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

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. © 2012 Elsevier B.V. All rights reserved.This work was supported by the Centre for Industrial Technological Development co-funded by FEDER through the Technology Fund (DREAM Project, IDI-20110718), by the Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) under Grant. No. FIS2010-21216-CO2-01TEO 2008/114.Moliner Martínez, L.; Correcher, C.; González Martínez, AJ.; Conde Castellanos, PE.; Hernández Hernández, L.; Orero Palomares, A.; Rodríguez Álvarez, MJ.... (2013). Implementation and analysis of list mode algorithm using tubes of response on a dedicated brain and breast PET. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 702:129-132. https://doi.org/10.1016/j.nima.2012.08.029S12913270

Effectiveness of sacubitril–valsartan in cancer patients with heart failure

Aims Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD. Methods and results We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardiooncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirtynine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline Nterminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril–valsartan dose (low or medium/high doses). Conclusions Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.This study was funded by the Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, Spain, and the EU—European Regional Development Fund, by means of a competitive call for excellence in research projects (PIE14/00066) as well as by the Spanish Cardiovascular Network (CIBERCV)

ALBIRA: A small animal PET/SPECT/CT imaging system

Purpose: The authors have developed a trimodal PET/SPECT/CT scanner for small animal imaging. The gamma ray subsystems are based on monolithic crystals coupled to multianode photomultiplier tubes (MA-PMTs), while computed tomography (CT) comprises a commercially available microfocus x-ray tube and a CsI scintillator 2D pixelated flat panel x-ray detector. In this study the authors will report on the design and performance evaluation of the multimodal system. Methods: X-ray transmission measurements are performed based on cone-beam geometry. Individual projections were acquired by rotating the x-ray tube and the 2D flat panel detector, thus making possible a transaxial field of view (FOV) of roughly 80 mm in diameter and an axial FOV of 65 mm for the CT system. The single photon emission computed tomography (SPECT) component has a dual head detector geometry mounted on a rotating gantry. The distance between the SPECT module detectors can be varied in order to optimize specific user requirements, including variable FOV. The positron emission tomography (PET) system is made up of eight compact modules forming an octagon with an axial FOV of 40 mm and a transaxial FOV of 80 mm in diameter. The main CT image quality parameters (spatial resolution and uniformity) have been determined. In the case of the SPECT, the tomographic spatial resolution and system sensitivity have been evaluated with a99mTc solution using single-pinhole and multi-pinhole collimators. PET and SPECT images were reconstructed using three-dimensional (3D) maximum likelihood and ordered subset expectation maximization (MLEM and OSEM) algorithms developed by the authors, whereas the CT images were obtained using a 3D based FBP algorithm. Results: CT spatial resolution was 85μm while a uniformity of 2.7% was obtained for a water filled phantom at 45 kV. The SPECT spatial resolution was better than 0.8 mm measured with a Derenzo-like phantom for a FOV of 20 mm using a 1-mm pinhole aperture collimator. The full width at half-maximum PET radial spatial resolution at the center of the field of view was 1.55 mm. The SPECT system sensitivity for a FOV of 20 mm and 15% energy window was 700 cps/MBq (7.8 × 10−2%) using a multi-pinhole equipped with five apertures 1 mm in diameter, whereas the PET absolute sensitivity was 2% for a 350–650 keV energy window and a 5 ns timing window. Several animal images are also presented. Conclusions: The new small animal PET/SPECT/CT proposed here exhibits high performance, producing high-quality images suitable for studies with small animals. Monolithic design for PET and SPECT scintillator crystals reduces cost and complexity without significant performance degradation.This study was supported by the Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) under Grant No. FIS2010-21216-CO2-01 and Valencian Local Government under Grant PROMETEO 2008/114. The authors also thank Brennan Holt for checking and correcting the text.Sánchez Martínez, F.; Orero Palomares, A.; Soriano Asensi, A.; Correcher Salvador, C.; Conde Castellanos, PE.; González Martínez, AJ.; Hernández Hernández, L.... (2013). ALBIRA: A small animal PET/SPECT/CT imaging system. Medical Physics. 40(5):5190601-5190611. https://doi.org/10.1118/1.4800798S5190601519061140

Calibration and performance tests of detectors for laser-accelerated protons

We present the calibration and performance tests carried out with two detectors for intense proton pulses accelerated by lasers. Most of the procedures were realized with proton beams of 0.46-5.60 MeV from a tandem accelerator. One approach made use of radiochromic films, for which we calibrated the relation between optical density and energy deposition over more than three orders of magnitude. The validity of these results and of our analysis algorithms has been confirmed by controlled irradiation of film stacks and reconstruction of the total beam charge for strongly non-uniform beam profiles. For the spectral analysis of protons from repeated laser shots, we have designed an online monitor based on a plastic scintillator. The resulting signal from a photomultiplier directly measured on a fast oscilloscope is especially useful for time-of-flight applications. Variable optical filters allow for suppression of saturation and an extension of the dynamic range. With pulsed proton beams we have tested the detector response to a wide range of beam intensities from single particles to 3 ×105 protons per 100 ns time interval.Project funded by the Spanish Ministry of Economy and Competitiveness and co-funded with FEDER's funds within the INNPACTO 2011 program under Grant No. IPT-2011-0862-900000. This work was supported by the Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+i) under Grant No. TEC 2013-48036-C3-1-R and the Valencian Local Government under Grants PROMETEOII/2013/010 and ISIC 2011/013. The work of A. J. Gonzalez is financed by CSIC with a JAE-Doc contract under Junta de Ampliacion de Estudios program, cofinanced by the European Social Fund.Peer Reviewe

Time-of-Flight Detector for the Characterisation of Laser-Accelerated Protons

[Otros] Lasers of ultra-high intensity focused on thin targets can form plasmas and release large numbers of charged particles with kinetic energies in the MeV region. The characterization of the accelerated particles requires suitable detectors. We present a time-of-flight detector based on a plastic scintillator optimized for the spectral analysis of laser-accelerated protons. All details of the detector layout are adapted to the expected properties of the proton beam. Particle energies will be separated by the time-of-flight technique over 200 cm path length. The active area (25 mm width) corresponds to a few mrad opening angle. With 5 mm thickness the detector is capable of absorbing protons up to 22.5 MeV. A very thin, aluminized mylar foil shields the scintillator from outer light while absorbing very little particle energy. The scintillation photons are measured with a photomultiplier tube coupled through a bundle of optical fibres. The coupling of these fibres via a PMMA light guide has been previously optimized in simulations with Litrani. A critical aspect of the detection of virtually large numbers of protons emitted in femtosecond pulses is the saturation of the PMT. The latter can be avoided by use of appropriate optical filters. With these the effective dynamic range starts from single particles over several orders of magnitude. Our time-of-flight detector has been calibrated at the Spanish National Accelerator Centre at Sevilla. Proton beams from 0.46 to 5.6 MeV from a tandem accelerator have been used to measure the relation between particle energy and pulse heights. Further tests have been performed with a pulsed electron beam to simulate many-particle hits.Project funded by the Spanish Ministry of Economy and Competitiveness and co-funded with FEDER¿s funds within the INNPACTO 2011 program, Grant No. IPT-2011-0862- 900000. This work was supported by the Spanish Plan Nacional de Investigacion Científica, Desarrollo e Innovacion Tecnológica (I+D+i) under Grant No. FIS2010-21216-CO2-01 and the Valencian Local Government under Grants PROMETEOII/2013/010 and ISIC 2011/013Seimetz, M.; Bellido, P.; Soriano, A.; Huertas, C.; García Lopez, J.; Jimenez-Ramos, MC.; Fernandez, B.... (2013). Time-of-Flight Detector for the Characterisation of Laser-Accelerated Protons. IEEE. 25-28. https://doi.org/10.1109/NSSMIC.2013.6829804S252

Dosimetric Calibration of Radiochromic Film For Laser-accelerated Proton Beams

[Otros] When an ultra-intense and ultra-short laser pulse interacts with solid matter a fraction of the laser pulse can be converted into kinetic energy of a beam of charged particles. Radiochromic film (RCF), widely used as radiation detector in the field of conventional radiotherapy, can be used as detector for laser-accelerated protons. If used in stack configuration it is a useful and versatile tool to obtain 2D spatial distribution and energetic information of proton beams. In order to obtain dosimetric information from RCF it must be properly calibrated. Irradiating film pieces under well known conditions allows us to establish a relation between the optical density (OD) of the radiochromic film, which is measured through a flat bed scanner operating in transmission mode, and the deposited energy in the active layer. A calibration curve over a large dynamic range (3 orders of magnitude) has been obtained for few MeV protons. Our calibration process has been performed at the Spanish National Accelerator Center at Sevilla. We have irradiated several areas of a single RCF with a constant 50 pA beam current and fixed 4 MeV energy from a 3 MV tandem accelerator. We have calculated the deposited energy in the films under the same conditions. We demonstrate that this technique can be used to measure the spectrum and total energy of a laser-accelerated mixed-energy proton beam. This detector has been calibrated for a near future application at the Center of Pulsed, Ultra-short, Ultra-intense Lasers (CLPU) at Salamanca (Spain). We present the calibration procedure and results, the design optimization, and a comparison with similar experiments.Project funded by the Spanish Ministry of Economy and Competitiveness and co-funded with FEDERs funds within the INNPACTO 2011 program. This work was supported by the Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e InnovacionTecnologica (I+D+i) under Grant No. FIS2010-21216-CO2-01 and the Valencian Local Government under Grants PROMETEOII/2013/010 and ISIC 2011/013.Bellido, P.; Seimetz, M.; Soriano, A.; Huertas, C.; García Lopez, J.; Jimenez-Ramos, MC.; Fernandez, B.... (2013). Dosimetric Calibration of Radiochromic Film For Laser-accelerated Proton Beams. IEEE. 20-23. https://doi.org/10.1109/NSSMIC.2013.6829806S202

Performance Evaluation of the Dual Ring MAMMI breast PET

[Otros] MAMMI is a dedicated breast positron emission tomograph (PET) based on monolythic LYSO crystals, with a transaxial field of view (FOV) of 170 mm. It has been upgraded by adding a second ring of detectors that extends the axial FOV from 40 mm to 94.4 mm, in order to improve its sensitivity and reduce the acquisition time. In this work we present the performance evaluation of the dual ring MAMMI breast PET and a discussion about the contribution of the addition of a second ring of detectors, the compensation of the detector blur and the increase of the scintillator thickness. Experimental measurements suggested on NEMA NU 4-2008 and NEMA NU 2-2007 have been conveniently adapted to the dimensions of the MAMMI. The addition of the second ring of detectors leads to a rise of the sensitivity from 1.8% to 3.6%. The spatial resolution at one-fourth of the axial FOV (1.5 mm axial, 1.6 mm tangential, 1.7 mm radial) is slightly better than that measured at the axial center (1.9 mm axial, 1.8 mm tangential and radial), because of the 14 mm gap in between detection rings. The results obtained after the evaluation reflect a substantial performance improvement, specially in the absolute sensitivity, because of the changes introduced in the MAMMI PET.This work was supported in part bythe Spanish Plan Nacional de Investigacion Científica, Desarrollo e Innovación Tecnologica (I+D+I) under Grant No. FIS2010-21216-CO2-01 and Valencian Local Government under Grants PROMETEOII/2013/010 and ISIC 2011/013Soriano, A.; Sánchez, F.; Carrilero, V.; Pardo, A.; Vidal San Sebastian, LF.; Vazquez, C.; Barbera, J.... (2013). Performance Evaluation of the Dual Ring MAMMI breast PET. IEEE. 1-4. https://doi.org/10.1109/NSSMIC.2013.6829103S1

Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods

The promiscuous activity of the enzyme o-succinylbenzoate synthase (OSBS) from the actinobacteria Amycolatopsis is investigated by means of QM/MM methods, using both density functional theory and semiempirical Hamiltonians. This enzyme catalyzes not only the dehydration of 2-succinyl-6R-hydroxy-2,4-cyclohexadiene-1R-carboxylate but also catalyzes racemization of different acylamino acids, with N-succinyl-R-phenylglycine being the best substrate. We investigated the molecular mechanisms for both reactions exploring the potential energy surface. Then, molecular dynamics simulations were performed to obtain the free energy profiles and the averaged interaction energies of enzymatic residues with the reacting system. Our results confirm the plausibility of the reaction mechanisms proposed in the literature, with a good agreement between theoretical and experimentally derived activation free energies. Our simulations unravel the role played by the different residues in each of the two possible reactions. The presence of flexible loops in the active site and the selection of structural modifications in the substrate seem to be key elements to promote the promiscuity of this enzyme.This work was supported by the Spanish Ministerio de Economia y Competitividad project CTQ2012-36253-C03-03 ́ and FEDER funds. K.S. thanks the Polish National Science Center (NCN) for Grant 2011/02/A/ST4/00246. The authors acknowledge computational facilities of the Servei d’Informatica ̀ de la Universitat de Valencia in the ̀ “Tirant” supercomputer, which is part of the Spanish Supercomputing Network

Fostering English-taught higher education programs in a Spanish university: the "TechEnglish" innovative project

In recent years, coinciding with adjustments to the Bologna process, many European universities have attempted to improve their international profile by increasing course offerings in English. According to the Institute of International Education (IIE), Spain has notably increased its English-taught higher education programs, ranking fifth in the list of European countries by number of English-taught Master's programs in 2013. This article presents the goals and preliminary results of an on-going innovative education project (TechEnglish) that aims to promote course offerings in English at the Technical University of Madrid (Universidad Politécnica de Madrid, UPM). The UPM is the oldest and largest of all Technical Universities in Spain. It offers graduate and postgraduate programs that cover all the engineering disciplines as well as architecture. Currently, the UPM has no specific bilingual/multilingual program to promote teaching in English, although there is an Educational Model Whitepaper (with a focus on undergraduate degrees) that promotes the development of activities like an International Semester or a unique shared curriculum. The TechEnglish project is an attempt to foster courses taught in English at 7 UPM Technical Schools, including students and 80 faculty members. Four tasks were identified: (1) to design a university wide framework to increase course offerings, (2) to identify administrative difficulties, (3) to increase visibility of courses offered, and (4) to disseminate the results of the project. First, to design a program we analyzed existing programs at other Spanish universities, and other projects and efforts already under way at the UPM. A total of 13 plans were analyzed and classified according to their relation with students (learning), professors (teaching), administration, course offerings, other actors/institutions within the university (e.g., language departments), funds and projects, dissemination activities, mobility plans and quality control. Second, to begin to identify administrative and organizational difficulties in the implementation of teaching in English, we first estimated the current and potential course offerings at the undergraduate level at the UPM using a survey (student, teacher and administrative demand, level of English and willingness to work in English). Third, to make the course offerings more attractive for both Spanish and international students we examined the way the most prestigious universities in Spain and in Europe try to improve the visibility of their academic offerings in English. Finally, to disseminate the results of the project we created a web page and a workspace on the Moodle education platform and prepared conferences and workshops within the UPM. Preliminary results show that increasing course offerings in English is an important step to promote the internationalization of the University. The main difficulties identified at the UPM were related to how to acknowledge/certify the departments, teachers or students involved in English courses, how students should register for the courses, how departments should split and schedule the courses (Spanish and English), and the lack of qualified personnel. A concerted effort could be made to increase the visibility of English-taught programs offered on-line