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The use of in vitro models to understand the interaction of bacteria with host cells is well established. In vitro bacterial infection models are often used to quantify intracellular bacterial load by lysing cell populations and subsequently enumerating the bacteria. Modern established techniques employ the use of fluorescence technologies such as flow cytometry, fluorescent microscopy, and/or confocal microscopy. However, these techniques often lack either the quantification of large data sets (microscopy) or use of gross fluorescence signal which lacks the visual confirmation that can provide additional confidence in data sets. Multispectral imaging flow cytometry (MIFC) is a novel emerging field of technology. This technology captures a bright field and fluorescence image of cells in a flow using a charged coupled device camera. It allows the analysis of tens of thousands of single cell images, making it an extremely powerful technology. Here MIFC was used as an alternative method of analyzing intracellular bacterial infection using Burkholderia thailandensis E555 as a model organism. It has been demonstrated that the data produced using traditional enumeration is comparable to data analyzed using MIFC. It has also been shown that by using MIFC it is possible to generate other data on the dynamics of the infection model rather than viable counts alone. It has been demonstrated that it is possible to inhibit the uptake of bacteria into mammalian cells and identify differences between treated and untreated cell populations. The authors believe this to be the first use of MIFC to analyze a Burkholderia bacterial species during intracellular infection. © 2016 Crown copyright. Published by Wiley Periodicals Inc. on behalf of ISAC. [ABSTRACT FROM AUTHOR]

Radioimmunotherapies with Zevalin® (RIT-Z) showed encouraging results in patients with relapsed/refractory follicular lymphoma (FL), leading frequently to failure-free intervals longer than those achieved by the last previous therapy. We compared time-to-event variables obtained before and after RIT-Z in patients with relapsed FL, previously exposed to rituximab. All patients with relapsed non-transformed, non-refractory, non-rituximab-naïve FL who have been treated with RIT-Z in two different centres in Europe were included. Staging and response were assessed by contrast-enhanced CT in all patients; PET/CT was performed according to local availability. Event-free survival (EFS) and time to next treatment (TTNT) following the last previous therapy and after RIT-Z were compared. Pre-therapy characteristics were tested in univariate analyses for prediction of outcomes. A description of the patterns of relapse was also provided. Among 70 patients treated, only 16 fulfilled the inclusion criteria. They were treated with a median of 3 prior lines of chemo-immunotherapies, including a median of 2 rituximab-containing regimens; 6 patients had undergone myeloablative chemotherapy with autologous stem cell rescue (ASCT). Overall response rates were 10 (62%) CR/CRu, 3 (19%) PR and 3 (19%) PD; response rates were similar in patients with prior ASCT. After RIT-Z only few patients obtained EFS and TTNT longer than after the last previous therapy. All four patients receiving rituximab maintenance were without progression 12 months after RIT-Z. Relapses occurred in both previously and newly involved sites; a significant association was found between the number of pathologic sites involved prior to RIT-Z and subsequent TTNT. Despite the excellent response rate, the duration of response was shorter than the previous one confirming the known trend of relapses to occur earlier after subsequent treatments. Rituximab maintenance after RIT-Z showed encouraging results in terms of prolonging EFS, warranting further studies. [ABSTRACT FROM AUTHOR]

Background: This study investigated sex differences in the associations between Alzheimer's disease (AD) biomarkers, cognitive performance, and decline in memory clinic settings., Methods: 249 participants (females/males:123/126), who underwent tau-PET, amyloid-PET, structural MRI, and plasma glial fibrillary acidic protein (GFAP) measurement were included from Geneva and Lausanne Memory Clinics. Mann-Whitney U tests investigated sex differences in clinical and biomarker data. Linear regression models estimated the moderating effect of sex on the relationship between biomarkers and cognitive performance and decline. Sex differences in cognitive decline were further evaluated using longitudinal linear mixed-effect models with three-way interaction effects., Results: Women and men present similar clinical features, amyloid, and neurodegeneration. Women had higher tau load and plasma levels of GFAP than men (p < 0.05). Tau associations with amyloid (standardized β = 0.54,p < 0.001), neurodegeneration (standardized β=-0.44,p < 0.001), and cognition (standardized β=-0.48,p < 0.001) were moderated by a significant interaction with sex. Specifically, the association between amyloid and tau was stronger among women than men (standardized β=-0.19,p = 0.047), whereas the associations between tau and cognition and between tau and neurodegeneration were stronger among men than in women (standardized β=-0.76,p = 0.001 and standardized β=-0.56,p = 0.044). Women exhibited faster cognitive decline than men in the presence of severe cortical thinning (p < 0.001)., Conclusion: Women showed higher tau load and stronger association between amyloid and tau than men. In individuals with high tau burden, men exhibited greater neurodegeneration and cognitive impairment than women. These findings support that sex differences may impact tau deposition through an upstream interplay with amyloid, leading to downstream effects on neurodegeneration and cognitive outcomes., Competing Interests: Declarations. Consent to participate: The local Ethics Committee approved the imaging studies, which have been conducted under the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice. Each subject or their relatives provided voluntary written informed consent to participate in the studies. Competing interests: VG received research support and speaker fees through her institution from Healthcare, Siemens Healthineers, Novo Nordisk. Janssen and Novartis. GBF has received support, payment, consulting fees, or honoraria through his institution for lectures, presentations, speaker bureaus, manuscript writing, or educations events from: Biogen, Roche, Diadem, Novo Nordisk, GE Healthcare, OM Pharma, and Eisai. GA has served at scientific advisory boards and consultants for Roche and Lilly and received honoraria for lectures from Lilly and Schwabe Pharma. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant and at advisory boards for Acumen, ALZPath, BioArctic, Biogen, Eisai, Julius Clinical, Lilly, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials, and participated in educational programs for Biogen, Eisai, and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this article. The other authors have no conflicts of interest to disclose., (© 2025. The Author(s).)

Purpose: Therapeutic administration of 90 Y-loaded microspheres is routinely used for primary and secondary liver tumours. For activity-based therapeutic prescription the activity must be within 10% of the intended activity. Previous studies reported significant discrepancies between manufacturer-declared vial activities and both experimental and Monte-Carlo assessments, greater than 10%, for resin/glass 90 Y-microspheres. The objective of this work was to investigate whether these discrepancies were also seen in patients., Methods: We analysed patient 90 Y-PET reconstructions (99 glass and 15 resin microspheres) from 4 different institutions and 4 different systems. We considered tail-fitting background scaling (TFBS) and absolute scaling (ABS), for scatter correction. Residuals after therapeutic injection were measured. Eighty-one patients were imaged with PET/CT and 33 with PET/MR. The PET measured activity (A PET ) was assessed in the whole liver. The ratio A PET /A calibrator was calculated for each patient, where A calibrator was the injected activity measured by the dose calibrator corrected for residual and lung shunt., Results: Quantification ratio between calibrators and PET was significantly different from 1, regardless of the scatter correction used. In glass microspheres, the mean A PET/CT /A calibrator was 0.84 ± 0.06 for TFBS and 0.90 ± 0.06 for ABS (0.66 ± 0.09 and 0.76 ± 0.07 for (A PET/MR /A calibrator )). The mean A PET/CT /A calibrator ratio for resin microspheres was 1.16 ± 0.09 for TFBS and 1.30 ± 0.12 for ABS., Conclusions: We observed in patients similar activity discrepancies as reported for vials, with a relative difference of 44 ± 16% between glass and resin 90 Y-loaded microspheres. In 90 Y hepatic radioembolization, the 10% accuracy prerequisite on knowing the administered therapeutic activity is then unlikely to be met., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. At the University Hospital of Nantes, France, ethical approval was waived by the local Ethics Committee (Groupe Nantais d’Éthique dans le Domaine de la Santé) in view of the retrospective nature of the study and all procedures being performed were part of the routine care. At Lausanne University Hospital, all patients participating in this retrospective study have signed or did not oppose to the general consent form for research and retrospective use of their images for clinical research (protocol submitted to the State of Vaud Ethics Committee CER-VD #2018-01513). At Luzerner Kantonsspital, Luzern, Switzerland, patients signed a general consent for retrospective use of their images for clinical research. At the University of Michigan, all patients signed an informed consent for 90Y-PET/CT imaging approved by the Institutional Review Board (Protocols HUM00118705 and HUM00181352). Competing interests: Maurizio Conti is full-time employee of Siemens Medical Solutions USA, Inc. Clément Bailly is a consultant for Boston Scientific and Sirtex Medical. The other authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s).)

Background: Effective follow-up of brain metastasis (BM) patients post-treatment is crucial for adapting therapies and detecting new lesions. Current guidelines (Response Assessment in Neuro-Oncology-BM) have limitations, such as patient-level assessments and arbitrary lesion selection, which may not reflect outcomes in high tumor burden cases. Accurate, reproducible, and automated response assessments can improve follow-up decisions, including (1) optimizing re-treatment timing to avoid treating responding lesions or delaying treatment of progressive ones, and (2) enhancing precision in evaluating responses during clinical trials., Methods: We compared manual and automatic (deep learning-based) lesion contouring using unidimensional and volumetric criteria. Analysis focused on (1) agreement in size and RANO-BM categories, (2) stability of measurements under scanner rotations and over time, and (3) predictability of 1-year outcomes. The study included 49 BM patients, with 184 MRI studies and 448 lesions, retrospectively assessed by radiologists., Results: Automatic contouring and volumetric criteria demonstrated superior stability ( P  < .001 for rotation; P  < .05 over time) and better outcome predictability compared to manual methods. These approaches reduced observer variability, offering reliable and efficient response assessments. The best outcome predictability, defined as 1-year response, was achieved using automatic contours and volumetric measurements. These findings highlight the potential of automated tools to streamline clinical workflows and provide consistency across evaluators, regardless of expertise., Conclusion: Automatic BM contouring and volumetric measurements provide promising tools to improve follow-up and treatment decisions in BM management. By enhancing precision and reproducibility, these methods can streamline clinical workflows and improve the evaluation of response in trials and practice., Competing Interests: None declared., (© The Author(s) 2025. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Competing Interests: HH serves without remuneration on an external advisory board of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, on the International Advisory Board of the University of Vienna, and on the external Executive Advisory Committee of the Sylvester Comprehensive Cancer Center, University of Miami Health System, and as a member of the Standing Advisory Group on Nuclear Applications of the International Atomic Energy Agency. Until Oct 31, 2024, HH also served without remuneration on the Scientific Committee of the German Cancer Research Center (DKFZ) and the Board of Trustees of the DKFZ. She is remunerated for serving on the Board of Directors of Ion Beam Applications and receives stock options for serving on the Board of Directors of iCAD. Her work is partly supported by funding to her institution (Memorial Sloan-Kettering Center support grant/core grant P30 CA008748) from the US National Institutes of Health (NIH)–National Cancer Institute (NCI). JOP reports uncompensated service as President of the Swiss Society of Nuclear Medicine, service to the World Federation of Nuclear Medicine and Biology as the focal point for technical collaboration with WHO, and service as the President of Section and Board of Nuclear Medicine of the European Union of Medical Specialists. AM reports that her work is partly supported by funding to her institution (Memorial Sloan-Kettering Center support grant/core grant P30 CA008748) from NIH–NCI. BA reports support for attending meetings or travel from the International Society of Radiology and the American College of Radiology. AMS reports institutional research funding from the Australian National Health and Medical Research Council, Medical Research Future Fund, and National Imaging Facility; patents planned, issued or pending for his role as an inventor of antibodies to HER2, ADAMs, EGFR, and Ephs; uncompensated participation on data safety monitoring or advisory boards for Telix and ImunOs; uncompensated service as a board member for the Australia and New Zealand Society of Nuclear Medicine and World Federation of Nuclear Medicine and Biology and as theme chair of the National Imaging Facility; stock holdings as founder and Director of Certis Therapeutics; and research and trial funding to his institution from Telix, Clarity, Fusion, Antengene, EMD Serono, ITM, Avid/Lily, Medimmune, and Cyclotek. All other authors declare no competing interests.

Manual segmentation of lesions, required for radiotherapy planning and follow-up, is time-consuming and error-prone. Automatic detection and segmentation can assist radiologists in these tasks. This work explores the automated detection and segmentation of brain metastases (BMs) in longitudinal MRIs. It focuses on several important aspects: identifying and segmenting new lesions for screening and treatment planning, re-segmenting lesions in successive images using prior lesion locations as an additional input channel, and performing multi-component segmentation to distinguish between enhancing tissue, edema, and necrosis. The key component of the proposed approach is to propagate the lesion mask from the previous time point to improve the detection performance, which we refer to as "re-segmentation". The retrospective data includes 518 metastases in 184 contrast-enhanced T1-weighted MRIs originating from 49 patients (63% male, 37% female). 131 time-points (36 patients, 418 BMs) are used for cross-validation, the remaining 53 time-points (13 patients, 100 BMs) are used for testing. The lesions were manually delineated with label 1: enhancing lesion, label 2: edema, and label 3: necrosis. One-tailed t-tests are used to compare model performance including multiple segmentation and detection metrics. Significance is considered as p < 0.05. A Dice Similarity Coefficient (DSC) of 0.79 and F 1 -score of 0.80 are obtained for the segmentation of new lesions. On follow-up scans, the re-segmentation model significantly outperforms the segmentation model (DSC and F 1 0.78 and 0.88 vs 0.56 and 0.60). The re-segmentation model also significantly outperforms the simple segmentation model on the enhancing lesion (DSC 0.76 vs 0.53) and edema (0.52 vs 0.47) components, while similar scores are obtained on the necrosis component (0.62 vs 0.63). Additionally, we analyze the correlation between lesion size and segmentation performance, as demonstrated in various studies that highlight the challenges in segmenting small lesions. Our findings indicate that this correlation disappears when utilizing the re-segmentation approach and evaluating with the unbiased normalized DSC. In conclusion, the automated segmentation of new lesions and subsequent re-segmentation in follow-up images was achievable, with high level of performance obtained for single- and multiple-component segmentation tasks., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The aim of this prospective, observational cohort study was to investigate and assess diverse neuroimaging biomarkers to predict patients' neurological recovery after coma. 32 patients (18-76 years, M = 44.8, SD = 17.7) with disorders of consciousness participated in the study. Multimodal neuroimaging data acquired during the patient's hospitalization were used to derive cortical glucose metabolism ( 18 F-fluorodeoxyglucose positron emission tomography/computed tomography), and structural (diffusion-weighted imaging) and functional connectivity (resting-state functional MRI) indices. The recovery outcome was defined as a continuous composite score constructed from a multivariate neurobehavioral recovery assessment administered upon the discharge from the hospital. Fractional anisotropy-based white matter integrity in the anterior forebrain mesocircuit (r = 0.72, p < .001, 95% CI: 0.87, 0.45), and the functional connectivity between the antagonistic default mode and dorsal attention resting-state networks (r = - 0.74, p < 0.001, 95% CI: - 0.46, - 0.88) strongly correlated with the recovery outcome. The association between the posterior glucose metabolism and the recovery outcome was moderate (r = 0.38, p = 0.040, 95% CI: 0.66, 0.02). Structural (adjusted R 2  = 0.84, p = 0.003) or functional connectivity biomarker (adjusted R 2  = 0.85, p = 0.001), but not their combination, significantly improved the model fit to predict the recovery compared solely to bedside neurobehavioral evaluation (adjusted R 2  = 0.75). The present study elucidates an important role of specific MRI-derived structural and functional connectivity biomarkers in diagnosis and prognosis of recovery after coma and has implications for clinical care of patients with severe brain injury., (© 2024. The Author(s).)

Background: Transarterial radio-embolization (TARE) became a routine procedure for non-resectable liver tumor mainly hepatocellular carcinoma (HCC). Personalized dosimetry to the index lesion increased tumor response rate. However, there is no requirement to measure the precise activity injected during TARE. We measured 90 Y-glass microspheres residue ( 90 Y-Res) in the application system after TARE and assessed its potential impact on the tumor absorbed dose (AD) previously planned with 99m Tc MAA SPECT/CT., Methods: We measured 90 Y-Res using PET/CT in all patients that underwent TARE using 90 Y-glass-microspheres for non-resectable liver tumors over one year., Results: 90 Y-Res was measured in 34 patients (HCC n = 22) with 61 injections, 93.1 ± 94.6 MBq [2-437] that was 4.8 ± 3.5% [0.2-13.7] in comparison to the activity measured in the sealed TheraSphere™ vial (ρ = 0.697; p < 0.001)., Conclusion: We reported an average of 5% 90 Y-Res using PET/CT after TARE with the strongest association to the activity in the TheraSphere™ vial. Therefore, when a high 90 Y-Res is suspected on the survey meter, a 90 Y-PET/CT scan of 90 Y-Res might be useful as a first step to estimate if the target lesion received the recommended AD, especially in HCC patients with borderline tumor dosimetry on the pre-treatment 99m Tc-MAA SPECT/CT., (© 2024. The Author(s).)

Purpose: Artificial intelligence (AI) in positron emission tomography/computed tomography (PET/CT) can be used to improve image quality when it is useful to reduce the injected activity or the acquisition time. Particular attention must be paid to ensure that users adopt this technological innovation when outcomes can be improved by its use. The aim of this study was to identify the aspects that need to be analysed and discussed to implement an AI denoising PET/CT algorithm in clinical practice, based on the representations of Nuclear Medicine Technologists (NMT) from Western-Switzerland, highlighting the barriers and facilitators associated., Methods: Two focus groups were organised in June and September 2023, involving ten voluntary participants recruited from all types of medical imaging departments, forming a diverse sample of NMT. The interview guide followed the first stage of the revised model of Ottawa of Research Use. A content analysis was performed following the three-stage approach described by Wanlin. Ethics cleared the study., Results: Clinical practice, workload, knowledge and resources were de 4 themes identified as necessary to be thought before implementing an AI denoising PET/CT algorithm by ten NMT participants (aged 31-60), not familiar with this AI tool. The main barriers to implement this algorithm included workflow challenges, resistance from professionals and lack of education; while the main facilitators were explanations and the availability of support to ask questions such as a "local champion"., Conclusion: To implement a denoising algorithm in PET/CT, several aspects of clinical practice need to be thought to reduce the barriers to its implementation such as the procedures, the workload and the available resources. Participants emphasised also the importance of clear explanations, education, and support for successful implementation., Implications for Practice: To facilitate the implementation of AI tools in clinical practice, it is important to identify the barriers and propose strategies that can mitigate it., Competing Interests: Conflict of interest statement The authors have non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists., Methods: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice., Results: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries., Conclusion: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics., (© 2024. The Author(s).)

Angiogenesis is an essential part of the cardiac repair process after myocardial infarction, but its spatiotemporal dynamics remain to be fully deciphered. 68 Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting α v β 3 integrin expression, which is a marker of angiogenesis. Methods: In this prospective single-center trial, we aimed to monitor angiogenesis through myocardial integrin α v β 3 expression in 20 patients with ST-segment elevation myocardial infarction (STEMI). In addition, the correlations between the expression levels of myocardial α v β 3 integrin and the subsequent changes in 82 Rb PET/CT parameters, including rest and stress myocardial blood flow (MBF), myocardial flow reserve (MFR), and wall motion abnormalities, were assessed. The patients underwent 68 Ga-NODAGA-RGD PET/CT and rest and stress 82 Rb-PET/CT at 1 wk, 1 mo, and 3 mo after STEMI. To assess 68 Ga-NODAGA-RGD uptake, the summed rest 82 Rb and 68 Ga-NODAGA-RGD images were coregistered, and segmental SUVs were calculated (RGD SUV). Results: At 1 wk after STEMI, 19 participants (95%) presented increased 68 Ga-NODAGA-RGD uptake in the infarcted myocardium. Seventeen participants completed the full imaging series. The values of the RGD SUV in the infarcted myocardium were stable 1 mo after STEMI (1 wk vs. 1 mo, 1.47 g/mL [interquartile range (IQR), 1.37-1.64 g/mL] vs. 1.47 g/mL [IQR, 1.30-1.66 g/mL]; P = 0.9), followed by a significant partial decrease at 3 mo (1.32 g/mL [IQR, 1.12-1.71 g/mL]; P = 0.011 vs. 1 wk and 0.018 vs. 1 mo). In segment-based analysis, positive correlations were found between RGD SUV at 1 wk and the subsequent changes in stress MBF (Spearman ρ: r = 0.17, P = 0.0033) and MFR (Spearman ρ: r = 0.31, P < 0.0001) at 1 mo. A negative correlation was found between RGD SUV at 1 wk and the subsequent changes in wall motion abnormalities at 3 mo (Spearman ρ: r = - 0.12, P = 0.035). Conclusion: The present study found that α v β 3 integrin expression is significantly increased in the infarcted myocardium 1 wk after STEMI. This expression remains stable after 1 mo and partially decreases after 3 mo. Initial α v β 3 integrin expression at 1 wk is significantly weakly correlated with subsequent improvements in stress MBF, MFR, and wall motion analysis., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: A physiological increase in the uptake of [ 68 Ga]Ga-labeled somatostatin analogues ([ 68 Ga]Ga-SST) PET tracers has been reported in the uncinate pancreatic process (UP) and might be even higher in latest generation of PET/CT scanners and might be falsely interpreted as NET. We aimed to investigate the uptake of UP in a large population of NET patients who underwent [ 68 Ga]Ga-SST PET/CT with digital SiPM detectors. We also explored potential associations between UP uptake and various clinical, imaging, and pathological factors routinely assessed in NET patients., Methods: We analyzed all consecutive NET patients from July 2018 to June 2022 in this retrospective, single-center study. All patients underwent a [ 68 Ga]Ga-SST PET/CT scan on a digital SiPM PET/CT scanner. On visual analysis, we distinguished between normal linear and homogenous UP uptake or abnormal if otherwise. We compared SUV max/mean in patients with normal UP uptake to those with abnormal UP uptake with suspicious NET lesions on contrast-enhanced CT (ce-CT) and according to the site of the primary NET (pancreatic NET vs. other), patient gender (female vs. male) and tumor grade (grade 1-2 vs. 3) using a Mann-Whitney test. We also assessed the correlation between SUV max/mean values in UP with patients' age, primary NET Ki-67 counting, and its SUV max/mean , TLA and MTV values., Results: We included 131 NET patients with a total of 34 [ 68 Ga]Ga-DOTATATE PET/CT and 113 [ 68 Ga]Ga-DOTATOC PET/CT scans. An abnormal UP uptake was seen in 32 patients with 65.7% of suspicious NET lesion or extrinsic compression on morphological imaging. Normal UP uptake SUV max/mean were measured in 115 [ 68 Ga]Ga-SST scans (78.2%) with normal UP uptake and without suspicious lesion on morphological imaging. We found an average SUV max of 12.3 ± 4.1 for [ 68 Ga]Ga-DOTATATE and 19.8 ± 9.8 g/ml for [ 68 Ga]Ga-DOTATOC, hence higher than those reported in the literature [SUVmax 5 ± 1.6 to 12.6 ± 2.2 g/ml] with significant difference with abnormal UP uptake and between both PET tracers (both p < 0.01). Significant results were a higher UP uptake on [ 68 Ga]Ga-DOTATOC in male patients (p = 0.02) and significant associations between UP uptake on [ 68 Ga]Ga-DOTATOC and SUV max/mean of the primary tumor (ρ [0.337-0.363]; p [0.01-0.02])., Conclusion: We confirmed a higher and very frequent UP uptake in latest SiPM-detector [ 68 Ga]Ga-SST PET/CT with an even higher uptake in patients that had [ 68 Ga]Ga-DOTATOC PET/CT. SUV mean/max were significantly higher in abnormal UP uptake but there were overlaps with UP SUV values for both [ 68 Ga]Ga-SST and a correlation to morphological imaging is crucial. Besides, significant associations between UP uptake and SUV mean/max of the primary NET as well as patients' gender were seen in the larger cohort of [ 68 Ga]Ga-DOTATOC patients suggesting that both physiological and pathological parameters could affect UP uptake., (© 2024. The Author(s).)

Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68 Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography ( 68 Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results : All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions : Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.

Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [ 82 Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model ( p < 0.001 ), where the best AUC of 73.9% (CI 72.5-75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3-74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) are reshaping the prognosis of many cancers, but often cause immune-related adverse events (irAEs). Among neurological irAEs, myositis is the most frequently reported. Our aim is to describe clinical and non-clinical characteristics, treatment and outcome of all irMyositis (skeletal limb-girdle and/or ocular myositis) and irMyocarditis cases in our reference center., Methods: We retrospectively enrolled all irMyositis/irMyocarditis patients seen between 2018 and 2022. We reviewed demographics, clinical characteristics, biological, neurophysiological, imaging workup, treatment and outcome., Results: We included 14 consecutive patients. The most frequent treatments were pembrolizumab (35%) or ipilimumab-nivolumab combination (35%). Limb-girdle, ocular (non-fluctuating palpebral ptosis and/or diplopia with or without ophthalmoparesis) and cardiac phenotypes were equally distributed, overlapping in 40% of cases. Ocular involvement was frequently misdiagnosed; review of brain MRIs disclosed initially missed signs of skeletal myositis in one patient and ocular myositis in 3. Seven patients had other co-existing irAEs. When performed, myography showed a myogenic pattern. CK was elevated in 8/15 patients, troponin-T in 12/12 and troponin-I in 7/9 tested patients. ICI were discontinued in all cases, with further immunosuppressive treatment in nine patients. In most cases, neurological and cardiological outcome was good at last follow-up., Conclusion: Myositis is a potentially severe irAE. Despite its heterogeneous presentation, some highly suggestive clinical symptoms, such as ocular involvement, or radiological signs should raise physicians' attention to avoid misdiagnosis. We thus recommend a multidisciplinary assessment (including complete neuromuscular evaluation) even in case of isolated myocarditis. Our series underlines the importance of an early diagnosis, since suspension of ICI and adequate treatment are usually associated with good functional outcome., (© 2023. The Author(s).)

Adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell-intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8 + TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor-reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network-based biomarkers that could improve patient selection and guide the design of ACT clinical trials.

Background : Factors affecting morphological changes in the liver following selective internal radiation therapy (SIRT) are unclear, and the available literature focuses on non-anatomical volumetric assessment techniques in a lobar treatment setting. This study aimed to investigate quantitative changes in the liver post-SIRT using an anatomical volumetric approach in hepatocellular carcinoma (HCC) patients with different levels of treatment selectivity and evaluate the parameters affecting those changes. This retrospective, single-institution, IRB-approved study included 88 HCC patients. Whole liver, liver segments, tumor burden, and spleen volumes were quantified on MRI at baseline and 3/6/12 months post-SIRT using a segmentation-based 3D software relying on liver vascular anatomy. Treatment characteristics, longitudinal clinical/laboratory, and imaging data were analyzed. The Student's t -test and Wilcoxon test evaluated volumetric parameters evolution. Spearman correlation was used to assess the association between variables. Uni/multivariate analyses investigated factors influencing untreated liver volume (uLV) increase. Results : Most patients were cirrhotic (92%) men (86%) with Child-Pugh A (84%). Absolute and relative uLV kept increasing at 3/6/12 months post-SIRT vs. baseline (all, p ≤ 0.005) and was maximal during the first 6 months. Absolute uLV increase was greater in Child-Pugh A5/A6 vs. ≥B7 at 3 months (A5, p = 0.004; A6, p = 0.007) and 6 months (A5, p = 0.072; A6, p = 0.031) vs. baseline. When the Child-Pugh class worsened at 3 or 6 months post-SIRT, uLV did not change significantly, whereas it increased at 3/6/12 months vs. baseline (all p ≤ 0.015) when liver function remained stable. The Child-Pugh score was inversely correlated with absolute and relative uLV increase at 3 months (rho = -0.21, p = 0.047; rho = -0.229, p = 0.048). In multivariate analysis, uLV increase was influenced at 3 months by younger age ( p = 0.013), administered 90 Y activity ( p = 0.003), and baseline spleen volume ( p = 0.023). At 6 months, uLV increase was impacted by younger age ( p = 0.006), whereas treatment with glass microspheres (vs. resin) demonstrated a clear trend towards better hypertrophy (f = 3.833, p = 0.058). The amount (percentage) of treated liver strongly impacted the relative uLV increase at 3/6/12 months (all f ≥ 8.407, p ≤ 0.01). Conclusion : Liver function (preserved baseline and stable post-SIRT) favored uLV hypertrophy. Younger patients, smaller baseline spleen volume, higher administered 90 Y activity, and a larger amount of treated liver were associated with a higher degree of untreated liver hypertrophy. These factors should be considered in surgical candidates undergoing neoadjuvant SIRT.

[ 68 Ga]Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting α v β 3 integrin, which is upregulated during angiogenesis soon after acute myocardial infarction (AMI). We prospectively evaluated determinants of myocardial uptake of [ 68 Ga]Ga-NODAGA-RGD and its associations with left ventricular (LV) function in patients after AMI. Methods: Myocardial blood flow and [ 68 Ga]Ga-NODAGA-RGD uptake (60 min after injection) were evaluated by PET in 31 patients 7.7 ± 3.8 d after primary percutaneous coronary intervention for ST-elevation AMI. Transthoracic echocardiography of LV function was performed on the day of PET and at the 6-mo follow-up. Results: PET images showed increased uptake of [ 68 Ga]Ga-NODAGA-RGD in the ischemic area at risk (AAR), predominantly in injured myocardial segments. The SUV in the segment with the highest uptake (SUV max ) in the ischemic AAR was higher than the SUV mean of the remote myocardium (0.73 ± 0.16 vs. 0.51 ± 0.11, P < 0.001). Multivariable predictors of [ 68 Ga]Ga-NODAGA-RGD uptake in the AAR included high peak N-terminal pro-B-type natriuretic peptide ( P < 0.001), low LV ejection fraction, low global longitudinal strain ( P = 0.01), and low longitudinal strain in the AAR ( P = 0.01). [ 68 Ga]Ga-NODAGA-RGD uptake corrected for myocardial blood flow and perfusable tissue fraction in the AAR predicted improvement in global longitudinal strain at follow-up ( P = 0.002), independent of peak troponin, N-terminal pro-B-type natriuretic peptide, and LV ejection fraction. Conclusion: [ 68 Ga]Ga-NODAGA-RGD uptake shows increased α v β 3 integrin expression in the ischemic AAR early after AMI that is associated with regional and global systolic dysfunction, as well as increased LV filling pressure. Increased [ 68 Ga]Ga-NODAGA-RGD uptake predicts improvement of global LV function 6 mo after AMI., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Presynaptic dopaminergic positron emission tomography (PET) imaging serves as an essential tool in diagnosing and differentiating patients with suspected parkinsonism, including idiopathic Parkinson's disease (PD) and other neurodegenerative and non-neurodegenerative diseases. The PET tracers most commonly used at the present time mainly target dopamine transporters (DAT), aromatic amino acid decarboxylase (AADC), and vesicular monoamine type 2 (VMAT2). However, established standards for the imaging procedure and interpretation of presynaptic dopaminergic PET imaging are still lacking. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform presynaptic dopaminergic PET imaging., Method: A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for presynaptic dopaminergic PET imaging in parkinsonism, focusing on standardized recommendations, procedures, interpretation, and reporting., Conclusion: This international consensus and practice guideline will help to promote the standardized use of presynaptic dopaminergic PET imaging in parkinsonism. It will become an international standard for this purpose in clinical practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

By focusing on metabolic and morphological tissue properties respectively, FluoroDeoxyGlucose (FDG)-Positron Emission Tomography (PET) and Computed Tomography (CT) modalities include complementary and synergistic information for cancerous lesion delineation and characterization (e.g. for outcome prediction), in addition to usual clinical variables. This is especially true in Head and Neck Cancer (HNC). The goal of the HEad and neCK TumOR segmentation and outcome prediction (HECKTOR) challenge was to develop and compare modern image analysis methods to best extract and leverage this information automatically. We present here the post-analysis of HECKTOR 2nd edition, at the 24th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2021. The scope of the challenge was substantially expanded compared to the first edition, by providing a larger population (adding patients from a new clinical center) and proposing an additional task to the challengers, namely the prediction of Progression-Free Survival (PFS). To this end, the participants were given access to a training set of 224 cases from 5 different centers, each with a pre-treatment FDG-PET/CT scan and clinical variables. Their methods were subsequently evaluated on a held-out test set of 101 cases from two centers. For the segmentation task (Task 1), the ranking was based on a Borda counting of their ranks according to two metrics: mean Dice Similarity Coefficient (DSC) and median Hausdorff Distance at 95th percentile (HD95). For the PFS prediction task, challengers could use the tumor contours provided by experts (Task 3) or rely on their own (Task 2). The ranking was obtained according to the Concordance index (C-index) calculated on the predicted risk scores. A total of 103 teams registered for the challenge, for a total of 448 submissions and 29 papers. The best method in the segmentation task obtained an average DSC of 0.759, and the best predictions of PFS obtained a C-index of 0.717 (without relying on the provided contours) and 0.698 (using the expert contours). An interesting finding was that best PFS predictions were reached by relying on DL approaches (with or without explicit tumor segmentation, 4 out of the 5 best ranked) compared to standard radiomics methods using handcrafted features extracted from delineated tumors, and by exploiting alternative tumor contours (automated and/or larger volumes encompassing surrounding tissues) rather than relying on the expert contours. This second edition of the challenge confirmed the promising performance of fully automated primary tumor delineation in PET/CT images of HNC patients, although there is still a margin for improvement in some difficult cases. For the first time, the prediction of outcome was also addressed and the best methods reached relatively good performance (C-index above 0.7). Both results constitute another step forward toward large-scale outcome prediction studies in HNC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Assessment of liver function is paramount before hepatectomy. This study aimed to assess future liver remnant function (FLR-F) using hepatobiliary scintigraphy (HBS) and to compare it to FLR volume (FLR-V) in the prediction of posthepatectomy liver failure (PHLF). The impact of volume and function gains were also assessed in patients undergoing portal vein embolization (PVE) or liver venous deprivation (LVD)., Methods: All consecutive patients undergoing major hepatectomy between 02/2018 and 09/2021 with preoperative HBS were included. FLR-V was expressed as percentage of total liver volume and analyzed using preoperative computed tomography. FLR-V and FLR-F gains after embolization were expressed in percentage. Receiver operating characteristic analysis was performed to compare both methods in predicting PHLF., Results: Thirty-six patients were included. PVE and LVD were performed in 4 (11%) and 28 patients (78%), respectively. Overall, PHLF occurred in eight patients (22%). FLR-F gain after embolization showed significant ability to predict PHLF (area under the curve [AUC] = 0.789), with cut-off value of 150% showing a sensitivity of 1.00, a specificity of 0.42, and a negative predictive value of 1.00., Conclusion: Preoperative HBS shows a high sensitivity to predict PHLF when HBS is performed twice to measure the function gain after venous embolization., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Purpose: To review eXplainable Artificial Intelligence/(XAI) methods available for medical imaging/(MI)., Method: A scoping review was conducted following the Joanna Briggs Institute's methodology. The search was performed on Pubmed, Embase, Cinhal, Web of Science, BioRxiv, MedRxiv, and Google Scholar. Studies published in French and English after 2017 were included. Keyword combinations and descriptors related to explainability, and MI modalities were employed. Two independent reviewers screened abstracts, titles and full text, resolving differences through discussion., Results: 228 studies met the criteria. XAI publications are increasing, targeting MRI (n = 73), radiography (n = 47), CT (n = 46). Lung (n = 82) and brain (n = 74) pathologies, Covid-19 (n = 48), Alzheimer's disease (n = 25), brain tumors (n = 15) are the main pathologies explained. Explanations are presented visually (n = 186), numerically (n = 67), rule-based (n = 11), textually (n = 11), and example-based (n = 6). Commonly explained tasks include classification (n = 89), prediction (n = 47), diagnosis (n = 39), detection (n = 29), segmentation (n = 13), and image quality improvement (n = 6). The most frequently provided explanations were local (78.1 %), 5.7 % were global, and 16.2 % combined both local and global approaches. Post-hoc approaches were predominantly employed. The used terminology varied, sometimes indistinctively using explainable (n = 207), interpretable (n = 187), understandable (n = 112), transparent (n = 61), reliable (n = 31), and intelligible (n = 3)., Conclusion: The number of XAI publications in medical imaging is increasing, primarily focusing on applying XAI techniques to MRI, CT, and radiography for classifying and predicting lung and brain pathologies. Visual and numerical output formats are predominantly used. Terminology standardisation remains a challenge, as terms like "explainable" and "interpretable" are sometimes being used indistinctively. Future XAI development should consider user needs and perspectives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Primary chronic sclerosing osteomyelitis is a rare and complex pathology and remains a diagnostic and therapeutic challenge. Our aim is to show our experience with a new diagnostic tool., Material and Methods: Four patients aged from 26 to 67 were referred to the department of oral and maxillofacial surgery of University Hospital CHUV in Lausanne between January 2010 and December 2018 for chronic mandibular pain without infectious signs nor symptoms. All patients underwent three-phase bone scintigraphy and anti-granulocyte antibody scintigraphy., Results: Three-phase bone scintigraphy demonstrated radiotracer uptake at the zone of pain, whereas anti-granulocyte antibody scintigraphy showed no uptake, thus rendering an infectious origin unlikely., Conclusion: A combination of the two different scintigraphies should be considered in order to guide the clinician in the diagnosis of primary chronic sclerosing osteomyelitis, thus preventing patients from undergoing unnecessary imagery and useless treatment, and also allowing an early diagnosis.