel state machine-based automation platform developed to handle the automation and supervisory control challenges of these detectors. The platform, called Guardian, consists of distributed, independent, state machine automaton nodes organized hierarchically for full detector control. User code is written in standard Python and the platform is designed to facilitatemore » the fast-paced development process associated with commissioning the complicated Advanced LIGO instruments. While developed specifically for the Advanced LIGO detectors, Guardian is a generic state machine automation platform that is useful for experimental control at all levels, from simple table-top setups to large-scale multi-million dollar facilities.« less

Life-finding detector development at NASA GSFC using a custom H4RG test bed

NASA Astrophysics Data System (ADS)

Mosby, Gregory; Rauscher, Bernard; Kutyrev, Alexander

2018-01-01

Chemical species associated with life, called biosignatures, should be visible in exoplanet atmospheres with larger space telescopes. These signals will be faint and require very low noise (~e-) detectors to robustly measure. At NASA Goddard we are developing a single detector H4RG test bed to characterize and identify potential technology developments needed for the next generation's large space telescopes. The vacuum and cryogenic test bed will include near infrared light sources from integrating spheres using a motorized shutter. The detector control and readout will be handled by a Leach controller. Detector cables have been manufactured and test planning has begun. Planned tests include testing minimum read noise capabilities, persistence mitigation strategies using long wavelength light, and measuring intrapixel variation which might affect science goals of future missions. In addition to providing a means to identify areas of improvement in detector technology, we hope to use this test bed to probe some fundamental physics of these infrared arrays.

Assembly and installation of the Belle II TOP detector

NASA Astrophysics Data System (ADS)

Suzuki, Kazuhito; Belle II TOP Group

2017-12-01

The Time-of-Propagation (TOP) detector is a new type of ring-imaging Cherenkov detector developed for particle identification in the barrel region of the Belle II spectrometer. In the assembly and installation, it is crucial for the detector performance to achieve precision alignment and secure gluing of the optical components as well as to mechanically support them managing the stress, attitude, optical and electrical contacts, and limited installation space. Various efforts were made to develop the procedures and jigs along with the development of the mechanical structure. Such efforts accomplished the assembly and installation in April and May 2016, respectively, without a significant incident.

Development of mercuric iodide uncooled x ray detectors and spectrometers

NASA Technical Reports Server (NTRS)

Iwanczyk, Jan S.

1990-01-01

The results obtained in the development of miniature, lowpower, light weight mercuric iodide, HgI2, x ray spectrometers for future space missions are summarized. It was demonstrated that HgI2 detectors can be employed in a high resolution x ray spectrometer, operating in a scanning electron microscope. Also, the development of HgI2 x ray detectors to augment alpha backscattering spectrometers is discussed. These combination instruments allow for the identification of all chemical elements, with the possible exception of hydrogen, and their respective concentrations. Additionally, further investigations of questions regarding radiation damage effects in the HgI2 x ray detectors are reported.

Carbon monoxide detector. [electrochemical gas detector for spacecraft use

NASA Technical Reports Server (NTRS)

Holleck, G. L.; Bradspies, J. L.; Brummer, S. B.; Nelsen, L. L.

1973-01-01

A sensitive carbon monoxide detector, developed specifically for spacecraft use, is described. An instrument range of 0 to 60 ppm CO in air was devised. The fuel cell type detector is used as a highly sensitive electrolysis cell for electrochemically detecting gases. The concept of an electrochemical CO detector is discussed and the CO oxidation behavior in phosphoric and sulfuric acid electrolytes is reported.

Separation system with a sheath-flow supported electrochemical detector

DOEpatents

Mathies, Richard A [Moraga, CA; Emrich, Charles A [Berkeley, CA; Singhal, Pankaj [Pasadena, CA; Ertl, Peter [Styria, AT

2008-10-21

An electrochemical detector including side channels associated with a separation channel of a sample component separation apparatus is provided. The side channels of the detector, in one configuration, provide a sheath-flow for an analyte exiting the separation channel which directs the analyte to the electrically developed electrochemical detector.

24 CFR 891.555 - Smoke detectors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Smoke detectors. 891.555 Section... Assistance § 891.555 Smoke detectors. (a) Performance requirement. After October 30, 1992, each dwelling unit must include at least one battery-operated or hard-wired smoke detector, in proper working condition...

24 CFR 891.555 - Smoke detectors.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Smoke detectors. 891.555 Section... Assistance § 891.555 Smoke detectors. (a) Performance requirement. After October 30, 1992, each dwelling unit must include at least one battery-operated or hard-wired smoke detector, in proper working condition...

24 CFR 891.555 - Smoke detectors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Smoke detectors. 891.555 Section... Assistance § 891.555 Smoke detectors. (a) Performance requirement. After October 30, 1992, each dwelling unit must include at least one battery-operated or hard-wired smoke detector, in proper working condition...

24 CFR 891.555 - Smoke detectors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Smoke detectors. 891.555 Section... Assistance § 891.555 Smoke detectors. (a) Performance requirement. After October 30, 1992, each dwelling unit must include at least one battery-operated or hard-wired smoke detector, in proper working condition...

24 CFR 965.805 - Smoke detectors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Smoke detectors. 965.805 Section... PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Fire Safety § 965.805 Smoke detectors. (a) Performance... battery-operated or hard-wired smoke detector, or such greater number as may be required by state or local...

24 CFR 965.805 - Smoke detectors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Smoke detectors. 965.805 Section... PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Fire Safety § 965.805 Smoke detectors. (a) Performance... battery-operated or hard-wired smoke detector, or such greater number as may be required by state or local...

24 CFR 965.805 - Smoke detectors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Smoke detectors. 965.805 Section... PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Fire Safety § 965.805 Smoke detectors. (a) Performance... battery-operated or hard-wired smoke detector, or such greater number as may be required by state or local...

24 CFR 891.555 - Smoke detectors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Smoke detectors. 891.555 Section... Assistance § 891.555 Smoke detectors. (a) Performance requirement. After October 30, 1992, each dwelling unit must include at least one battery-operated or hard-wired smoke detector, in proper working condition...

24 CFR 965.805 - Smoke detectors.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Smoke detectors. 965.805 Section... PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Fire Safety § 965.805 Smoke detectors. (a) Performance... battery-operated or hard-wired smoke detector, or such greater number as may be required by state or local...

24 CFR 965.805 - Smoke detectors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Smoke detectors. 965.805 Section... PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Fire Safety § 965.805 Smoke detectors. (a) Performance... battery-operated or hard-wired smoke detector, or such greater number as may be required by state or local...

Development of slow control system for the Belle II ARICH counter

NASA Astrophysics Data System (ADS)

Yonenaga, M.; Adachi, I.; Dolenec, R.; Hataya, K.; Iori, S.; Iwata, S.; Kakuno, H.; Kataura, R.; Kawai, H.; Kindo, H.; Kobayashi, T.; Korpar, S.; Križan, P.; Kumita, T.; Mrvar, M.; Nishida, S.; Ogawa, K.; Ogawa, S.; Pestotnik, R.; Šantelj, L.; Sumiyoshi, T.; Tabata, M.; Yusa, Y.

2017-12-01

A slow control system (SCS) for the Aerogel Ring Imaging Cherenkov (ARICH) counter in the Belle II experiment was newly developed and coded in the development frameworks of the Belle II DAQ software. The ARICH is based on 420 Hybrid Avalanche Photo-Detectors (HAPDs). Each HAPD has 144 pixels to be readout and requires 6 power supply (PS) channels, therefore a total number of 2520 PS channels and 60,480 pixels have to be configured and controlled. Graphical User Interfaces (GUIs) with detector oriented view and device oriented view, were also implemented to ease the detector operation. The ARICH SCS is in operation for detector construction and cosmic rays tests. The paper describes the detailed features of the SCS and preliminary results of operation of a reduced set of hardware which confirm the scalability to the full detector.

Magnetic Microcalorimeter (MMC) Gamma Detectors with Ultra-High Energy Resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedrich, Stephen

The goal of this LCP is to develop ultra-high resolution gamma detectors based on magnetic microcalorimeters (MMCs) for accurate non-destructive analysis (NDA) of nuclear materials. For highest energy resolution, we will introduce erbium-doped silver (Ag:Er) as a novel sensor material, and implement several geometry and design changes to improve the signal-to-noise ratio. The detector sensitivity will be increased by developing arrays of 32 Ag:Er pixels read out by 16 SQUID preamplifiers, and by developing a cryogenic Compton veto to reduce the spectral background. Since best MMC performance requires detector operation at ~10 mK, we will purchase a dilution refrigerator withmore » a base temperature <10 mK and adapt it for MMC operation. The detector performance will be tested with radioactive sources of interest to the safeguards community.« less

GEM detector performance with innovative micro-TPC readout in high magnetic field

NASA Astrophysics Data System (ADS)

Garzia, I.; Alexeev, M.; Amoroso, A.; Baldini Ferroli, R.; Bertani, M.; Bettoni, D.; Bianchi, F.; Calcaterra, A.; Canale, N.; Capodiferro, M.; Cassariti, V.; Cerioni, S.; Chai, J. Y.; Chiozzi, S.; Cibinetto, G.; Cossio, F.; Cotta Ramusino, A.; De Mori, F.; Destefanis, M.; Dong, J.; Evangelisti, F.; Evangelisti, F.; Farinelli, R.; Fava, L.; Felici, G.; Fioravanti, E.; Gatta, M.; Greco, M.; Lavezzi, L.; Leng, C. Y.; Li, H.; Maggiora, M.; Malaguti, R.; Marcello, S.; Melchiorri, M.; Mezzadri, G.; Mignone, M.; Morello, G.; Pacetti, S.; Patteri, P.; Pellegrino, J.; Pelosi, A.; Rivetti, A.; Rolo, M. D.; Savrié, M.; Scodeggio, M.; Soldani, E.; Sosio, S.; Spataro, S.; Tskhadadze, E.; Verma, S.; Wheadon, R.; Yan, L.

2018-01-01

Gas detector development is one of the pillars of the research in fundamental physics. Since several years, a new concept of detectors, called Micro Pattern Gas Detector (MPGD), allowed to overcome several problems related to other types of commonly used detectors, like drift chamber and micro strips detectors, reducing the rate of discharges and providing better radiation tolerance. Among the most used MPGDs are the Gas Electron Multipliers (GEMs). Invented by Sauli in 1997, nowadays GEMs have become an important reality for particle detectors in high energy physics. Commonly deployed as fast timing detectors and triggers, their fast response, high rate capability and high radiation hardness make them also suitable as tracking detectors. The readout scheme is one of the most important features in tracking technology. Analog readout based on the calculation of the center of gravity technique allows to overcome the limit imposed by digital pads, whose spatial resolution is limited by the pitch dimensions. However, the presence of high external magnetic fields can distort the electronic cloud and affect the performance. The development of the micro-TPC reconstruction method brings GEM detectors into a new prospective, improving significantly the spatial resolutionin presence of high magnetic fields. This innovative technique allows to reconstruct the 3-dimensional particle position, as Time Projection Chamber, but within a drift gap of a few millimeters. In these report, the charge centroid and micro-TPC methods are described in details. We discuss the results of several test beams performed with planar chambers in magnetic field. These results are one of the first developments of micro-TPC technique for GEM detectors, which allows to reach unprecedented performance in a high magnetic field of 1 T.

Quantum efficiency test set up performances for NIR detector characterization at ESTEC

NASA Astrophysics Data System (ADS)

Crouzet, P.-E.; Duvet, L.; De Wit, F.; Beaufort, T.; Blommaert, S.; Butler, B.; Van Duinkerken, G.; ter Haar, J.; Heijnen, J.; van der Luijt, K.; Smit, H.; Viale, T.

2014-07-01

The Payload Technology Validation Section (Future mission preparation Office) at ESTEC is in charge of specific mission oriented validation activities, for science and robotic exploration missions, aiming at reducing development risks in the implementation phase. These activities take place during the early mission phases or during the implementation itself. In this framework, a test set up to characterize the quantum efficiency of near infrared detectors has been developed. The first detector to be tested will an HAWAII-2RG detector with a 2.5μm cut off, it will be used as commissioning device in preparation to the tests of prototypes European detectors developed under ESA funding. The capability to compare on the same setup detectors from different manufacturers will be a unique asset for the future mission preparation office. This publication presents the performances of the quantum efficiency test bench to prepare measurements on the HAWAII-2RG detector. A SOFRADIR Saturn detector has been used as a preliminary test vehicle for the bench. A test set up with a lamp, chopper, monochromator, pinhole and off axis mirrors allows to create a spot of 1mm diameter between 700nm and 2.5μm.The shape of the beam has been measured to match the rms voltage read by the Merlin Lock -in amplifier and the amplitude of the incoming signal. The reference detectors have been inter-calibrated with an uncertainty up to 3 %. For the measurement with HAWAII-2RG detector, the existing cryostat [1] has been modified to adapt cold black baffling, a cold filter wheel and a sapphire window. An statistic uncertainty of +/-2.6% on the quantum efficiency on the detector under test measurement is expected.

Gamma-Ray Detectors: From Homeland Security to the Cosmos (443rd Brookhaven Lecture)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolotnikov, Aleksey

2008-12-03

Many radiation detectors are first developed for homeland security or industrial applications. Scientists, however, are continuously realizing new roles that these detectors can play in high-energy physics and astrophysics experiments. On Wednesday, December 3, join presenter Aleksey Bolotnikov, a physicist in the Nonproliferation and National Security Department (NNSD) and a co-inventor of the cadmium-zinc-telluride Frisch-ring (CdZnTe) detector, for the 443rd Brookhaven Lecture, entitled Gamma-Ray Detectors: From Homeland Security to the Cosmos. In his lecture, Bolotnikov will highlight two primary radiation-detector technologies: CdZnTe detectors and fluid-Xeon (Xe) detectors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Arvind, E-mail: anita@barc.gov.in; Topkar, Anita

In order to improve the gamma discrimination capability for thermal neutron measurements using silicon PIN detectors, a novel approach of use of thin epitaxial silicon PIN detectors was investigated. Thin epitaxial silicon detectors with thickness of 15 µm were developed and their performance was tested with thermal neutrons using {sup 10}B converter. The performance of this detector was compared with the performance of a 300 µm silicon detector. The results of experiments presented in this paper indicate that thin epitaxial silicon detectors can significantly improve γ discrimination for thermal neutron measurements.

Analysis of Measurements for Solid State Lidar Development

NASA Technical Reports Server (NTRS)

Amzajerdian, Farzin

1996-01-01

A Detector Characterization Facility (DCF), capable of measuring 2-micron detection devices and evaluating heterodyne receivers, was developed at the Marshall Space Flight Center. The DCF is capable of providing all the necessary detection parameters for design, development, and calibration of coherent and incoherent solid state laser radar (lidar) systems. The coherent lidars in particular require an accurate knowledge of detector heterodyne quantum efficient, nonlinearity properties, and voltage-current relationship as a function of applied optical power. At present, no detector manufacturer provides these qualities or adequately characterizes their detectors for heterodyne detection operation. In addition, the detector characterization facility measures the detectors DC and AC quantum efficiencies noise equivalent power and frequency response up to several GHz. The DCF is also capable of evaluating various heterodyne detection schemes such as balanced detectors and fiber optic interferometers. The design and analyses of measurements for the DCF were preformed over the previous year and a detailed description of its design and capabilities was provided in the NASA report NAS8-38609/DO77. It should also be noted that the DCF design was further improved to allow for the characterization of diffractive andholographical optical elements and other critical components of coherent lidar systems.

Development of Si-APD Timing Detectors for Nuclear Resonant Scattering using High-energy Synchrotron X-rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kishimoto, Shunji; Zhang Xiaowei; Yoda, Yoshitaka

2007-01-19

A timing detector with silicon avalanche photodiodes (Si-APDs) has been developed for nuclear resonant scattering using synchrotron x-rays. The detector had four pairs of a germanium plate 0.1mm thick and a Si-APD (3 mm in dia., a depletion layer of 30-{mu}m thickness). Using synchrotron x-rays of 67.4 keV, the efficiency increased to 1.5% for the incident beam, while the efficiency was 0.76 % without the germanium converters. A measurement of SR-PAC on Ni-61 was executed by using the detector. Some other types of timing detectors are planned for x-rays of E>20 keV.

Desarrollo de un detector de rayos cósmicos de la colaboración LAGO en Buenos Aires - Aplicaciones en meteorología espacial

NASA Astrophysics Data System (ADS)

Coppola, M.; Bezzecchi, F.; Gulisano, A. M.; Masías-Meza, J. J.; Areso, O.; Ramelli, M.; Dasso, S.; LAGO Collaboration

2016-08-01

The study of low energy cosmic particles allows to analyze several aspects of major interest for space weather. Ground detectors permit to observe secundary particles produced during the cascades developed in the atmosphere. The characterization of a prototype for a water Cherenkov radiation particles detector, in the frame of the LAGO collaboration (Latin American Giant Observatory), is presented in this work. The collaboration plans to install this detector at the LAGO antarctic site. The developed acquisition system and the method used to make the energy callibration of the detector are detailed here, as also corrections for atmospheric effects.

Ring Imaging Cerenkov Detector for CLAS12

NASA Astrophysics Data System (ADS)

Muhoza, Mireille; Aaron, Elise; Smoot, Waymond; Benmokhtar, Fatiha

2017-09-01

The CLAS12 detector at Thomas Jefferson National Accelerator Facility (TJNAF) is undergoing an upgrade. One of the additions to this detector is a Ring Imaging Cherenkov (RICH) detector to improve particle identification in the 3-8 GeV/c momentum range. Approximately 400 multi anode photomultiplier tubes (MAPMTs) will be used to detect Cherenkov Radiation in the single photoelectron spectra (SPS). Detector tests are taking place at Jefferson Lab, while analysis software development is ongoing at Duquesne. I will be summarizing the work done at Duquesne on the Database development and the analysis of the ADC and TDCs for the Hamamatsu Multi-Anode PMTs that are used for Cerenkov light radiation. National Science Foundation, Award 1615067.

Development of a Compton camera for medical applications based on silicon strip and scintillation detectors

NASA Astrophysics Data System (ADS)

Krimmer, J.; Ley, J.-L.; Abellan, C.; Cachemiche, J.-P.; Caponetto, L.; Chen, X.; Dahoumane, M.; Dauvergne, D.; Freud, N.; Joly, B.; Lambert, D.; Lestand, L.; Létang, J. M.; Magne, M.; Mathez, H.; Maxim, V.; Montarou, G.; Morel, C.; Pinto, M.; Ray, C.; Reithinger, V.; Testa, E.; Zoccarato, Y.

2015-07-01

A Compton camera is being developed for the purpose of ion-range monitoring during hadrontherapy via the detection of prompt-gamma rays. The system consists of a scintillating fiber beam tagging hodoscope, a stack of double sided silicon strip detectors (90×90×2 mm3, 2×64 strips) as scatter detectors, as well as bismuth germanate (BGO) scintillation detectors (38×35×30 mm3, 100 blocks) as absorbers. The individual components will be described, together with the status of their characterization.

Advanced technologies for future ground-based, laser-interferometric gravitational wave detectors

PubMed Central

Hammond, Giles; Hild, Stefan; Pitkin, Matthew

2014-01-01

We present a review of modern optical techniques being used and developed for the field of gravitational wave detection. We describe the current state-of-the-art of gravitational waves detector technologies with regard to optical layouts, suspensions and test masses. We discuss the dominant sources and noise in each of these subsystems and the developments that will help mitigate them for future generations of detectors. We very briefly summarise some of the novel astrophysics that will be possible with these upgraded detectors. PMID:25705087

SURFACTANT DYSFUNCTION IN LUNG CONTUSION WITH AND WITHOUT SUPERIMPOSED GASTRIC ASPIRATION IN A RAT MODEL

PubMed Central

Raghavendran, Krishnan; Davidson, Bruce A.; Knight, Paul R.; Wang, Zhengdong; Helinski, Jadwiga; Chess, Patricia R.; Notter, Robert H.

2009-01-01

This study investigates surfactant dysfunction in rats with lung contusion (LC) induced by blunt chest trauma. Rats at 24 h postcontusion had a decreased percent content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL) and altered large-aggregate composition with decreased phosphatidylcholine (PC), increased lyso-PC, and increased protein compared with uninjured controls. The surface activity of large aggregates on a pulsating bubble surfactometer was also severely impaired at 24 h postcontusion. Decreases in large surfactant aggregate content and surface activity were improved, but still apparent, at 48 and 72 h postcontusion compared with uninjured control rats and returned to normal by 96 h postcontusion. The functional importance of surfactant abnormalities in LC injury was documented in pilot studies showing that exogenous surfactant replacement at 24 h postcontusion improved inflation/deflation lung volumes. Additional experiments investigated a clinically relevant combination of LC plus gastric aspiration (combined acid and small gastric food particles) and found reductions in large surfactant aggregates in BAL similar to those for LC. However, rats given LC + combined acid and small gastric food particles versus LC had more severe surfactant dysfunction based on decreases in surface activity and alterations in large aggregate composition. Combined data for all animal groups had strong statistical correlations between surfactant dysfunction (increased minimum surface tension, decreased large aggregates in BAL, decreased aggregate PC, and increased aggregate lyso-PC) and the severity of inflammatory lung injury (increased total protein, albumin, protein/phospholipid ratio, neutrophils, and erythrocytes in BAL plus increased whole lung myeloperoxidase activity). These results show that surfactant dysfunction is important in the pathophysiology of LC with or without concurrent gastric aspiration and provides a rationale for surfactant replacement therapy in these prevalent clinical conditions. PMID:18323743

Membrane protein crystallization in meso: lipid type-tailoring of the cubic phase.

PubMed Central

Cherezov, Vadim; Clogston, Jeffrey; Misquitta, Yohann; Abdel-Gawad, Wissam; Caffrey, Martin

2002-01-01

Hydrated monoolein forms the cubic-Pn3m mesophase that has been used for in meso crystallization of membrane proteins. The crystals have subsequently provided high-resolution structures by crystallographic means. It is possible that the hosting cubic phase created by monoolein alone, which itself is not a common membrane component, will limit the range of membrane proteins crystallizable by the in meso method. With a view to expanding the range of applicability of the method, we investigated by x-ray diffraction the degree to which the reference cubic-Pn3m phase formed by hydrated monoolein could be modified by other lipid types. These included phosphatidylcholine (PC), phosphatidylethanolamine, phosphatidylserine, cardiolipin, lyso-PC, a polyethylene glycol-lipid, 2-monoolein, oleamide, and cholesterol. The results show that all nine lipids were accommodated in the cubic phase to some extent without altering phase identity. The positional isomer, 2-monoolein, was tolerated to the highest level. The least well tolerated were the anionic lipids, followed by lyso-PC. The others were accommodated to the extent of 20-25 mol %. Beyond a certain concentration limit, the lipid additives either triggered one or a series of phase transitions or saturated the phase and separated out as crystals, as seen with oleamide and cholesterol. The series of phases observed and their order of appearance were consistent with expectations in terms of interfacial curvature changes. The changes in phase type and microstructure have been rationalized on the basis of lipid molecular shape, interfacial curvature, and chain packing energy. The data should prove useful in the rational design of cubic phase crystallization matrices with different lipid profiles that match the needs of a greater range of membrane proteins. PMID:12496106

Serum metabonomics of NAFLD plus T2DM based on liquid chromatography-mass spectrometry.

PubMed

Chen, Yang; Li, Chunlong; Liu, Liyan; Guo, Fuchuan; Li, Songtao; Huang, Lina; Sun, Changhao; Feng, Rennan

2016-09-01

Nonalcoholic fatty liver disease (NAFLD), a main liver disease around the world, is closely associated with insulin resistance, type 2 diabetes mellitus (T2DM) and other metabolic diseases. The objective of this study is to identify distinct metabolites of NAFLD patients with or without T2DM. We used a biomarker-discovery population to find distinct metabolites of NAFLD patients with or without T2DM. Then, a validation population was applied to test the model of the biomarker-discovery population. All the individuals received anthropometric and common biochemical measurements. The metabolic data were analyzed by multivariable statistical analyses using ultra-high-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry. There were 7, 7, 2 metabolites in the positive electrospray ionization (ESI(+)) mode, which were identified between groups from both the biomarker-discovery and validation population. The NAFLD group showed higher concentrations of oleamide, l-phenylalanine, l-proline, bilirubin, l-palmitoylcarnitine, and PC (20:5) and a lower concentration of Lyso-PAF C-18 than those of control. Compared with the control group, the NAFLD+T2DM group displayed higher oleamide, l-leucine, LysoPC (14:0), bilirubin, tetradecenoylcarnitine, linoleyl carnitine, and tetradecadiencarnitine in serum. Tetradecenoylcarnitine and tetradecadiencarnitine were more elevated in patients with NAFLD+T2DM than in the NAFLD group. Serum metabonomic analyses displayed great metabolic changes in patients with NAFLD and NAFLD plus T2DM. Our study is beneficial in providing a further view into the pathogenesis and pathophysiology of NAFLD and NAFLD plus T2DM, which might be useful for the prevention and therapy of NAFLD and NAFLD plus T2DM. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids.

PubMed

Subbaiah, P V; Liu, M

1996-05-31

Oxidation of lipoproteins results in the formation of several polar phospholipids with pro-inflammatory and pro-atherogenic properties. To examine the possible role of lecithin/cholesterol acyltransferase (LCAT) in the metabolism of these oxidized phospholipids, we oxidized whole plasma with either Cu(2+) or a free-radical generator, and determined the various activities of LCAT. Oxidation caused a reduction in plasma phosphatidylcholine (PC), an increase in a short-chain polar PC (SCP-PC), and an inhibition of the transfer of long-chain acyl groups to cholesterol (LCAT activity) or to lyso PC (lysolecithin acyltransferase (LAT) I activity). However, the transfer of short-chain acyl groups from SCP-PC to lyso PCLAT II activity) was stimulated several fold, in direct correlation with the degree of oxidation. LAT II activity was not stimulated by oxidation in LCAT-deficient plasma, showing that it is carried out by LCAT. Oxidized normal plasma exhibited low LCAT activity even in the presence of exogenous proteoliposome substrate, indicating that the depletion of substrate PC was not responsible for the loss of activity. Oxidation of isolated LDL or HDL abolished their ability to support LCAT and LAT I activities of exogenous enzyme, but promoted the LAT II activity. Purified LCAT lost its LCAT and LAT I functions, but not its LAT II function, when oxidized in vitro. These results show that while oxidation of plasma causes a loss of LCAT's ability to transfer long-chain acyl groups, its ability to transfer short-chain acyl groups, from SCP-PC is retained, and even stimulated, suggesting that LCAT may have a physiological role in the metabolism of oxidized PC in plasma.

The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics.

PubMed

Liu, Yue-tao; Jia, Hong-mei; Chang, Xing; Ding, Gang; Zhang, Hong-wu; Zou, Zhong-Mei

2013-11-01

Myocardial infarction (MI) is a leading cause of morbidity and mortality but the precise mechanism of its pathogenesis remains obscure. To achieve the most comprehensive screening of the entire metabolome related to isoproterenol (ISO) induced-MI, we present a tissue targeted metabonomic study using an integrated approach of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) and proton nuclear magnetic resonance (1H NMR). Twenty-two metabolites were detected as potential biomarkers related to the formation of MI, and the levels of pantothenic acid (), lysoPC(18:0) (), PC(18:4(6Z,9Z,12Z,15Z)/18:0) (), taurine (), lysoPC(20:3(8Z,11Z,14Z)) (), threonine (), alanine (), creatine (), phosphocreatine (), glucose 1-phosphate (), glycine (), xanthosine (), creatinine () and glucose () were decreased significantly, while the concentrations of histamine (), L-palmitoylcarnitine (), GSSG (), inosine (), arachidonic acid (), linoelaidic acid (), 3-methylhistamine () and glycylproline () were increased significantly in the MI rats compared with the control group. The identified potential biomarkers were involved in twelve metabolic pathways and achieved the most entire metabolome contributing to the injury of the myocardial tissue. Five pathways, including taurine and hypotaurine metabolism, glycolysis, arachidonic acid metabolism, glycine, serine and threonine metabolism and histidine metabolism, were significantly influenced by ISO-treatment according to MetPA analysis and suggested that the most prominent changes included inflammation, interference of calcium dynamics, as well as alterations of energy metabolism in the pathophysiologic process of MI. These findings provided a unique perspective on localized metabolic information of ISO induced-MI, which gave us new insights into the pathogenesis of MI, discovery of targets for clinical diagnosis and treatment.

The Serotonin Transporter Undergoes Constitutive Internalization and Is Primarily Sorted to Late Endosomes and Lysosomal Degradation*

PubMed Central

Rahbek-Clemmensen, Troels; Bay, Tina; Eriksen, Jacob; Gether, Ulrik; Jørgensen, Trine Nygaard

2014-01-01

The serotonin transporter (SERT) plays a critical role in regulating serotonin signaling by mediating reuptake of serotonin from the extracellular space. The molecular and cellular mechanisms controlling SERT levels in the membrane remain poorly understood. To study trafficking of the surface resident SERT, two functional epitope-tagged variants were generated. Fusion of a FLAG-tagged one-transmembrane segment protein Tac to the SERT N terminus generated a transporter with an extracellular epitope suited for trafficking studies (TacSERT). Likewise, a construct with an extracellular antibody epitope was generated by introducing an HA (hemagglutinin) tag in the extracellular loop 2 of SERT (HA-SERT). By using TacSERT and HA-SERT in antibody-based internalization assays, we show that SERT undergoes constitutive internalization in a dynamin-dependent manner. Confocal images of constitutively internalized SERT demonstrated that SERT primarily co-localized with the late endosomal/lysosomal marker Rab7, whereas little co-localization was observed with the Rab11, a marker of the “long loop” recycling pathway. This sorting pattern was distinct from that of a prototypical recycling membrane protein, the β2-adrenergic receptor. Furthermore, internalized SERT co-localized with the lysosomal marker LysoTracker and not with transferrin. The sorting pattern was further confirmed by visualizing internalization of SERT using the fluorescent cocaine analog JHC1-64 and by reversible and pulse-chase biotinylation assays showing evidence for lysosomal degradation of the internalized transporter. Finally, we found that SERT internalized in response to stimulation with 12-myristate 13-acetate co-localized primarily with Rab7- and LysoTracker-positive compartments. We conclude that SERT is constitutively internalized and that the internalized transporter is sorted mainly to degradation. PMID:24973209

Metabolic Disturbances in Adult-Onset Still's Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis.

PubMed

Chen, Der-Yuan; Chen, Yi-Ming; Chien, Han-Ju; Lin, Chi-Chen; Hsieh, Chia-Wei; Chen, Hsin-Hua; Hung, Wei-Ting; Lai, Chien-Chen

2016-01-01

Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still's disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome. Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites. Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05). Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.

Cerebral metabonomics study on Parkinson's disease mice treated with extract of Acanthopanax senticosus harms.

PubMed

Li, Xu-zhao; Zhang, Shuai-nan; Lu, Fang; Liu, Chang-feng; Wang, Yu; Bai, Yu; Wang, Na; Liu, Shu-min

2013-10-15

Extract of Acanthopanax senticosus harms (EAS) has neuroprotective effect on Parkinson's disease (PD) mice against dopaminergic neuronal damage. However, studies of its anti-PD mechanism are challenging, owing to the complex pathophysiology of PD, and complexity of EAS with multiple constituents acting on different metabolic pathways. Here, we have investigated the metabolic profiles and potential biomarkers in a mice model of MPTP-induced PD after treatment of EAS. Metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of mesencephalon obtained from 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Hydrochloride (MPTP-HCl)-induced PD mice model with and without EAS treatment. Through partial least squares-discriminate analysis (PLS-DA), it was observed that metabolic perturbations induced by MPTP were restored after treatment with EAS. Metabolites with significant changes induced by MPTP, including L-dopa, 5'-methylthioadenosine, tetradecanoylcarnitine, phytosphingosine-1-P, Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), L-palmitoyl -carnitine, tetracosanoylglycine, morphiceptin and stearoylcarnitine, were characterized as potential biomarkers involved in the pathogenesis of PD. The derivations of all those biomarkers can be regulated by EAS treatment except Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), morphiceptin. The therapeutic effect of EAS on PD may involve in regulating the tyrosine metabolism, mitochondrial beta-oxidation of long chain saturated fatty acids, fatty acid metabolism, methionine metabolism, and sphingolipid metabolism. This study indicated that changed metabolites can be certainly recovered by EAS, and the treatment of EAS can be connected with the regulation of related metabolic pathways. Copyright © 2013 Elsevier GmbH. All rights reserved.

Characterization of NAADP-mediated calcium signaling in human spermatozoa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sánchez-Tusie, A.A.; Vasudevan, S.R.; Churchill, G.C.

Highlights: •Human sperm cells synthesize NAADP. •NAADP-AM mediates [Ca{sup 2+}]{sub i} increases in human sperm in the absence of [Ca{sup 2+}]{sub o}. •Human sperm have two acidic compartments located in the head and midpiece. -- Abstract: Ca{sup 2+} signaling in spermatozoa plays a crucial role during processes such as capacitation and release of the acrosome, but the underlying molecular mechanisms still remain unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca{sup 2+}-releasing second messenger in a variety of cellular processes. The presence of a NAADP synthesizing enzyme in sea urchin sperm has been previously reported, suggesting a possiblemore » role of NAADP in sperm Ca{sup 2+} signaling. In this work we used in vitro enzyme assays to show the presence of a novel NAADP synthesizing enzyme in human sperm, and to characterize its sensitivity to Ca{sup 2+} and pH. Ca{sup 2+} fluorescence imaging studies demonstrated that the permeable form of NAADP (NAADP-AM) induces intracellular [Ca{sup 2+}] increases in human sperm even in the absence of extracellular Ca{sup 2+}. Using LysoTracker®, a fluorescent probe that selectively accumulates in acidic compartments, we identified two such stores in human sperm cells. Their acidic nature was further confirmed by the reduction in staining intensity observed upon inhibition of the endo-lysosomal proton pump with Bafilomycin, or after lysosomal bursting with glycyl-L-phenylalanine-2-naphthylamide. The selective fluorescent NAADP analog, Ned-19, stained the same subcellular regions as LysoTracker®, suggesting that these stores are the targets of NAADP action.« less

Clinical and Metabolic Characterization of Lean Caucasian Subjects With Non-alcoholic Fatty Liver.

PubMed

Feldman, Alexandra; Eder, Sebastian K; Felder, Thomas K; Kedenko, Lyudmyla; Paulweber, Bernhard; Stadlmayr, Andreas; Huber-Schönauer, Ursula; Niederseer, David; Stickel, Felix; Auer, Simon; Haschke-Becher, Elisabeth; Patsch, Wolfgang; Datz, Christian; Aigner, Elmar

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity; however, 5-8% of lean subjects also have evidence of NAFLD. We aimed to investigate clinical, genetic, metabolic and lifestyle characteristics in lean Caucasian subjects with NAFLD. Data from 187 subjects allocated to one of the three groups according to body mass index (BMI) and hepatic steatosis on ultrasound were obtained: lean healthy (BMI≤25 kg/m 2 , no steatosis, N=71), lean NAFLD (BMI≤25 kg/m 2 , steatosis, N=55), obese NAFLD (BMI≥30 kg/m 2 , steatosis; N=61). All subjects received a detailed clinical and laboratory examination including oral glucose tolerance test. The serum metabolome was assessed using the Metabolomics AbsoluteIDQ p180 kit (BIOCRATES Life Sciences). Genotyping for single-nucleotide polymorphisms (SNPs) associated with NAFLD was performed. Lean NAFLD subjects had fasting insulin concentrations similar to lean healthy subjects but had markedly impaired glucose tolerance. Lean NAFLD subjects had a higher rate of the mutant PNPLA3 CG/GG variant compared to lean controls (P=0.007). Serum adiponectin concentrations were decreased in both NAFLD groups compared to controls (P<0.001 for both groups) The metabolomics study revealed a potential role for various lysophosphatidylcholines (lyso-PC C18:0, lyso-PC C17:0) and phosphatidylcholines (PCaa C36:3; false discovery rate (FDR)-corrected P-value<0.001) as well as lysine, tyrosine, and valine (FDR<0.001). Lean subjects with evidence of NAFLD have clinically relevant impaired glucose tolerance, low adiponectin concentrations and a distinct metabolite profile with an increased rate of PNPLA3 risk allele carriage.

IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 3. Monitoring DPPC lipolysis in mixed micelles.

PubMed

Mateos-Diaz, Eduardo; Sutto-Ortiz, Priscila; Sahaka, Moulay; Rodriguez, Jorge A; Carrière, Frédéric

2018-03-01

Usual methods for the continuous assay of lipolytic enzyme activities are mainly based on the titration of free fatty acids, surface pressure monitoring or spectrophotometry using substrates labeled with specific probes. These approaches only give a partial information on the chemistry of the lipolysis reaction and additional end-point analyses are often required to quantify both residual substrate and lipolysis products. We used transmission infrared (IR) spectroscopy to monitor simultaneously the hydrolysis of phospholipids by guinea pig pancreatic lipase-related protein 2 (GPLRP2) and the release of lipolysis products. The substrate (DPPC, 1,2-Dipalmitoyl phosphatidylcholine) was mixed with sodium taurodeoxycholate (NaTDC) to form mixed micelles in D 2 O buffer at pD 6 and 8. After hydrogen/deuterium exchange, DPPC hydrolysis by GPLRP2 (100nM) was monitored at 35°C in a liquid cell by recording IR spectra and time-course variations in the CO stretching region. These changes were correlated to variations in the concentrations of DPPC, lysophospholipids (lysoPC) and palmitic acid (Pam) using calibration curves established with these compounds individually mixed with NaTDC. We were thus able to quantify each compound and its time-course variations during the phospholipolysis reaction and to estimate the enzyme activity. To validate the IR analysis, variations in residual DPPC, lysoPC and Pam were also quantified by thin-layer chromatography coupled to densitometry and similar hydrolysis profiles were obtained using both methods. IR spectroscopy can therefore be used to monitor the enzymatic hydrolysis of phospholipids and obtain simultaneously chemical and physicochemical information on substrate and all reaction products (H-bonding, hydration, acyl chain mobility). Copyright © 2017 Elsevier B.V. All rights reserved.

Oral hydroxysafflor yellow A reduces obesity in mice by modulating the gut microbiota and serum metabolism.

PubMed

Liu, Juan; Yue, Shijun; Yang, Zhirui; Feng, Wuwen; Meng, Xintong; Wang, Aiting; Peng, Cheng; Wang, Changyun; Yan, Dan

2018-05-19

Given the high and increasing prevalence of obesity, the safe and effective treatment of obesity would be beneficial. Here, we examined whether oral hydroxysafflor yellow A (HSYA), an active compound from the dried florets of Carthamus tinctorius L., can reduce high-fat (HF) diet-induced obesity in C57BL/6 J mice. Our results showed that the average body weight of HF group treated by HSYA was significantly lower than that of the HF group (P < 0.01). HSYA also reduced fat accumulation, ameliorated insulin resistance, restored glucose homeostasis, reduced inflammation, enhanced intestinal integrity, and increased short-chain fatty acids (SCFAs) production in HF diet-fed mice. Sequencing of 16S rRNA genes in fecal samples demonstrated that HSYA reversed HF diet induced gut microbiota dysbiosis. Particularly, HSYA increased the relative abundances of genera Akkermansia and Romboutsia, as well as SCFAs-producing bacteria, including genera Butyricimonas and Alloprevotella, whereas it decreased the phyla Firmicutes/Bacteroidetes ratio of HF diet-fed mice. Additionally, serum metabolomics analysis revealed that HSYA increased lysophosphatidylcholines (lysoPCs), L-carnitine and sphingomyelin, and decreased phosphatidylcholines in mice fed a HF diet, as compared to HF group. These changed metabolites were mainly linked with the pathways of glycerophospholipid metabolism and sphingolipid metabolism. Spearman's correlation analysis further revealed that Firmicutes was positively while Bacteroidetes and Akkermansia were negatively correlated with body weight, fasting serum glucose and insulin. Moreover, Akkermansia and Butyricimonas had positive correlations with lysoPCs, suggestive of the role of gut microbiota in serum metabolites. Our findings suggest HSYA may be a potential therapeutic drug for obesity and the gut microbiota may be potential territory for targeting of HSYA. Copyright © 2018 Elsevier Ltd. All rights reserved.