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Positron emission tomography (PET) is an important technique in cardiovascular research. Vascular inflammation detected by fluorodeoxyglucose (FDG)-PET has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. The use of PET imaging in mouse models of atherosclerosis is challenged by the reduced size of the scanned organs. However, the last generation of dedicated PET scanners has an improved spatial resolution (

Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [18F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [18F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [18F]FDG. The retention of [18F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controls.

Fully 3D iterative tomographic image reconstruction is computationally very demanding. Graphics Processing Unit(GPU) has be enproposed formany years as potential accelerators incomplex scientific problems, but it has not be enuseduntil there cent advances in the programmability of GPU sthat the best available reconstruction code shave started tobe implemented toberunon GPUs. This work presents a GPU based fully 3D PET iterative reconstruction sofware. This new code may reconstruct sinogram data from several commercially available PET scanners. The most important and time consuming part soft he code,the forward and backward projection operations, arebasedonan accurate model of the scanner obtained with the MonteCarlo code PeneloPET and they have been massively parallelize don the GPU.For the PET scanners considered, the GPU based code is more than 70 times faster than asimilar code running on a single core of a fast CPU, obtainingin both cases the same images. The code has been designed to be easily adapted to reconstruct sinograms from any other PET scanner, including scanner prototypes. This work has been supported by MEC(FPA200762216), UCM (Grupos UCM,910059), CPAN(Consolider Ingenio 2010) CSPD 200700042,the RECAVARETIC network, ARTEMISS2009/ DPI 1802, European Regional Development,ENTEPRASE grant, PSE 30000020095 and TEC20080675C0201, Ministerio de Ciencia e Innovación, Spanish Government. Publicado

Dynamic contrast enhanced CT can be used to measure perfusion, thus enabling a quantitative assessment of vascular integrity. Conventional dynamic CT involves the reconstruction of dynamic sequences of 3D images from complete projections acquired at relatively short time intervals. This approach is suitable for spiral scanners but it is unfeasible for most of small-animal cone-beam scanners, as the distribution of the contrast agent changes during the acquisition and leads to inconsistent projections. We present a new algorithm to achieve 4D reconstructions of dynamic CT in case of slow cone-beam scanners.

One of the most common topologies for the scintillator crystals used in gamma radiation detectors for PET scanners is pixelation. The size of these pixels, the crystal surface treatment and the reflector thickness inserted between crystals directly affects the energy and the spatial resolution as well as the sensitivity of the detector. The fabrication of pixels is laborious, complex and expensive. Here we investigate the possibility of creating pixels within monolithic LYSO scintillators crystals using the proven technique of sub-surface laser engraving with a Nd:YAG laser. To evaluate possible designs considering the limitations of the engraving procedure, we used the simulation software GAMOS to analyze the light propagation inside the crystals engraved with a variety of patterns. We carried out different experimental procedures, including microscopy and laser reflectometry to assess the relative reflective quality of the engraved surfaces. We compared the results of different engraving procedures to a reference reflector commonly used in this type of pixelated crystal matrices. We have configured different engraved surfaces with variable transparency in several pixel geometries including depth-of-interaction encoding patterns. Our results demonstrate that pixels engraved with this method can also be configured to compensate for the multiplexed readout penalties, and at the same time preserve the detector performance requirements. Such modifications of the engraving pattern takes place at practically no cost and constitute a highly promising solution for industrial fabrication, reducing substantially the cost of the detector.

We describe a PET detector module that provides three levels of depth-of-interaction (DOI) information. The detector is a 9 x 9 array of 2 mm x 2 mm x 12 mm deep phoswich crystal elements, each consisting of 4 mm long LSO (entrance layer), GSO (middle layer) and BGO (exit layer) crystals joined optically together end-to-end. The BGO exit layer is directly coupled to a miniature position-sensitive photomultiplier tube (PSPMT). Delayed charge integration, a method that exploits differences in the light decay times of these scintillators, is used to determine the layer-of-interaction. DO1 accuracy, measured by scanning a slit source of 5 1 1 keV radiation along the length of the module was 86% for the LSO layer, 80% for the GSO layer and 84% for the BGO layer. Energy resolution at 511 keV was 19% for LSO, 21% for GSO and 40% for BGO. Apparent gain differed between layers in the ratios 2.7: 1.9: 1 .O (LS0:GSO:BGO). Crystal separation was good between crystals in the LSO layer, acceptable between crystals in the GSO layer and poor between crystals in the BGO layer due, primarily, to the pronounced spatial non-linearity of the PSPMT. The delayed charge integration method, however, does appear suitable for obtaining multi-level depth information when DO1 effects are particularly significant, e.g. in very small ring diameter PET scanners for small animal imaging. Was supported, in part, by a grant from CICYT (Spanish Government). S. S. was supported by a grant from the National Research Council. Publicado

Over the lasts years many works have addressed the potential of compressed sensing techniques to accelerate acquisition of cardiac MRI. However, most of these works claimed the achievement of acceleration factors solely based on simulated data or on fully sampled acquisition data retrospectively undersampled. In this work the practical feasibility of compressed sensing acquisitions for the acceleration of cardiac cine imaging in small animals is proved with real acquisitions. Our experiments using a combined spatiotemporal technique confirm that high acceleration factors of about 10 are feasible. Future work involving the optimization of undersampling patterns and cardiac artifact correction might further improve this acceleration factor.

Motion-Based Reconstruction (MBR) and Prior-Based Reconstruction (PBR) are compressed sensing approaches for cardiac cine MRI that achieve high acceleration factors by exploiting temporal sparsity based on a prior image. It would be appealing to reconstruct only the image variation with respect to the prior image, as this is sparser than the image itself, but this leads to low signal-to-noise ratio and has been generally avoided.

Dynamic PET imaging can provide information regarding metabolism, blood flow or other physiological properties of biological tissues beyond what static imaging may offer. A common technique for analyzing these images is compartmental modeling, whose mathematical resolution generally involves solving a set of differential equations using a non-linear least squares algorithm. This paper presents a guide that shows how the R programming language can be used to perform this analysis. To test the suitability of the proposed implementations, a comparison with the PMOD software package has been carried out. We show that the R programming language provides easy to use libraries that can be combined to implement solutions for different compartmental models whose results match those obtained using a commercial tool.

Dual energy x-ray computed tomography (DECT) is a valuable research tool for both clinical and preclinical studies and a field of extensive research. Current implementations of DECT rely on the acquisition of two datasets either by using two source-detector pairs or by rapidly switching the kVp of the x-ray source between consecutive projections. Both alternatives require specific hardware, only available in a small number of systems.

A personal radiation level monitoring system has been developed based on an autonomous, advanced personal dosimeter. This dosimeter uses a scintillator-SiPM combination for the radiation detection, it integrates spectroscopy and isotope identification capabilities. In order to choose the optimum scintillator crystal and photosensor for a portable gamma dosimeter, several tests on energy resolution and internal activity were performed. We have chosen a 9x9x20mm3 CsI:Tl crystal and a 50 μM SiPM. All measurements are time and location stamped, even for indoor locations. The system implements Wireless Sensor Networks access in such a way that several networked personal dosimeters can be considered mobile sensors providing a high sampling rate over an extended area. The system developed is modular, it consists of three elements: the Personal Dosimeters, a Wireless Gateway deployment and a web-based remote storage, monitoring and management system, named Central System.

Compressed Sensing (CS) techniques are becoming increasingly popular to speed up data acquisition in many modalities. However, most of CS theory is devoted to undetermined problems and there are few contributions that apply it to ill-posed problems. In this work we present a novel approach to CS for fluorescence diffuse optical tomography (fDOT), named the Split Bregman-Singular Value Analysis (SB-SVA) iterative method. This approach is based on the combination of Split Bregman (SB) algorithm to solve CS problems with a theorem about the effect of ill-conditioning on L1 regularization. Our method restricts the solution reached at each SB iteration to a determined space where the singular values of forward matrix and the sparsity structure of each iteration solution combine in a beneficial manner. Taking Battle-Lemarie basis for wavelet transform, where fDOT is sparse, we tested the method with fDOT simulated and experimental data, and found improvement with respect to the results of standard SB algorithm.

This work presents an approach to extend the dynamic range of x-ray flat panel detectors by combining two acquisitions of the same sample taken with two different x-ray photon flux levels and the same beam spectral configuration. In order to combine both datasets, the response of detector pixels was modelled in terms of mean and variance using a linear model. The model was extended to take into account the effect of pixel saturation. We estimated a joint probability density function (j-pdf) of the pixel values by assuming that each dataset follows an independent Gaussian distribution. This j-pdf was used for estimating the final pixel value of the high-dynamic-range dataset using a maximum likelihood method. The suitability of the pixel model for the representation of the detector signal was assessed using experimental data from a small-animal cone-beam micro-CT scanner equipped with a flat panel detector. The potential extension in dynamic range offered by our method was investigated for generic flat panel detectors using analytical expressions and simulations. The performance of the proposed dual-exposure approach in realistic imaging environments was compared with that of a regular single-exposure technique using experimental data from two different phantoms. Image quality was assessed in terms of signal-to-noise ratio, contrast, and analysis of profiles drawn on the images. The dynamic range, measured as the ratio between the exposure for saturation and the exposure equivalent to instrumentation noise, was increased from 76.9 to 166.7 when using our method. Dual-exposure results showed higher contrast-to-noise ratio and contrast resolution than the single-exposure acquisitions for the same x-ray dose. In addition, image artifacts were reduced in the combined dataset. This technique to extend the dynamic range of the detector without increasing the dose is particularly suited to image samples that contain both low and high attenuation regions. This work was funded by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115337, which comprises financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. This work was also partially funded by the AMIT project (CEN-20101014) from the CDTI-CENIT program, projects TEC2010-21619-C04-01, TEC2011-28972-C02-01, and PI11/00616 from the Spanish Ministerio de Ciencia e Innovaci´on. AS is funded by an FPU grant from the Spanish Ministerio de Educación. Publicado

Este trabajo describe una actividad de aprendizaje transdisciplinar destinado a impulsar la creatividad y fomentar actitudes innovadoras. Combina biología molecular con programación de computadoras, pero más que el caso concreto, es un ejemplo de abordaje dirigido a impulsar la capacidad de innovación en el proceso educativo. Se basa en la convicción de que un conocimiento amplio y multidisciplinar es el sustrato más eficiente para transformar la creatividad individual en innovación práctica. Esta actividad, ya aplicada en más de seis cursos, utiliza una metodología de aprendizaje activo inscrita en el marco del Aprendizaje Basado en Proyectos y se diseñó inicialmente para las clases prácticas de laboratorio de una asignatura de Biología Molecular. Los participantes tienen que desarrollar una herramienta de software real, capaz de realizar un análisis de secuencias de ácidos nucleicos, incluyendo una interfaz de usuario interactiva. Comienzan a escribir el código real y a aprender los rudimentos de un la programación directamente aplicándolos a resolver un problema. Se trata de un “aprendizaje basado en programación” ya que la escritura del programa no es la finalidad, sino el medio para crear un entorno en el que los alumnos tienen que repensar y entender realmente la lógica detrás de muchos conceptos biológicos fundamentales ya aprendidos, pero que en esta actividad tienen que enfrentar en un contexto diferente y con un nuevo lenguaje y objetivos prácticos. En lugar de descripciones teóricas, el proceso de aprendizaje involucra a los participantes en un reto divertido y motivador, una meta exigente pero estimulante de crear su propia solución para un problema auténtico, que se reconoce como difícil, pero también como comprensible y realizable. Es una actividad realmente transdisciplinar que también trata de dar a los estudiantes una visión de un nuevo campo, ampliando su mente y motivándoles a explorar y aprender más, estimulando su creatividad y sembrando una semilla de innovación en la actitud de los futuros profesionales.

La dramatización creativa es una estrategia didáctica con muchos antecedentes (Ward, W. Creative Dramatics. D. Appleton & Co., N.Y. 1930), pero poco conocida en la enseñanza superior de ciencias (Scherr, R.E., et al. PER Conference 2010, 1289:293-296). Es una estrategia educativa sin finalidad de exhibición y percibida como improvisada por los participantes, los cuales interpretan y recrean un proceso con sus acciones guiadas sobre la marcha por un instructor. Su propósito no es formar actores ni actuar para otros, sino facilitar la adquisición de un conocimiento desde la vivencia interna y la autoobservación. En humanidades suele consistir en la interpretación de roles humanos o sociales en situaciones determinadas, pero en ciencias es una representación figurada de un proceso científico complejo, donde los participantes asumen el papel de distintos componentes o elementos que intervienen, teniendo que representar objetos o conceptos abstractos y alejados de la percepción real o de la escala humana. La dramatización facilita el aprendizaje significativo y la clarificación de conceptos abstractos, así como la comprensión de procesos complejos a través de una toma de consciencia “desde dentro” de los propios elementos que juegan un papel en los mismos (Michael, J. In pursuit of meaningful learning. Advances in Physiology Education, 2001, 25:145-158; Dee Fink, L. Creating Significant Learning Experiences: An Integrated Approach to Designing College Courses. 2003, Josey-Bass, Wiley. San Francisco, CA 94103-1741). Esta actividad promueve un aprendizaje mediante la autoobservación, aprovechando la capacidad humana natural de representar la propia percepción de fenómenos complejos para comprenderlos. La dramatización creativa estimula el pensamiento lógico e intuitivo, interioriza el conocimiento y genera un placer estético que facilita un aprendizaje significativo y memorable. En esta comunicación se presentan ejemplos prácticos, como la contracción muscular, el bombeo de protones en la cadena respiratoria, la eliminación de intrones, compuestos intercalantes de ADN y fluorescencia, o la electroforesis en gel. Todos ellos son originales y han sido aplicados en muchos cursos para estimular la participación de los alumnos y activar un aprendizaje significativo.

The metal radionuclides 60Cu (T 1/2 = 23 min), 52mMn (T 1/2 = 21 min) and 94mTc (T 1/2 = 53 min) can be used to label tracers of high clinical and preclinical interest in PET studies. Furthermore, as they emit prompt gamma-rays right after the positron emission, they can be distinguished from standard positron emitters like 18F, enabling multiplexed PET (mPET) imaging. In this work we studied the feasibility of their production using a relatively low-energy (10 MeV) proton beam from a linear accelerator. These radionuclides were produced by bombardment on target foils of natural Nickel, Chromium and Molybdenum respectively. After activation, the emissions from the foils were analyzed by a Ge spectrometer and the absolute activity for each produced species was obtained. The activity generated was in agreement with the expected cross-sections and the isotopes present in the samples. These results show the feasibility of production of these radionuclides with a 10 MeV proton beam.

Fluorescence diffuse optical tomography (fDOT) is a noninvasive imaging technique that makes it possible to quantify the spatial distribution of fluorescent tracers in small animals. fDOT image reconstruction is commonly performed by means of iterative methods such as the algebraic reconstruction technique (ART). The useful results yielded by more advanced l1-regularized techniques for signal recovery and image reconstruction, together with the recent publication of Split Bregman (SB) procedure, led us to propose a new approach to the fDOT inverse problem, namely, ART-SB. This method alternates a cost-efficient reconstruction step (ART iteration) with a denoising filtering step based on minimization of total variation of the image using the SB method, which can be solved efficiently and quickly. We applied this method to simulated and experimental fDOT data and found that ART-SB provides substantial benefits over conventional ART This work was supported by Spanish Ministry of Science and Innovation (FPI program, TEC2008-06715), EU-FP7 project FMTXCT-201792, the Community of Madrid (ARTEMIS S2009/DPI-1802), European Regional development Funds (FEDER), and CDTI under the CENIT program (AMIT Project, CEN-20101014). (European Community's Seventh Framework Program) Publicado

Technical advances towards high resolution PET imaging try to overcome the inherent physical limitations to spatial resolution. Positrons travel in tissue until they annihilate into the two gamma photons detected. This range is the main detector-independent contribution to PET imaging blurring. To a large extent, it can be remedied during image reconstruction if accurate estimates of positron range are available. However, the existing estimates differ, and the comparison with the scarce experimental data available is not conclusive. In this work we present positron annihilation distributions obtained from Monte Carlo simulations with the PeneloPET simulation toolkit, for several common PET isotopes (18F, 11C, 13N, 15O, 68Ga and 82Rb) in different biological media (cortical bone, soft bone, skin, muscle striated, brain, water, adipose tissue and lung). We compare PeneloPET simulations against experimental data and other simulation results available in the literature. To this end the different positron range representations employed in the literature are related to each other by means of a new parameterization for positron range profiles. Our results are generally consistent with experiments and with most simulations previously reported with differences of less than 20% in the mean and maximum range values. From these results, we conclude that better experimental measurements are needed, especially to disentangle the effect of positronium formation in positron range. Finally, with the aid of PeneloPET, we confirm that scaling approaches can be used to obtain universal, material and isotope independent, positron range profiles, which would considerably simplify range correction. We kindly acknowledge support from Comunidad de Madrid (ARTEMIS S2009/DPI-1802), Spanish Ministry of Science and Innovation (grants FPA2010-17142 and ENTEPRASE, PSE-300000-2009-5), by European Regional Funds, by CDTI under the CENIT Programme (AMITProject) and by CPAN, CSPD-2007-00042@Ingenio2010. Part of the calculations of this work were performed in the “Cluster de Cálculo de Alta Capacidad para Técnicas Físicas” funded in part by UCM and in part by UE under FEDER programme. This is a contribution to the Campus of International Excellence of Moncloa Publicado

Self-gated cine sequences are a common choice for cardiac MRI in preclinical applications. The aims of our work were to apply the compressed sensing technique to IntraGateFLASH cardiac MRI studies on rats and to find the maximum acceleration factor achievable with this technique.Our reconstruction method extended the Split Bregman formulation to minimize the total variation in both space and time. In addition, we analyzed the influence of the undersampling pattern on the acceleration factor achievable.Our results show that acceleration factors of up to 15 are achievable with our technique when appropriate undersampling patterns are used. The introduction of a time-varying random sampling clearly improved the efficiency of the undersampling schemes. In terms of computational efficiency, the proposed reconstruction method has been shown to be competitive as compared with the fastest methods found in the literature.We successfully applied our compressed sensing technique to self-gated cardiac cine acquisition in small animals, obtaining an acceleration factor of up to 15 with almost unnoticeable image degradation.

Pile-up and dead-time are two main causes of nonlinearity in the response of a PET scanner as a function of activity in the field of view (FOV). For a given scanner and acquisition system, pile-up effects depend on the material and size of the object being imaged and on the distribution of activity inside and outside the FOV, because these factors change the singles-to-coincidences ratio (SCR). Thus, it is difficult to devise an accurate correction that would be valid for any acquisition. In this work, we demonstrate a linear relationship between SCR and effective dead-time, which measures the effects of both dead-time (losses) and pile-up (gains and losses). This relationship allows us to propose a simple method to accurately estimate dead-time and pile-up corrections using only two calibration acquisitions with, respectively, a high and low SCR. The method has been tested with simulations and experimental data for two different scanner geometries: a scanner with large area detectors and no pile-up rejection, and a scanner composed of two full rings of smaller detectors. Our results show that the SCR correction method is accurate within 7%, even for high activities in the FOV, and avoids the bias of the standard single-parameter method. © 2013 Institute of Physics and Engineering in Medicine., This work was partially funded by AMIT project (CEN-20101014) from the CDTICENIT program, CIBERsam (CB07/09/0031), projects TEC2010-21619-C04-01 and TEC2011-28972-C02-01 from Spanish Ministerio de Ciencia e Innovación, Spanish Government (ENTEPRASE Grant, PSE-300000-2009-5), PRECISION grant IPT-300000- 2010-3, CPAN (CSD-2007-00042@Ingenio2010), MEC (FPA2010-17142) and ARTEMIS program (S2009/DPI-1802) from Spanish Comunidad de Madrid and EU-ERDF program.

This work describes a new iterative method for extracting time-activity curves (TAC) from dynamic imaging studies using a priori information from generic models obtained from TAC templates. Analytical expressions of the TAC templates were derived from TACs obtained by manual segmentation of three 13NH3 pig studies (gold standard). An iterative method for extracting both ventricular and myocardial TACs using models of the curves obtained as an initial template was then implemented and tested. These TACs were extracted from masked and unmasked images; masking was applied to remove the lungs and surrounding non-relevant structures. The resulting TACs were then compared with TACs obtained manually; the results of kinetic analysis were also compared. Extraction of TACs for each region was sensitive to the presence of other organs (e.g., lungs) in the image. Masking the volume of interest noticeably reduces error. The proposed method yields good results in terms of TAC definition and kinetic parameter estimation, even when the initial TAC templates do not accurately match specific tracer kinetics. This work is supported by the following grants: RD07/0014/2009, Subprograma RETICS, Ministerio de Ciencia e Innovación. S2009/DPI-1802 (ARTEMIS), Comunidad de Madrid. CEN-20101014, Programa CENIT, CDTI, Ministerio de Ciencia e Innovación. European Commission, EFPIA, INNOVATIVE MEDICINE INITIATIVE (PredDICT-TB project, 115337-1) Publicado

We present jClustering, an open framework for the design of clustering algorithms in dynamic medical imaging. We developed this tool because of the difficulty involved in manually segmenting dynamic PET images and the lack of availability of source code for published segmentation algorithms. Providing an easily extensible open tool encourages publication of source code to facilitate the process of comparing algorithms and provide interested third parties with the opportunity to review code. The internal structure of the framework allows an external developer to implement new algorithms easily and quickly, focusing only on the particulars of the method being implemented and not on image data handling and preprocessing. This tool has been coded in Java and is presented as an ImageJ plugin in order to take advantage of all the functionalities offered by this imaging analysis platform. Both binary packages and source code have been published, the latter under a free software license (GNU General Public License) to allow modification if necessary. Funded by TEC2011-28972-C02-01, Ministerio de Ciencia e Innovación, CEN-20101014; Programa CENIT-CDTI, Ministerio de Ciencia e Innovación; S2009/DPI-1802 (ARTEMIS), Comunidad de Madrid. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publicado

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of smallanimal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: micro- PET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand. This work was funded by the Natural Sciences and Engineering Research Council of Canada under Discovery Grant 341628-2007. No other potential conflict of interest relevant to this article was reported. En prensa

A novel cone-beam CT (CBCT) system has been developed with promising capabilities for musculoskeletal imaging (e.g., weight-bearing extremities and combined radiographic / volumetric imaging). The prototype system demonstrates diagnostic-quality imaging performance, while the compact geometry and short scan orbit raise new considerations for scatter management and dose characterization that challenge conventional methods. The compact geometry leads to elevated, heterogeneous x-ray scatter distributions - even for small anatomical sites (e.g., knee or wrist), and the short scan orbit results in a non-uniform dose distribution. These complex dose and scatter distributions were investigated via experimental measurements and GPU-accelerated Monte Carlo (MC) simulation. The combination provided a powerful basis for characterizing dose distributions in patient-specific anatomy, investigating the benefits of an antiscatter grid, and examining distinct contributions of coherent and incoherent scatter in artifact correction. Measurements with a 16 cm CTDI phantom show that the dose from the short-scan orbit (0.09 mGy/mAs at isocenter) varies from 0.16 to 0.05 mGy/mAs at various locations on the periphery (all obtained at 80 kVp). MC estimation agreed with dose measurements within 10-15%. Dose distribution in patient-specific anatomy was computed with MC, confirming such heterogeneity and highlighting the elevated energy deposition in bone (factor of ~5-10) compared to soft-tissue. Scatter-to-primary ratio (SPR) up to ~1.5-2 was evident in some regions of the knee. A 10:1 antiscatter grid was found earlier to result in significant improvement in soft-tissue imaging performance without increase in dose. The results of MC simulations elucidated the mechanism behind scatter reduction in the presence of a grid. A ~3-fold reduction in average SPR was found in the MC simulations; however, a linear grid was found to impart additional heterogeneity in the scatter distribution, mainly due to the increase in the contribution of coherent scatter with increased spatial variation. Scatter correction using MC-generated scatter distributions demonstrated significant improvement in cupping and streaks. Physical experimentation combined with GPU-accelerated MC simulation provided a sophisticated, yet practical approach in identifying low-dose acquisition techniques, optimizing scatter correction methods, and evaluating patientspecific dose.

Proceedings of: 2012 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Anaheim, California, USA. October 29 - November 3, 2012 Respiratory gating is necessary in cardio-thoracic small-animal imaging because of the physiological motions that are present during scanning. When applying a low-dose protocol, fewer than 180 noisy projections may be left for the reconstruction of each respiratory phase, leading to streaking artifacts. The Prior Image Constrained Compressed Sensing (PICCS) algorithm enables accurate reconstruction of highly undersampled data when a prior image is available. The gradient domain is the preferred choice for enforcing the sparsity of the variation of each phase with respect to the prior. We evaluate three CS algorithms based on the Split-Bregman approach, with different transformations of the prior penalty function: Gradient (TV-PICCS), L1-norm (L1-PICCS), and Wavelet Transform (WT-PICCS), on low-dose data acquired on a micro-CT scanner. High-dose projection data, acquired with a cone-beam micro-CT scanner, were arranged into four gates using a software-based retrospective gating and reconstructed with an FDK algorithm. To simulate the low-dose case, we took 120 projections from each gate and added Poisson noise. Prior image was obtained by the addition of all low-dose gates with Gaussian filtering. All CS methods performed very similarly in terms of noise and resolution, greatly improving FBP (79 % noise reduction) and eliminating streaks. Pixel and wavelet domains were found to be sparser than the commonly used gradient domain. In conclusion, compressed sensing using a Split-Bregman methodology is a feasible approach to reduce dose in CT respiratory gating. The selection of the sparsity transform for the prior term does not affect resolution and noise performance but it has an influence on the final image texture: Wavelet transform showed a more natural pattern than TV and L1-norm. This work was supported in part by projects TEC2008-06715 and TEC2007-64731 (Ministerio de Ciencia e innovacion), EU-FP7 FMTXCT-201792, ARTEMIS S2009/DPI-1802 (Comunidad de Madrid), and European Regional Development Funds (FEDER) and CDTI under the CENIT program (AMIT project, CEN- 20101014). Publicado

Most small-animal X-ray computed tomography (CT) scanners are based on cone-beam geometry with a flat-panel detector orbiting in a circular trajectory. Image reconstruction in these systems is usually performed by approximate methods based on the algorithm proposed by Feldkamp et al. (FDK). Besides the implementation of the reconstruction algorithm itself, in order to design a real system it is necessary to take into account numerous issues so as to obtain the best quality images from the acquired data. This work presents a comprehensive, novel software architecture for small-animal CT scanners based on cone-beam geometry with circular scanning trajectory. The proposed architecture covers all the steps from the system calibration to the volume reconstruction and conversion into Hounsfield units. It includes an efficient implementation of an FDK-based reconstruction algorithm that takes advantage of system symmetries and allows for parallel reconstruction using a multiprocessor computer. Strategies for calibration and artifact correction are discussed to justify the strategies adopted. New procedures for multi-bed misalignment, beam-hardening, and Housfield units calibration are proposed. Experiments with phantoms and real data showed the suitability of the proposed software architecture for an X-ray small animal CT based on cone-beam geometry. This work was partially funded by AMIT project from the CDTI CENIT program, TEC2007-64731, TEC2008-06715- C02-01, RD07/0014/2009, TRA2009 0175, RECAVA-RETIC, and RD09/0077/00087 (Ministerio de Ciencia e Inovación), and ARTEMIS S2009/DPI-1802 (Comunidad de Madrid). Publicado

Proceedings of: 2012 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Anaheim, California, USA. October 29 - November 3, 2012 CT images are often affected by beam hardening artifacts (cupping and dark streaks) due to the polyenergetic nature of the X-ray beam. FDK is still the favorite reconstruction algorithm in commercial X-ray CT scanners. Several correction methods have been proposed to be included in an FDK reconstruction scheme. We present a complete correction scheme for beam hardening artifact correction in an FDK based reconstruction scenario that accounts for both cupping artifact and dark streaks avoiding the need of the knowledge of the source spectrum. The proposed correction scheme includes two steps: a linearization step of projection data and a post-reconstruction step. The first step assumes that the object is homogeneous and uses a linearization function that is calculated empirically in a previous calibration process with a simple phantom. The second step is based in the theoretical study described in Joseph and Spital, and calculates the non-linear beam-hardening distortion from a bone segmentation of the reconstructed image. The proposed correction scheme was evaluated in real studies acquired with a cone-beam micro-CT scanner: three polymethylmethacrylate cylinders (3, 4, and 6 cm diameter), a two-density cylindrical phantom and three rodent studies. Results show an average cupping reduction of 84 % in the three homogeneous phantoms and an average dark streaks reduction of 80 % in the two-density phantom and the three rodent studies. The proposed method could be incorporated easily in any cone beam micro-CT scanner and substitutes the need of the knowledge of the spectrum by empirical measurements and two parameters. Since it is based on empirical measurements, we expected to correct the artifacts derived from scattering. This work was supported in part by projects TEC2008-06715 and TEC2007-64731 (Ministerio de Ciencia e Innovaci6n), EU-FP7 FMTXCT-201792, ARTEMIS S2009/DPI-1802 (Comunidad de Madrid), and European Regional Development Funds (FEDER) and CDTI under the CENIT program (AMIT project, CEN-20101014). Publicado

Small-animal positron-emission tomography/computed tomography (PET/ CT) scanners provide anatomical and molecular imaging, which enables the joint visualization and analysis of both types of data. A proper alignment calibration procedure is essential for small-animal imaging since resolution is much higher than that in human devices. This work presents an alignment phantom and two different calibration methods that provide a reliable and repeatable measurement of the spatial geometrical alignment between the PET and the CT subsystems of a hybrid scanner. The phantom can be built using laboratory materials, and it is meant to estimate the rigid spatial transformation that aligns both modalities. It consists of three glass capillaries filled with a positron-emitter solution and positioned in a non-coplanar triangular geometry inside the system field of view. The calibration methods proposed are both based on automatic line detection, but with different approaches to calculate the transformation of the lines between both modalities. Our results show an average accuracy of the alignment estimation of 0.39 mm over the whole field of view. This study was funded by CDTI under the CENIT Program (AMIT Project), projects ARTEMIS S2009/DPI-1802 (CAM) and TEC2010-21619-C04-01, and supported by the Spanish Ministry of Economy and Competitiveness. Publicado

Quantitative analysis of dynamic cardiac PET studies provides useful diagnostic information regarding different heart diseases. To correctly perform the kinetic analysis, tracer time-activity curves (TAC) must be precisely extracted from the chosen tissue on the imaging data. In this work we present an alternative clustering algorithm for segmentation of dynamic studies using a leader-follower clustering approach, in which the number of clusters is unknown.

This work presents a graphics processing unit (GPU)- based implementation of a fully 3-D PET iterative reconstruction code, FIRST (Fast Iterative Reconstruction Software for [PET] Tomography), which was developed by our group. We describe the main steps followed to convert the FIRST code (which can run on several CPUs using the message passing interface [MPI] protocol) into a code where the main time-consuming parts of the reconstruction process (forward and backward projection) are massively parallelized on a GPU. Our objective was to obtain significant acceleration of the reconstruction without compromising the image quality or the flexibility of the CPU implementation. Therefore, we implemented a GPU version using an abstraction layer for the GPU, namely, CUDA C. The code reconstructs images from sinogram data, and with the same System Response Matrix obtained from Monte Carlo simulations than the CPU version. The use of memory was optimized to ensure good performance in the GPU. The code was adapted for the VrPET small-animal PET scanner. The CUDA version is more than 70 times faster than the original code running in a single core of a high-end CPU, with no loss of accuracy. This work was supported in part by AMIT Project funded by CDTI (CENIT Programme), UCM (Grupos UCM, 910059), CPAN (Consolider-Ingenio 2010, CSPD-2007-00042), RECAVA- RETIC network, Comunidad de Madrid (ARTEMIS S2009/DPI-1802), Ministerio de Ciencia e Innovación, Spanish Government (ENTEPRASE grant, PSE-300000-2009-5 and TEC2007-64731/TCM), and European Regional funds. Publicado

Proceedings of: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Valencia, Spain, 23-29 October 2011 Scattered photons highly degrade the quality of X-ray images and their effect has become more important due to the increasing interest in cone-beam geometry for the acquisition of CT (CBCT) and micro-CT data. The random nature of scatter events and the great influence of the sample suggest that the most accurate methods for their estimation are Monte Carlo (MC) techniques, but their use is usually hampered by the large computation time required to obtain an acceptable estimation of the scattered radiation. We present an approach for scatter correction in CBCT by MC estimation, speeding up the computation by means of general purpose graphic processing units (GPGPU) and developing a framework for the automatic correction and reconstruction of projection data. The method consists of five stages: FDK reconstruction of the original data; histogram based automatic segmentation of the volume assigning a material and density to each voxel; fast MC estimation of the scatter signal; denoising of the independent scatter components and subtraction from original data; and FDK reconstruction of the corrected data. Every stage runs in a GPGPU using Nvidia CUD A. The MC stage is based on the MC-GPU code. To simulate polychromatic X-ray beams, the Spektr model is used to generate the source spectrum. Photon scattering is forced in order to reduce the number of events needed to obtain an acceptable scatter image weighting the photon histories to assure the correctness of the result. Further reduction in the variance is obtained by split the photon in several virtual photons which are forced point to the detector and are transported with no further interaction to the detector's surface. Furthermore, the divergence of the execution path of GPGPU kernels has been minimized. These techniques achieve a reduction of the variance of the scatter signal of two orders of magnitude and the final efficiency is improved by a factor of ~30. This work has been partially funded by the Spain Ministry of Education, FPU program; Spain Ministry of Science and Innovation, projects TEC2008-06715 and TEC2007-64731; CDTI under the CENIT Programme (AMIT Project); Comunidad de Madrid (ARTEMIS S2009/DPI-1802); and EU-FP7, FMTXCT-201792 Publicado

Proceedings of: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Valencia, Spain, 23-29 October 2011 Monte Carlo simulations are widely used in positron emission tomography (PET) for optimizing detector design, acquisition protocols, as well as for developing and assessing corrections and reconstruction methods. PeneloPET is a Monte Carlo code for PET simulations which considers detector geometry, acquisition electronics and materials, and source definitions. PeneloPET is based on PENELOPE, a Monte Carlo code for the simulation of the transport in matter of electrons, positrons and photons, with energies up to 1 GeV. In this work we use PeneloPET to simulate the Biograph TruePoint (B-TP), Biograph TruePoint with TrueV (B-TPTV) and Biograph mCT PET/CT scanners. These configurations consist of three (B-TP) and four (B-TPTV and mCT) rings of 48 detector blocks. Each block comprises a 13 × 13 matrix of 4 × 4 × 20 mm3 LSO crystals. Simulations were adjusted to reproduce some experimental results from the actual scanners and validated by comparing their predictions to further experimental results. Sensitivity, spatial resolution, noise equivalent count (NEC) rate and scatter fraction (SF) were estimated. The simulations were then employed to estimate the optimum values of system parameters, such as energy and time coincidence windows and to assess the effect of system modifications (such as number of rings) on performance. This work was supported in part by Comunidad de Madrid (ARTEMIS S2009IDPI 1802), Spanish Ministry of Science and Innovation (ENTEPRASE Grant, PSE 300000 2009 5) and PRECISION grant IPT 300000 2010 3 and european regional funds and CPAN, Centro de Fisica de Particulas, Astroparticulas y Nuclear (CSD 2007 00042@Ingenio2010 12). This study has been (partially) funded by CDTI under the CENIT Programme (AMIT Project). Part of the calculations of this work was performed in the "Cluster de Calculo de Alta Capacidad para Tecnicas Fisicas "funded in part by UCM and in part by UE with European regional funds" Publicado

Proceedings of: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Valencia, Spain, 23-29 October 2011 PET detector modules that implement depth of interaction information reduce uncertainties about the actual line-of-response after positron annihilation. This, in turn, has an effect in the spatial resolution and uniformity across the field of view of the reconstructed image. It also has an effect on the system sensitivity since it enables the use of thicker crystal with respect to a non-DOI system without deteriorating significantly the spatial resolution. In this work we evaluate a DOI detector design based on a scintillator phoswich of two types of pixelated crystals with different time decay constants. A matrix of silicon phomultipliers (SiPM) was coupled to this crystal array without any light-guide, and its outputs were connected to an anger logic type of charge divider which outputs were buffered using a transimpedance amplifier. These position signals were digitized using charge-to-digital converters, and the time decay constant of the crystal of interaction was measured using a delayed charge method. Previous works reported in the literature have demonstrated that this scheme for DOI PET detectors produce very good results in terms of spatial and energy resolution; however, the replacement of PMT with a SiPM matrix introduces some uncertainties that required further study. SiPM have demonstrated their good imaging capabilities when used with pixelated crystal scintillators, and their good timing performance allow us to predict that the DOI resolution was not going to be a problem with this technology. In this work we present quantitative results that assess the goodness of these detectors for its use on small-animal PET scanners. This work was supported in part by the CENIT-AMIT Ingenio 2010, TEC2008-06715 (Ministerio de Ciencia e Innovacion) RETIC-RECAVA (Ministerio de Sanidad y Consumo) ARTEMIS S2009/DPI-1802 (Comunidad de Madrid), and EU-FP7, FMT-XCT-201792. Publicado

Proceedings of: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Valencia, Spain, 23-29 October 2011 The measurement of absolute nuclear transition probabilities is a very sensitive tool to study the structure of the atomic nucleus. Direct access to transition rates can be achieved via the lifetime of the nuclear levels de-populated in radioactive decay. The Advanced Time-Delayed (ATD) method, or Fast Timing, is a well-established technique to measure lifetimes down to a few ps. The development of the technique was based on the use of BaF_2 detectors, but a recent major breakthrough occurred with the introduction of LaBr_3(Ce) crystals, uniting excellent time response with much superior energy resolution than BaF_2 crystals. Relatively large LaBr_3(Ce) cylindrical detectors of typically 1.5"×1.5" are employed for fast timing, in combination with fast 2-inch photomultiplier tubes from Photonis such as the linear focused 8-stage XP20D0. Another option for a 2-inch fast phototube is the 8-stage Hamamatsu R9779, whose timing properties have already been tested with small LSO crystals. New possibilities are also offered by novel photosensors such as silicon photomultipliers, which are intrinsically fast. In this work we have investigated the performance of the Hamamatsu R9779 photomultiplier tube, and the viability of CeBr_3 crystals for fast-timing applications. This work was supported in part by Comunidad de Madrid (ARTEMIS S2009/DPI-1802) and the Spanish Ministry of Science and Innovation (grants FPA201O-l7l42 and CSPD-2007-00042, Ingenio2010). Publicado

Proceeding of: 2011 Nuclear Science Symposium and Medical Imaging Conference, Valencia, España, 23-29 October, 2011 In this work, we investigate PET imaging with 68Ga and 66Ga after proton irradiation on a natural zinc foil. The nuclides 68Ga and 66Ga are ideally suited for off line PET monitoring of proton radiotherapy due to their beta decay halflives of 67.71(9) minutes and 9.49(3) hours, respectively, and suitable fl end point energy. The purpose of this work is to explore the feasibility of PET monitoring in hadrontherapy treatments, and to study how the amount of activity and the positron range affect the PET image reconstruction. Profiting from the low energy reaction threshold for production via (p,n) reactions, both 68Ga and 66Ga gallium isotopes have been produced by activation on a natural zinc target by a proton pencil beam. In this way, it is possible to create detailed patterns, such as the Derenzo inspired one employed here. The proton beam was produced by the 5 MV tandetron accelerator at CMAM in Madrid. The energy of this beam (up to 10 MeV) is similar to the residual energy of the protons used for therapy at the distal edge of their path. The activated target was imaged in an ARGUS small animal PETtCT scanner and reconstructed with a fully 3D iterative algorithm, with and without positron range corrections. This work was supported in part by Comunidad de Madrid (ARTEMIS S2009/DPI 1802), Spanish Ministry of Science and Innovation (grants FPA2010 17142 and ENTEPRASE, PSE 300000 2009 5), by European Regional Funds, by CDTI under the CENIT Programme (AMIT Project), UCM (grupos UCM, 910059) and by CPAN, CSPD 2007 00042@lngenio2010. Publicado

Proceeding of: 2011 Nuclear Science Symposium and Medical Imaging Conference, Valencia, España, 23-29 October, 2011 Quantification of tracer kinetics is often accomplished from time-activity curves of a region of interest of dynamic PET images. The choice of reconstruction method may affect the timeactivity curves and hence the estimated kinetic parameters. Several studies have shown that statistical-iterative methods, due to non-negativity constrains, may exhibit a quantification bias in low activity regions and thus these methods, in spite of the better image quality they provide, are seldom used to estimate kinetic constants. By means of realistic dynamic simulations, we have investigated the quantitative properties of statistical-iterative (OS EM, both 2D and 3D) and FBP reconstruction methods and the accuracy of the kinetic parameters derived from images reconstructed with each algorithm. We focus on the procedure to fit kinetic constants to data. Our results show that, with appropriate measures to account for quantification bias, iterative reconstructions may be suited to derive kinetic constants from dynamic PET acquisitions. This work was supported from Comunidad de Madrid (ARTEMIS Spanish Ministry of Science and Innovation (ENTEPRASE Grant, PSE-300000-2009-5) and PRECISION grant IPT-300000-2010-3, UCM (Grupos UCM, 910059), and european regional funds and CPAN, Centro de Fisica de Particulas, Astroparticulas y Nuclear (CSD-2007-00042@Ingenio2010-12). This study has been (partially) funded by CDTI under the CENIT Programme (AM IT Project). Part of the calculations of this work was performed in the "Cluster de Calculo de Alta Capacidad para Tecnicas Fisicas" funded in part by UCM and in part by UE with European regional funds" Publicado

Proceedings of: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Valencia, Spain, 23-29 October 2011 Dynamic cardiac magnetic resonance imaging in small animals is an important tool in the study of cardiovascular diseases. The reduction of the long acquisition times required for cardiovascular applications is crucial to achieve good spatiotemporal resolution and signal-to-noise ratio. Nowadays there are many acceleration techniques which can reduce acquisition time, including compressed sensing technique. Compressed sensing allows image reconstruction from undersampled data, by means of a non linear reconstruction which minimizes the total variation of the image. The recently appeared Split Bregman methodology has proved to be more computationally efficient to solve this problem than classic optimization methods. In the case of dynamic magnetic resonance imaging, compressed sensing can exploit time sparsity by the minimization of total variation across both space and time. In this work, we propose and validate the Split Bregman method to minimize spatial and time total variation, and apply this method to accelerate cardiac cine acquisitions in rats. We found that applying a quasi-random variable density pattern along the phase-encoding direction, accelerations up to a factor 5 are possible with low error. In the future, we expect to obtain higher accelerations using spatiotemporal undersampling. This work is supported in part by Ministerio de Ciencia e Innovacion (Red RECA VA), Comunidad de Madrid and Fondos FEDER (ARTEMIS project S2009DPI 1802). Publicado

In this work, we compare two commercial positron emission tomography (PET) scanners installed at CIEMAT (Madrid, Spain): the ClearPET and the rPET-1. These systems have significant geometrical differences, such as the axial field of view (110 mm on ClearPET versus 45.6 mm on rPET-1), the configuration of the detectors (whole ring on ClearPET versus one pair of planar blocks on rPET-1) and the use of an axial shift between ClearPET detector modules.We used an assessment procedure that fulfilled the recommendations of the National Electrical Manufacturers Association (NEMA) NU 4-2008 standard. The methodology includes studies of spatial resolution, sensitivity, scatter fraction, count losses and image quality. Our experiments showed a central spatial resolution of 1.5 mm (transaxial), 3.2 mm (axial) for the ClearPET and 1.5 mm (transaxial), 1.6 mm (axial) for the rPET-1, with a small variation across the transverse axis on both scanners (~1 mm). The absolute sensitivity at the centre of the field of view was 4.7% for the ClearPET and 1.0% for the rPET-1. The peak noise equivalent counting rate for the mouse-sized phantom was 73.4 kcps reached at 0.51 MBq/mL on the ClearPET and 29.2 kcps at 1.35 MBq/mL on the rPET-1. The recovery coefficients measured using the image quality phantom ranged from 0.11 to 0.89 on the ClearPET and from 0.14 to 0.81 on the rPET-1. The overall performance shows that both the ClearPET and the rPET-1 systems are very suitable for preclinical research and imaging of small animals Publicado

Proceedings of: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Valencia, Spain, 23-29 October 2011 he count rate in a PET scanner as a function of the activity in the Field of View (FOV) has a non-linear contribution coming from deadtime, pile-up and random coincidences. These effects must be estimated accurately and corrected in order to perform quantitative PET studies. For a given scanner and acquisition system, the relative importance of deadtime and pile-up effects still depends on the size and materials of the objects being imaged. These facts difficult to devise a universal correction method that yields accurate results for any kind of acquisition. In this work we show that, in a PET scanner, there is a linear relationship between the effective deadtime for coincidences, tau, (which takes into account deadtime and pile-up losses and gains within the energy window) and the Singles to Coincidences Ratio (SCRm) measured by the scanner. This relation has been recovered both in simulations and real data. This allows us to devise a simple method which, requiring only two calibration acquisitions for each energy window, one with high SCRm and one with low SCRm, is able to estimate accurately deadtime and pile up corrections for any other acquisition performed in the same scanner. Simulations show that corrected count rates are accurate within 5%, even when high activities are present in the FOV. This work was supported from Comunidad de Madrid (ARTEMIS S2009/DPI 1802), Spanish Ministry of Science and Innovation (ENTEPRASE Grant, PSE 300000 2009 5) and PRECISION grant IPT 300000 2010 3, UCM (Grupos UCM, 910059), and european regional funds and CPAN, Centro de Fisica de Particulas, Astroparticulas y Nuclear (CSD 2007 00042@lngenio2010 12). This study has been (partially) funded by CDTI under the CENIT Programme (AMIT Project). Part of the calculations of this work was performed in the "Cluster de Calculo de Alta Capacidad para Tecnicas Fisicas" funded in part by UCM and in part by UE with European regional funds". Publicado

Proceeding of: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference and 17th Room Temperature Semiconductor Detector Workshop (IEEE), Knoxville, Tennessee, USA, October 30 - November 6, 2010 Positron range depends on the materials in which positron propagates and on positron emitter isotope. As positron range limits the spatial resolution of PET images, good quantitative estimates of it should be included in any realistic simulation of PET acquisitions. In this work we compare positron range estimates obtained with PeneloPET to previous available simulations and experimental data. PeneloPET was used to simulate the positron range of 18F, 11C, 13N, 15O, 68Ga and 82Rb in the following tissues: cortical bone, soft bone, skin, muscle, brain, water, adipose tissue and lung. The 3D and 1D annihilation Point Spread Functions (aPSF) were calculated for each isotope-material combination. We have studied with more detail the 3D aPSF (radial distributions) and the cumulative fraction of annihilation events. These aPSF distributions were also studied for non-uniform media. Results obtained were consistent with other results previously reported in the literature as well as with experimentally measured data. This work has been supported by MEC (FPA2007-62216), UCM (Grupos UCM, 910059), CPAN (Consolider- Ingenio 2010) CSPD-2007-00042, European Regional Development and ENTEPRASE grant, PSE-300000-2009-5, and the CENIT program project AMIT, Ministerio de Ciencia e Innovación, Spanish Government. Part of the calculations of this work were performed in the “Clúster de Cálculo de Alta Capacidad para Técnicas Físicas” funded in part by UCM and in part by UE under FEDER programme”. Publicado

We developed a cost-effective SPECT scanner prototype (rSPECT) for in vivo imaging of rodents based on small-area gamma cameras. Each detector consists of a position-sensitive photomultiplier tube (PS-PMT) coupled to a 30 30 NaI(Tl) scintillator array and electronics attached to the PS-PMT sockets for adapting the detector signals to an in-house developed data acquisition system. The detector components are enclosed in a leadshielded case with a receptacle to insert the collimators. System performance was assessed using 􀀀􀀀 􀀀 for a high-resolution parallel- hole collimator, and for a 0.75-mm pinhole collimator with a 60 aperture angle and a 42-mm collimator length. The energy resolution is about 10.7% of the photopeak energy. The overall system sensitivity is about and planar spatial resolution ranges from 2.4 mm at 1 cm source-to-collimator distance to 4.1 mm at 4.5 cm with parallel-hole collimators. With pinhole collimators planar spatial resolution ranges from 1.2 mm at 1 cm source-to-collimator distance to 2.4 mm at 4.5 cm; sensitivity at these distances ranges from 2.8 to . Tomographic hot-rod phantom images are presented together with images of bone, myocardium and brain of living rodents to demonstrate the feasibility of preclinical small-animal studies with the rSPECT. This work was supported in part by the CD-TEAM project, CENIT program, Spanish Ministerio de Industria and with grants from the Ministerio de Educación y Ciencia, Projects TEC2007-64731/TCM, TEC2008-06715-C02-01, SAF2009-08076, program ARTEMIS S2009/DPI-1802, Comunidad de Madrid, and the RECAVA-RETIC Network Publicado

68Ga is one of the non-conventional nuclides that are being used in preclinical imaging. One disadvantage of 68Ga versus 18F is its larger positron range, which deteriorates the effective spatial resolution and the overall image quality. In this work we present a performance evaluation of the ARGUS small-animal positron emission tomography (PET) scanner for two positron emitters, 68Ga and 18F. These experiments followed the procedure based on the National Electrical Manufacturers Association (NEMA) NU 4–2008 standard. We show how the use of 68Ga may affect the NEMA performance of the system in terms of image quality and spatial resolution. The recovery coefficients (RC) measured in the image-quality phantom ranged from 0.17 to 0.72 for 68Ga and from 0.28 to 0.92 for 18F, using iterative image reconstruction methods and applying all corrections. Under the same conditions the image noise (%STD) in a uniform region was 17.0% for 68Ga and 15.1% for 18F. The respective spillover ratios (SOR) were 0.13 and 0.09 in air, and 0.21 and 0.12 in water. Attenuation correction yielded an improvement of the SOR close to 50% for both radionuclides in the air-filled region. This work evaluates the image reconstruction methods and corrections available in the ARGUS PET for 68Ga and 18F to assess the influence of their physical properties on the NEMA parameters.

The scatter fraction (SF) in PET data represents the fraction of coincidence events in which at least one of the two emitted photons have been scattered before being detected. It is usually estimated as the ratio of scattered events to total number of coincidences, when the number of random counts is negligible (less than 1% of true rates). SF provides a measurement of the relative sensitivity of the scanner to scattered radiation. It depends on object size, density and location inside the field of view, as well as on detector size, type of detector crystal and energy window. The performance evaluation guideline for smallanimal PET NEMA (National Electrical Manufacturers Association) NU4–2008 proposes the estimation of the SF for three test phantoms made in proportion to the most widely used small animals in the laboratory: mouse, rat and monkey. The method estimates the different coincidence types in sinogram profiles from an off-centered line source inserted in these phantoms. We benchmark the procedure proposed by NEMA to estimate SF with 18F and also with 68Ga, a radionuclide with lager positron range. Real data acquired with the ARGUS smallanimal PET scanner (SEDECAL, Madrid, Spain) as well as simulations of the same scanner with peneloPET are used. The results show that, though SF should be practically the same with both 18F and 68Ga isotopes (and indeed our simulations indicate this) NEMA SF estimations with 68Ga acquisitions are higher. This is due to the fact that 68Ga positron range affects on the width of the line source profiles. Suggestions to modify the protocol to obtain similar SF estimations when using isotopes with larger positron range than 18F are made.

Purpose: To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence. Procedures: The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[18F]fluoro D glucose (FDG) uptake were studied by positron emission tomography. Results: The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP. Conclusions: These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated. This work was supported by grants from the Ministerio de Educación y Ciencia (Grants nº SAF2004-08148 and SAF2007-064890); Ministerio de Sanidad y Consumo (Grants RD06/ 00170029 of Instituto de Salud Carlos III, PNSD 2004 2007 and 2008 2010); Dirección General de Investigación de la Comunidad de Madrid (Grant S-SAL/0261/2006, I+D CANNAB-CM Consortium); and UNED (Plan de Promoción de la Investigación) to EA, and grants from the “Ministerio de Ciencia y Tecnología” (TEC2004-07052-C02-01/TCM), “Ministerio de Sanidad y Consumo” (CIBER CB06/01/0079, PNSD 2007 2010, FIS CP08/00017), “Ministerio de Industria” (CENIT program) and “Fundación de Investigación Médica Mutua Madrileña” (2007 2010 and 2008 2011) to MD. Publicado

We present a new high-performance and low-cost approach for implementing radiation detection acquisition systems. The basic elements used are chargeintegrating 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-channelADCcards (12-bit resolution) for data digitization and a 32-bit digital I/OPCI 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 This project was supported and funded by the CENIT Program (Ministerio de Industria), CIBER CB07/09/0031 (Ministerio de Sanidad y Consumo), TEC2007-64731/TCM and TEC2008-06715-C02-01 (Ministerio de Educación y Ciencia), and the ARTEMIS program P2009/DPI-1802, Comunidad de Madrid Publicado

The multi pixel photon counter (MPPC) or silicon photomultiplier (SiPM), recently introduced as a solid state photodetector, consists of an array of Geiger mode photodiodes (microcells). It is a promising device for PET due to its potential for high photon detection efficiency (PDE) and its foreseeable immunity to magnetic fields. It is also easy to use with simple read outs, has a high gain and a small size. In this work we evaluate the in field performance of three 1x1mm2 (with 100, 400 and 1600 microcells, respectively) and one 6x6mm2 (arranged as a 2x2 array) Hamamatsu MPPCs for their use in PET imaging. We examine the dependence of the energy resolution and the gain of these devices on the temperature and reverse bias voltage, when coupled to LYSO scintillator crystals under conditions that one would find in a PET system. We find that the 400 and 1600 microcells models and the 2x2 array are suitable for small size crystals, like those employed in high resolution small animal scanners. We have confirmed the good performance of these devices up to magnetic fields of 7 T as well as their suitability for performing PET acquisitions in the presence of fast switching gradients and high duty radiofrequency MRI sequences This work was supported in part by the CDTEAM project of the CENIT program, and by Ministerio de Ciencia e Innovacio´n under projects FPA2007 62216TEC2008 06715 C02 01, UCM (Grupos UCM; 910059), CPAN (Consolider Ingenio 2010) CSPD 2007 00042 projects, and project SENSORCZT S 0505/MAT/000279, Comunidad de Madrid. Part of the computations of this work were done at the ‘‘High Capacity Cluster for Physical Techniques’’ of UCM, funded in part by the UE under the FEDER program and in part by UCM Publicado

Proceeding of: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference and 17th Room Temperature Semiconductor Detector Workshop (IEEE), Knoxville, Tennessee, USA, October 30 - November 6, 2010 Conventional kinetic parameter estimation based on compartmental models requires an accurate estimation of arterial blood input function. To avoid invasive blood sampling, an image-derived input function can be obtained by manually defining a Region of Interest. Here we propose a new and simple, iterative method for automatic segmentation and input function calculation of PET cardiac studies using correlation as a distance metric between a priori information regarding the approximate shape of the final time-activity curve (TAC) and the actual TAC extracted from the image temporal series. This work was supported in part by the CENIT-AMIT Ingenio 2010, Ministerio de Ciencia e Innovación, TEC2007-64731, TEC 2008-06715-C02-1, RETIC-RECAVA, Ministerio de Sanidad y Consumo, and the ARTEMIS de la Comunidad de Madrid (S2009/DPI-1802) programs Publicado

Monte Carlo simulations play an important role in positron emission tomography (PET) imaging, as an essential tool for the research and development of new scanners and for advanced image reconstruction. PeneloPET, a PET-dedicated Monte Carlo tool, is presented and validated in this work. PeneloPET is based on PENELOPE, a Monte Carlo code for the simulation of the transport in matter of electrons, positrons and photons, with energies from a few hundred eV to 1 GeV. PENELOPE is robust, fast and very accurate, but it may be unfriendly to people not acquainted with the FORTRAN programming language. PeneloPET is an easy-to-use application which allows comprehensive simulations of PET systems within PENELOPE. Complex and realistic simulations can be set by modifying a few simple input text files. Different levels of output data are available for analysis, from sinogram and lines-of-response (LORs) histogramming to fully detailed list mode. These data can be further exploited with the preferred programming language, including ROOT. PeneloPET simulates PET systems based on crystal array blocks coupled to photodetectors and allows the user to define radioactive sources, detectors, shielding and other parts of the scanner. The acquisition chain is simulated in high level detail; for instance, the electronic processing can include pile-up rejection mechanisms and time stamping of events, if desired. This paper describes PeneloPET and shows the results of extensive validations and comparisons of simulations against real measurements from commercial acquisition systems. PeneloPET is being extensively employed to improve the image quality of commercial PET systems and for the development of new ones We acknowledge support from MEC (FPA2007-07393), CDTEAM (CENIT-Ingenio 2010) Ministerio de Industria, Spain, CPAN (Consolider-Ingenio 2010) CSPD-2007-00042 projects and the RECAVA-RETIC network. Part of the computations of this work were done at the ‘High Capacity Cluster for Physical Techniques’ of the Faculty for Physical Sciences of the UCM, funded in part by the UE under the FEDER program and in part by UCM. J L Herraiz and E Vicente acknowledge support from UCM-FPU and CSIC-JAE pre-doctoral fellowships Publicado

Proceeding of: 2008 IEEE Nuclear Science Symposium Conference Record (NSS '08), Dresden, Germany, 19-25 Oct. 2008 The multi-pixel photon counter (MPPC) or silicon photo-multiplier (SiPM), recently introduced as a solid-state photodetector, consists of an array of Geiger-mode photodiodes(microcells). is a promising device for PET thanks to its potential for high photon detection efficiency (PDE) and immunity to high magnetic fields. is also very easy to use, with simple electronic read-out, high gain and small size. In this work we evaluate the performance of three 1 x 1 mm2 and one 6 x 6 mm2 (2 x 2 array) SiPMs offered by Hamamatsu for their use in PET. We examine the dependence of the energy resolution and the gain of these devices on the thermal and reverse bias when coupled to LYSO scintillator crystals. We find that the 400 and 1600 microcells models and the 2 x 2 array are suitable for small size crystals, like those employed in high resolution small animal scanners. The good performance of these devices up to 7 Tesla has also been confirmed. This work was supported in part by the MEC (FPA2007-07393), CDTEAM (CENIT-Ingenio 2010) Ministerio de Industria, Spain, UCM (Grupos UCM: 910059), CPAN (ConsoliderIngenio 2010) CSPD-2007-00042 projects, and the RECAVA-RETIC network.

Proceeding of: 2008 IEEE Nuclear Science Symposium Conference Record (NSS '08), Dresden, Germany, 19-25 Oct. 2008 This work compares two different X-ray flat-panel detectors for its use in high-speed, cone-beam CT applied to small-animal imaging. The main differences between these two devices are the scintillators and the achievable frame rate. Both devices have been tested in terms of system linearity, sensitivity, resolution, stability and noise properties, taking into account the different timing schemes for each one of them and the mandatory corrections on the raw data. Tomographic scans have been carried out using both detectors to evaluate its final performance as well as the delivered dose needed to achieve similar quality scans. An experimental cone-beam CT test-bench has been designed and implemented to perform the different measurements. It uses a micro-focus X-ray source and a rotating stage where the samples are placed. A modified FDK algorithm has been used to reconstruct the acquired data. Both detectors show similar results for pixel linearity and stability measurements, and their noise levels are comparable. The resolution and sensitivity features are better for the direct grown scintillator detector (9 Ipmm vs. 6 Ipmm, and -4 times more sensitive for similar delivered dose). Since tomographic reconstructed images for the higher frame-rate detector show acceptable quality, it can be used to implement a faster system for high-speed acquisition techniques like, for example, dynamic imaging or gated protocols. This work is partially funded by the CD-TEAM Project, CENIT Program, Spanish Ministerio de Industria, and with grants from the Ministerio de Educacion y Ciencia, projects TEC2007-64731 and TEC2008-06715-C02Ol.