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Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Niñerola Baizán, Aida, Aguiar Fernández, Pablo, Silva-Rodríguez, Jesús, Nowadays, Nuclear Medicine techniques are of great importance in the clinical practice, especially in Neurology and Oncology, for both Diagnostics and Treatment. Focusing on imaging techniques, quantitative methods have shown to be an alternative to the traditional interpreting of images to give support to the clinician for a more accurate diagnostic. The lack of ground-truths has difficulted the implementation of these quantitative methods in the clinical practice, and consequently the use of simulation has raised as a solution for obtaining reference images. In particular, SimPET is a platform that aims to simulate and reconstruct Positron Emission Tomograph (PET) images while being able to model any scanner by introducing its parameters. The introduction of a new scanner requires a validation process to ensure it works in accordance of the manufacturer’s specifications. To do so, the NEMA protocols are a set of tests to allow a comparison with these specifications. In this work we are developing an implementation in Python and automatization of these tests to allow the easy validation of new scanners for SimPET. Four of the five specified tests were implemented, concerning the Spatial Resolution and the Sensitivity of the tomograph, and the Image Quality and the fraction of Scattering of the reconstructed images. The results were tested and compared with the experimental ones of the Discovery ST scanner. The results show that the values of Resolution and Sensitivity do not strictly coincide with the experimental ones, and further work on tuning the adjustments of the simulation need to be done. For the Image Quality test we obtained parameters that seem to be in accordance with the theoretical behaviour, but the lack of comparative results does not allow us to extract relevant conclusions. In the case of the Scatter Fraction test, we have shown that the suggested method does not work for very low activities. Thus, due to time and computational limitations further work needs to be done in the development of the techniques, but this work has shown the feasibility of its implementation.

REM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson’s disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients unaffected by RBD (PD-RBD−). To elucidate this, we evaluated the availability of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in 15 PD patients with probable RBD (PD-RBD+), 15 PD-RBD−, and 15 age-matched healthy controls (HC) using [11C]DTBZ PET imaging. This technique measured VMAT2 availability within striatal regions of interest (ROI). A mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. We observed a significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, our results revealed that PD-RBD+ had lower VMAT2 availability compared to HC in all these regions except for the subthalamus and substantia nigra, while PD-RBD− was significantly lower than HC in all these regions. PD-RBD− showed a negative relationship between motor severity and VMAT2 availability within the left caudate. Our findings reflect that both PD patient subgroups had similar denervation within the nigrostriatal pathway. There were no significant interactions detected between radioligand binding and clinical scores in PD-RBD+. Taken together, VMAT2 and striatal dopamine denervation in general may not be a significant contributor to the pathophysiology of RBD in PD patients. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by polysomnography-confirmed REM sleep without atonia and dream-enacting behaviors. This disorder is considered a prodromal syndrome of alpha-synucleinopathies like Parkinson's disease (PD), where it affects more than 50% of PD patients. The underlying pathology of RBD has been generally understood to involve the pontine nuclei within the brainstem. However, the complete pathophysiology beyond the brainstem remains unclear as does its relationship with PD pathology. Therefore, this review aims to survey the neuroimaging literature involving PET, SPECT, and MR imaging techniques to provide an updated understanding of the neuro-chemical, structural, and functional changes in both RBD and PD patients comorbid with RBD. This review found neuroimaging evidence that indicate alterations to the dopaminergic and cholinergic system, blood perfusion, and glucose metabolism in both RBD patients and PD patients with RBD. Beyond the brainstem, structural and functional changes were found to involve the nigrostriatal system, limbic system, and the cortex-suggesting that RBD is a multi-systemic neurodegenerative process. Future investigations are encouraged to follow RBD patients longitudinally using multimodal imaging techniques to enhance our understanding of this parasomnia disorder. Uncovering which individuals are most likely to develop an alpha-synuclein disorder in the prodromal phase will improve patient outcomes and potentially aid in the development of novel treatments for patients affected by RBD.

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Curs: 2020, Tutor: Eugeni Graugés, The HRFlexToT control software was designed to be used through command-line. In this project a graphical interface has been programmed in order to simplify the software configuration process. The interface has been programmed via PyQt libraries. It also includes a new feature to plot the data registered by the HRFlexToT board. Finally it's explained how to calibrate by the HRFlexToT acquisition system.

The HRFlexToT is a 16-channel ASIC for SiPM anode readout designed for Positron Emission Tomography (PET) applications that features high dynamic range (>8 bits), low input impedance, common cathode connection, high speed and low power (~3.5 mW/ch). The ASIC has been manufactured using XFAB 0.18 mm CMOS technology. The main characteristics of the HRFlexToT, compared to its predecessor, are a new energy measurement readout providing a linear Time Over Threshold (ToT) with an extended dynamic range, lower power consumption and better timing response. Initial measurements show a linearity error below 3%. Single Photon Time Resolution (SPTR) measurements performed using a Hamamatsu MPPC S13360-3050CS (3x3 mm2 pixel, 50 umm cell) shows 30% improvement with respect to the previous version of the ASIC, setting this specification in the order of 141 ps FWHM and reducing 3 times power consumption. It is important to highlight that an SPTR of 141 ps FWHM is, according to the best of our knowledge, the best resolution achieved so far for this sensor. Coincidence Time Resolution (CTR) measurements are expected to be performed during 2018.

Introduction The aim of this study was to evaluate the behavior of a penalized-likelihood image reconstruction method (Q.Clear) under different count statistics and lesion-to-background ratios (LBR) on a BGO scanner, in order to obtain an optimum penalization factor (β value) to study and optimize for different acquisition protocols and clinical goals. Methods Both phantom and patient images were evaluated. Data from an image quality phantom were acquired using different Lesion-to-Background ratios and acquisition times. Then, each series of the phantom was reconstructed using β values between 50 and 500, at intervals of 50. Hot and cold contrasts were obtained, as well as background variability and contrast-to-noise ratio (CNR). Fifteen 18 F-FDG patients (five brain scans and 10 torso acquisitions) were acquired and reconstructed using the same β values as in the phantom reconstructions. From each lesion in the torso acquisition, noise, contrast, and signal-to-noise ratio (SNR) were computed. Image quality was assessed by two different nuclear medicine physicians. Additionally, the behaviors of 12 different textural indices were studied over 20 different lesions. Results Q.Clear quantification and optimization in patient studies depends on the activity concentration as well as on the lesion size. In the studied range, an increase on β is translated in a decrease in lesion contrast and noise. The net product is an overall increase in the SNR, presenting a tendency to a steady value similar to the CNR in phantom data. As the activity concentration or the sphere size increase the optimal β increases, similar results are obtained from clinical data. From the subjective quality assessment, the optimal β value for torso scans is in a range between 300 and 400, and from 100 to 200 for brain scans. For the recommended torso β values, texture indices present coefficients of variation below 10%. Conclusions Our phantom and patients demonstrate that improvement of CNR and SNR of Q.Clear algorithm which depends on the studied conditions and the penalization factor. Using the Q.Clear reconstruction algorithm in a BGO scanner, a β value of 350 and 200 appears to be the optimal value for 18F-FDG oncology and brain PET/CT, respectively.

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Any: 2015, Tutor: Domènec Ros, The surgical removal of the epileptogenic region is considered as a possible treatent in intractable partial epilepsy. To guarantee surgery to be successful, an accurate localization of epileptogenic focus is crucial. A new proposal for its location is described and discussed. Six patients were used in the evaluation and the results were compared with other techniques routinely used for this purpose. All the processed studies showed a good agreement. As a result, it is seen great promise in this new methodology and further evaluation makes sense.

[cat] L’objectiu d’aquesta tesi és presentar una solució per a la lectura de matrius de fotomultiplicadors de silici (SiPM) millorant les característiques de sistemes actuals. Amb aquesta finalitat s’ha dissenyat i provat el circuit d’una nova etapa d’entrada. En primer lloc s’ha dissenyat pensant en aplicacions genèriques i per a imatge mèdica, concretament per a escàners PET (Positron Emission Tomography). Però més endavant s’aplica la mateixa topologia per a una aplicació més concreta i específica com és un detector de partícules (l’actualització del Tracker a l’experiment LHCb). Els SiPM són uns dispositius electrònics relativament nous amb la possibilitat de comptar fotons i millorant algunes característiques dels sensors actuals, com serien la tensió d’operació més baixa, més guany o immunitat a camps magn`etics, mentre manté unes prestacions excel•lents respecte el guany, resolució temporal i rang dinàmic. Aquest tipus de dispositius es troben en constant evolució encara i una gran varietat de fabricants intenten millorar les prestacions, sobretot respecte la eficiència en la detecció de llum, reduir el corrent d’obscuritat, construir matrius més grans i augmentar l’espectre al qual són sensibles. En aquest document es presenta el disseny d’un circuit integrat específic amb les següents característiques: gran rang dinàmic, alta velocitat, multicanal, amb entrada en corrent i baixa impedància d’entrada, baix consum, control de la tensió de polarització del SiPM i amb les sortides de; temps, càrrega i apilament., [eng] The aim of this thesis is to present a solution for the readout of Silicon Photo-Multipliers (SiPMs) arrays improving currently implemented systems. Using as a starting point previous designs with similar objectives a novel current mode input stage has been designed and tested. To start with the design a valid model has been used to generate realistic output from the SiPMs depending on light input. Design has been performed in first place focusing in general applications for medical imaging Positron Emission Tomography (PET) and then using the same topology for a more constrained design in particle detectors (upgrade of Tracker detector at LHCb experiment). A 16 channel ASIC for PET applications including the novel input stage has demonstrated an excellent timing measurement with good energy resolution measurement and pile-up detection. This document starts with the analysis of the requirements needed to fit such a system, followed by a detailed description of the input stage and analog processing. Signal is divided in the input stage into three different signal paths: timing, energy and pileup. Every channel performs different signal analysis to deliver; a fast time signal output (digital edge), energy output (a linear time over threshold digital output) and a digital bit to signal pile-up. The time information is then ORed between all channels to generate a single timing output. All the pile-up bits are combined in a digital word ready to be readout for the 16 channels. Design has been optimized for reduced power consumption and no components needed to interface inputs and outputs. Digital slow control to tune the circuit behaviour is also included. The prototype measurements have proved to be a valid option for integration in a full system scanner. An adapted prototype of the input stage using different technology and adapted to the different constraints from a particle detector is also presented. Only simulation results are available since device is still under production. An analysis of the different requirements needed by the SciFi tracker design is summarized. Current specifications are still evolving since final sensor is still not defined, but other requirements and some tunable elements permits to design such prototypes.

The Voxel Imaging PET (VIP) Path nder project got the 4 year European Research Council FP7 grant in 2010 to prove the feasibility of using CdTe detectors in a novel conceptual design of PET scanner. The work presented in this thesis is a part of the VIP project and consists of, on the one hand, the characterization of a CdTe detector in terms of energy resolution and coincidence time resolution and, on the other hand, the simulation of the setup with the single detector in order to extend the results to the full PET scanner. An energy resolution of 0.98% at 511 keV with a bias voltage of 1000 V/mm has been measured at low temperature T=-8 ºC. The coincidence time distribution of two twin detectors has been found to be as low as 6 ns FWHM for events with energies above 500 keV under the same temperature and bias conditions. The measured energy and time resolution values are compatible with similar ndings available in the literature and prove the excellent potential of CdTe for PET applications. This results have been presented in form of a poster contribution at the IEEE NSS/MIC & RTSD 2011 conference in October 2011 in Valencia and at the iWoRID 2012 conference in July 2012 in Coimbra, Portugal. They have been also submitted for publication to "Journal of Instrumentation (JINST)" in September 2012.

Localization of sentinel lymph nodes can be challenging if they are in difficult anatomic locations or near high radiotracer activity. The purpose of this study was to assess the value of intraoperative real-time imaging using a portable gamma-camera in conjunction with a conventional gamma-counting probe when it is difficult to localize the sentinel node.After (99m)Tc-nanocolloid injection, patients with various malignancies underwent presurgical lymphoscintigraphy followed by surgery (usually the next day). We evaluated 20 patients who required sentinel lymph node biopsy and in whom the location or other characteristics of the sentinel node would make intraoperative retrieval difficult. During surgery, the sentinel node was localized using a portable gamma-camera together with a hand-held gamma-probe. A (153)Gd pointer or (125)I seed was used to better depict the sentinel node location in real time.Using only a conventional hand-held gamma-probe, surgeons were able to definitively localize the sentinel node in 15 of 20 patients. Intraoperatively, the portable gamma-camera showed uptake by the definite sentinel node in 19 of 20 patients and helped to precisely localize the node with the hand-held gamma-probe in 4 patients. In 1 of these patients, the sentinel node was metastatic.The combination of a standard hand-held gamma-probe and real-time imaging provided by a portable gamma-camera offers a high intraoperative detection rate in patients with difficult sentinel node localization as assessed by presurgical lymphoscintigraphy.

We propose and compare different registration approaches to align small-animal PET studies and a procedure to validate the results by means of objective registration consistency measurements. Procedures: We have applied a registration algorithm based on information theory, using different approaches to mask the reference image. The registration consistency allows for the detection of incorrect registrations. This methodology has been evaluated on a test dataset(FDG-PET rat brain images). Results: The results show that a multiresolution two-step registration approach based on the use of the whole image at the low resolution step, while masking the brain at the high resolution step, provides the best robustness (87.5% registration success) and highest accuracy (0.67-mm average). Conclusions: The major advantages of our approach are minimal user interaction and automatic assessment of the registration error, avoiding visual inspection of the results, thus facilitating the accurate, objective, and rapid analysis of large groups of rodent PET images This work was supported by projects CIBER CB06/01/0079 (Ministerio de Sanidad y Consumo) and CDTEAM (CENIT program, Ministerio de Industria). Further support came from NIAAA Intramural Research Program (AA 11034 and AA07574, AA07611) and the US Department of Energy (DE-AC02-98CH10886) Publicado