Development and Testing of a High Resolution PET Detector for Prostate Imaging

According to the American Cancer Society one in six men will be diagnosed with prostate cancer in their lifetime. Current methods for screening of prostate cancer including various PSA blood tests, as well as the digital rectal exam, are unreliability while current imaging modalities clinically employed (US, CT, MRI) are unable to localize intraprostatic cancer(s). Consequently, diagnosis via core needle biopsy is problematic and a game of chance at best. Therefore, in response to new radiopharmaceuticals applicable to both internal and external prostate cancer visualization and localization, novel prostate specific nuclear medical imagers are being developed.;The first prototype of a compact prostate specific PET detector utilizing silicon photomultiplier (SiPM) technology has been developed and tested at West Virginia University. The compact detector is proposed as an endorectal probe placed proximally to the rectal wall/prostate interface and operating in coincidence with one or more externally mounted large area gamma detectors or in tandem with a clinical whole body PET scanner. To ensure high reconstruction resolution, the scintillation array of the compact detector will be coupled to SiPMs on both axial ends in a dual ended readout approach. Such an approach allows for the extraction of continuous depth of interaction (DOI) information thus minimizing the effects of parallax error and providing nearly isotropic and uniform spatial resolution throughout the entire detector field of view (FOV).;Two compact DOI based prototype detectors were developed and tested. While both utilize pixelated LYSO scintillation crystal arrays, the first has a crystal pitch of 1.0 mm and is coupled to SensL SiPMs, while the second has a crystal pitch of 0.7mm and is coupled to Hamamatsu SiPMs. Initial proof of concept studies were preformed using the SensL based detector while more extensive and systematic studies were preformed using the Hamamatsu based detector. Ultimately, when averaged over all crystals and all depths the Hamamatsu based detector achieved a depth of interaction resolution of 0.78+/-0.09 mm FWHM and an energy resolution of 13.2+/-0.7 % FWHM. Validation studies with regards to the efficacy of incorporating DOI information extracted from a small compact DOI based PET detector module into image reconstruction algorithms were also preformed

The MINDVIEW project: First results

[EN] We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient. The achieved spatial resolution, close to 1 mm, will enable differentiation of relevant brain structures for schizophrenia. A cost-effective and simple method of radiopharmaceutical production from C-11-carbon monoxide and a mini-clean room has been demonstrated. It has been shown that C-11-raclopride has higher binding potential in a new VAAT null mutant mouse model of schizophrenia compared to wild type control animals. A significant reduction in TSPO binding has been found in gray matter in a small sample of drug-naive, first episode psychosis patients, suggesting a reduced number or an altered function of immune cells in brain at early stage schizophrenia. (c) 2018 Elsevier Masson SAS. All rights reserved.This project is funded by EU grant FP7-HEALTH-F2-2013-603002.Benlloch Baviera, JM.; González Martínez, AJ.; Pani, R.; Preziosi, E.; Jackson, C.; Murphy, J.; Barbera Ballester, J.... (2018). The MINDVIEW project: First results. European Psychiatry. 50:21-27. https://doi.org/10.1016/j.eurpsy.2018.01.002S212750Gonzalez, A. J., Gonzalez-Montoro, A., Aguilar, A., Conde, P., Canizares, G., Hernandez, L., … Benlloch, J. M. (2016). A brain PET insert MR compatible: Final design and first results. 2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop (NSS/MIC/RTSD). doi:10.1109/nssmic.2016.8069619Dahl, K., Schou, M., Ulin, J., Sjöberg, C.-O., Farde, L., & Halldin, C. (2015). 11C-carbonylation reactions using gas–liquid segmented microfluidics. RSC Advances, 5(108), 88886-88889. doi:10.1039/c5ra20646d[26] Långström B and Sjöberg CO, System for controlling environment in reaction box, From PCT Int. Appl. (2013), WO 2013103312 A1 20130711.Autret, A., Bert, J., Strauss, O., & Visvikis, D. (2012). Projector with realistic detector scatter modelling for PET list-mode reconstruction. 2012 IEEE Nuclear Science Symposium and Medical Imaging Conference Record (NSS/MIC). doi:10.1109/nssmic.2012.6551759[10] Young JW Head and Face Antropometry of Adult U.S. Citizens, Civil Aeromedical Institute, Federal Aviation Administration, U.S. Department of Transportation, Report number DOT/FAA/AM-93/10, July 1993.Braff, D. L. (1990). Sensorimotor Gating and Schizophrenia. Archives of General Psychiatry, 47(2), 181. doi:10.1001/archpsyc.1990.01810140081011Preziosi, E., Sánchez, S., González, A. J., Pani, R., Borrazzo, C., Bettiol, M., … Benlloch, J. M. (2016). Performance study of a PET scanner based on monolithic scintillators for different DoI-dependent methods. Journal of Instrumentation, 11(12), C12076-C12076. doi:10.1088/1748-0221/11/12/c12076Howes, O., McCutcheon, R., & Stone, J. (2015). Glutamate and dopamine in schizophrenia: An update for the 21st century. Journal of Psychopharmacology, 29(2), 97-115. doi:10.1177/0269881114563634Moliner, L., Correcher, C., González, A. J., Conde, P., Hernández, L., Orero, A., … Benlloch, J. M. (2013). Implementation and analysis of list mode algorithm using tubes of response on a dedicated brain and breast PET. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 702, 129-132. doi:10.1016/j.nima.2012.08.029Zelano, J., Mikulovic, S., Patra, K., Kühnemund, M., Larhammar, M., Emilsson, L., … Kullander, K. (2013). The synaptic protein encoded by the gene Slc10A4 suppresses epileptiform activity and regulates sensitivity to cholinergic chemoconvulsants. Experimental Neurology, 239, 73-81. doi:10.1016/j.expneurol.2012.09.006Antich, P., Malakhov, N., Parkey, R., Slavin, N., & Tsyganov, E. (2002). 3D position readout from thick scintillators. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 480(2-3), 782-787. doi:10.1016/s0168-9002(01)01214-1Gonzalez-Montoro, A., Benlloch, J. M., Gonzalez, A. J., Aguilar, A., Canizares, G., Conde, P., … Sanchez, F. (2017). Performance Study of a Large Monolithic LYSO PET Detector With Accurate Photon DOI Using Retroreflector Layers. IEEE Transactions on Radiation and Plasma Medical Sciences, 1(3), 229-237. doi:10.1109/trpms.2017.2692819Rahman, O., Takano, A., Amini, N., Dahl, K., Kanegawa, N., Långström, B., … Halldin, C. (2015). Synthesis of ([11C]carbonyl)raclopride and a comparison with ([11C]methyl)raclopride in a monkey PET study. Nuclear Medicine and Biology, 42(11), 893-898. doi:10.1016/j.nucmedbio.2015.07.003Howes, O. D., Kambeitz, J., Kim, E., Stahl, D., Slifstein, M., Abi-Dargham, A., & Kapur, S. (2012). The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment. Archives of General Psychiatry, 69(8). doi:10.1001/archgenpsychiatry.2012.169Ling, T., Lewellen, T. K., & Miyaoka, R. S. (2007). Depth of interaction decoding of a continuous crystal detector module. Physics in Medicine and Biology, 52(8), 2213-2228. doi:10.1088/0031-9155/52/8/012González, A. J., Majewski, S., Sánchez, F., Aussenhofer, S., Aguilar, A., Conde, P., … Benlloch, J. M. (2016). The MINDView brain PET detector, feasibility study based on SiPM arrays. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 818, 82-90. doi:10.1016/j.nima.2016.02.046Wong, D. F., Waterhouse, R., Kuwabara, H., Kim, J., Brasic, J. R., Chamroonrat, W., … Mozley, P. D. (2013). 18F-FPEB, a PET Radiopharmaceutical for Quantifying Metabotropic Glutamate 5 Receptors: A First-in-Human Study of Radiochemical Safety, Biokinetics, and Radiation Dosimetry. Journal of Nuclear Medicine, 54(3), 388-396. doi:10.2967/jnumed.112.107995Jackson, C., O’Neill, K., Wall, L., & McGarvey, B. (2014). High-volume silicon photomultiplier production, performance, and reliability. Optical Engineering, 53(8), 081909. doi:10.1117/1.oe.53.8.081909Rahman, O., Långström, B., & Halldin, C. (2016). Alkyl Iodides and [11 C]CO in Nickel-Mediated Cross-Coupling Reactions: Successful Use of Alkyl Electrophiles containing a β Hydrogen Atom in Metal-Mediated [11 C]Carbonylation. ChemistrySelect, 1(10), 2498-2501. doi:10.1002/slct.201600643Sullivan, J. M., Lim, K., Labaree, D., Lin, S., McCarthy, T. J., Seibyl, J. P., … Morris, E. D. (2012). Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [18F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans. Journal of Cerebral Blood Flow & Metabolism, 33(4), 532-541. doi:10.1038/jcbfm.2012.195Levin, C. S. (2003). Detector design issues for compact nuclear emission cameras dedicated to breast imaging. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 497(1), 60-74. doi:10.1016/s0168-9002(02)01893-4Larhammar, M., Patra, K., Blunder, M., Emilsson, L., Peuckert, C., Arvidsson, E., … Kullander, K. (2015). SLC10A4 Is a Vesicular Amine-Associated Transporter Modulating Dopamine Homeostasis. Biological Psychiatry, 77(6), 526-536. doi:10.1016/j.biopsych.2014.07.017Kaul, M., Surti, S., & Karp, J. S. (2013). Combining Surface Treatments With Shallow Slots to Improve the Spatial Resolution Performance of Continuous, Thick LYSO Detectors for PET. IEEE Transactions on Nuclear Science, 60(1), 44-52. doi:10.1109/tns.2013.2240315Bleich, A., Brown, S.-L., Kahn, R., & van Praag, H. M. (1988). The Role of Serotonin in Schizophrenia. Schizophrenia Bulletin, 14(2), 297-315. doi:10.1093/schbul/14.2.29

Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube

[EN] There are drawbacks with using a Positron Emission Tomography (PET) scanner design employing the traditional arrangement of multiple detectors in an array format. Typically PET systems are constructed with many regular gaps between the detector modules in a ring or box configuration, with additional axial gaps between the rings. Although this has been significantly reduced with the use of the compact high granularity SiPM photodetector technology, such a scanner design leads to a decrease in the number of annihilation photons that are detected causing lower scanner sensitivity. Moreover, the ability to precisely determine the line of response (LOR) along which the positron annihilated is diminished closer to the detector edges because the spatial resolution there is degraded due to edge effects. This happens for both monolithic based designs, caused by the truncation of the scintillation light distribution, but also for detector blocks that use crystal arrays with a number of elements that are larger than the number of photosensors and, therefore, make use of the light sharing principle. In this report we present a design for a small-animal PET scanner based on a single monolithic annulus-like scintillator that can be used as a PET insert in high-field Magnetic Resonance systems. We provide real data showing the performance improvement when edge-less modules are used. We also describe the specific proposed design for a rodent scanner that employs facetted outside faces in a single LYSO tube. In a further step, in order to support and prove the proposed edgeless geometry, simulations of that scanner have been performed and lately reconstructed showing the advantages of the design.This project was funded in part by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the Spanish Ministerio de Economia, Industria y Competitividad under Grant TEC2016-79884-C2-1-R and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad. AR is a postdoctoral fellow of the FWO (project 12T7118N). The University of Virginia School of Medicine has provided seed funding for this project.González Martínez, AJ.; Berr, SS.; Cañizares-Ledo, G.; Gonzalez-Montoro, A.; Orero Palomares, A.; Correcher Salvador, C.; Rezaei, A.... (2018). Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube. Frontiers in Medicine. 5:1-8. https://doi.org/10.3389/fmed.2018.00328S185Kuntner, C., & Stout, D. (2014). Quantitative preclinical PET imaging: opportunities and challenges. Frontiers in Physics, 2. doi:10.3389/fphy.2014.00012Judenhofer, M. S., & Cherry, S. R. (2013). Applications for Preclinical PET/MRI. Seminars in Nuclear Medicine, 43(1), 19-29. doi:10.1053/j.semnuclmed.2012.08.004España, S., Marcinkowski, R., Keereman, V., Vandenberghe, S., & Van Holen, R. (2014). DigiPET: sub-millimeter spatial resolution small-animal PET imaging using thin monolithic scintillators. Physics in Medicine and Biology, 59(13), 3405-3420. doi:10.1088/0031-9155/59/13/3405Yang, Y., Bec, J., Zhou, J., Zhang, M., Judenhofer, M. S., Bai, X., … Cherry, S. R. (2016). A Prototype High-Resolution Small-Animal PET Scanner Dedicated to Mouse Brain Imaging. Journal of Nuclear Medicine, 57(7), 1130-1135. doi:10.2967/jnumed.115.165886Yamamoto, S., Watabe, H., Kanai, Y., Watabe, T., Kato, K., & Hatazawa, J. (2013). Development of an ultrahigh resolution Si-PM based PET system for small animals. Physics in Medicine and Biology, 58(21), 7875-7888. doi:10.1088/0031-9155/58/21/7875Yang, Y., James, S. S., Wu, Y., Du, H., Qi, J., Farrell, R., … Cherry, S. R. (2010). Tapered LSO arrays for small animal PET. Physics in Medicine and Biology, 56(1), 139-153. doi:10.1088/0031-9155/56/1/009Godinez, F., Gong, K., Zhou, J., Judenhofer, M. S., Chaudhari, A. J., & Badawi, R. D. (2018). Development of an Ultra High Resolution PET Scanner for Imaging Rodent Paws: PawPET. IEEE Transactions on Radiation and Plasma Medical Sciences, 2(1), 7-16. doi:10.1109/trpms.2017.2765486Gonzalez, A. J., Aguilar, A., Conde, P., Hernandez, L., Moliner, L., Vidal, L. F., … Benlloch, J. M. (2016). A PET Design Based on SiPM and Monolithic LYSO Crystals: Performance Evaluation. IEEE Transactions on Nuclear Science, 63(5), 2471-2477. doi:10.1109/tns.2016.2522179Moses, W. W. (2011). Fundamental limits of spatial resolution in PET. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 648, S236-S240. doi:10.1016/j.nima.2010.11.092Jones, T., & Townsend, D. (2017). History and future technical innovation in positron emission tomography. Journal of Medical Imaging, 4(1), 011013. doi:10.1117/1.jmi.4.1.011013Lewellen, T. K. (2008). Recent developments in PET detector technology. Physics in Medicine and Biology, 53(17), R287-R317. doi:10.1088/0031-9155/53/17/r01Lee, J. S. (2010). Technical Advances in Current PET and Hybrid Imaging Systems. The Open Nuclear Medicine Journal, 2(1), 192-208. doi:10.2174/1876388x01002010192Ren, S., Yang, Y., & Cherry, S. R. (2014). Effects of reflector and crystal surface on the performance of a depth-encoding PET detector with dual-ended readout. Medical Physics, 41(7), 072503. doi:10.1118/1.4881097Benlloch, J. M., González, A. J., Pani, R., Preziosi, E., Jackson, C., Murphy, J., … Schwaiger, M. (2018). The MINDVIEW project: First results. European Psychiatry, 50, 21-27. doi:10.1016/j.eurpsy.2018.01.002Gonzalez-Montoro, A., Benlloch, J. M., Gonzalez, A. J., Aguilar, A., Canizares, G., Conde, P., … Sanchez, F. (2017). Performance Study of a Large Monolithic LYSO PET Detector With Accurate Photon DOI Using Retroreflector Layers. IEEE Transactions on Radiation and Plasma Medical Sciences, 1(3), 229-237. doi:10.1109/trpms.2017.2692819Moliner, L., González, A. J., Soriano, A., Sánchez, F., Correcher, C., Orero, A., … Benlloch, J. M. (2012). Design and evaluation of the MAMMI dedicated breast PET. Medical Physics, 39(9), 5393-5404. doi:10.1118/1.4742850Morrocchi, M., Ambrosi, G., Bisogni, M. G., Bosi, F., Boretto, M., Cerello, P., … Del Guerra, A. (2017). Depth of interaction determination in monolithic scintillator with double side SiPM readout. EJNMMI Physics, 4(1). doi:10.1186/s40658-017-0180-9Xie, S., Zhao, Z., Yang, M., Weng, F., Huang, Q., Xu, J., & Peng, Q. (2017). LOR-PET: a novel PET camera constructed with a monolithic scintillator ring. 2017 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). doi:10.1109/nssmic.2017.8532627Stolin, A. V., Martone, P. F., Jaliparthi, G., & Raylman, R. R. (2017). Preclinical positron emission tomography scanner based on a monolithic annulus of scintillator: initial design study. Journal of Medical Imaging, 4(1), 011007. doi:10.1117/1.jmi.4.1.011007Gonzalez, A. J., Aguilar, A., Conde, P., Gonzalez-Montoro, A., Sanchez, S., Moliner, L., … Benlloch, J. M. (2016). Pilot tests of a PET insert based on monolithic crystals in a 7T MR. 2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop (NSS/MIC/RTSD). doi:10.1109/nssmic.2016.8069496Jan, S., Santin, G., Strul, D., Staelens, S., Assié, K., Autret, D., … Bloomfield, P. M. (2004). GATE: a simulation toolkit for PET and SPECT. Physics in Medicine and Biology, 49(19), 4543-4561. doi:10.1088/0031-9155/49/19/007Strulab, D., Santin, G., Lazaro, D., Breton, V., & Morel, C. (2003). GATE (geant4 application for tomographic emission): a PET/SPECT general-purpose simulation platform. Nuclear Physics B - Proceedings Supplements, 125, 75-79. doi:10.1016/s0920-5632(03)90969-8Pani, R., Gonzalez, A. J., Bettiol, M., Fabbri, A., Cinti, M. N., Preziosi, E., … Majewski, S. (2015). Preliminary evaluation of a monolithic detector module for integrated PET/MRI scanner with high spatial resolution. Journal of Instrumentation, 10(06), C06006-C06006. doi:10.1088/1748-0221/10/06/c06006Iida, H., Kanno, I., Miura, S., Murakami, M., Takahashi, K., & Uemura, K. (1986). A Simulation Study of a Method to Reduce Positron Annihilation Spread Distributions Using a Strong Magnetic Field in Positron Emission Tomography. IEEE Transactions on Nuclear Science, 33(1), 597-600. doi:10.1109/tns.1986.433717

Design and Characterisation of an MRI Compatible Human Brain PET Insert by Means of Simulation and Experimental Studies

Positron emission tomography (PET) is a widely used in-vivo imaging technique to visualise metabolism, allowing for a broad spectrum of applications in oncology, cardiology and neuroscience. At present, an MRI compatible human brain PET scanner for applications in neuroscience is being constructed in the scope of a Helmholtz Validation Fund project. In this thesis, a detector for this novel PET device was designed. The detector concept combined three scintillator layers with a lightguide and digital silicon photomultipliers (dSiPMs). Monte Carlo simulations were used to optimise the dimensions of the scintillator arrays, so that the new scanner design yielded the maximum possible sensitivity. The benefit from the additional depth information, which can be acquired with three scintillator layers, was evaluated and proven to be higher compared to a less expensive two layer geometry. Since a more homogeneous spatial resolution was achieved in the whole field of view, this finding had a high relevance for the envisaged neuroscientific applications. In order to accurately acquire the depth information, new strategies for decoding the flood map during the calibration of a detector module were developed. This required realistic simulation data with ground truth information, so that the simulation toolkit GATE was extended to model the electronic readout of the dSiPMs. To overcome extended simulation times and to provide simulations on a statistically sound basis, the GATE studies were executed on the supercomputer JURECA. The simulated data were matched to measured data from test detectors. This allowed the determination of an optimum thickness of a lightguide between the scintillators and the dSiPMs. Moreover, the number of correctly identified scintillation events was evaluated by means of different event positioning approaches and different clustering methods during the calibration step. The highest amount of correctly identified events in a single detector block was achieved with model-based clustering and Maximum Likelihood positioning (61.5 %). By simulating the whole propagation and detection of scintillation photons including ground truth information, this study provides the opportunity to improve the positioning approaches and to enhance this number in future. The gained insights were further applied to select a surface finish of the scintillators. Measurements with crystal samples of the final detector dimensions showed that rough lateral crystal surfaces yielded the best signal separation in the calibration flood map. The experimental and simulation studies presented in this thesis had a major influence on the final detector design of the novel brain PET. The detailed simulations including the propagation and detection of scintillation photons were in good agreement with measured data, and could be a promising approach for future detector design studies

Development and Performance Evaluation of High Resolution TOF-PET Detectors Suitable for Novel PET Scanners

Tesis por compendio[ES] La Tomografía por Emisión de Positrones (PET) es una de las técnicas más importantes en la medicina de diagnóstico actual y la más representativa en el campo de la Imagen Molecular. Esta modalidad de imagen es capaz de producir información funcional única, que permite la visualización en detalle, cuantificación y conocimiento de una variedad de enfermedades y patologías. Áreas como la oncología, neurología o la cardiología, entre otras, se han beneficiado en gran medida de esta técnica. A pesar de que un elevado número de avances han ocurrido durante el desarrollo del PET, existen otros que son de gran interés para futuras investigaciones. Uno de los principales pilares actualmente en PET, tanto en investigación como en desarrollo, es la obtención de la información del tiempo de vuelo (TOF) de los rayos gamma detectados. Cuando esto ocurre, aumenta la sensibilidad efectiva del PET, mejorando la calidad señal-ruido de las imágenes. Sin embargo, la obtención precisa de la marca temporal de los rayos gamma es un reto que requiere, además de técnicas y métodos específicos, compromisos entre coste y rendimiento. Una de las características que siempre se ve afectada es la resolución espacial. Como discutiremos, la resolución espacial está directamente relacionada con el tipo de centellador y, por lo tanto, con el coste del sistema y su complejidad. En esta tesis, motivada por los conocidos beneficios en imagen clínica de una medida precisa del tiempo y de la posición de los rayos gamma, proponemos configuraciones de detectores TOF- PET novedosos capaces de proveer de ambas características. Sugerimos el uso de lo que se conoce como métodos de "light-sharing", tanto basado en cristales monolíticos como pixelados de tamaño diferente al del fotosensor. Estas propuestas hacen que la resolución espacial sea muy alta. Sin embargo, sus capacidades temporales han sido muy poco abordadas hasta ahora. En esta tesis, a través de varios artículos revisados, pretendemos mostrar los retos encontrados en esta dirección, proponer determinadas configuraciones y, además, indagar en los límites temporales de éstas. Hemos puesto un gran énfasis en estudiar y analizar las distribuciones de la luz centellante, así como su impacto en la determinación temporal. Hasta nuestro conocimiento, este es el primer trabajo en el que se estudia la relación de la determinación temporal y la distribución de luz de centelleo, en particular usando SiPM analógicos y ASICs. Esperamos que esta tesis motive y permita otros muchos trabajos orientados en nuevos diseños, útiles para instrumentación PET, así como referencia para otros trabajos. Esta tesis esta organizada como se describe a continuación. Hay una introducción compuesta por tres capítulos donde se resumen los conocimientos sobre imagen PET, y especialmente aquellos relacionados con la técnica TOF-PET. Algunos trabajos recientes, pero aún no publicados se muestran también, con el objetivo de corroborar ciertas ideas. En la segunda parte se incluyen las cuatro contribuciones que el candidato sugiere para el compendio de artículos.[CA] La Tomografia per Emissió de Positrons (PET) és una de les tècniques més importants en la medicina de diagnòstic actual i la més representativa en el camp de la Imatge Molecular. Esta modalitat d'imatge és capaç de produir informació funcional única, que permet la visualització en detall, quantificació i coneixement d'una varietat de malalties i patologies. Àrees com l'oncologia, neurologia o la cardiologia, entre altres, s'han beneficiat en gran manera d'aquesta tècnica. Tot i que un elevat nombre d'avanços han ocorregut durant el desenvolupament del PET, hi ha altres que són de gran interés per a futures investigacions. Un dels principals pilars actuals en PET, tant en investigació com en desenvolupament, és l'obtenció de la informació del temps de vol (TOF en anglès) dels raigs gamma detectats. Quan açò ocorre, augmenta la sensibilitat efectiva del PET, millorant la qualitat senyal-soroll de les imatges. No obstant això, l'obtenció precisa de la marca temporal dels raigs gamma és un repte que requerix, a més de tècniques i mètodes específics, compromisos entre cost i rendiment. Una de les característiques que sempre es veu afectada és la resolució espacial. Com discutirem, la resolució espacial està directament relacionada amb el tipus de centellador, i per tant, amb el cost del sistema i la seua complexitat. En aquesta tesi, motivada pels coneguts beneficis en imatge clínica d'una mesura precisa del temps i de la posició dels raigs gamma, proposem nouves configuracions de detectors TOF-PET capaços de proveir d'ambduess característiques. Suggerim l'ús del que es coneix com a mètodes de "light-sharing", tant basat en cristalls monolítics com pixelats de diferent tamany del fotosensor. Aquestes propostes fan que la resolució espacial siga molt alta. No obstant això, les seues capacitats temporals han sigut molt poc abordades fins ara. En aquesta tesi, a través de diversos articles revisats, pretenem mostrar els reptes trobats en aquesta direcció, proposar determinades configuracions i, a més, indagar en els límits temporals d'aquestes. Hem posat un gran èmfasi a estudiar i analitzar les distribucions de la llum centellejant, així com el seu impacte en la determinació temporal. Fins al nostre coneixement, aquest és el primer treball en què s'estudia la relació de la determinació temporal i la distribució de llum de centelleig, en particular utilitzant SiPM analògics i ASICs. Esperem que aquesta tesi motive i permeta molts altres treballs orientats en nous dissenys, útils per a instrumentació PET, així com referència per a altres treballs. Aquesta tesi esta organitzada com es descriu a continuació. Hi ha una introducció composta per tres capítols on es resumeixen els coneixements sobre imatge PET i, especialmente, aquells relacionats amb la tècnica TOF-PET. Alguns treballs recents, però encara no publicats es mostren també, amb l'objectiu de corroborar certes idees. La segona part de la tesi conté els quatre articles revisats que el candidat suggereix.[EN] Positron Emission Tomography (PET) is one of the greatest tools of modern diagnostic medicine and the most representative in the field of molecular imaging. This imaging modality, is capable of providing a unique type of functional information which permits a deep visualization, quantification and understanding of a variety of diseases and pathologies. Areas like oncology, neurology, or cardiology, among others, have been well benefited by this technique. Although numerous important advances have already been achieved in PET, some other individual aspects still seem to have a great potential for further investigation. One of the main trends in modern PET research and development, is based in the extrapolation of the Time- Of-Flight (TOF) information from the gamma-ray detectors. In such case, an increase in the effective sensitivity of PET is accomplished, resulting in an improved image signal-to-noise ratio. However, the direction towards a precise decoding of the photons time arrival is a challenging task that requires, besides specific approaches and techniques, tradeoffs between cost and performance. A performance characteristic very habitually compromised in TOF-PET detector configurations is the spatial resolution. As it will be discussed, this feature is directly related to the scintillation materials and types, and consequently, with system cost and complexity. In this thesis, motivated by the well-known benefits in clinical imaging of a precise time and spatial resolution, we propose novel TOF-PET detector configurations capable of inferring both characteristics. Our suggestions are based in light sharing approaches, either using monolithic detectors or crystal arrays with different pixel-to-photosensor sizes. These approaches, make it possible to reach a precise impact position determination. However, their TOF capabilities have not yet been explored in depth. In the present thesis, through a series of peer-reviewed publications we attempt to demonstrate the challenges encountered in these kinds of configurations, propose specific approaches improving their performance and eventually reveal their limits in terms of timing. High emphasis is given in analyzing and studying the scintillation light distributions and their impact to the timing determination. To the best of our knowledge, this is one of the first works in which such detailed study of the relation between light distribution and timing capabilities is carried out, especially when using analog SiPMs and ASICs. Hopefully, this thesis will motivate and enable many other novel design concepts, useful in PET instrumentation as well as it will serve as a helpful reference for similar attempts. The present PhD thesis is organized as follows. There is an introduction part composed by three detailed sections. We attempt to summarize here some of the knowledge related to PET imaging and especially with the technique of TOF-PET. Some very recent but still unpublished results are also presented and included in this part, aiming to support statements and theories. The second part of this thesis lists the four peer-reviewed papers that the candidate is including.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the Spanish Ministerio de Economía, Industria y Competitividad under Grants No. FIS2014-62341-EXP and TEC2016-79884-C2-1-R. Efthymios Lamprou has also been supported by Generalitat Valenciana under grant agreement GRISOLIAP-2018-026.Lamprou, E. (2021). Development and Performance Evaluation of High Resolution TOF-PET Detectors Suitable for Novel PET Scanners [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/162991TESISCompendi

Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems

Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positronemitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges.This work was supported in part by National Institutes of Health grants R01-CA042593, U01-CA148131, R01CA160253, R01CA169072, and R01CA164371; by Human Frontier Science Program grant RGP0004/2013; and by the Innovative Medicines Initiative under grant agreement 115337, which comprises financial contributions from the European Union’s Seventh Framework Program (FP7/2007–2013

Optimized PET module for both pixelated and monolithic scintillator crystals

[eng] Time-of-Flight Positron Emission Tomography (TOF-PET) scanners demand fast and efficient photo-sensors and scintillators coupled to fast readout electronics. Nowadays, there are two main configurations regarding the scintillator crystal geometry: the segmented or pixelated and the monolithic approach. Depending on the cost, spatial resolution and time requirements of the PET module, one can choose between one or another. The pixelated crystal is the most extensive configuration on TOF-PET scanners as the coincidence time resolution is better compared to the monolithic. On the contrary, monolithic scintillator crystals for Time-of-Flight Positron Emission Tomography (ToF-PET) are increasing in popularity this last years due to their performance potential and price in front of the commonly used segmented crystals. On one hand, monolithic blocks allows to determine 3D information of the gamma-ray interaction inside the crystal, which enables the possibility to correct the parallax error (radial astigmatism) at off-center positions within a PET scanner, resulting in an improvement of the spatial resolution of the device. On the other hand, due to the simplicity during the crystal manufacturing process as well as for the detector design, the price is reduced compared to a regular pixelated detector. The thesis starts with the use of HRFlexToT, an ASIC developed in this group, as the readout electronics for measurements with single pixelated crystals coupled to different SiPMs. These measurements show an energy linearity error of 3% and an energy resolution below 10% of the 511 keV photopeak. Single Photon Time Resolution (SPTR) measurements performed using an FBK SiPM NUV-HD (4 mm x 4 mm pixel size) and a Hamamatsu SiPM S13360-3050CS gave a 141 ps and 167 ps FWHM respectively. Coincidence Time Resolution (CTR) measurements with small cross-section pixelated crystals (LFS crystal, 3 m x 3 mm x 20 mm ) coupled to a single Hamamatsu SiPM S13360-3050CS provides a CTR of 180 ps FWHM. Shorter crystals (LSO:Ce Ca 0.4%) coupled to a Hamamatsu S13360-3050CS SiPM or FBK-NUVHD yields a CTR of 117 ps and 119 ps respectively. Then, the results with different monolithic crystals and SiPM sensors using HRFlexToT ASIC will be presented. A Lutetium Fine Silicate (LFS) of 25 mm x 25 mm x 20 mm, a small LSO:Ce Ca 0.2% of 8 mm x 8 mm x 5 mm and a Lutetium-Yttrium Oxyorthosilicate (LYSO) of 25 mm x 25 mm x 10 mm has been experimentally tested. After subtracting the TDC contribution (82 ps FWHM), a coincidence time resolution of 244 ps FWHM for the small LFS crystal and 333 ps FWHM for the largest LFS one is reported. Additionally, a novel time calibration correction method for CTR improvement that involves a pico-second pulsed laser will be detailed. In the last part of the dissertation, a new developed simulation framework that will enable the cross-optimization of the whole PET system will be explained. It takes into consideration the photon physics interaction in the scintillator crystal, the sensor response (sensor size, pixel pitch, dead area, capacitance) and the readout electronics behavior (input impedance, noise, bandwidth, summation). This framework has allowed us to study a new promising approach that will help reducing the CTR parameter by segmenting a large area SiPM into "m" smaller SiPMs and then summing them to recover all the signal spread along these smaller sensors. A 15% improvement on time resolution is expected by segmenting a 4 mm x 4 mm single sensor into 9 sensors of 1.3 mm x 1.3 mm with respect to the case where no segmentation is applied.[cat] Aquesta tesi tenia com a objectiu la fabricació i avaluació d'un prototip per a detecció de fotons gamma en aplicació per imatge mèdica, més concretament en Tomografia per Emissió de Positrons amb mesura de temps de vol (TOF-PET). L'avaluació del mòdul va començar fent una caracterització completa del chip (ASIC) anomenat HRFlexToT, una versió nova i millorada de l'antic chip FlexToT, desenvolupat i fabricat pel grup de la Unitat Tecnològica del ICC de la Universitat de Barcelona. Aquesta avaluació inicial del chip compren des de la comprovació de les funcionalitats bàsiques fins a la generació d'un test automàtic per generar les gràfiques de linealitat corresponents durant el test elèctric. Un cop donat per bo, es va muntar en una placa demostrada, també ideada per l'equip d'enginyers del grup, i ja quedava llesta per realitzar les mesures pertinents. Tot seguit, es varen realitzar les mesures òptiques, que incloïa mesures de Singe Photon Time Resolution (SPTR) i de Coincidence Time Resolution (CTR). Aquest valors actuen com a figures de mèrit a l'hora de comparar les prestacions amb d'altres ASICs competidors del HRFlexToT. Es van obtenir valors de 60 ps de resposta pel que respecta al SPTR i de 115 ps de CTR en cristalls segmentats, una millora entorn del 20-30% respecte a la versió predecessora del chip. Aquests valors mostren ser el límit de l'estat de l'art actual i amb aquesta idea es van començar a fer altres mesures, en aquest cas amb cristall monolítics, blocs grans llegits per diversos fotosensors de les empreses Hamamatsu i FBK. Per altra banda, es va provar el funcionament del ASIC en configuració anomenada monolítica, on el cristall centellejador s'utilitza en blocs grans en coptes d’emprar cristalls segmentats, això abarateix el cost total del detector. Aquesta configuració degrada les propietats de CTR, un paràmetre crític a l'hora de tenir un producte bo i eficient. S’han obtingut mesures de 250 ps de CTR amb aquesta configuració, d’on es pot dir que l’HRFlexToT es trobar a l’estat de l’art de la tecnologia electrònica dedicada a TOF-PET amb cristalls segmentats i monolítics. Finalment, es va desenvolupar una nova eina simulació que consisteix en un sistema híbrid entre un simulador físic i un electrònic per tal de tenir una idea del comportament complet del mòdul detector. Una solució que ningú havia provat fins ara o que no es pot trobar en la literatura

Design and implementation of PET detectors based on monolithic crystals and SiPMs

Esta tesis doctoral se centra tanto en el diseño como en la validación experimental de detectores de rayos gamma para escáneres de tomografía por emisión de positrones (PET, del inglés Positron Emission Tomography). El objetivo principal de esta tesis es el diseño de innovadores bloques detectores PET de alto rendimiento. La técnica PET constituye una de las principales herramientas diagnósticas en medicina nuclear, que es una especialidad médica que utiliza sustancias radiactivas con fines diagnósticos y terapéuticos. Esta técnica de imagen médica permite visualizar procesos fisiológicos y bioquímicos del cuerpo humano in vivo, mediante la administración del elemento radiotrazador. Los radiotrazadores son compuestos químicos, similares a las sustancias naturales del cuerpo, en las que uno o más átomos son sustituidos por radionúclidos emisores de fotones, para su uso en gamma cámaras y SPECT, o de positrones (la antipartícula del electrón) para PET. En el primer capítulo de la tesis se introducen las principales técnicas de imagen médicas utilizadas en la actualidad, incluyendo las técnicas de imagen funcional, de imagen anatómica y su fusión para dar lugar a imágenes multimodales. En el segundo capítulo, dado que la técnica PET es el foco de estudio central de la tesis, se describe en detalle su historia mostrando los avances de los últimos 60 años, hasta establecerse en la actualidad como una herramienta diagnóstica imprescindible en medicina. En este capítulo se describen también los principios físicos de la técnica, los algoritmos de reconstrucción y las correcciones de imagen que se emplean. Así mismo el capítulo describe el papel fundamental del tiempo de vuelo de los fotones producidos en la aniquilación del positrón y el electrón, y de la coordenada de profundidad de interacción (DOI, del inglés Depth of Interaction). A continuación, en el tercer capítulo, se describen con detalle los materiales y métodos empleados en PET, haciendo especial énfasis en aquellos utilizados para el desarrollo de esta tesis. En la actualidad, la mayoría de sistemas PET comerciales están constituidos por bloques detectores basados en cristales centelleadores pixelados (matrices de pequeños cristales). Dichos cristales permiten estimar las coordenadas (x, y) del impacto del fotón de manera sencilla, sin embargo, la obtención de la coordenada de profundidad de interacción (z), imprescindible para obtener una buena resolución espacial sobretodo en los bordes del campo de visión del escáner, resulta una tarea difícil que requiere el uso de materiales adicionales y por tanto incrementan el precio del escáner. Una alternativa a la configuración anterior, es el uso de cristales monolíticos o continuos los cuales están constituidos por una única pieza de material centelleador que permite “observar” la distribución de fotones ópticos generada. Esta información es utilizada para obtener con precisión las coordenadas 3D de impacto del fotón (x, y, z) en el cristal sin necesidad de otros materiales. Por este motivo, en esta tesis doctoral se ha llevado a cabo el diseño de detectores basados en estos cristales monolíticos acoplados a fotosensores de estado sólido compatibles con equipos de resonancia magnética. En este capítulo se muestran los resultados obtenidos en la caracterización de diferentes tipos de cristales, geometrías y tratamientos aplicados a la superficie de los bloques detectores. Finalmente se presenta una breve descripción de los equipos que han motivado los estudios realizados en la tesis. Dado que el formato de esta tesis esta basado en un compendio de los artículos más relevantes publicados durante el transcurso de los estudios de doctorado, el cuarto capítulo incluye una copia de los artículos publicados más relevantes tal y como se muestran en las revistas científicas. Se presentan un total de 6 artículos que recogen los principales resultados obtenidos durante los estudios de doctorado. Dada la calidad de los resultados globales obtenidos, dos de los bloques detectores diseñados constituyen la base de dos sistemas PET dedicados al estudio del cerebro humano, el inserto MINDView (proyecto europeo FP7) y el escáner CareMiBrain (proyecto europeo Horizont 2020). El equipo MINDView, que es un inserto compatible con todas las resonancias magnéticas del mundo, ha sido instalado en el hospital de la Universidad Técnica de Múnich y actualmente está en la fase previa a comenzar un estudio con pacientes. En la tesis se recogen las pruebas de validación realizadas tanto a nivel del bloque detector como del equipo final. Respecto al equipo CareMiBrain, que es un escáner PET dedicado al estudio del Alzheimer y de otras enfermedades de deterioro cognitivo, ha sido instalado en Madrid y los primeros pacientes ya han sido escaneados satisfactoriamente. En la tesis se recoge el diseño y los resultados de caracterización del bloque detector. Además del diseño y caracterización de dichos bloques detectores, se muestran también los resultados y conclusiones obtenidas en otros estudios de investigación, tales como la caracterización de una gran variedad de geometrías de detectores, la optimización de la extracción de la luz en cristales BGO (fueron pioneros en los equipos PET pero se sustituyeron por los nuevos cristales que son más rápidos), tanto en forma pixelada como en bloques monolíticos, y un enfoque de detector híbrido que utiliza capas monolíticas y pixeladas en un mismo bloque detector. Se ha prestado especial atención a la caracterización y determinación de la DOI dentro de los bloques monolíticos, reduciendo el error de paralaje en la imagen final reconstruida. El quinto capítulo contiene un resumen y conclusiones de los resultados de esta tesis. El sexto y séptimo capítulo, contienen un resumen en castellano y valenciano respectivamente, de los objetivos, motivación, materiales, métodos, resultados y conclusiones de la tesis doctoral. Finalmente, el Apéndice A muestra una lista completa de los artículos científicos publicados durante la tesis (incluyendo los seleccionados para el compendio).This doctoral thesis focuses on both the design and experimental validation of gamma-ray detectors suitable for Positron Emission Tomography (PET) scanners. The main objective is the design of high efficiency PET detector blocks. The PET technique constitutes one of the main diagnostic tools in Nuclear Medicine, which is a medical specialty that uses radioactive substances for diagnostic and therapeutic purposes. This Medical Imaging technique allows one to visualize physiological and biochemical processes of the human body in vivo, by means of the administration of a radiotracer element. Radiotracers are chemical compounds, similar to the body's natural substances, in which one or more atoms are replaced by radionuclides that emit photons, for use in gamma and SPECT cameras, or positrons (the antiparticle of the electron) for PET. The first chapter of the thesis introduces the main Medical Imaging techniques that are currently used, including functional and anatomical imaging as well as their possible merging generating multimodal images. In the second chapter, since PET imaging is the focus of this thesis, an extensive description of this technique is outlined. The chapter begins with a brief history of PET, showing the advances over the last 60 years until being established as an essential diagnostic tool in medicine. This chapter also describes the physical principles of PET, the reconstruction algorithms and the applied image corrections techniques. In addition to the basic concepts, the role of Time of Flight (TOF) and DOI in PET are described in this chapter. The third chapter describes in detail the materials and methods used in PET, making special emphasis on those used for the development of this work. Currently, most commercial PET systems consist of detector blocks based on pixelated scintillation crystals (matrices of small crystals). These crystals allow one for an easy estimation of the planar impact coordinates of the gamma-ray within the crystal (x, y). However, estimating the depth of interaction coordinate (z), which is essential to obtain a good spatial resolution especially at the edges of the field of view of the scanner, is a difficult task that requires the use of extra materials and therefore increases the price of the scanner. An alternative to that configuration is the use of monolithic crystals, which are constituted by a single piece of scintillating material that permits to characterize the complete, flashing light distribution. This information is used to obtain the 3D impact coordinates of the photon (x, y, z) within the crystal with high resolution and without the need for extra materials. For this reason, this doctoral thesis focusses on the design of PET detector blocks based on monolithic crystals coupled to solid state photosensors. These components are compatible with magnetic fields and therefore, suitable for their simultaneous use with Magnetic Resonance Imaging (MRI) systems. This chapter summarizes the results obtained in the characterization of different types of crystals, geometries and treatments applied to the crystal surface of the detector blocks. Finally, a brief description of the PET systems that have motivated the studies carried out in the thesis is presented. Since this thesis is based on a compendium of the most relevant articles published during the course of the PhD studies, Chapter 4 presents a copy of those research articles, as exactly shown in the different per-reviewed journals, including a brief introduction highlighting their main results. A total of 6 articles are presented, which contain the main results obtained during the doctoral studies. Given the quality of the overall obtained results, two of the designed detector blocks have been selected as the basis of two PET systems dedicated to the study of the human brain namely, i) the MINDView insert (European Union FP7 project) and, ii) the CareMiBrain stand-alone scanner (European Union project Horizon 2020). The MINDView system, which is a PET insert compatible with MRI scanners, has been installed at Technical University of Munich and is currently starting scanning patients with depression and schizophrenia. The thesis includes the validation tests carried out at the level of the detector block and of the final equipment. The CareMiBrain system, which is a PET scanner dedicated to the study of the Alzheimer disease and other causes of cognitive decline, has been installed in a hospital in Madrid and the first patients have already been successfully scanned. The thesis contains the design and results of characterization of the CareMiBrain detector block. In addition to the design and characterization of those detector blocks, other research studies have been carried out during the course of this thesis, such as the characterization of a large variety of photosensor geometries, the optimization of light extraction in BGO crystals, both in pixelated and monolithic geometries, and a hybrid detector approach that uses monolithic and pixellated layers in the same detector block. Special emphasis has been given to the characterization and estimation of the DOI coordinate within monolithic blocks, reducing the parallax error in the reconstructed final image. Chapter 5 contains a summary of the results and conclusions of this thesis. Chapters 6 and 7 summarize, in Spanish and Valencian, respectively, the objectives, motivation, materials, methods, results and conclusions of this doctoral thesis. A complete list of all the per-reviewed articles (including those selected for this compendium) and the conference proceedings published during the development of this thesis can be found in Appendix A

NEMA NU4-2008 Performance Evaluation of Albira: A Two-Ring Small-Animal PET System Using Continuous LYSO Crystals

Goals: This paper presents the performance review based on a dual-ring Positron Emission Tomography (PET) scanner being a part of Bruker Albira: a multi-modal small-animal imaging platform. Each ring of Albira PET contains eight detectors arranged as octagon, and each detector is built using a single continuous lutetium-yttrium oxyorthosilicate crystal and multi-anode photo multiplier tube. In two-ring configuration, the scanner covers 94.4 mm in axial- and 80´80 mm in trans-axial direction, which is sufficient to acquire images of small animals (e.g. mice) without the need of moving the animal bed during the scan. Methods: All measurements and majority of data processing were performed according to the NEMA NU4-2008 standard with one exception. Due to the scanner geometry, the spatial resolution test was reconstructed using iterative algorithm instead of the analytical one. The main performance characteristics were compared with those of the other PET sub-systems of tri-modal smallanimal scanners. Results: The measured spatial resolution at the centre of the axial field of view in radial, tangential and axial directions was 1.72, 1.70 and 2.45 mm, respectively. The scatter fraction for the mouse-like phantom was 9.8% and for the rat-like phantom, 21.8%. The maximum absolute sensitivity was 5.30%. Finally, the recovery co-efficients for 5, 4, 3, 2, 1 mm diameter rods in image quality phantom were: 0.90, 0.77, 0.66, 0.30 and 0.05, respectively. Conclusion: The Bruker Albira is a versatile small-animal multi-modal device that can be used for variety of studies. Overall the PET sub-system provides a good spatial resolution coupled with better-than average sensitivity and the ability to produce good quality animal images when administering low activities

Improving the Timing Resolution of Positron Emission Tomography Detectors Using Boosted Learning -- A Residual Physics Approach

Artificial intelligence (AI) is entering medical imaging, mainly enhancing image reconstruction. Nevertheless, improvements throughout the entire processing, from signal detection to computation, potentially offer significant benefits. This work presents a novel and versatile approach to detector optimization using machine learning (ML) and residual physics. We apply the concept to positron emission tomography (PET), intending to improve the coincidence time resolution (CTR). PET visualizes metabolic processes in the body by detecting photons with scintillation detectors. Improved CTR performance offers the advantage of reducing radioactive dose exposure for patients. Modern PET detectors with sophisticated concepts and read-out topologies represent complex physical and electronic systems requiring dedicated calibration techniques. Traditional methods primarily depend on analytical formulations successfully describing the main detector characteristics. However, when accounting for higher-order effects, additional complexities arise matching theoretical models to experimental reality. Our work addresses this challenge by combining traditional calibration with AI and residual physics, presenting a highly promising approach. We present a residual physics-based strategy using gradient tree boosting and physics-guided data generation. The explainable AI framework SHapley Additive exPlanations (SHAP) was used to identify known physical effects with learned patterns. In addition, the models were tested against basic physical laws. We were able to improve the CTR significantly (more than 20%) for clinically relevant detectors of 19 mm height, reaching CTRs of 185 ps (450-550 keV)