Instituto de Instrumentación para Imagen Molecular
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- PublicaciónPADC nuclear track detector for ion spectroscopy in laser-plasma acceleration(Elsevier, 2020-08) Seimetz, Michael; Peñas, J.; Llerena, J. J.; Benlliure, J.; García López, J.; Millán-Callado, M. A.; Benlloch Baviera, Jose María; Instituto de Instrumentación para Imagen Molecular; Consejo Superior de Investigaciones Científicas; Ministerio de Economía y Competitividad[EN] The transparent polymer polyallyl-diglycol-carbonate (PADC), also known as CR-39, is widely used as detector for heavy charged particles at low fluence. It allows for detection of single protons and ions via formation of microscopic tracks after etching in NaOH or KOH solutions. PADC combines a high sensitivity and high specificity with inertness towards electromagnetic noise. Present fields of application include laser-ion acceleration, inertial confinement fusion, radiobiological studies with cell cultures, and dosimetry of nuclear fragments in particle therapy. These require precise knowledge of the energy-dependent response of PADC to different ion species. We present calibration data for a new type of detector material, Radosys RS39, to protons (0.2-3 MeV) and carbon ions (0.6-12 MeV). RS39 is less sensitive to protons than other types of PADC. Its response to carbon ions, however, is similar to other materials. Our data indicate that RS39 allows for measuring carbon ion energies up to 10 MeV only from the track diameters. In addition, it can be used for discrimination between protons and carbon ions in a single etching process.
- PublicaciónPSMA-Targeted Mesoporous Silica Nanoparticles for Selective Intracellular Delivery of Docetaxel in Prostate Cancer Cells(American Chemical Society, 2019-01-31) Rivero Buceta, Eva María; Vidaurre Agut, Carla María; VERA DONOSO, CESAR DAVID; Benlloch Baviera, Jose María; MORENO MANZANO, VICTORIA; Botella Asuncion, Pablo; Instituto Universitario Mixto de Tecnología Química; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; Ministerio de Economía y Competitividad[EN] Although docetaxel is currently broadly used in prostate cancer treatment, poor water solubility and systemic toxicity limit the dose and duration of therapy. In this context, although different nanoplatforms have been proposed to overcome these issues, selective therapy needs developing methodologies to target malignant cells and minimizing the impact on healthy tissue. We here present a novel drug delivery system obtained by covalent conjugation of docetaxel and an anti-prostate specific membrane antigen (PSMA) molecule (anti-FOLH1 monoclonal antibody, clone C803N) over mesoporous silica nanoparticles. This conjugate remains stable in physiological medium and shows high selectivity for LNCaP, a specific cell line that overexpresses PSMA. As a consequence, cell internalization is increased by 25%. Furthermore, cytotoxic activity of the targeted system increases by 2-fold with regard to nontargeted nanoparticles and by 2 orders with regard to the naked drug. Conversely, no targeting effect is observed over PC3, a nonbearing PSMA cell line. We expect that this therapeutic system shows strong potential for treating nonmetastatic prostate cancer, mostly through intraprostatic administration.
- PublicaciónCalibration of Gamma Ray Impacts in Monolithic-Based Detectors Using Voronoi Diagrams(Institute of Electrical and Electronics Engineers, 2020-05) Freire, Marta; Gonzalez-Montoro, Andrea; Sánchez Martínez, Filomeno; Benlloch Baviera, Jose María; González Martínez, Antonio Javier; Instituto de Instrumentación para Imagen Molecular; European Commission; Ministerio de Economía y Competitividad[EN] Molecular imaging systems, such as positron emission tomography (PET), use detectors providing energy and a 3-D interaction position of a gamma ray within a scintillation block. Monolithic crystals are becoming an alternative to crystal arrays in PET. However, calibration processes are required to correct for nonuniformities, mainly produced by the truncation of the scintillation light distribution at the edges. We propose a calibration method based on the Voronoi diagrams. We have used $50 \times 50 \times 15$ mm(3) LYSO blocks coupled to a $12\times 12$ SiPMs array. We have first studied two different interpolation algorithms: 1) weighted average method (WAM) and 2) natural neighbor (NN). We have compared them with an existing calibration based on 1-D monomials. Here, the crystal was laterally black painted and a retroreflector (RR) layer added to the entrance face. The NN exhibited the best results in terms of XY impact position, depth of Interaction, and energy, allowing us to calibrate the whole scintillation volume. Later, the NN interpolation has been tested against different crystal surface treatments, allowing always to correct edge effects. Best energy resolutions were observed when using the reflective layers (12%-14%). However, better linearity was observed with the treatments using black paint. In particular, we obtained the best overall performance when lateral black paint is combined with the RR.
- PublicaciónAcoustic Holograms for Bilateral Blood-Brain Barrier Opening in a Mouse Model(Institute of Electrical and Electronics Engineers, 2022-04) Jiménez-Gambín, Sergio; Jiménez González, Noé; Pouliopoulos, Antonios N.; Benlloch Baviera, Jose María; Konofagou, Elisa E.; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; GENERALITAT VALENCIANA; AGENCIA ESTATAL DE INVESTIGACION; AGENCIA VALENCIANA DE LA INNOVACION; National Institutes of Health, EEUU; Agència Valenciana de la Innovació[EN] Transcranial focused ultrasound (FUS) in conjunction with circulating microbubbles injection is the sole non-invasive technique that temporally and locally opens the blood-brain barrier (BBB), allowing targeted drug delivery into the central nervous system (CNS). However, single-element FUS technologies do not allow the simultaneous targeting of several brain structures with high-resolution, and multi-element devices are required to compensate the aberrations introduced by the skull. In this work, we present the first preclinical application of acoustic holograms to perform a bilateral BBB opening in two mirrored regions in mice. The system consisted of a single-element focused transducer working at 1.68 MHz, coupled to a 3D-printed acoustic hologram designed to produce two symmetric foci in anesthetized mice in vivo and, simultaneously, compensate the aberrations of the wavefront caused by the skull bones. T1-weighed MR images showed gadolinium extravasation at two symmetric quasi-spherical focal spots. By encoding time-reversed fields, holograms are capable of focusing acoustic energy with a resolution near the diffraction limit at multiple spots inside the skull of small preclinical animals. This work demonstrates the feasibility of hologram-assisted BBB opening for low-cost and highly-localized targeted drug delivery in the CNS in symmetric regions of separate hemispheres.
- PublicaciónSmall animal PET scanner based on monolithic LYSO crystals: Performance evaluation(American Association of Physicists in Medicine: Medical Physics, 2012) Sánchez Martínez, Filomeno; Moliner Martínez, Laura; Correcher, C.; González Martínez, Antonio Javier; Orero Palomares, Abel; Carles Fariña, Montserrat; Soriano Asensi, Antonio; Rodríguez Álvarez, María José; Medina, L.A; Mora Mas, Francisco José; Benlloch Baviera, Jose María; Departamento de Ingeniería Electrónica; Escuela Técnica Superior de Ingeniería de Telecomunicación; Departamento de Matemática Aplicada; Escuela Técnica Superior de Ingeniería Informática; Instituto de Instrumentación para Imagen Molecular; Ministerio de Ciencia e Innovación; Generalitat ValencianaPurpose: The authors have developed a small animal Positron emission tomography(PET)scanner based on monolithic LYSO crystals coupled to multi-anode photomultiplier tubes (MA-PMTs). In this study, the authors report on the design, calibration procedure, and performance evaluation of a PET system that the authors have developed using this innovative nonpixelated detector design. Methods : The scanner is made up of eight compact modules forming an octagon with an axial field of view (FOV) of 40 mm and a transaxial FOV of 80 mm diameter. In order to fully determine its performance, a recently issued National Electrical Manufacturers Association (NEMA) NU-4 protocol, specifically developed for small animal PETscanners, has been followed. By measuring the width of light distribution collected in the MA-PMT the authors are able to determine depth of interaction (DOI), thus making the proper identification of lines of response (LORs) with large incidence angles possible. PET performances are compared with those obtained with currently commercially available small animal PETscanners. Results : At axial center when the point-like source is located at 5 mm from the radial center, the spatial resolution measured was 1.65, 1.80, and 1.86 mm full width at half maximum (FWHM) for radial, tangential, and axial image profiles, respectively. A system scatter fraction of 7.5% (mouse-like phantom) and 13% (rat-like phantom) was obtained, while the maximum noise equivalent count rate (NECR) was 16.9 kcps at 12.7 MBq (0.37 MBq/ml) for mouse-like phantom and 12.8 kcps at 12.4 MBq (0.042 MBq/ml) for rat-like phantom The peak absolute sensitivity in the center of the FOV is 2% for a 30% peak energy window. Several animal images are also presented. Conclusions: The overall performance of our small animal PET is comparable to that obtained with much more complex crystal pixelated PET systems. Moreover, the new proposed PET produces high-quality images suitable for studies with small animals.
- PublicaciónA proof-of-concept of cross-luminescent metascintillators: testing results on a BGO: BaF2metapixel(IOP Publishing, 2023-01-21) Konstantinou, G.; Latella, Riccardo; Moliner Martínez, Laura; Zhang, L.; Benlloch Baviera, Jose María; González Martínez, Antonio Javier; Lecoq, Paul; Instituto de Instrumentación para Imagen Molecular; European Commission[EN] Objective: Time-of-flight positron emission tomography (PET)is the next frontier in improving the effective sensitivity. To achieve superior timing for time-of-flight PET, combined with high detection efficiency and cost-effectiveness, we have studied the applicability of BaF2 in metascintillators driven by the timing of cross-luminescence photon production. Approach: Based on previous simulation studies of energy sharing and analytic multi-exponential scintillation pulse, as well as sensitivity characteristics, we have experimentally tested a pixel of 3 × 3 × 15 mm3 based on 300 ¿m BGO and 300 ¿m BaF2 layers. To harness the deep ultraviolet cross-luminescent light component, which carries improved timing, we use the FBK VUV SiPM. Metascintillator energy sharing is addressed through a double integration approach. Main results: We reach an energy resolution of 22%, comparable to an 18% resolution of simple BGO pixels using the same readout, through the optimized use of the integrals of the metascintillator pulse in energy sharing calculation. We measure the energy sharing extent of each pulse with a resolution of 25% and demonstrate that experimental and simulation results agree well. Based on the energy sharing, a timewalk correction is applied, exhibiting significant improvements for both the coincidence time resolution (CTR) and the shape of the timing histogram. We reach 242 ps CTR for the entire photopeak, while for a subset of 13% of the most shared events, the CTR value improves to 108 ps, comparable to the 3 × 3 × 5 mm3 LYSO:Ce:Ca reference crystal. Significance: While we are considering different ways to improve further these results, this proof-ofconcept demonstrates the applicability of cross-luminescence for metascintillator designs through the application of VUV compatible SiPM coupling, and easily implementable digital algorithms. This is the first test of BaF2-based metascintillators of sufficient stoppng power to be included in a PET scanner, demonstrating the industrial applicability of such cross-luminescent metascintillators.
- PublicaciónPETIROC2 based readout electronics optimization for Gamma Cameras and PET detectors(IOP Publishing, 2017) Monzó Ferrer, José María; Aguilar -Talens, Albert; González Montoro, Andrea; Lamprou,E.; González Martínez, Antonio Javier; Hernández Hernández, Liczandro; Mázur, Dmytro; Colom Palero, Ricardo José; Benlloch Baviera, Jose María; Departamento de Ingeniería Electrónica; Escuela Técnica Superior de Ingeniería de Telecomunicación; Instituto de Instrumentación para Imagen Molecular; Ministerio de Economía, Industria y Competitividad[EN] Developing front-end electronics to improve charge detection and time resolution in gamma-ray detectors is one of the main tasks to improve performance in new multimodal imaging systems that merge information of Magnetic Resonance Imaging and Gamma Camera or PET tomographs. The aim of this work is to study the behaviour and to optimize the performance of an ASIC for PET and Gamma Camera applications based on SiPMs detectors. PETIROC2 is a commercial ASIC developed by Weeroc to provide accurate charge and time coincidence resolutions. It has 32 analog input channels that are independently managed. Each channel is divided into two signals, one for time stamping using a TDC and another for charge measurement. In this work, PETIROC2 is evaluated in an experimental setup composed of two pixelated LYSO crystals based detectors, each coupled to a Hamamatsu 4 x 4 SiPM array. Both detectors are working in coincidence with a separation distance between them that can be modified. In the present work, an energy resolution of 13 : 6% FWHM and a time coincidence resolution of 815 ps FWHM have been obtained. These results will be useful to optimize and improve PETIROC2 based PET and Gamma Camera systems.
- PublicaciónIn-depth evaluation of TOF-PET detectors based on crystal arrays and the TOFPET2 ASIC(Elsevier, 2020-10-11) Lamprou, Efthymios; Sánchez Martínez, Filomeno; Benlloch Baviera, Jose María; González Martínez, Antonio Javier; Instituto de Instrumentación para Imagen Molecular; European Commission; Generalitat Valenciana; Ministerio de Economía y Competitividad[EN] In recent years high efforts have been devoted to enhance spatial and temporal resolutions of PET detectors. However, accurately combining these two main features is, in most of the cases, challenging. Typically, a compromise has to be made between the number of readout channels, scintillator type and size, and photosensors arrangement if aiming for a good system performance, while keeping a moderate cost. In this work, we have studied several detector configurations for PET based on a set of 8x8 Silicon Photomultiplier (SiPMs) of 3x3 mm(2) active area, and LYSO crystal arrays with different pixel sizes. An exhaustive evaluation in terms of spatial, energy and timing resolution was made for all detector configurations. In some cases, when using pixel sizes different than SiPM active area, a significant amount of scintillation light may spread among several SiPMs. Therefore, we made use of a calibration method considering the different SiPM timing contributions. Best Detector Time Resolution (DTR) of 156 ps FWHM was measured when using 3x3 mm(2) crystal pixels directly coupled to the 3x3 mm(2) SiPMs. However, when using 1.5 mm crystal pixels with the same photosensor array, although we could clearly resolve all crystal pixels, an average DTR of 250 ps FWHM was achieved. We also shed light in this work on the timing dependency of the crystal pixel and photosensor alignment.
- PublicaciónResults of a combined monolithic crystal and an array of ASICs controlled SiPMs(Elsevier, 2014-01) Conde Castellanos, Pablo Eloy; González Martínez, Antonio Javier; Hernández Hernández, Liczandro; Bellido, P.; Iborra Carreres, Amadeo; Crespo Navarro, Efren; Moliner Martínez, Laura; Rigla, JP.; Rodríguez Álvarez, María José; Sánchez, F.; Seimetz, Michael; Soriano Asensi, Antonio; Vidal San Sebastián, Luis Fernando; Benlloch Baviera, Jose María; Departamento de Matemática Aplicada; Escuela Técnica Superior de Ingeniería Informática; Instituto de Instrumentación para Imagen Molecular; European Regional Development Fund; Generalitat Valenciana; Ministerio de Ciencia e Innovación; Centro para el Desarrollo Tecnológico Industrial[EN] In this work we present the energy and spatial resolutions we have obtained for a γ ray detector based on a monolithic LYSO crystal coupled to an array of 256 SiPMs. Two crystal configurations of the same trapezoidal shape have been tried. In one approach all surfaces were black painted but the exit one facing the photosensor array which was polished. The other approach included a retroreflector (RR) layer coupled to the entrance face of the crystal powering the amount of transmitted light to the photosensors. Two coupling media between the scintillator and the SiPM array were used, namely direct coupling by means of optical grease and coupling through an array of light guides. Since the same operational voltage was supplied to the entire array, it was needed to equalize their gains before feeding their signals to the Data Acquisition system. Such a job was performed by means of 4 scalable Application Specific Circuits (ASICs). An energy resolution of about 24.4% has been achieved for the direct coupling with the RR layer together with a spatial resolution of approximately 2.9 mm at the detector center. With the light guides coupling the effects of image compression at the edges are significantly minimized, but worsening the energy resolution to about 33.1% with a spatial resolution nearing 4 mm at the detector center. & 2013 Elsevier B.V. All rights reserved.
- PublicaciónDynamic beamforming for large area scan in array-based photoacoustic microscopy(IEEE, 2020-09-11) Cebrecos Ruiz, Alejandro; García Garrigós, Juan José; Descals, Andreu; Jiménez González, Noé; Benlloch Baviera, Jose María; Camarena Femenia, Francisco; Departamento de Física Aplicada; Escuela Técnica Superior de Ingeniería Industrial; Escuela Politécnica Superior de Gandia; Instituto de Instrumentación para Imagen Molecular; Generalitat Valenciana; Agencia Estatal de Investigación; European Regional Development Fund; Universitat Politècnica de València[EN] We explore the use of a beamforming method intended for large-area scanning in optical-resolution photoacoustic microscopy. It has been evaluated in a experimental setup that comprises a low-cost laser diode and a phase array with a 128-elements linear probe. Three different beamforming strategies are discussed: no-beamforming, static beamforming and dynamic beamforming. The method has been tested in gelatine-based phantoms as well as ex-vivo organs. Results show that, compared with the other two, dynamic beamforming increases up to 15dB and homogenizes signal-to-noise ratio (SNR) along images of roughly 1 cm2. The method and system presented here could be the baseline for more advanced array-based systems that leverage the low-cost laser sources for clinical applications.