Santiago Jiménez-Serrano

Most preclinical PET scanners are based on pixelated detectors without Depth of Interaction (DOI) capabilities, which is crucial to correct for parallax errors. Semi-monolithic crystals have the potential to combine the timing capabilities of pixelated crystals and the 3D positioning accuracy of monolithic scintillators. In this work, we present a preclinical PET prototype consisting of 2 rings defining an inner diameter of 106 mm and an axial length of 52 mm. Each ring contains 14 arrays of 1 × 22 LYSO slabs of 0.97 mm × 25.6 mm × 12 mm, coupled to 8 × 8 SiPMs arrays. The sensitivity, spatial resolution, count rate performance and image quality were studied using the NEMA NU 4-2008 protocol. All images were reconstructed using the MLEM algorithm with 0.5 mm voxel size, including DOI information and normalization correction. A mean spatial resolution for all measured positions and across the three directions (axial, transaxial and radial) of 1.61 ± 0.19 mm was obtained at the center of the FOV. A peak sensitivity of 3.5% was obtained at the center of the scanner, for an energy window (EW) between 358 keV -664 keV. The noise equivalent count rate peak reached 106.9 kcps for an activity of 11.7 MBq using the mouse-sized phantom, the same EW window and a time coincidence window of 10 ns. For the image quality phantom, contrast recovery coefficients of 0.20, 0.62, 0.75, 0.81 and 0.85 were found for the 1, 2, 3, 4 and 5 mm rods, respectively. Spill-over-ratio values of 0.10 for air-filled and 0.23 for water-filled cylinders were measured. Also, according to the Rayleigh criterion, 1.5, 1.2 and 1 mm hot spots of a micro-Derenzo phantom were well distinguished.

Combining positron emission tomography (PET) with magnetic resonance imaging (MRI) and focused ultrasound (FUS) has emerged as a promising hybrid technique in the medical imaging field. Despite the potential benefits of using simultaneous PET and MRI acquisitions to monitor therapeutic effects and ensure precision and safety during FUS applications, no commercial or academic PET/MRI-guided FUS system (referred in the following as trimodal PET-MRI-FUS) exists. This work presents the design and evaluation of a preclinical PET insert for simultaneous operation with MRI and FUS systems. The proposed PET insert is based on monolithic LYSO crystals arranged in two octagonal rings that define inner and outer diameters of 72 and 114 mm, respectively, with an axial length of 67 mm. The system performance was evaluated according to the NEMA NU 4 2008 protocol. It achieves a uniform spatial resolution of ~0.9 mm along the whole PET Field of View (FOV) when enabling Depth of Interaction (DOI) capabilities. Moreover, we found a sensitivity peak of 3.8% for an energy window of 255–766 keV and a peak noise equivalent count rate peak of 80 kcps at an activity of 19 MBq. The compatibility of the PET insert with both low- and high-field MRI systems, as well as with custom and commercially available FUS devices, was studied using phantoms and in vivo experiments, respectively. The results of the trimodal tests have proven that the PET insert works simultaneously with both MRI and FUS systems.

Positron Emission Tomography (PET) imaging is the molecular technique of choice for studying many illnesses, including the ones related to the brain. Nevertheless, the use of PET scanners in neurology is limited by several factors, such as their limited availability for brain imaging due to the high oncology demand for PET and the low sensitivity and poor spatial resolution in the brain of the standard PET scanners. To expand the PET application in neurology, brain-specific systems with increased clinical and physical sensitivities and higher spatial resolution are required. The present work reports on the design and development process of a compact dedicated PET scanner suitable for human brain imaging. This paper includes the description and experimental validation of the detector components and their implementation in a full-size system called 4D-PET. The detector has been designed to simultaneously provide photon DOI and TOF information. It is based on the semi-monolithic LYSO modules optically coupled to SiPMs and connected to a multiplexing readout. The analog output signals are fed to the PETsys TOFPET2 ASIC circuits enabling scalability of the readout. The evaluation of the 4D-PET modules resulted in average detector resolutions of 2.111.0 mm, 3.411.8 mm, and 38619 ps for the y-(transaxial direction), DOI-, and CTR TOF, respectively. The preliminary 4D-PET imaging performance is reported through simulations and, for the first time, through the real reconstructed images (collected in the La Fe Hospital, Valencia).

Total Body Positron Emission Tomography (TB-PET) scanners provide high-quality images due to the large sensitivity. Our motivation is to design a TB-PET system with up to 70 cm axial coverage that mitigates the parallax error degradation by using a detector concept based on semi-monolithic LYSO crystals. Furthermore, this detector approach allows to simultaneously reach an accurate Coincidence Time Resolution (CTR) to enhance the image quality by means of Time of Flight (TOF) reconstruction algorithms. We have simulated and compared two Positron Emission Tomography (PET) prototypes with about 70 cm but a different number of detector rings (7 vs. 5). The NEMA NU 2 2018 protocol has been implemented. By correcting the parallax error with the Depth of Interaction (DOI) information, the spatial resolution remains homogeneous and below 3 mm in the entire Field of View (FOV), differently from designs based on pixelated crystals. The sensitivity reaches values of 58 and 115 cps/kBq, for the 5 and 7 rings configurations, respectively. The Noise Equivalent Count Rate (NECR) was found at 563 kcps/mL. This value is lower than other systems, most likely due to the requirement to process a larger number of channels to characterize the DOI. Percent contrasts obtained for two different phantoms are in general beyond 80% for the largest spheres, nearly 100% for the 7 rings configuration once TOF is applied during the reconstruction process. In conclusion, although the sensitivity and NECR results for the 5-rings configuration are lower compared to the 7-rings approach, its overall performance is enhanced by the addition of TOF and parallax error correction, improving that of conventional Whole Body PET scanners (axial length: 20 – 30 cm) in terms of image quality.

In this article, we present the geometrical design and preliminary results of a high sensitivity organ-specific Positron Emission Tomography (PET) system dedicated to the study of the human brain. The system, called 4D-PET, will allow accurate imaging of brain studies due to its expected high sensitivity, high 3D spatial resolution and, by including precise photon time of flight (TOF) information, a boosted signal-to-noise ratio (SNR). The 4D-PET system incorporates an innovative detector design based on crystal slabs (semi-monolithic) that enables accurate 3D photon impact positioning (including photon Depth of Interaction (DOI) measurement), while providing a precise determination of the photon arrival time to the detector. The detector includes a novel readout system that reduces the number of detector signals in a ratio of 4:1 thus, alleviating complexity and cost. The analog output signals are fed to the TOFPET2 ASIC (PETsys) for scalability purposes. The present manuscript reports the evaluation of the 4D-PET detector, achieving best values 3D resolution values of <1.6 mm (pixelated axis), 2.7±0.5 mm (monolithic axis) and 3.4±1.1 (DOI axis) mm; 359 ± 7 ps coincidence time resolution (CTR); 10.2±1.5 % energy resolution; and sensitivity of 16.2% at the center of the scanner (simulated). Moreover, a comprehensive description of the 4D-PET architecture (that includes 320 detectors), some pictures of its mechanical assembly, and simulations on the expected image quality are provided.

Objective. Detecting different cardiac diseases using a single or reduced number of leads is still challenging. This work aims to provide and validate an automated method able to classify ECG recordings. Performance using complete 12-lead systems, reduced lead sets, and single-lead ECGs is evaluated and compared. Approach. Seven different databases with 12-lead ECGs were provided during the PhysioNet/Computing in Cardiology Challenge 2021, where 88 253 annotated samples associated with none, one, or several cardiac conditions among 26 different classes were released for training, whereas 42 896 hidden samples were used for testing. After signal preprocessing, 81 features per ECG-lead were extracted, mainly based on heart rate variability, QRST patterns and spectral domain. Next, a One-versus-Rest classification approach made of independent binary classifiers for each cardiac condition was trained. This strategy allowed each ECG to be classified as belonging to none, one or several classes. For each class, a classification model among two binary supervised classifiers and one hybrid unsupervised-supervised classification system was selected. Finally, we performed a 3-fold cross-validation to assess the system’s performance. Main results. Our classifiers received scores of 0.39, 0.38, 0.39, 0.38, and 0.37 for the 12, 6, 4, 3 and 2-lead versions of the hidden test set with the Challenge evaluation metric ( C M ). Also, we obtained a mean G -score of 0.80, 0.78, 0.79, 0.79, 0.77 and 0.74 for the 12, 6, 4, 3, 2 and 1-lead subsets with the public training set during our 3-fold cross-validation. Significance. We proposed and tested a machine learning approach focused on flexibility for identifying multiple cardiac conditions using one or more ECG leads. Our minimal-lead approach may be beneficial for novel portable or wearable ECG devices used as screening tools, as it can also detect multiple and concurrent cardiac conditions.

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (R_e < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.

Molecular epidemiology of SARS-CoV-2 aims to monitor the appearance of new variants with the potential to change the virulence or transmissibility of the virus. During the first year of SARS-CoV-2 evolution, numerous variants with possible public health impact have emerged. We have detected two mutations in the Spike protein at amino acid positions 1163 and 1167 that have appeared independently multiple times in different genetic backgrounds, indicating they may increase viral fitness. Interestingly, the majority of these sequences appear in transmission clusters, with the genotype encoding mutations at both positions increasing in frequency more than single-site mutants. This genetic outcome that we denote as Lineage B.1.177.637, belongs to clade 20E and includes 12 additional single nucleotide polymorphisms but no deletions with respect to the reference genome (first sequence in Wuhan). B.1.177.637 appeared after the first wave of the epidemic in Spain, and subsequently spread to eight additional countries, increasing in frequency among sequences in public databases. Positions 1163 and 1167 of the Spike protein are situated in the HR2 domain, which is implicated in the fusion of the host and viral membranes. To better understand the effect of these mutations on the virus, we examined whether B.1.177.637 altered infectivity, thermal stability, or antibody sensitivity. Unexpectedly, we observed reduced infectivity of this variant relative to the ancestral 20E variant in vitro while the levels of viral RNA in nasopharyngeal swabs did not vary significantly. In addition, we found the mutations do not impact thermal stability or antibody susceptibility in vaccinated individuals but display a moderate reduction in sensitivity to neutralization by convalescent sera from early stages of the pandemic. Altogether, this lineage could be considered a Variant of Interest (VOI), we denote VOI1163.7. Finally, we detected a sub-cluster of sequences within VOI1163.7 that have acquired two additional changes previously associated with antibody escape and it could be identified as VOI1163.7.V2. Overall, we have detected the spread of a new Spike variant that may be advantageous to the virus and whose continuous transmission poses risks by the acquisition of additional mutations that could affect pre-existing immunity.

In this work we present the BiPlanar Breast PET (BBPET) system. It is composed of two movable paddles than can be placed in several configurations in order to allow the imaging of the breast and the pectoral wall. Each paddle is formed by several detectors formed by continuous crystals, coupled to SiPM arrays. The system has been evaluated measuring the spatial resolution, NECR, uniformity and contrast coefficients. The results show a transaxial resolution of 1.5mm, a NECR peak of 319kcps at 12.6MBq, a uniformity of 10% and recovery coefficients >0.7 for the 3, 4 and 5mm rods. The system has good imaging capabilities for imaging patients in the clinical routine.