1,166 results on '"positron emission tomography (PET)"'
Search Results
2. Deep learning-based techniques for estimating high-quality full-dose positron emission tomography images from low-dose scans: a systematic review.
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Seyyedi, Negisa, Ghafari, Ali, Seyyedi, Navisa, and Sheikhzadeh, Peyman
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MACHINE learning ,POSITRON emission tomography ,GENERATIVE adversarial networks ,DEEP learning ,ESTIMATION theory - Abstract
This systematic review aimed to evaluate the potential of deep learning algorithms for converting low-dose Positron Emission Tomography (PET) images to full-dose PET images in different body regions. A total of 55 articles published between 2017 and 2023 by searching PubMed, Web of Science, Scopus and IEEE databases were included in this review, which utilized various deep learning models, such as generative adversarial networks and UNET, to synthesize high-quality PET images. The studies involved different datasets, image preprocessing techniques, input data types, and loss functions. The evaluation of the generated PET images was conducted using both quantitative and qualitative methods, including physician evaluations and various denoising techniques. The findings of this review suggest that deep learning algorithms have promising potential in generating high-quality PET images from low-dose PET images, which can be useful in clinical practice. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Physicochemical characterization and potential cancer therapy applications of hydrogel beads loaded with doxorubicin and GaOOH nanoparticles.
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Żmuda, Aleksandra, Kamińska, Weronika, Bartel, Marta, Głowacka, Karolina, Chotkowski, Maciej, Medyńska, Katarzyna, Wiktorska, Katarzyna, and Mazur, Maciej
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DOXORUBICIN , *POSITRON emission tomography , *CANCER treatment , *NANOPARTICLES , *POLYETHYLENE terephthalate , *ANTINEOPLASTIC agents , *POLYMERS - Abstract
A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 μm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Chelator boosted tumor-retention and pharmacokinetic properties: development of 64Cu labeled radiopharmaceuticals targeting neurotensin receptor.
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Zhang, Tao, Ma, Xinrui, Xu, Muyun, Cai, Jinghua, Cai, Jianhua, Cao, Yanguang, Zhang, Zhihao, Ji, Xin, He, Jian, Cabrera, German Oscar Fonseca, Wu, Xuedan, Zhao, Weiling, Wu, Zhanhong, Xie, Jin, and Li, Zibo
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POSITRON emission tomography , *LEAD compounds , *LIVER tumors , *LUNG cancer , *NEUROTENSIN - Abstract
Purpose: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. Method: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. Results: For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24 h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48 h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48 h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. Conclusions: Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Two-step optimization for accelerating deep image prior-based PET image reconstruction.
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Hashimoto, Fumio, Onishi, Yuya, Ote, Kibo, Tashima, Hideaki, and Yamaya, Taiga
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Deep learning, particularly convolutional neural networks (CNNs), has advanced positron emission tomography (PET) image reconstruction. However, it requires extensive, high-quality training datasets. Unsupervised learning methods, such as deep image prior (DIP), have shown promise for PET image reconstruction. Although DIP-based PET image reconstruction methods demonstrate superior performance, they involve highly time-consuming calculations. This study proposed a two-step optimization method to accelerate end-to-end DIP-based PET image reconstruction and improve PET image quality. The proposed two-step method comprised a pre-training step using conditional DIP denoising, followed by an end-to-end reconstruction step with fine-tuning. Evaluations using Monte Carlo simulation data demonstrated that the proposed two-step method significantly reduced the computation time and improved the image quality, thereby rendering it a practical and efficient approach for end-to-end DIP-based PET image reconstruction. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Design and proof of concept of a double-panel TOF-PET system.
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Gonzalez-Montoro, Andrea, Pavón, Noriel, Barberá, Julio, Cuarella, Neus, González, Antonio J., Jiménez-Serrano, Santiago, Lucero, Alejandro, Moliner, Laura, Sánchez, David, Vidal, Koldo, and Benlloch, José M.
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POSITRON emission tomography , *SURFACE preparation , *SPATIAL resolution , *PROOF of concept , *SCINTILLATORS , *IMAGING phantoms - Abstract
Objective: Positron Emission Tomography (PET) is a well-known imaging technology for the diagnosis, treatment, and monitoring of several diseases. Most PET scanners use a Ring-Shaped Detector Configuration (RSDC), which helps obtain homogeneous image quality but are restricted to an invariable Field-of-View (FOV), scarce spatial resolution, and low sensitivity. Alternatively, few PET systems use Open Detector Configurations (ODC) to permit an accessible FOV adaptable to different target sizes, thus optimizing sensitivity. Yet, to compensate the lack of angular coverage in ODC-PET, developing a detector with high-timing performance is mandatory to enable Time-of-Flight (TOF) techniques during reconstruction. The main goal of this work is to provide a proof of concept PET scanner appropriate for constructing the new generation of ODC-PET suitable for biopsy guidance and clinical intervention during acquisition. The designed detector has to be compact and robust, and its requirements in terms of performance are spatial and time resolutions < 2 mm and < 200 ps, respectively. Methods: The present work includes a simulation study of an ODC-PET based on 2-panels with variable distance. The image quality (IQ) and Derenzo phantoms have been simulated and evaluated. The phantom simulations have also been performed using a ring-shaped PET for comparison purposes of the ODC approach with conventional systems. Then, an experimental evaluation of a prototype detector that has been designed following the simulation results is presented. This study focused on tuning the ASIC parameters and evaluating the scintillator surface treatment (ESR and TiO2), and configuration that yields the best Coincidence Time Resolution (CTR). Moreover, the scalability of the prototype to a module of 64 × 64mm2 and its preliminary evaluation regarding pixel identification are provided. Results: The simulation results reported sensitivity (%) values at the center of the FOV of 1.96, 1.63, and 1.18 for panel distances of 200, 250, and 300 mm, respectively. The IQ reconstructed image reported good uniformity (87%) and optimal CRC values, and the Derenzo phantom reconstruction suggests a system resolution of 1.6–2 mm. The experimental results demonstrate that using TiO2 coating yielded better detector performance than ESR. Acquired data was filtered by applying an energy window of ± 30% at the photopeak level. After filtering, best CTR of 230 ± 2 ps was achieved for an 8 × 8 LYSO pixel block with 2 × 2 × 12mm3 each. The detector performance remained constant after scaling-up the prototype to a module of 64 × 64mm2, and the flood map demonstrates the module's capabilities to distinguish the small pixels; thus, a spatial resolution < 2 mm (pixel size) is achieved. Conclusions: The simulated results of this biplanar scanner show high performance in terms of image quality and sensitivity. These results are comparable to state-of-the-art PET technology and, demonstrate that including TOF information minimizes the image artifacts due to the lack of angular projections. The experimental results concluded that using TiO2 coating provide the best performance. The results suggest that this scanner may be suitable for organ study, breast, prostate, or cardiac applications, with good uniformity and CRC. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Preparation and Preclinical Evaluation of 18 F-Labeled Olutasidenib Derivatives for Non-Invasive Detection of Mutated Isocitrate Dehydrogenase 1 (mIDH1).
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Cologni, Roberta, Holschbach, Marcus, Schneider, Daniela, Bier, Dirk, Schulze, Annette, Stegmayr, Carina, Endepols, Heike, Ermert, Johannes, Neumaier, Felix, and Neumaier, Bernd
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ISOCITRATE dehydrogenase , *GLIOMAS , *LONGITUDINAL method , *BIOMARKERS , *PERFUSION - Abstract
Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that could enable non-invasive assessment of the IDH status. In the present work, we developed efficient protocols for the preparation of four 18F-labeled derivatives of the mIDH1-selective inhibitor olutasidenib. All four probes were characterized by cellular uptake studies with U87 glioma cells harboring a heterozygous IDH1 mutation (U87-mIDH) and the corresponding wildtype cells (U87-WT). In addition, the most promising probe was evaluated by PET imaging in healthy mice and mice bearing subcutaneous U87-mIDH and U87-WT tumors. Although all four probes inhibited mIDH1 with variable potencies, only one of them ([18F]mIDH-138) showed significantly higher in vitro uptake into U87-mIDH compared to U87-WT cells. In addition, PET imaging with [18F]mIDH-138 in mice demonstrated good in vivo stability and low non-specific uptake of the probe, but also revealed significantly higher uptake into U87-WT compared to U87-mIDH tumors. Finally, application of a two-tissue compartment model (2TCM) to the PET data indicated that preferential tracer uptake into U87-WT tumors results from higher specific binding rather than from differences in tracer perfusion. In conclusion, these results corroborate recent findings that mIDH1-selective inhibition may not directly correlate with mIDH1-selective target engagement and indicate that in vivo engagement of wildtype and mutated IDH1 may be governed by factors that are not faithfully reproduced by in vitro assays, both of which could complicate development of PET probes. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Automatic reorientation to generate short-axis myocardial PET images.
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Yang, Yuling, Wang, Fanghu, Han, Xu, Xu, Hui, Zhang, Yangmei, Xu, Weiping, Wang, Shuxia, and Lu, Lijun
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IMAGE recognition (Computer vision) , *POSITRON emission tomography , *IMAGE analysis , *PEARSON correlation (Statistics) , *RANK correlation (Statistics) - Abstract
Background: Accurately redirecting reconstructed Positron emission tomography (PET) images into short-axis (SA) images shows great significance for subsequent clinical diagnosis. We developed a system for automatic redirection and quantitative analysis of myocardial PET images. Methods: A total of 128 patients were enrolled for 18 F-FDG PET/CT myocardial metabolic images (MMIs), including 3 image classifications: without defects, with defects, and excess uptake. The automatic reorientation system includes five modules: regional division, myocardial segmentation, ellipsoid fitting, image rotation and quantitative analysis. First, the left ventricular geometry-based canny edge detection (LVG-CED) was developed and compared with the other 5 common region segmentation algorithms, the optimized partitioning was determined based on partition success rate. Then, 9 myocardial segmentation methods and 4 ellipsoid fitting methods were combined to derive 36 cross combinations for diagnostic performance in terms of Pearson correlation coefficient (PCC), Kendall correlation coefficient (KCC), Spearman correlation coefficient (SCC), and determination coefficient. Finally, the deflection angles were computed by ellipsoid fitting and the SA images were derived by affine transformation. Furthermore, the polar maps were used for quantitative analysis of SA images, and the redirection effects of 3 different image classifications were analyzed using correlation coefficients. Results: On the dataset, LVG-CED outperformed other methods in the regional division module with a 100% success rate. In 36 cross combinations, PSO-FCM and LLS-SVD performed the best in terms of correlation coefficient. The linear results indicate that our algorithm (LVG-CED, PSO-FCM, and LLS-SVD) has good consistency with the reference manual method. In quantitative analysis, the similarities between our method and the reference manual method were higher than 96% at 17 segments. Moreover, our method demonstrated excellent performance in all 3 image classifications. Conclusion: Our algorithm system could realize accurate automatic reorientation and quantitative analysis of PET MMIs, which is also effective for images suffering from interference. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Prostate-Specific Membrane Antigen Expression in Patients with Primary Prostate Cancer: Diagnostic and Prognostic Value in Positron Emission Tomography-Prostate-Specific Membrane Antigen.
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Tayara, Omar, Poletajew, Sławomir, Malewski, Wojciech, Kunikowska, Jolanta, Pełka, Kacper, Kryst, Piotr, and Nyk, Łukasz
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PROSTATE-specific membrane antigen , *POSITRON emission tomography , *MAGNETIC resonance imaging , *CANCER diagnosis , *PROSTATE cancer patients , *PROSTATE cancer - Abstract
Prostate cancer represents a significant public health challenge, with its management requiring precise diagnostic and prognostic tools. Prostate-specific membrane antigen (PSMA), a cell surface enzyme overexpressed in prostate cancer cells, has emerged as a pivotal biomarker. PSMA's ability to increase the sensitivity of PET imaging has revolutionized its application in the clinical management of prostate cancer. The advancements in PET-PSMA imaging technologies and methodologies, including the development of PSMA-targeted radiotracers and optimized imaging protocols, led to diagnostic accuracy and clinical utility across different stages of prostate cancer. This highlights its superiority in staging and its comparative effectiveness against conventional imaging modalities. This paper analyzes the impact of PET-PSMA on prostate cancer management, discussing the existing challenges and suggesting future research directions. The integration of recent studies and reviews underscores the evolving understanding of PET-PSMA imaging, marking its significant but still expanding role in clinical practice. This comprehensive review serves as a crucial resource for clinicians and researchers involved in the multifaceted domains of prostate cancer diagnosis, treatment, and management. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Prognostic Value of Left Ventricular 18F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.
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Clerc, Olivier F., Datar, Yesh, Cuddy, Sarah A.M., Bianchi, Giada, Taylor, Alexandra, Benz, Dominik C., Robertson, Matthew, Kijewski, Marie Foley, Jerosch-Herold, Michael, Kwong, Raymond Y., Ruberg, Frederick L., Liao, Ronglih, Di Carli, Marcelo F., Falk, Rodney H., and Dorbala, Sharmila
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Positron emission tomography/computed tomography (PET/CT) with
18 F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known. The authors' aim was to evaluate the prognostic value of LV amyloid burden quantified by18 F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes. A total of 81 participants with newly diagnosed AL amyloidosis underwent18 F-florbetapir PET/CT imaging. Amyloid burden was quantified using18 F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months. Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage. In this first study to link cardiac18 F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE. [Display omitted] [ABSTRACT FROM AUTHOR]- Published
- 2024
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11. Development and first-in-human study of PSMA-targeted PET tracers with improved pharmacokinetic properties.
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Hou, Haodong, Pan, Yuan, Wang, Yanzhi, Ma, Yuze, Niu, Xiaobing, Sun, Suan, Hou, Guihua, Tao, Weijing, and Gao, Feng
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POSITRON emission tomography , *PROSTATE-specific membrane antigen , *DECANOIC acid , *RADIOCHEMICAL purification , *COMPUTED tomography - Abstract
Purpose: A series of new 68Ga-labeled tracers based on [68Ga]Ga-PSMA-617 were developed to augment the tumor-to-kidney ratio and reduce the activity accumulation in bladder, ultimately minimize radiation toxicity to the urinary system. Methods: We introduced quinoline group, phenylalanine and decanoic acid into different tracers to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Their binding affinity onto LNCaP cells was determined through in vitro saturation assays and competition binding assays. In vivo metabolic study, PET imaging and biodistribution experiment were performed in LNCaP tumor-bearing B-NSG male mice. The most promising tracer was selected for first-in-human study. Results: Four radiotracers were synthesized with radiochemical purity (RCP) > 95% and molar activity in a range of 20.0-25.5 GBq/μmol. The binding affinities (Ki) of TWS01, TWS02 to PSMA were in the low nanomolar range (< 10 nM), while TWS03 and TWS04 exhibited binding affinities with Ki > 20 nM (59.42 nM for TWS03 and 37.14 nM for TWS04). All radiotracers exhibited high stability in vivo except [68Ga]Ga-TWS03. Micro PET/CT imaging and biodistribution analysis revealed that [68Ga]Ga-TWS02 enabled clear tumor visualization in PET images at 1.5 h post-injection, with higher tumor-to-kidney ratio (T/K, 0.93) and tumor-to-muscle ratio (T/M, 107.62) compared with [68Ga]Ga-PSMA-617 (T/K: 0.39, T/M: 15.01) and [68Ga]Ga-PSMA-11 (T/K: 0.15, T/M: 24.00). In first-in-human study, [68Ga]Ga-TWS02 effectively detected PCa-associated lesions including primary and metastatic lesions, with lower accumulation in urinary system, suggesting that [68Ga]Ga-TWS02 might be applied in the detection of bladder invasion, with minimized radiation toxicity to the urinary system. Conclusion: Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects. Trial registration: The clinical evaluation of this study was registered On October 30, 2021 at https://www.chictr.org.cn/ (No: ChiCTR2100052545). [ABSTRACT FROM AUTHOR]
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- 2024
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12. Characterization of a Syngeneic Orthotopic Model of Cholangiocarcinoma by [ 18 F]FDG-PET/MRI.
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Zachhuber, Lena, Filip, Thomas, Mozayani, Behrang, Löbsch, Mathilde, Scheiner, Stefan, Vician, Petra, Stanek, Johann, Hacker, Marcus, Helbich, Thomas H., Wanek, Thomas, Berger, Walter, and Kuntner, Claudia
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BIOLOGICAL models , *LIVER tumors , *RADIOPHARMACEUTICALS , *RESEARCH funding , *CHOLANGIOCARCINOMA , *DEOXY sugars , *POSITRON emission tomography , *MAGNETIC resonance imaging , *MICE , *METASTASIS , *BLOOD sugar , *ANIMAL experimentation - Abstract
Simple Summary: Cholangiocarcinoma (CCA) is a type of liver cancer with few treatment options and low survival rates in advanced stages. Our study developed a mouse model to study this cancer type by implanting CCA cells into the liver of mice. We used advanced imaging techniques (MRI and PET scans) to monitor tumor growth and metabolism over four weeks. We observed that tumors became visible early and grew steadily over time. PET scans showed increasing tumor activity, and blood tests revealed liver damage. Most mice developed lung metastases after four weeks. Our research shows that combining MRI and PET scans effectively tracks CCA progression in mice, providing valuable insights into cancer development and investigating potential treatments. Cholangiocarcinoma (CCA) is a type of primary liver cancer originating from the biliary tract epithelium, characterized by limited treatment options for advanced cases and low survival rates. This study aimed to establish an orthotopic mouse model for CCA and monitor tumor growth using PET/MR imaging. Murine CCA cells were implanted into the liver lobe of male C57BL/6J mice. The imaging groups included contrast-enhanced (CE) MR, CE-MR with static [18F]FDG-PET, and dynamic [18F]FDG-PET. Tumor volume and FDG uptake were measured weekly over four weeks. Early tumor formation was visible in CE-MR images, with a gradual increase in volume over time. Dynamic FDG-PET revealed an increase in the metabolic glucose rate (MRGlu) over time. Blood analysis showed pathological changes in liver-related parameters. Lung metastases were observed in nearly all animals after four weeks. The study concludes that PET-MR imaging effectively monitors tumor progression in the CCA mouse model, providing insights into CCA development and potential treatment strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Enhanced PET image reconstruction utilizing morphological filtering and MLEM algorithm.
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He, Qian and Wang, Ke
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POSITRON emission tomography ,IMAGE reconstruction ,IMAGE reconstruction algorithms ,DIGITAL preservation ,ALGORITHMS - Abstract
Positron Emission Tomography (PET) image reconstruction remains a pivotal area in PET technology, critically influencing clinical diagnostic outcomes. Addressing the need for enhanced image quality, this study introduces a novel algorithm for PET image reconstruction. This algorithm integrates a penalty mechanism, morphological filtering, and the Maximum Likelihood Expectation Maximization (MLEM) algorithm, aiming to improve reconstructed image quality significantly. The operational process of the algorithm within each iteration encompasses two primary phases. Initially, image reconstruction is accomplished via the MLEM algorithm, followed by the application of a morphological filter to attenuate noise in the reconstructed image. Simulation experiments demonstrate that this algorithm effectively mitigates noise while preserving crucial details, such as image edges. Notably, this method presents the dual benefits of straightforward parameter configuration and ease of implementation. The results indicate a substantial enhancement in noise suppression and fine structure preservation in the reconstructed images, marking a significant advancement in PET image reconstruction techniques. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Deep learning based bilateral filtering for edge-preserving denoising of respiratory-gated PET.
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Maus, Jens, Nikulin, Pavel, Hofheinz, Frank, Petr, Jan, Braune, Anja, Kotzerke, Jörg, and van den Hoff, Jörg
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DEEP learning , *POSITRON emission tomography , *NOISE control , *STANDARD deviations , *COMPUTED tomography , *ADAPTIVE filters - Abstract
Background: Residual image noise is substantial in positron emission tomography (PET) and one of the factors limiting lesion detection, quantification, and overall image quality. Thus, improving noise reduction remains of considerable interest. This is especially true for respiratory-gated PET investigations. The only broadly used approach for noise reduction in PET imaging has been the application of low-pass filters, usually Gaussians, which however leads to loss of spatial resolution and increased partial volume effects affecting detectability of small lesions and quantitative data evaluation. The bilateral filter (BF) — a locally adaptive image filter — allows to reduce image noise while preserving well defined object edges but manual optimization of the filter parameters for a given PET scan can be tedious and time-consuming, hampering its clinical use. In this work we have investigated to what extent a suitable deep learning based approach can resolve this issue by training a suitable network with the target of reproducing the results of manually adjusted case-specific bilateral filtering. Methods: Altogether, 69 respiratory-gated clinical PET/CT scans with three different tracers ( [ 18 F ] FDG, [ 18 F ] L-DOPA, [ 68 Ga ] DOTATATE) were used for the present investigation. Prior to data processing, the gated data sets were split, resulting in a total of 552 single-gate image volumes. For each of these image volumes, four 3D ROIs were delineated: one ROI for image noise assessment and three ROIs for focal uptake (e.g. tumor lesions) measurements at different target/background contrast levels. An automated procedure was used to perform a brute force search of the two-dimensional BF parameter space for each data set to identify the "optimal" filter parameters to generate user-approved ground truth input data consisting of pairs of original and optimally BF filtered images. For reproducing the optimal BF filtering, we employed a modified 3D U-Net CNN incorporating residual learning principle. The network training and evaluation was performed using a 5-fold cross-validation scheme. The influence of filtering on lesion SUV quantification and image noise level was assessed by calculating absolute and fractional differences between the CNN, manual BF, or original (STD) data sets in the previously defined ROIs. Results: The automated procedure used for filter parameter determination chose adequate filter parameters for the majority of the data sets with only 19 patient data sets requiring manual tuning. Evaluation of the focal uptake ROIs revealed that CNN as well as BF based filtering essentially maintain the focal SUV max values of the unfiltered images with a low mean ± SD difference of δ SUV max CNN , STD = (−3.9 ± 5.2)% and δ SUV max BF , STD = (−4.4 ± 5.3)%. Regarding relative performance of CNN versus BF, both methods lead to very similar SUV max values in the vast majority of cases with an overall average difference of δ SUV max CNN , BF = (0.5 ± 4.8)%. Evaluation of the noise properties showed that CNN filtering mostly satisfactorily reproduces the noise level and characteristics of BF with δ Noise CNN , BF = (5.6 ± 10.5)%. No significant tracer dependent differences between CNN and BF were observed. Conclusions: Our results show that a neural network based denoising can reproduce the results of a case by case optimized BF in a fully automated way. Apart from rare cases it led to images of practically identical quality regarding noise level, edge preservation, and signal recovery. We believe such a network might proof especially useful in the context of improved motion correction of respiratory-gated PET studies but could also help to establish BF-equivalent edge-preserving CNN filtering in clinical PET since it obviates time consuming manual BF parameter tuning. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Proton spot dose estimation based on positron activity distributions with neural network.
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Zhang, Ruilin, Mu, Dengyun, Ma, Qiuhui, Wan, Lin, Xiao, Peng, Qi, Pengyuan, Liu, Gang, Zhang, Sheng, Yang, Kunyu, Yang, Zhiyong, and Xie, Qingguo
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RECURRENT neural networks , *ARTIFICIAL neural networks , *POSITRONS , *POSITRON emission tomography , *TRANSFORMER models - Abstract
Background Purpose Methods Results Conclusions Positron emission tomography (PET) has been investigated for its ability to reconstruct proton‐induced positron activity distributions in proton therapy. This technique holds potential for range verification in clinical practice. Recently, deep learning‐based dose estimation from positron activity distributions shows promise for in vivo proton dose monitoring and guided proton therapy.This study evaluates the effectiveness of three classical neural network models, recurrent neural network (RNN), U‐Net, and Transformer, for proton dose estimating. It also investigates the characteristics of these models, providing valuable insights for selecting the appropriate model in clinical practice.Proton dose calculations for spot beams were simulated using Geant4. Computed tomography (CT) images from four head cases were utilized, with three for training neural networks and the remaining one for testing. The neural networks were trained with one‐dimensional (1D) positron activity distributions as inputs and generated 1D dose distributions as outputs. The impact of the number of training samples on the networks was examined, and their dose prediction performance in both homogeneous brain and heterogeneous nasopharynx sites was evaluated. Additionally, the effect of positron activity distribution uncertainty on dose prediction performance was investigated. To quantitatively evaluate the models, mean relative error (MRE) and absolute range error (ARE) were used as evaluation metrics.The U‐Net exhibited a notable advantage in range verification with a smaller number of training samples, achieving approximately 75% of AREs below 0.5 mm using only 500 training samples. The networks performed better in the homogeneous brain site compared to the heterogeneous nasopharyngeal site. In the homogeneous brain site, all networks exhibited small AREs, with approximately 90% of the AREs below 0.5 mm. The Transformer exhibited the best overall dose distribution prediction, with approximately 92% of MREs below 3%. In the heterogeneous nasopharyngeal site, all networks demonstrated acceptable AREs, with approximately 88% of AREs below 3 mm. The Transformer maintained the best overall dose distribution prediction, with approximately 85% of MREs below 5%. The performance of all three networks in dose prediction declined as the uncertainty of positron activity distribution increased, and the Transformer consistently outperformed the other networks in all cases.Both the U‐Net and the Transformer have certain advantages in the proton dose estimation task. The U‐Net proves well suited for range verification with a small training sample size, while the Transformer outperforms others at dose‐guided proton therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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16. A PET-based radiomics nomogram for individualized predictions of seizure outcomes after temporal lobe epilepsy surgery.
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Wu, Huanhua, Liao, Kai, Tan, Zhiqiang, Zeng, Chunyuan, Wu, Biao, Zhou, Ziqing, Zhou, Hailing, Tang, Yongjin, Gong, Jian, Ye, Weijian, Ling, Xueying, Guo, Qiang, and Xu, Hao
- Abstract
• Metabolic PET radiomics features were strong predictors of seizure recurrence. • PET-based radiomics score, SGS, and Durmon were significant predictors of seizure-free outcomes. • A nomogram incorporating PET-based radiomics and clinical risk factors demonstrated good performance in predicting surgery outcomes. To establish and validate a novel nomogram based on clinical characteristics and [
18 F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). 234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). Eight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59–0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. A PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery. [ABSTRACT FROM AUTHOR]- Published
- 2024
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17. Exploratory Tau PET/CT with [11C]PBB3 in Patients with Suspected Alzheimer's Disease and Frontotemporal Lobar Degeneration: A Pilot Study on Correlation with PET Imaging and Cerebrospinal Fluid Biomarkers.
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Strobel, Joachim, Yousefzadeh-Nowshahr, Elham, Deininger, Katharina, Bohn, Karl Peter, von Arnim, Christine A. F., Otto, Markus, Solbach, Christoph, Anderl-Straub, Sarah, Polivka, Dörte, Fissler, Patrick, Glatting, Gerhard, Riepe, Matthias W., Higuchi, Makoto, Beer, Ambros J., Ludolph, Albert, and Winter, Gordon
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POSITRON emission tomography ,ALZHEIMER'S disease ,COMPUTED tomography ,MINI-Mental State Examination ,ALZHEIMER'S patients - Abstract
Accurately diagnosing Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is challenging due to overlapping symptoms and limitations of current imaging methods. This study investigates the use of [11C]PBB3 PET/CT imaging to visualize tau pathology and improve diagnostic accuracy. Given diagnostic challenges with symptoms and conventional imaging, [11C]PBB3 PET/CT's potential to enhance accuracy was investigated by correlating tau pathology with cerebrospinal fluid (CSF) biomarkers, positron emission tomography (PET), computed tomography (CT), amyloid-beta, and Mini-Mental State Examination (MMSE). We conducted [11C]PBB3 PET/CT imaging on 24 patients with suspected AD or FTLD, alongside [11C]PiB PET/CT (13 patients) and [18F]FDG PET/CT (15 patients). Visual and quantitative assessments of [11C]PBB3 uptake using standardized uptake value ratios (SUV-Rs) and correlation analyses with clinical assessments were performed. The scans revealed distinct tau accumulation patterns; 13 patients had no or faint uptake (PBB3-negative) and 11 had moderate to pronounced uptake (PBB3-positive). Significant inverse correlations were found between [11C]PBB3 SUV-Rs and MMSE scores, but not with CSF-tau or CSF-amyloid-beta levels. Here, we show that [11C]PBB3 PET/CT imaging can reveal distinct tau accumulation patterns and correlate these with cognitive impairment in neurodegenerative diseases. Our study demonstrates the potential of [11C]PBB3-PET imaging for visualizing tau pathology and assessing disease severity, offering a promising tool for enhancing diagnostic accuracy in AD and FTLD. Further research is essential to validate these findings and refine the use of tau-specific PET imaging in clinical practice, ultimately improving patient care and treatment outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Deep learning-based techniques for estimating high-quality full-dose positron emission tomography images from low-dose scans: a systematic review
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Negisa Seyyedi, Ali Ghafari, Navisa Seyyedi, and Peyman Sheikhzadeh
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Deep Learning ,Positron Emission Tomography (PET) ,Denoising Techniques ,Low-Dose PET Images ,Medical technology ,R855-855.5 - Abstract
Abstract This systematic review aimed to evaluate the potential of deep learning algorithms for converting low-dose Positron Emission Tomography (PET) images to full-dose PET images in different body regions. A total of 55 articles published between 2017 and 2023 by searching PubMed, Web of Science, Scopus and IEEE databases were included in this review, which utilized various deep learning models, such as generative adversarial networks and UNET, to synthesize high-quality PET images. The studies involved different datasets, image preprocessing techniques, input data types, and loss functions. The evaluation of the generated PET images was conducted using both quantitative and qualitative methods, including physician evaluations and various denoising techniques. The findings of this review suggest that deep learning algorithms have promising potential in generating high-quality PET images from low-dose PET images, which can be useful in clinical practice.
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- 2024
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19. Physicochemical characterization and potential cancer therapy applications of hydrogel beads loaded with doxorubicin and GaOOH nanoparticles
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Aleksandra Żmuda, Weronika Kamińska, Marta Bartel, Karolina Głowacka, Maciej Chotkowski, Katarzyna Medyńska, Katarzyna Wiktorska, and Maciej Mazur
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Hydrogel polymer particles ,Doxorubicin ,GaOOH nanoparticles ,Cancer therapy ,Ga-68 radioisotope ,Positron emission tomography (PET) ,Medicine ,Science - Abstract
Abstract A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 μm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET.
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- 2024
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20. Design and proof of concept of a double-panel TOF-PET system
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Andrea Gonzalez-Montoro, Noriel Pavón, Julio Barberá, Neus Cuarella, Antonio J. González, Santiago Jiménez-Serrano, Alejandro Lucero, Laura Moliner, David Sánchez, Koldo Vidal, and José M. Benlloch
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Positron emission tomography (PET) ,Portable PET ,Organ ,Specific PET ,Double ,Panel PET ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Objective Positron Emission Tomography (PET) is a well-known imaging technology for the diagnosis, treatment, and monitoring of several diseases. Most PET scanners use a Ring-Shaped Detector Configuration (RSDC), which helps obtain homogeneous image quality but are restricted to an invariable Field-of-View (FOV), scarce spatial resolution, and low sensitivity. Alternatively, few PET systems use Open Detector Configurations (ODC) to permit an accessible FOV adaptable to different target sizes, thus optimizing sensitivity. Yet, to compensate the lack of angular coverage in ODC-PET, developing a detector with high-timing performance is mandatory to enable Time-of-Flight (TOF) techniques during reconstruction. The main goal of this work is to provide a proof of concept PET scanner appropriate for constructing the new generation of ODC-PET suitable for biopsy guidance and clinical intervention during acquisition. The designed detector has to be compact and robust, and its requirements in terms of performance are spatial and time resolutions
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- 2024
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21. Automatic reorientation to generate short-axis myocardial PET images
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Yuling Yang, Fanghu Wang, Xu Han, Hui Xu, Yangmei Zhang, Weiping Xu, Shuxia Wang, and Lijun Lu
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Positron emission tomography (PET) ,Automatic reorientation ,Regional division ,Image segmentation ,Fitting algorithm ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background Accurately redirecting reconstructed Positron emission tomography (PET) images into short-axis (SA) images shows great significance for subsequent clinical diagnosis. We developed a system for automatic redirection and quantitative analysis of myocardial PET images. Methods A total of 128 patients were enrolled for 18 F-FDG PET/CT myocardial metabolic images (MMIs), including 3 image classifications: without defects, with defects, and excess uptake. The automatic reorientation system includes five modules: regional division, myocardial segmentation, ellipsoid fitting, image rotation and quantitative analysis. First, the left ventricular geometry-based canny edge detection (LVG-CED) was developed and compared with the other 5 common region segmentation algorithms, the optimized partitioning was determined based on partition success rate. Then, 9 myocardial segmentation methods and 4 ellipsoid fitting methods were combined to derive 36 cross combinations for diagnostic performance in terms of Pearson correlation coefficient (PCC), Kendall correlation coefficient (KCC), Spearman correlation coefficient (SCC), and determination coefficient. Finally, the deflection angles were computed by ellipsoid fitting and the SA images were derived by affine transformation. Furthermore, the polar maps were used for quantitative analysis of SA images, and the redirection effects of 3 different image classifications were analyzed using correlation coefficients. Results On the dataset, LVG-CED outperformed other methods in the regional division module with a 100% success rate. In 36 cross combinations, PSO-FCM and LLS-SVD performed the best in terms of correlation coefficient. The linear results indicate that our algorithm (LVG-CED, PSO-FCM, and LLS-SVD) has good consistency with the reference manual method. In quantitative analysis, the similarities between our method and the reference manual method were higher than 96% at 17 segments. Moreover, our method demonstrated excellent performance in all 3 image classifications. Conclusion Our algorithm system could realize accurate automatic reorientation and quantitative analysis of PET MMIs, which is also effective for images suffering from interference.
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- 2024
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22. Prostate-Specific Membrane Antigen Expression in Patients with Primary Prostate Cancer: Diagnostic and Prognostic Value in Positron Emission Tomography-Prostate-Specific Membrane Antigen
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Omar Tayara, Sławomir Poletajew, Wojciech Malewski, Jolanta Kunikowska, Kacper Pełka, Piotr Kryst, and Łukasz Nyk
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prostate-specific antigen (PSA) ,prostate-specific membrane antigen (PSMA) ,positron emission tomography (PET) ,computed tomography (CT) ,magnetic resonance imaging (MRI) ,Food and Drug Administration (FDA) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Prostate cancer represents a significant public health challenge, with its management requiring precise diagnostic and prognostic tools. Prostate-specific membrane antigen (PSMA), a cell surface enzyme overexpressed in prostate cancer cells, has emerged as a pivotal biomarker. PSMA’s ability to increase the sensitivity of PET imaging has revolutionized its application in the clinical management of prostate cancer. The advancements in PET-PSMA imaging technologies and methodologies, including the development of PSMA-targeted radiotracers and optimized imaging protocols, led to diagnostic accuracy and clinical utility across different stages of prostate cancer. This highlights its superiority in staging and its comparative effectiveness against conventional imaging modalities. This paper analyzes the impact of PET-PSMA on prostate cancer management, discussing the existing challenges and suggesting future research directions. The integration of recent studies and reviews underscores the evolving understanding of PET-PSMA imaging, marking its significant but still expanding role in clinical practice. This comprehensive review serves as a crucial resource for clinicians and researchers involved in the multifaceted domains of prostate cancer diagnosis, treatment, and management.
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- 2024
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23. Deep learning based bilateral filtering for edge-preserving denoising of respiratory-gated PET
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Jens Maus, Pavel Nikulin, Frank Hofheinz, Jan Petr, Anja Braune, Jörg Kotzerke, and Jörg van den Hoff
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Positron emission tomography (PET) ,Image quantification ,Deep learning ,Post-filtering ,Neural networks ,Image denoising ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background Residual image noise is substantial in positron emission tomography (PET) and one of the factors limiting lesion detection, quantification, and overall image quality. Thus, improving noise reduction remains of considerable interest. This is especially true for respiratory-gated PET investigations. The only broadly used approach for noise reduction in PET imaging has been the application of low-pass filters, usually Gaussians, which however leads to loss of spatial resolution and increased partial volume effects affecting detectability of small lesions and quantitative data evaluation. The bilateral filter (BF) — a locally adaptive image filter — allows to reduce image noise while preserving well defined object edges but manual optimization of the filter parameters for a given PET scan can be tedious and time-consuming, hampering its clinical use. In this work we have investigated to what extent a suitable deep learning based approach can resolve this issue by training a suitable network with the target of reproducing the results of manually adjusted case-specific bilateral filtering. Methods Altogether, 69 respiratory-gated clinical PET/CT scans with three different tracers ( $$[^{18}\text {F}]$$ [ 18 F ] FDG, $$[^{18}\text {F}]$$ [ 18 F ] L-DOPA, $$[^{68}\text {Ga}]$$ [ 68 Ga ] DOTATATE) were used for the present investigation. Prior to data processing, the gated data sets were split, resulting in a total of 552 single-gate image volumes. For each of these image volumes, four 3D ROIs were delineated: one ROI for image noise assessment and three ROIs for focal uptake (e.g. tumor lesions) measurements at different target/background contrast levels. An automated procedure was used to perform a brute force search of the two-dimensional BF parameter space for each data set to identify the “optimal” filter parameters to generate user-approved ground truth input data consisting of pairs of original and optimally BF filtered images. For reproducing the optimal BF filtering, we employed a modified 3D U-Net CNN incorporating residual learning principle. The network training and evaluation was performed using a 5-fold cross-validation scheme. The influence of filtering on lesion SUV quantification and image noise level was assessed by calculating absolute and fractional differences between the CNN, manual BF, or original (STD) data sets in the previously defined ROIs. Results The automated procedure used for filter parameter determination chose adequate filter parameters for the majority of the data sets with only 19 patient data sets requiring manual tuning. Evaluation of the focal uptake ROIs revealed that CNN as well as BF based filtering essentially maintain the focal $$\text {SUV}_\text {max}$$ SUV max values of the unfiltered images with a low mean ± SD difference of $$\delta \text {SUV}_\text {max}^{\text {CNN},\text {STD}}$$ δ SUV max CNN , STD = (−3.9 ± 5.2)% and $$\delta \text {SUV}_\text {max}^{\text {BF},\text {STD}}$$ δ SUV max BF , STD = (−4.4 ± 5.3)%. Regarding relative performance of CNN versus BF, both methods lead to very similar $$\text {SUV}_\text {max}$$ SUV max values in the vast majority of cases with an overall average difference of $$\delta \text {SUV}_\text {max}^{\text {CNN},\text {BF}}$$ δ SUV max CNN , BF = (0.5 ± 4.8)%. Evaluation of the noise properties showed that CNN filtering mostly satisfactorily reproduces the noise level and characteristics of BF with $$\delta \text {Noise}^{\text {CNN},\text {BF}}$$ δ Noise CNN , BF = (5.6 ± 10.5)%. No significant tracer dependent differences between CNN and BF were observed. Conclusions Our results show that a neural network based denoising can reproduce the results of a case by case optimized BF in a fully automated way. Apart from rare cases it led to images of practically identical quality regarding noise level, edge preservation, and signal recovery. We believe such a network might proof especially useful in the context of improved motion correction of respiratory-gated PET studies but could also help to establish BF-equivalent edge-preserving CNN filtering in clinical PET since it obviates time consuming manual BF parameter tuning.
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- 2024
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24. Enhanced PET image reconstruction utilizing morphological filtering and MLEM algorithm
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Qian He and Ke Wang
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Positron Emission Tomography (PET) ,Image reconstruction ,Maximum likelihood Expectation Maximization (MLEM) algorithm ,Morphological filter ,Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
Positron Emission Tomography (PET) image reconstruction remains a pivotal area in PET technology, critically influencing clinical diagnostic outcomes. Addressing the need for enhanced image quality, this study introduces a novel algorithm for PET image reconstruction. This algorithm integrates a penalty mechanism, morphological filtering, and the Maximum Likelihood Expectation Maximization (MLEM) algorithm, aiming to improve reconstructed image quality significantly. The operational process of the algorithm within each iteration encompasses two primary phases. Initially, image reconstruction is accomplished via the MLEM algorithm, followed by the application of a morphological filter to attenuate noise in the reconstructed image. Simulation experiments demonstrate that this algorithm effectively mitigates noise while preserving crucial details, such as image edges. Notably, this method presents the dual benefits of straightforward parameter configuration and ease of implementation. The results indicate a substantial enhancement in noise suppression and fine structure preservation in the reconstructed images, marking a significant advancement in PET image reconstruction techniques.
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- 2024
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25. Multimodal Optoacoustic Imaging
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Chen, Zhenyue, Gezginer, Irmak, Zhou, Quanyu, Razansky, Daniel, and Xia, Wenfeng, editor
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- 2024
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26. Nuclear Medicine in Oncology
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Rangarajan, Venkatesh, Purandare, Nilendu C., Basu, Sandip, Badwe, Rajendra A., editor, Gupta, Sudeep, editor, Shrikhande, Shailesh V., editor, and Laskar, Siddhartha, editor
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- 2024
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27. [18F]FB(ePEG12)12-exendin-4 noninvasive imaging of insulinoma negative for insulin immunostaining on specimen from endoscopic ultrasonography-guided fine needle aspiration: a case report with review of literature
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Daisuke Otani, Takaaki Murakami, Saeko Murakami, Ikuko Hanaoka, Hiroyuki Fujimoto, Yoichi Shimizu, Kanae Kawai Miyake, Kentaro Sakaki, Yohei Ueda, Daisuke Tanaka, Tsuyoshi Ohno, Hironori Shimizu, Naoki Uyama, Norishige Iizuka, Daisuke Yabe, Yuji Nakamoto, and Nobuya Inagaki
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exendin-4 ,positron emission tomography (pet) ,insulinoma ,glucagon-like peptide-1 receptor (glp-1r) ,pancreatic β-cell imaging ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Insulinomas are the most common functional pancreatic neuroendocrine neoplasm; when treatment is delayed, they induce hyperinsulinemic hypoglycemia, which is life-threatening. As surgical resection is the only curative treatment for insulinoma, preoperative localization is crucial; however, localization based on conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging is often inconclusive. Somatostatin receptor-targeted imaging is another option for detecting pancreatic neuroendocrine neoplasms but has low sensitivity and is not specific for insulinoma. The clinical application of other localizing approaches such as selective arterial calcium stimulation and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is limited by their being invasive and/or technically complex. Moreover, an EUS-FNA specimen of an insulinoma may be negative on insulin immunostaining. Thus, a noninvasive and clinically practical insulinoma-specific diagnostic tool to discriminate insulinomas with high accuracy is anticipated. Glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged in the effort to fulfill this need. We recently developed the novel fluorine-18-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4) for positron emission tomography (PET) imaging and reported its clinical benefit in a case of insulinoma in the pancreatic tail. We report here a case of insulinoma in the pancreatic head in which an EUS-FNA specimen was negative on insulin immunostaining while precise preoperative localization and conclusive evidence for curative enucleation was provided by 18F-exendin-4 PET/CT (Japan Registry of Clinical Trials; jRCTs051200156).
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- 2024
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28. Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT
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Sangkyung Choen, Michael S. Kent, F. Alexandra Loucks, Jonathan A. Winger, and Allison L. Zwingenberger
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Tumor hypoxia ,Oxygen carrier ,H-NOX protein ,Canine tumors ,[18F]Fluoromisonidazole ([18F]FMISO) ,Positron emission tomography (PET) ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors. Results Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV. Conclusions [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.
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- 2024
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29. Neuroimaging evaluation of the long term impact of a novel paired meditation practice on brain function.
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Newberg, Andrew B., Wintering, Nancy A., Hriso, Chloe, Vedaei, Faezeh, Gottfried, Sara, and Ross, Reneita
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BRAIN imaging ,BRAIN function localization ,MEDITATION ,EMOTION regulation ,COGNITION - Abstract
Background: A growing number of advanced neuroimaging studies have compared brain structure and function in long term meditators to non-meditators. The goal is to determine if there may be long term effects on the brain from practicing meditation. In this paper, we present new data on the long term effects of a novel meditation practice in which the focus is on clitoral stimulation. The findings from such a study have implications for potential therapeutic uses with regard to various neurological or psychiatric conditions. Methods: We evaluated the cerebral glucose metabolism in 40 subjects with an extended history (>1 year of practice, 2-3 times per week) performing the meditation practice called Orgasmic Meditation (OM) and compared their brains to a group of non-meditating healthy controls (N = 19). Both meditation and non-meditation subjects underwent brain PET after injection with 148 to 296 MBq of FDG using a standard imaging protocol. Resting FDG PET scans of theOM group were compared to the resting scans of healthy, non-meditating, controls using statistical parametric mapping. Results: The OM group showed significant differences in metabolic activity at rest compared to the controls. Specifically, there was significantly lower metabolism in select areas of the frontal, temporal, and parietal lobes, as well as the anterior cingulate, insula, and thalamus, in the OM group compared to the controls. In addition, there were notable distinctions between the males and females with the females demonstrating significantly lower metabolism in the thalamus and insula. Conclusions: Overall, these findings suggest that the long term meditation practitioners of OM have different patterns of resting brain metabolism. Since these areas of the brain in which OM practitioners differ from controls are involved in cognition, attention, and emotional regulation, such findings have implications for understanding how this meditation practice might affect practitioners over long periods of time. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Utilizing MRI, [18F]FDG-PET and [89Zr]Zr-DFO-28H1 FAP-PET tracer to assess inflammation and fibrogenesis in a reproducible lung injury rat model: a multimodal imaging study.
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Boswinkel, Milou, Raavé, René, Veltien, Andor, Scheenen, Tom WJ, Petterson, Nina Fransén, 't Zandt, René in, Olsson, Lars E., Wachenfeldt, Karin von, Heskamp, Sandra, and Persson, Irma Mahmutovic
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PREVENTION of weight loss ,DATA analysis ,T-test (Statistics) ,STATISTICAL hypothesis testing ,RESEARCH funding ,STATISTICAL sampling ,COMPUTED tomography ,MAGNETIC resonance imaging ,LUNG injuries ,POSITRON emission tomography ,MANN Whitney U Test ,BLEOMYCIN ,TRACHEA intubation ,FIBROBLASTS ,RATS ,ANIMAL experimentation ,ONE-way analysis of variance ,STATISTICS ,INFLAMMATION ,DATA analysis software ,BIOMARKERS ,DISEASE progression - Abstract
Objective: Accurate imaging biomarkers that indicate disease progression at an early stage are highly important to enable timely mitigation of symptoms in progressive lung disease. In this context, reproducible experimental models and readouts are key. Here, we aim to show reproducibility of a lung injury rat model by inducing disease and assessing disease progression by multi-modal non-invasive imaging techniques at two different research sites. Furthermore, we evaluated the potential of fibroblast activating protein (FAP) as an imaging biomarker in the early stage of lung fibrosis. Methods: An initial lung injury rat model was set up at one research site (Lund University, Lund, Sweden) and repeated at a second site (Radboudumc, Nijmegen, The Netherlands). To induce lung injury, Sprague-Dawley rats received intratracheal instillation of bleomycin as one single dose (1,000 iU in 200 µL) or saline as control. Thereafter, longitudinal images were acquired to track inflammation in the lungs, at 1 and 2 weeks after the bleomycin challenge by magnetic resonance imaging (MRI) and [
18 F]FDG-PET. After the final [18 F] FDG-PET scan, rats received an intravenous tracer [89 Zr]Zr-DFO-28H1 (anti-FAP antibody) and were imaged at day 15 to track fibrogenesis. Upon termination, bronchoalveolar lavage (BAL) was performed to assess cell and protein concentration. Subsequently, the biodistribution of [89 Zr]Zr-DFO-28H1 was measured ex vivo and the spatial distribution in lung tissue was studied by autoradiography. Lung sections were stained and fibrosis assessed using the modified Ashcroft score. Results: Bleomycin-challenged rats showed body weight loss and increased numbers of immune cells and protein concentrations after BAL compared with control animals. The initiation and progression of the disease were reproduced at both research sites. Lung lesions in bleomycin-exposed rats were visualized by MRI and confirmed by histology. [18F]FDG uptake was higher in the lungs of bleomycin-challenged rats compared with the controls, similar to that observed in the Lund study. [89 Zr]Zr-DFO-28H1 tracer uptake in the lung was increased in bleomycin-challenged rats compared with control rats (p = 0.03). Conclusion: Here, we demonstrate a reproducible lung injury model and monitored disease progression using conventional imaging biomarkers MRI and [18 F]FDG-PET. Furthermore, we showed the first proof-of-concept of FAP imaging. This reproducible and robust animal model and imaging experimental set-up allows for future research on new therapeutics or biomarkers in lung disease. [ABSTRACT FROM AUTHOR]- Published
- 2024
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31. Motion-correction strategies for enhancing whole-body PET imaging.
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Wang, James, Bermudez, Dalton, Chen, Weijie, Durgavarjhula, Divya, Randell, Caitlin, Uyanik, Meltem, and McMillan, Alan
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DIAGNOSTIC imaging ,RESPIRATION ,POSITRON emission tomography ,CARDIAC-gated imaging ,BODY movement ,EMISSION-computed tomography ,DIGITAL image processing - Abstract
Positron Emission Tomography (PET) is a powerful medical imaging technique widely used for detection and monitoring of disease. However, PET imaging can be adversely affected by patient motion, leading to degraded image quality and diagnostic capability. Hence, motion gating schemes have been developed to monitor various motion sources including head motion, respiratory motion, and cardiac motion. The approaches for these techniques have commonly come in the form of hardware-driven gating and data-driven gating, where the distinguishing aspect is the use of external hardware to make motion measurements vs. deriving these measures from the data itself. The implementation of these techniques helps correct for motion artifacts and improves tracer uptake measurements. With the great impact that these methods have on the diagnostic and quantitative quality of PET images, much research has been performed in this area, and this paper outlines the various approaches that have been developed as applied to whole-body PET imaging. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Development and Validation of Prognostic Models Using Radiomic Features from Pre-Treatment Positron Emission Tomography (PET) Images in Head and Neck Squamous Cell Carcinoma (HNSCC) Patients.
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Philip, Mahima Merin, Watts, Jessica, McKiddie, Fergus, Welch, Andy, and Nath, Mintu
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SQUAMOUS cell carcinoma , *RANDOM forest algorithms , *PREDICTION models , *RESEARCH funding , *CANCER relapse , *RADIOMICS , *HEAD & neck cancer , *RESEARCH methodology evaluation , *POSITRON emission tomography , *EXPERIMENTAL design , *METASTASIS , *LONGITUDINAL method , *RESEARCH methodology , *MACHINE learning - Abstract
Simple Summary: Time-to-event analysis holds significant relevance for diseases like cancer since accurate disease prognosis is crucial for better patient management and for personalizing treatment. In recent years, survival models using machine learning (ML)-based tools have shown promise in cancer prognosis. We compared four survival models in the ML framework to predict adverse outcomes—all-cause mortality (ACM), locoregional recurrence/residual disease (LR), and distant metastasis (DM)—in head and neck cancer patients. Using radiomic features from pre-treatment positron emission tomography (PET) images, we assessed the performance of these models in an external independent validation cohort. The best-performing model for each outcome was identified based on the highest concordance index and the lowest error in training data. The penalized Cox model for ACM and DM and the random forest model for LR showed promising results. Further training and validation of these models in a larger cohort is required for clinical implementation. High-dimensional radiomics features derived from pre-treatment positron emission tomography (PET) images offer prognostic insights for patients with head and neck squamous cell carcinoma (HNSCC). Using 124 PET radiomics features and clinical variables (age, sex, stage of cancer, site of cancer) from a cohort of 232 patients, we evaluated four survival models—penalized Cox model, random forest, gradient boosted model and support vector machine—to predict all-cause mortality (ACM), locoregional recurrence/residual disease (LR) and distant metastasis (DM) probability during 36, 24 and 24 months of follow-up, respectively. We developed models with five-fold cross-validation, selected the best-performing model for each outcome based on the concordance index (C-statistic) and the integrated Brier score (IBS) and validated them in an independent cohort of 102 patients. The penalized Cox model demonstrated better performance for ACM (C-statistic = 0.70, IBS = 0.12) and DM (C-statistic = 0.70, IBS = 0.08) while the random forest model displayed better performance for LR (C-statistic = 0.76, IBS = 0.07). We conclude that the ML-based prognostic model can aid clinicians in quantifying prognosis and determining effective treatment strategies, thereby improving favorable outcomes in HNSCC patients. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Diagnostic accuracy of the latest-generation digital PET/CT scanner for detection of metastatic lymph nodes in head and neck cancer.
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Butt, Frederick, Dominguez-Konicki, Lillian, Tocci, Noah, Paydarfar, Joseph, Seltzer, Marc, and Pastel, David
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LYMPH node surgery ,LYMPH nodes ,PREDICTIVE tests ,BIOPSY ,COMPUTER-assisted image analysis (Medicine) ,DIGITAL diagnostic imaging ,HEAD & neck cancer ,COMPUTED tomography ,POSITRON emission tomography ,RETROSPECTIVE studies ,METASTASIS ,MEDICAL records ,ACQUISITION of data ,SENSITIVITY & specificity (Statistics) - Abstract
Purpose: The aim of this retrospective analysis was to assess the diagnostic accuracy of the latest-generation digital positron emission tomography/computed tomography (PET/CT) scanner in the detection of cervical lymph node metastasis in patients undergoing staging work-up for head and neck cancer. Materials and methods: A total of 55 consecutive patients with head and neck cancer at our institution who had a PET/CT after installation of the latestgeneration PET/CT (Siemens Biograph Vision) who subsequently underwent surgical neck dissection were included. The nodal station location and number of reported PET/CT-positive metastatic lymph nodes were compared to a gold standard of final surgical pathology after neck dissection. Results: In total, 188 neck levels and 1,373 lymph nodes were resected; 56 neck levels (118 nodes) in 31 (56%) patients contained nodal metastases on surgical pathology. On a nodal level-by-level analysis, the overall sensitivity for the detection of lymph node metastases on the latest-generation PET/CT scanner was 96.4% and the specificity was 86.4%. The sensitivity and specificity for the neck side analysis were 94.0% and 63.7%, and for the individual patient analysis were 100% and 71%, respectively. Conclusions: In this single-institution study, latest-generation PET/CT had a high sensitivity and moderate to high specificity for detecting cervical node metastasis in head and neck cancer. Compared to data from older PET/CT scanners, the sensitivity of the latest-generation PET/CT was slightly higher, while the specificity was similar or slightly lower. Physicians involved in the management of head and neck cancer should be aware of possible changes in the overall diagnostic accuracy when changing to a latest-generation PET/CT scanner. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Preclinical evaluation of 68 Ga-labeled peptide CK2 for PET imaging of NRP-1 expression in vivo.
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Liu, Qingzhu, Cai, Shuyue, Ye, Jiacong, Xie, Quan, Liu, Rongbin, Qiu, Ling, and Lin, Jianguo
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POSITRON emission tomography , *PEPTIDES , *GIBBERELLINS , *BREAST cancer prognosis , *RADIOCHEMICAL purification , *CANCER prognosis , *AUTORADIOGRAPHY - Abstract
Purpose: Neuropilin-1 (NRP-1) is a multifunctional protein involved in a variety of biological processes such as angiogenesis, tumorigenesis and immunomodulation. It was usually overexpressed in many cancer cell lines and correlated with poor prognosis of breast cancer. Positron emission tomography (PET) is an advanced imaging technique for detecting the function and metabolism of tumor-associated molecules in real time, dynamically, quantitatively and noninvasively. To improve the level of early diagnosis and evaluate the prognosis of breast cancer, an NRP-1 targeting peptide-based tracer [68 Ga]Ga-NOTA-PEG4-CK2 was designed to sensitively and specifically detect the NRP-1 expression in vivo via PET imaging. Methods: In silico modeling and microscale thermophoresis (MST) assay were carried out to design the NRP-1 targeting peptide NOTA-PEG4-CK2, and it was further radiolabeled with 68 Ga to prepare the tracer [68 Ga]Ga-NOTA-PEG4-CK2. The radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), lipid-water partition coefficient (Log P) and stability of [68 Ga]Ga-NOTA-PEG4-CK2 were assessed. The targeting specificity of the tracer for NRP-1 was investigated by in vitro cellular uptake assay and in vivo PET imaging as well as blocking studies. The sensitivity of the tracer in monitoring the dynamic changes of NRP-1 expression induced by chemical drug was also investigated in vitro and in vivo. Ex vivo biodistribution, autoradiography, western blot, and immunofluorescence staining were also performed to study the specificity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1. Results: [68 Ga]Ga-NOTA-PEG4-CK2 was designed and synthesized with high RCY (> 98%), high stability (RCP > 95%) and high affinity to NRP-1 (KD = 25.39 ± 1.65 nM). In vitro cellular uptake assay showed that the tracer [68 Ga]Ga-NOTA-PEG4-CK2 can specifically bind to NRP-1 positive cancer cells MDA-MB-231 (1.04 ± 0.04% at 2 h) rather than NRP-1 negative cancer cells NCI-H1299 (0.43 ± 0.05%). In vivo PET imaging showed the maximum tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 in MDA-MB-231 xenografts (4.16 ± 0.67%ID/mL) was significantly higher than that in NCI-H1299 xenografts (1.03 ± 0.19%ID/mL) at 10 min post injection, and the former exhibited higher tumor-to-muscle uptake ratio (5.22 ± 0.18) than the latter (1.07 ± 0.27) at 60 min post injection. MDA-MB-231 xenografts pretreated with nonradioactive precursor NOTA-PEG4-CK2 showed little tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 (1.67 ± 0.38%ID/mL at 10 min post injection). Both cellular uptake assay and PET imaging revealed that NRP-1 expression in breast cancer MDA-MB-231 could be effectively suppressed by SB-203580 treatment and can be sensitively detected by [68 Ga]Ga-NOTA-PEG4-CK2. Ex vivo analysis also proved the high specificity and sensitivity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1 expression in MDA-MB-231 xenografts. Conclusion: A promising NRP-1 targeting PET tracer [68 Ga]Ga-NOTA-PEG4-CK2 was successfully prepared. It showed remarkable specificity and sensitivity in monitoring the dynamic changes of NRP-1 expression. Hence, it could provide valuable information for early diagnosis of NRP-1 relevant cancers and evaluating the prognosis of cancer patients. A novel promising NRP-1 targeting PET tracer [68 Ga]Ga-NOTA-PEG4-CK2 was developed based on a series of in vitro and in vivo investigations. The tracer showed remarkable specificity and sensitivity in detecting the expression of NRP-1. It could be applied for noninvasively and dynamically monitoring the NRP-1 expression in tumors and predicting the prognosis of breast cancer. [ABSTRACT FROM AUTHOR]
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- 2024
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35. An overview of PET SCANNING and patient & staff SAFETY ISSUES.
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Maggs, Paul and Matthews, Shona
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CARDIOVASCULAR disease diagnosis ,TUMOR diagnosis ,DIAGNOSIS of brain diseases ,SAFETY standards ,SAFETY ,RADIATION protection ,PATIENT safety ,RADIOPHARMACEUTICALS ,HAZARDOUS substance release ,COMPUTED tomography ,DEOXY sugars ,RADIATION injuries ,CLAUSTROPHOBIA ,DOSIMETERS ,POSITRON emission tomography computed tomography ,RADIOISOTOPES ,MAGNETIC resonance imaging ,RADIATION doses ,DISEASE risk factors - Abstract
A PET CT uses x-rays and radionucleotide combined with a pharmaceutical to help reveal the metabolic or biochemical function of tissues or organs. It is an effective and highly sensitive way to detect a variety of conditions including cancer, heart disease and brain disorders. The length of the scanner and scan itself, in combination with the radiation dose can present challenges both the patient and staff. [ABSTRACT FROM AUTHOR]
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- 2024
36. Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT.
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Choen, Sangkyung, Kent, Michael S., Loucks, F. Alexandra, Winger, Jonathan A., and Zwingenberger, Allison L.
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POSITRON emission tomography , *TUMOR treatment , *HYPOXEMIA , *COMPUTED tomography , *INTRAVENOUS injections , *OXYGEN carriers , *TUMORS - Abstract
Background: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors. Results: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV. Conclusions: [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Acute Myelomonoblastic Leukemia (My1/De): A Preclinical Rat Model.
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ARATÓ, VIKTÓRIA, KÉPES, ZITA, SZABÓ, JUDIT P., FARKASINSZKY, GERGELY, SASS, TAMÁS, DÉNES, NOÉMI, KIS, ADRIENN, OPPOSITS, GÁBOR, JÓSZAI, ISTVÁN, KÁLMÁN, FERENC KRISZTIÁN, HAJDU, ISTVÁN, TRENCSÉNYI, GYÖRGY, and KERTÉSZ, ISTVÁN
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MYELOID leukemia ,LEUKEMIA diagnosis ,POSITRON emission tomography ,AUTORADIOGRAPHY ,LEUKEMIA treatment - Abstract
Background/Aim: Since acute myeloid leukemias still represent the most aggressive type of adult acute leukemias, the profound understanding of disease pathology is of paramount importance for diagnostic and therapeutic purposes. Hence, this study aimed to explore the real-time disease fate with the establishment of an experimental myelomonoblastic leukemia (My1/De) rat model using preclinical positron emission tomography (PET) and wholebody autoradiography. Materials and Methods: In vitro [18F]F-FDG uptake studies were performed to compare the tracer accumulation in the newly cultured My1/De tumor cell line (blasts) with that in healthy control and My1/De bone marrow suspensions. Post transplantation of My1/De cells under the left renal capsule of Long-Evans rats, primary My1/De tumorigenesis, and metastatic propagation were investigated using [18F]F-FDG PET imaging, whole-body autoradiography and phosphorimage analyses. To assess the organ uptake profile of the tumor-carrying animals we accomplished ex vivo biodistribution studies. Results: The tracer accumulation in the My1/De culture cells exceeded that of both the tumorous and the healthy bone marrow suspensions (p<0.01). Based on in vivo imaging, the subrenally transplanted My1/De cells resulted in the development of leukemia in the abdominal organs, and metastasized to the mesenterial and thoracic parathymic lymph nodes (PTLNs). The lymphatic spread of metastasis was further confirmed by the significantly higher %ID/g values of the metastatic PTLNs (4.25±0.28) compared to the control (0.94±0.34). Cytochemical staining of the peripheral blood, autopsy findings, and wright-Giemsa-stained postmortem histological sections proved the leukemic involvement of the assessed tissues/organs. Conclusion: The currently established My1/De model appears to be wellsuited for further leukemia-related therapeutic and diagnostic investigations. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Machine learning techniques based on 18F-FDG PET radiomics features of temporal regions for the classification of temporal lobe epilepsy patients from healthy controls.
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Kai Liao, Huanhua Wu, Yuanfang Jiang, Chenchen Dong, Hailing Zhou, Biao Wu, Yongjin Tang, Jian Gong, Weijian Ye, Youzhu Hu, Qiang Guo, and Hao Xu
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TEMPORAL lobe epilepsy ,RADIOMICS ,MACHINE learning ,PEOPLE with epilepsy ,THREE-dimensional imaging - Abstract
Background: This study aimed to investigate the clinical application of 18F-FDG PET radiomics features for temporal lobe epilepsy and to create PET radiomics-based machine learning models for differentiating temporal lobe epilepsy (TLE) patients from healthy controls. Methods: A total of 347 subjects who underwent 18F-FDG PET scans from March 2014 to January 2020 (234 TLE patients: 25.50 ± 8.89 years, 141 male patients and 93 female patients; and 113 controls: 27.59 ± 6.94 years, 48 male individuals and 65 female individuals) were allocated to the training (n = 248) and test (n = 99) sets. All 3D PET images were registered to theMontreal Neurological Institute template. PyRadiomics was used to extract radiomics features from the temporal regions segmented according to the Automated Anatomical Labeling (AAL) atlas. The least absolute shrinkage and selection operator (LASSO) and Boruta algorithms were applied to select the radiomics features significantly associated with TLE. Eleven machine-learning algorithms were used to establish models and to select the best model in the training set. Results: The final radiomics features (n = 7) used for model training were selected through the combinations of the LASSO and the Boruta algorithms with cross-validation. All data were randomly divided into a training set (n = 248) and a testing set (n = 99). Among 11 machine-learning algorithms, the logistic regression (AUC 0.984, F1-Score 0.959)model performed the best in the training set. Then, we deployed the corresponding online website version (https://wane199.shinyapps.io/TLE_Classification/), showing the details of the LR model for convenience. The AUCs of the tuned logistic regression model in the training and test sets were 0.981 and 0.957, respectively. Furthermore, the calibration curves demonstrated satisfactory alignment (visually assessed) for identifying the TLE patients. Conclusion: The radiomics model from temporal regions can be a potential method for distinguishing TLE. Machine learning-based diagnosis of TLE from preoperative FDG PET images could serve as a useful preoperative diagnostic tool. [ABSTRACT FROM AUTHOR]
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- 2024
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39. Aortic Angiosarcoma Manifesting as Multiple Musculoskeletal Metastases: A Case Report.
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Bahk, Won Jong, Na, Sae Jung, Whang, In Yong, Kim, Yongju, and Seo, Kyung Jin
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ANGIOSARCOMA , *SOFT tissue tumors , *POSITRON emission tomography , *AORTA , *MAGNETIC resonance imaging , *METASTASIS - Abstract
Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases. A 59-year-old male patient presented with left thigh pain. Plain radiographs revealed multifocal osteolytic lesions in the left femur shaft. Abdominopelvic computed tomography showed a lobulated osteolytic lesion in the left iliac bone. Magnetic resonance images revealed multifocal soft tissue lesions in the thigh musculature. A positron emission tomography/computed tomography (PET/CT) scan demonstrated multiple foci of increased uptake in the left femur bone, pelvis, left thigh, and calf musculature. Focal increased uptake in the lower abdominal aorta was newly detected. Pelvis biopsy showed tumor cell nests of epithelioid cells. The tumor cells showed vasoformative features. Immunohistochemically, the tumor cells showed positivity for vimentin, CD31, and ERG. The pathologic diagnosis of epithelioid angiosarcoma was established. The origin of the tumor was presumed to be the aorta. This case underscores the importance of PET scans in identifying primary lesions. In terms of the histopathologic diagnosis of biopsy samples with tumor cells exhibiting epithelioid neoplastic morphology, employing appropriate ancillary techniques such as immunocytochemistry with vascular markers may assist in accurately diagnosing metastatic angiosarcoma. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer.
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Yang, Qi, Chen, Zhao, Qiu, Yongkang, Huang, Wenpeng, Wang, Tianyao, Song, Lele, Sun, Xinyao, Li, Cuicui, Xu, Xiaojie, and Kang, Lei
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CHELATING agents , *BREAST cancer , *PLACENTAL growth factor , *VASCULAR endothelial growth factors , *TRIPLE-negative breast cancer , *AFLIBERCEPT , *LUTETIUM compounds - Abstract
Purpose: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30–60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. Methods: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin–eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. Results: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. Conclusion: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC. [ABSTRACT FROM AUTHOR]
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- 2024
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41. In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study.
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Farkasinszky, Gergely, Péliné, Judit Szabó, Károlyi, Péter, Rácz, Szilvia, Dénes, Noémi, Papp, Tamás, Király, József, Szabo, Zsuzsanna, Kertész, István, Mező, Gábor, Halmos, Gabor, Képes, Zita, and Trencsényi, György
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ANIMAL disease models , *ANIMAL models in research , *ISCHEMIA , *ALANINE aminopeptidase , *PERIPHERAL vascular diseases , *REPERFUSION - Abstract
Background: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD). Methods: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[18F]FDG and [68Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts. Results: Due to a cellular adaptation to hypoxia, a gradual increase in [68Ga]Ga-NOTA-c(NGR) and 2-[18F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups. Conclusions: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD. [ABSTRACT FROM AUTHOR]
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- 2024
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42. A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma.
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Pan, Yue, Dang, Haodan, Zhou, Haoxi, Fu, Huaping, Wu, Shina, Liu, Huanhuan, Zhang, Jinming, Wang, Ruimin, Tian, Yuan, and Xu, Baixuan
- Abstract
Purpose: To investigate and compare the dynamic positron emission tomography (PET) imaging with [18F]Alfatide II Imaging and [11C]Methionine ([11C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [18F]Alfatide II in detecting and evaluating neoangiogenesis in GBM. Methods: [18F]Alfatide II and [11C]MET were injected into the orthotopic GBM rat models (n = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation. Results: Compared to 11C-MET, [18F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time–activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [18F]Alfatide II (time to peak:255 s) and 40 min for [11C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K1 (0.23/0.07) and K3 (0.26/0.09) in the tumor region compared to the normal brain with [18F]Alfatide II. Compared to [11C]MET imaging, PKM confirmed both significantly higher K1/K2 (1.24 ± 0.79/1.05 ± 0.39) and K3/K4 (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [18F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region. Conclusion: [18F]Alfatide II demonstrates potential in imaging tumor-associated neovascularization in the context of glioblastoma multiforme (GBM), suggesting its utility as a tool for further exploration in neovascular characterization. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Estimation of target occupancy in repeated dosing design studies using positron emission tomography: Biases due to target upregulation.
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Rabiner, Eugenii A and Gunn, Roger N
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Positron emission tomography (PET) has become indispensable in the quantification of target engagement by brain targeting medications. The relationship between the drug plasma concentration (or drug dose administered) and target occupancy determined during a PET occupancy study has provided valuable information for the assessment of novel pharmaceuticals in the early phases of drug development. Such information is also critical for the understanding of the mechanisms of action and side-effect profile of approved medication commonly used in the clinic. Occupancy studies conducted following repeated drug dosing (RD) can produce systematic differences from those conducted following single drug dose (SD), differences that have not been adequately explored. We have hypothesised that when differences are observed between RD and SD studies, they are related to changes in target density induced by repeated drug accumulation. We have developed a modified occupancy model to account for potential changes in target density and tested it on a sample dataset. We found that target upregulation can parsimoniously explain the differences in drug affinity estimated in SD and RD studies. Our findings have implications for the interpretation of RD occupancy data in the literature and the relationship between specific target occupancy levels and drug efficacy and tolerability. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Evaluation of peripheral nerve injury according to the severity of damage using 18F-FDG PET/MRI in a rat Model of sciatic nerve injury.
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Park, Jong Yeol, Lee, Mi Jee, Kim, Hyung Jun, and Nam, Jung Woo
- Abstract
We ascertained that the PET scan may be a valuable imaging modality for the noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury through the previous study. This study aimed to assess peripheral nerve damage according to severity using
18 F-FDG PET/MRI of the rat sciatic nerve. Eighteen rats were divided into three groups: 30-second (G1), 2-minute (G2), and 5-minute (G3) crushing injuries. The severity of nerve damage was measured in the third week after the crushing injury using three methods: the paw withdrawal threshold test (RevWT), standardized uptake values on PET (SUVR), and intensity analysis on immunohistochemistry (IntR). There were significant differences between G1 and G3 in both SUVR and IntR (p = 0.012 and 0.029, respectively), and no significant differences in RevWT among the three groups (p = 0.438). There was a significant difference in SUVR (p = 0.012), but no significant difference in IntR between G1 and G2 (p = 0.202). There was no significant difference between G2 and G3 in SUVR and IntR (p = 0.810 and 0.544, respectively). Although PET did not show results consistent with those of immunohistochemistry in all respects, this study demonstrated that PET uptake tended to increase with severe nerve damage. If this research is supplemented by further experiments, PET/MRI can be used as an effective diagnostic modality. [ABSTRACT FROM AUTHOR]- Published
- 2024
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45. Evaluation of MRI post-processing methods combined with PET in detecting focal cortical dysplasia lesions for patients with MRI-negative epilepsy.
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Qian, Zhe, Lin, Jiuluan, Jiang, Rifeng, Jean, Stéphane, Dai, Yihai, Deng, Donghuo, Tagu, Panashe Tevin, Shi, Lin, and Song, Shiwei
- Abstract
Accurate detection of focal cortical dysplasia (FCD) through magnetic resonance imaging (MRI) plays a pivotal role in the preoperative assessment of epilepsy. The integration of multimodal imaging has demonstrated substantial value in both diagnosing FCD and devising effective surgical strategies. This study aimed to enhance MRI post-processing by incorporating positron emission tomography (PET) analysis. We sought to compare the diagnostic efficacy of diverse image post-processing methodologies in patients presenting MRI-negative FCD. In this retrospective investigation, we assembled a cohort of patients with negative preoperative MRI results. T1-weighted volumetric sequences were subjected to morphometric analysis program (MAP) and composite parametric map (CPM) post-processing techniques. We independently co-registered images derived from various methods with PET scans. The alignment was subsequently evaluated, and its correlation was correlated with postoperative seizure outcomes. A total of 41 patients were enrolled in the study. In the PET-MAP(p = 0.0189) and PET-CPM(p = 0.00041) groups, compared with the non-overlap group, the overlap group significantly associated with better postoperative outcomes. In PET(p = 0.234), CPM(p = 0.686) and MAP(p = 0.672), there is no statistical significance between overlap and seizure-free outcomes. The sensitivity of using the CPM alone outperformed the MAP (0.65 vs 0.46). The use of PET-CPM demonstrated superior sensitivity (0.96), positive predictive value (0.83), and negative predictive value (0.91), whereas the MAP displayed superior specificity (0.71). Our findings suggested a superiority in sensitivity of CPM in detecting potential FCD lesions compared to MAP, especially when it is used in combination with PET for diagnosis of MRI-negative epilepsy patients. Moreover, we confirmed the superiority of synergizing metabolic imaging (PET) with quantitative maps derived from structural imaging (MAP or CPM) to enhance the identification of subtle epileptogenic zones (EZs). This study serves to illuminate the potential of integrated multimodal techniques in advancing our capability to pinpoint elusive pathological features in epilepsy cases. [ABSTRACT FROM AUTHOR]
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- 2024
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46. Trait-anxiety and glial-related neuroinflammation of the amygdala and its associated regions in Alzheimer's disease: A significant correlation
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Fumihiko Yasuno, Yasuyuki Kimura, Aya Ogata, Hiroshi Ikenuma, Junichiro Abe, Hiroyuki Minami, Takashi Nihashi, Kastunori Yokoi, Saori Hattori, Nobuyoshi Shimoda, Atsushi Watanabe, Kensaku Kasuga, Takeshi Ikeuchi, Akinori Takeda, Takashi Sakurai, Kengo Ito, and Takashi Kato
- Subjects
Alzheimer's disease ,Positron emission tomography (PET) ,Inflammation ,State-Trait Anxiety Inventory (STAI) ,Anxiety ,amygdala ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: Positron emission tomography, which assesses the binding of translocator protein radiotracers, 11C-DPA-713, may be a sensitive method for determining glial-mediated neuroinflammation levels. This study investigated the relationship between regional 11C-DPA713 binding potential (BPND) and anxiety in patients with Alzheimer's disease (AD) continuum. Methods: Nineteen patients with AD continuum determined to be amyloid-/p-tau 181-positive via cerebrospinal fluid analysis were included in this cross-sectional study (mild cognitive impairment [MCI, n = 5] and AD [n = 14]). Anxiety was evaluated using the State-Trait Anxiety Inventory (STAI). A whole-brain voxel-based analysis was performed to examine the relationship between 11C-DPA-713-BPND values at each voxel and the STAI score. Stepwise multiple regression analysis was performed to determine the predictors of STAI scores using independent variables, including 11C-DPA-713-BPND values within significant clusters. 11C-DPA-713-BPND values were compared between patients with AD continuum with low-to-moderate and high STAI scores. Results: Voxel-based analysis revealed a positive correlation between trait anxiety severity and 11C-DPA713-BPND values in the centromedial amygdala and the left inferior occipital area [P
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- 2024
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47. Developing a selective sphingosine-1-phosphate-5 (s1p5) radiotracer to image oligodendrocytes using preclinical positron emission tomography (PET)
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Shaw, Robert, Tavares, Adriana, and Lucatelli, Christophe
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radiotracer ,sphingosine-1-phosphate-5 (s1p5) ,oligodendrocytes ,positron emission tomography (PET) ,multiple sclerosis (MS) ,Positron Emission Tomography (PET) ligands ,TEFM180 ,TEFM78 ,agonist radiotracer ,agonists targeting S1P5 ,G-protein coupled receptor ,MS pathobiology ,S1P5 PET radiotracer ,[3H]TEFM180 ,[18F]TEFM78 - Abstract
In multiple sclerosis (MS), the myelin sheaths (the lipid sheathing around neurons, which are produced by oligodendrocytes) degenerate, leading to a loss of function, neuronal degeneration and disability. Although there have been advances in recent years, there is still no cure for MS or even a method to facilitate imaging oligodendrocytes activity in vivo, other than the established structural techniques such as Magnetic Resonance Imaging (MRI). In this thesis we aimed to develop novel Positron Emission Tomography (PET) ligands to specifically bind to oligodendrocytes in the central nervous system in vivo. The ligands target the sphingosine-1-phosphate-5 (S1P5) receptor as a potential marker of oligodendrocyte function with PET. The ligands selected (TEFM180 and TEFM78) were developed from a drug development library of agonists targeting S1P5 that had shown high affinity and selectivity for their target. An agonist radiotracer would be of particular interest as S1P5 is a G-protein coupled receptor and agonists show a bias to binding receptors in the active state. If successfully translated, these ligands could aid in improving trials of novel therapeutics, improving assessment of disease progression and importantly furthering our understanding of MS pathobiology. To deliver on this project's overarching aim (developing a new S1P5 PET radiotracer), the first priority was to evaluate S1P5 as a specific target on oligodendrocytes. For this, in situ hybridisation and immunofluorescence staining techniques were applied on adult naïve rat brain tissue sections. S1P5 was stained alongside various markers of oligodendrocyte developmental stage as well as markers for other central nervous system (CNS) cell types (astrocytes, microglia, and neurons). This enabled the staging of S1P5 expression at the protein level and its co-localisation and co-expression with specific cell type markers. Alongside characterisation of S1P5 expression at the RNA and protein level in the mammalian brain, two lead small molecules were investigated as potential selective PET radiotracers for S1P5. One of those molecules was TEFM180, a compound amenable to carbon-11 labelling, which was labelled with tritium and used to conduct receptor ligand binding assays and autoradiography experiments on naïve rat brain tissue. The other compound was TEFM78, a lead candidate for fluorine-18 radiolabelling. [18F]TEFM78 was radiolabelled and used for in vivo radiometabolite experiments, plasma free-fraction experiments, and dynamic PET scans on naïve rats. Kinetic modelling was conducted on the [18F]TEFM78 PET scans with input function data collected. Results from experiments conducted in this project showed there was co-localisation between S1P5 and Plp1 using in situ hybridisation and between S1P5 positive cells and CC1 positive cells using immunofluorescence staining techniques. Olig2 positive cells did not co-localise with S1P5 positive cells in the majority of cases however there was some co-localisation in a subset of cells. NG2 positive cells did not co-localise with S1P5 positive cells. GFAP and Iba1 did not co-localise with S1P5 positive cells and the cells were morphologically distinct. There was co-localization between NeuN positive cells and S1P5. In vitro receptor ligand binding assays showed that total and non-specific binding rose at increasing [3H]TEFM180 concentrations and high concentrations of rat brain protein were required to obtain a low degree of specific binding. Higher specific binding was measured using in vitro autoradiography techniques (37.62 to 70.96%). However the binding did not correlate with S1P5 immunofluorescence staining. TEFM78 was successfully radiolabelled with [18F] and used for in vivo PET studies, however productions did have a low yield and relatively low molar activity. Radiometabolite studies showed moderate metabolism of [18F]TEFM78 in rats (44% at 1 hour post-injection) and high plasma protein binding in both rat and human blood (>98%). In in vivo PET scans, [18F]TEFM78 cleared the blood rapidly, entered the rat brain and had higher uptake in white matter rich regions compared with grey matter regions. Kinetic modelling was completed on the scans with invasive input function and it was found that a 1-tissue model was preferred for this data. The total volume of distribution (VT) was 1.39 ± 0.06 mL/ccm in the whole brain, 1.58 ± 0.04 mL/ccm in the white matter and 1.39 ± 0.07 mL/ccm in grey matter. The immunofluorescence results confirm that S1P5 remains a target of interest to investigate oligodendrocytes in the context of MS, however the neuronal expression seen requires further investigation. [3H]TEFM180 is a sub-optimal ligand with low specific target engagement, however we demonstrated that this chemical scaffold is capable of crossing the blood-brain barrier and entering the CNS at time points favourable for a PET radiotracer, meaning future and optimised candidates from this structure could be more successful. [18F]TEFM78 is a promising ligand for PET imaging, however the radiosynthesis of [18F]TEFM78 should be improved to gain a higher molar activity to enable application of this technology in preclinical models of MS and potentially augment translational potential to clinical use.
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- 2023
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48. Machine learning aided bioimpedance tomography for tissue engineering
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Chen, Zhou, Yang, Yunjie, Jia, Jlabin, Bagnaninchi, Pierre, and Polydorides, Nicholas
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Machine learning ,bioimpedance tomography ,tissue engineering ,miniature Electrical Impedance Tomography (mEIT) ,3-D cellular dynamics ,Computed Tomography (CT) ,Positron Emission Tomography (PET) ,Magnetic Resonance Imaging (MRI) ,3D cancer cell spheroids (MCF-7) ,Multi-frequency Electrical Impedance Tomography (mfEIT) ,Multiple Measurement Vector (MMV) ,Alternating Direction Method of Multipliers ,MMV-ADMM ,Convolutional Long Short-Term Memory (ConvLSTM) ,Electrical Impedance Tomography (EIT) - Abstract
In tissue engineering, miniature Electrical Impedance Tomography (mEIT) (or bioimpedance tomography), is an emerging tomographic modality that contributes to non-destructive and label-free imaging and monitoring of 3-D cellular dynamics. The main challenge of mEIT comes from the nonlinear and ill-posed image reconstruction problem, leading to the increased sensitivity to imperfect measurement signals. Physical model-based image reconstruction methods have been successfully applied to conventional setups, but are less satisfying for the mEIT setup regarding image quality, conductivity retrieval and computational efficiency. Data-driven or learning-based methods have recently become a new frontier for tomographic image reconstruction, particularly for medical imaging modalities, e.g., Computed Tomography (CT), Positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI). However, the study of learning-based image reconstruction methods in challenging micro-scale sensor setups and the seamless integration of such algorithms with the tomography instrument remains a gap. This thesis aims to develop 2-D and 3-D imaging platforms integrating multi-frequency EIT and machine learning-based image reconstruction algorithms to extract spectroscopic electrical properties of 3-D cultivated cells under in vitro conditions, in a non-destructive, robust, and computation-efficient manner. Recent advances in deep learning have pointed out a promising alternative for EIT image reconstruction. However, it is still challenging to image multiple objects with varying conductivity levels with a single neural network. A deep learning and group sparsity regularization-based hybrid image reconstruction framework was proposed to enable high-quality cell culture imaging with mEIT. A deep neural network was proposed to estimate the structural information in binary masks, given the limited number of data sets. Then the structural information is encoded in group sparsity regularization to obtain the final conductivity estimation. We validated our approach by imaging 3D cancer cell spheroids (MCF-7). Our method can be readily translated to spheroids, organoids, and cell culture in scaffolds of biomaterials. As the measured conductivity is a proxy for cell viability, mEIT has excellent potential to enable non-invasive, real-time, long-term monitoring of 3D cell growth, opening new avenues in regenerative medicine and drug testing. Deep learning provides binary structural information in the above-mentioned hybrid learning approach, whereas the regularization algorithm determines conductivity contrasts. Despite the advancement of structure distribution, the exact conductivity values of different objects are less accurately estimated by the regularization-based framework, which essentially prevents EIT's transition from generating qualitative images to quantitative images. A structure-aware dual-branch deep learning method was proposed to further tackle this issue to predict structure distribution and conductivity values. The proposed network comprises two independent branches to encode the structure and conductivity features, respectively, and the two branches are joined later to make final predictions of conductivity distributions. Numerical and experimental evaluation results on MCF-7 human breast cancer cell spheroids demonstrate the superior performance of the proposed method in dealing with the multi-level, continuous conductivity reconstruction problem. Multi-frequency Electrical Impedance Tomography (mfEIT) is an emerging biomedical imaging modality to reveal frequency-dependent conductivity distributions in biomedical applications. Conventional model-based image reconstruction methods suffer from low spatial resolution, unconstrained frequency correlation and high computational cost. Most existing learning-based approaches deal with the single-frequency setup, which is inefficient and ineffective when extended to the multi-frequency setup. A Multiple Measurement Vector (MMV) model-based learning algorithm named MMV-Net was proposed to solve the mfEIT image reconstruction problem. MMV-Net considers the correlations between mfEIT images and unfolds the update steps of the Alternating Direction Method of Multipliers for the MMV problem (MMV-ADMM). The nonlinear shrinkage operator associated with the weighted l_{1,2} regularization term of MMV-ADMM is generalized in MMV-Net with a cascade of a Spatial Self-Attention module and a Convolutional Long Short-Term Memory (ConvLSTM) module to capture intra- and inter-frequency dependencies better. The proposed MMV-Net was validated on our Edinburgh mfEIT Dataset and a series of comprehensive experiments. The results show superior image quality, convergence performance, noise robustness and computational efficiency against the conventional MMV-ADMM and the state-of-the-art deep learning methods. Finally, few work on image reconstruction for Electrical Impedance Tomography (EIT) focuses on 3D geometries. Existing reconstruction algorithms adopt voxel grids for representation, which typically results in low image quality and considerable computational cost, and limits their applicability to real-time applications. In contrast, point clouds are a more efficient format for 3D surfaces, and such representation can naturally handle 3D shapes of arbitrary topologies with fine-grained details. Therefore, a learning-based 3D EIT reconstruction algorithm with efficient 3D representations (i.e., point cloud) was proposed to achieve higher image accuracy, spatial resolution and computational efficiency. A transformer-like point cloud network is adopted for 3D image reconstruction. This network simultaneously recovers the 3D coordinates of points to adaptively portray the objects' surface and predicts each point's conductivity. The results show that point cloud provides more efficient fine-shape descriptions and effectively alleviates computational costs. In summary, the work demonstrated in this thesis addressed the research void in tissue imaging with bioimpedance tomography by developing learning-based imaging approaches. The results achieved in this thesis could promote bioimpedance tomography as a robust, intelligent imaging technique for tissue engineering applications.
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- 2023
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49. STING-targeted PET imaging: unveiling tumor immunogenicity post-chemotherapy in colorectal cancer.
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Li, Chao, Saladin, Rachel J., Cai, Weibo, and Chen, Weiyu
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POSITRON emission tomography , *IMMUNE response , *COLORECTAL cancer , *T cells , *REGULATORY T cells , *COLORECTAL liver metastasis - Abstract
A study published in the European Journal of Nuclear Medicine & Molecular Imaging explores the potential of STING-targeted PET imaging in monitoring tumor immunogenicity in colorectal cancer (CRC) patients after chemotherapy. The study uses a novel PET tracer called [18F]FBTA, which demonstrates higher specificity and sensitivity compared to conventional [18F]FDG. The research findings indicate that [18F]FBTA accurately reflects the impact of different chemotherapeutic agents on the immune activity of CRC tumors. The study suggests that [18F]FBTA holds promise as a reliable clinical tool for guiding treatment decisions and facilitating the combination of immunotherapy with chemotherapy in CRC patients. [Extracted from the article]
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- 2024
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50. Dual-Tracer Positron Emission Tomography/Computed Tomography with [ 18 F]FDG and [ 18 F]fluorocholine in a Patient with Metastatic Parathyroid Carcinoma.
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Iacovitti, Cesare Michele, Cuzzocrea, Marco, Gianola, Lauro, Paone, Gaetano, and Treglia, Giorgio
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POSITRON emission tomography , *COMPUTED tomography , *CANCER chemotherapy , *LUNG diseases , *NUCLEAR medicine - Abstract
Here, we describe the case of a 43-year-old male patient with a metastatic parathyroid carcinoma who underwent dual-tracer whole-body positron emission tomography/computed tomography (PET/CT) with [18F]fluorocholine and fluorodeoxyglucose ([18F]FDG) for staging. [18F]FDG PET/CT detected multiple cervical and mediastinal lymph nodal lesions with increased tracer uptake, whereas [18F]fluorocholine PET/CT detected increased tracer uptake on cervical and mediastinal lymph nodal lesions and bone and lung lesions with a better evaluation of metastatic spread. Due to these imaging findings, the patient underwent systemic treatment with chemotherapy. This case demonstrates the added value of dual-tracer PET/CT in this rare metastatic tumor. [ABSTRACT FROM AUTHOR]
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- 2024
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