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BackgroundAs differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility.MethodsThree study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists.FindingsThe validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85).InterpretationThe radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics.FundingHanarth fonds.

Dupilumab, blocking IL‐4 and IL‐13 signals, improves atopic dermatitis and Quality of Life but might be also associated with the occurrence of ocular adverse events (OAEs). The main objective of our prospective study was to characterize the cytokine and chemokine profile in the tear fluid of dupilumab‐treated patients with moderate‐to‐ severe atopic dermatitis and to identify biomarkers predicting the occurrence of ocular adverse events. Patients with moderate‐to‐severe AD underwent dermatological and ophthalmological evaluation at the baseline (T0) and week 16 or at the time of an eventual ocular adverse events (T1). A multiplex immunoassay measuring multiple cytokines and chemokines in the tear fluid extracted during ocular examination at both T0 and T1 was performed. Thirty‐nine patients with moderate‐to‐severe AD and treated with dupilumab were included in the study. Baseline tear fluid levels revealed a significantly higher concentration of type 2 cytokines and chemokines in AD patients than healthy controls. The occurrence of ocular adverse events during dupilumab therapy was associated with a significant increase of IL‐33 tear fluid levels and a significantly lower tear break‐up time, this latter also identified as predictive factor. Our findings suggest that the ophthalmological examination should be considered a valid support to identify patients at risk of developing OAEs and to provide their appropriate management. [ABSTRACT FROM AUTHOR]

Abstract: Accidental intra-arterial injections of radiotracers are rare events resulting in a specific imaging pattern, described as "hot-forearm," "hot-hand," "glove-phenomenon," or "glove-like pattern." We present a case 68 Ga-DOTATATE total-body PET/CT for restaging of a neuroendocrine tumor, where intra-arterial misinjection resulted in a glove phenomenon. Since patients may present with minimal symptoms, like in this case, and PET findings may only be seen at the distal upper extremity (placed above the head), these accidental injections may be more frequently detected with total-body PET/CT due to the longer field-of-view. Radiologists and technologists should be aware of this possibility to avoid accidental misinjections., Competing Interests: Conflicts of interest and sources of funding: L.N. is principal investigator of service agreement with United Imaging Healthcare. L.N. is site principal investigator of clinical trials supported by Novartis Pharmaceuticals Corporation. L.N. is principal investigator of a clinical trial supported by Telix Pharmaceuticals. L.N. is principal investigator of a clinical trial supported by Lantheus Medical Imaging. L.N. is principal investigator of a clinical trial supported by GE Healthcare. L.N. is coinvestigator of a clinical trial supported by Lilly. L.N. has a speaker engagement agreement with Lilly. UC Davis has a revenue sharing agreement with United Imaging Healthcare. All other authors have no conflicts of interest to report. F.S. is site principal investigator of clinical research supported by Biogen. J.W.R. has received fees for consulting/advisory board from Novartis, Janssen, Catalyst, Biodesix, Amgen, Seattle Genetics, Merck, BMS, Beigene, Regeneron, Sanofi, Turning Point, Bayer, Merus NV, Daiichi Sankyo, and OncoHost; travel support from AstraZeneca and IO Biotech; and research funding to institution from ArriVent, Merck, Novartis, Nuvalent, Revolution Medicines, Spectrum, Calithera, Kinnate, AstraZeneca, and IO Biotech., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Despite the significant recent advances in manufacturing materials supporting advanced dental therapies, peri-implantitis still represents a severe complication in dental implantology. Herein, a sol-gel process is proposed to easily deposit antibacterial zirconia coatings onto bulk zirconia, material, which is becoming very popular for the manufacturing of abutments. The coatings' physicochemical properties were analyzed through x-ray diffraction and scanning electron microscopy-energy-dispersive x-ray spectroscopy investigations, while their stability and wettability were assessed by microscratch testing and static contact angle measurements. Uniform gallium-doped tetragonal zirconia coatings were obtained, featuring optimal mechanical stability and a hydrophilic behavior. The biological investigations pointed out that gallium-doped zirconia coatings: (i) displayed full cytocompatibility toward human gingival fibroblasts; (ii) exhibited significant antimicrobial activity against the Aggregatibacter actinomycetemcomitans pathogen; (iii) were able to preserve the commensal Streptococcus salivarius. Furthermore, the proteomic analyses revealed that the presence of Ga did not impair the normal oral microbiota. Still, interestingly, it decreased by 17% the presence of Fusobacterium nucleatum, a gram-negative, strictly anaerobic bacteria that is naturally present in the gastrointestinal tract. Therefore, this work can provide a valuable starting point for the development of coatings aimed at easily improving zirconia dental implants' performance., (© 2024 Wiley Periodicals LLC.)

Inflammatory disorders historically have been difficult to monitor with conventional PET imaging due to limitations including radiation exposure, lack of validated imaging biomarkers, low spatial resolution, and long acquisition durations. However, the recent development of long-axial field-of-view (LAFOV) PET/CT scanners may allow utilization of novel noninvasive biomarkers to diagnose, predict outcomes, and monitor therapeutic response of inflammatory conditions. LAFOV PET scanners can image most of the human body (if not the entire body) simultaneously in one bed position, with improved signal collection efficiency compared to conventional PET scanners. This allows for imaging with shorter acquisition durations, decreased injected radiotracer dose, prolonged uptake times, or a combination of any of these. In addition, LAFOV PET scanners enable whole-body dynamic imaging. Altogether, these intrinsically superior capabilities in assessing both local and systemic diseases, have allowed these scanners to make increasingly significant contributions to the assessment of inflammatory conditions. This review aims to further explore the role and benefits of LAFOV scanners for imaging various inflammatory conditions while addressing future developments and challenges faced by this technology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: UC Davis has a research agreement and a sales-based revenue sharing agreement with United Imaging Healthcare, the manufacturer of the total-body PET/CT scanner. No other potential conflicts of interest relevant to this article exist including employment, royalties, stock options, or patents. The authors would like to acknowledge funding from the National Institutes of Health via grants R01 AR076088, R01 AR085314 and R01 CA206187. Lorenzo Nardo is principal investigator of a service agreement with United Imaging Healthcare. Lorenzo Nardo has been the PI of more than 1 service agreements with United Imaging Healthcare. Lorenzo Nardo is mentioned in a recurrent gift from United Imaging Healthcare that support the American Board of Radiology Alternate Pathway at UC Davis. Lorenzo Nardo is site PI of clinical trials supported by Novartis Pharmaceuticals Corporation. Lorenzo Nardo is PI of a clinical trial supported by Telix Pharmaceuticals. Lorenzo Nardo is PI of clinical trial supported by Lantheus Medical Imaging. Lorenzo Nardo is PI of a clinical trials supported by Curium Pharma Healthcare. Lorenzo Nardo is Co-I of a clinical trial supported by Lilly. Lorenzo Nardo has a SPEAKING ENGAGEMENT AGREEMENT with Lilly. Lorenzo Nardo is associate editor for Current Problems in Cancer. Lorenzo Nardo served a panel reviewer for the European Health and Digital Executive Agency. Lorenzo Nardo served a panel reviewer for the National Cancer Center Network (NCCN) – multiple panels. Lorenzo Nardo served a panel reviewer for the National Institutes for Health (NIH). Lorenzo Nardo is PI and co-PI of multiple National Institutes for Health (NIH) grants. Lorenzo Nardo served a committee member for the American Board of Radiology - multiple committees. Ramsey Badawi is an investigator with Lilly. Ramsey Badawi is an investigator with United Imaging Healthcare. If there are other authors, they 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin areas, clinically characterized by recurrent inflamed nodules, abscesses, sinus tracts, and severe scars. Systemic treatments may provide temporary relief, while wide surgical excision offers prolonged disease-free periods. We evaluated the most efficient wound closure methods following wide excision of HS lesions in terms of recurrence, functionality, and quality of life. A systematic literature search was conducted in PubMed, Embase, Cochrane, and ClinicalTrials.gov, adhering to the PRISMA 2020 criteria. We included original studies published until February 2024, focusing on wound closure methods post-wide excision for HS. Data from 121 papers were analyzed using network and direct meta-analysis methods to compare recurrence and postoperative complication rates. From 1181 articles, 121 were included in the meta-analysis after removing duplicates and excluding publications that did not meet the inclusion criteria. Recurrence rates were associated with the type of reconstruction technique as follows: primary closure, 25% (95% confidence interval [CI], 20-30%); skin grafts, 18% (95% CI, 14-22%), and flaps, 12% (95% CI, 9-15%). Secondary intention healing showed a recurrence rate of 28% (95% CI, 23-33%). Flaps were associated with the lowest recurrence rates compared to other surgery techniques., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: 177 Lu-based radiopharmaceuticals (RPs) are the most used for targeted radionuclide therapy (TRT) due to their good response rates. However, the worldwide availability of 177 Lu is limited. 161 Tb represents a potential alternative for TRT, as it emits photons for SPECT imaging, β - -particles for therapy, and also releases a significant yield of internal conversion (IE) and Auger electrons (AE). This research aimed to evaluate cell dosimetry with the MIRDcell code considering a realistic localization of three 161 Tb- and 177 Lu-somatostatin (SST) analogs in different subcellular regions as reported in the literature, various cell cluster sizes (25-1000 µm of radius) and percentage of labeled cells. Experimental values of the α- and β-survival coefficients determined by external beam photon irradiation were used to estimate the survival fraction (SF) of AR42J pancreatic cell clusters and micrometastases., Results: The different localization of RPs labeled with the same radionuclide within the cells, resulted in only slight variations in the dose absorbed by the nuclei (AD N ) of the labeled cells with no differences observed in either the unlabeled cells or the SF. AD N of labeled cells (MDLC) produced by 161 Tb-RPs were from 2.8-3.7 times higher than those delivered by 177 Lu-RPs in cell clusters with a radius lower than 0.1 mm and 10% of labeled cells, due to the higher amount of energy emitted by 161 Tb-disintegration in form of IE and AE. However, the 161 Tb-RPs/ 177 Lu-RPs MDLC ratio decreased below 1.6 in larger cell clusters (0.5-1 mm) with > 40% labeled cells, due to the significantly higher 177 Lu-RPs cross-irradiation contribution. Using a fixed number of disintegrations, SFs of 161 Tb-RPs in clusters with > 40% labeled cells were lower than those of 177 Lu-RPs, but when the same amount of emitted energy was used no significant differences in SF were observed between 177 Lu- and 161 Tb-RPs, except for the smallest cluster sizes., Conclusions: Despite the emissions of IE and AE from 161 Tb-RPs, their localization within different subcellular regions exerted a negligible influence on the AD N . The same cell damage produced by 177 Lu-RPs could be achieved using smaller quantities of 161 Tb-RPs, thus making 161 Tb a suitable alternative for TRT., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Total-body (TB) positron emission tomography (PET) scanners are classified by their axial field of view (FOV). Long axial field of view (LAFOV) PET scanners can capture images from eyes to thighs in a one-bed position, covering all major organs with an axial FOV of about 100 cm. However, they often miss essential areas like distal lower extremities, limiting their use beyond oncology.TB-PET is reserved for scanners with a FOV of 180 cm or longer, allowing coverage of most of the body. LAFOV PET technology emerged about 40 years ago but gained traction recently due to advancements in data acquisition and cost. Early research highlighted its benefits, leading to the first FDA-cleared TB-PET/CT device in 2019 at UC Davis. Since then, various LAFOV scanners with enhanced capabilities have been developed, improving image quality, reducing acquisition times, and allowing for dynamic imaging. The uEXPLORER, the first LAFOV scanner, has a 194 cm active PET AFOV, far exceeding traditional scanners. The Panorama GS and others have followed suit in optimizing FOVs. Despite slow adoption due to the COVID pandemic and costs, over 50 LAFOV scanners are now in use globally. This review explores the future of LAFOV technology based on recent literature and experiences, covering its clinical applications, implications for radiation oncology, challenges in managing PET data, and expectations for technological advancements., Competing Interests: Declaration of competing interest LN is principal investigator of a service agreement with United Imaging Healthcare. LN is site PI of clinical trials supported by Novartis Pharmaceuticals Corporation. LN is PI of clinical trials supported by Telix Pharmaceuticals, Lantheus Medical Imaging and GE Healthcare. LN is co-PI of a clinical trial supported by Lilly. LN is consultant for Lilly. UC Davis has a revenue sharing agreement with United Imaging Healthcare. All other authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Positron emission tomography/computed tomography (PET/CT) imaging has been widely used in clinical practice. Long axial field-of-view (LAFOV) systems have enhanced clinical practice by leveraging their technological advantages and have emerged as the new state-of-the-art PET imaging modalities. A consensus was conducted to explore expert views in this emerging field to comprehensively elucidate the proposed workflow in LAFOV PET/CT examinations and highlight the potential challenges inherent in the workflow., Methods: A multidisciplinary task group formed by 28 experts from six countries over the world discussed and approved the consensus based on the published guidelines, peer-reviewed articles of LAFOV PET/CT, and the collective experience from clinical practice. This consensus focuses on the workflow that allows for a broader range of imaging protocols of LAFOV PET/CT, catering to diverse patient needs and in line with precision medicine principles., Results: This consensus describes the workflows and imaging protocols of LAFOV PET/CT for various imaging scenarios including routine static imaging, dynamic imaging, low-activity imaging, fast imaging, prolonged imaging, delayed imaging, and dual-tracer imaging. In addition, imaging reconstruction and reviewing specific to LAFOV PET/CT imaging, as well as the main challenges facing installation and application of LAFOV PET/CT scanner were also summarized., Conclusion: This consensus summarized the various imaging workflow, imaging protocol, and challenges of LAFOV PET/CT imaging, aiming to enhance the clinical and research applications of these scanners., Competing Interests: Declarations. Conflict of interest: Zhongshan Hospital affiliated to Fudan University has a strategic partnership with United Imaging Healthcare (UIH) and professor Hongcheng Shi has been commonly invited to offer a lecture to UIH. UC Davis has a research agreement and a sales-based revenue-sharing agreement with United Imaging Healthcare. UIH partially supports a fellowship training program at UC Davis. Harshad Kulkarni from BAMF Health is part of the Speaker bureau of United Imaging within the past 2 years. Some investigator-initiated research projects at BAMF Health were funded by United Imaging. Axel Rominger receives speaker honoraria from Siemens and has research agreement ongoing. Martina Sollini is a member of the EJNMMI Editorial Board and an Associate Editor for the “Artificial intelligence, machine learning and radiomics” section of Cancer Imaging. Other authors declare no conflict of interest regarding this article. Ethics approval: Institutional Review Board approval was not required because this is a expert consensus. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Targeted and immune therapies have recently been associated with the occurrence of multiple cutaneous toxicities, often challenging to differentiate by clinical examination alone without histology. Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive and innovative imaging technique that has been shown to be almost as effective as histology in diagnosing several skin conditions. Our study aimed to assess the effectiveness of LC-OCT in predicting the clinical evolution of early maculopapular eruptions related to antineoplastic targeted therapy and immunotherapy., Methods: In the period between May 2023 and December 2023, consecutive patients with clinical cutaneous maculopapular reactions caused by oncologic targeted therapy or immunotherapy were enrolled at the dermatologic outpatient clinic of the Fondazione Policlinico A. Gemelli IRCCS, Rome. Patients underwent clinical dermatological examination, video-dermoscopy, LC-OCT, and incisional skin biopsy of a target cutaneous lesion. To investigate the evolutionary pattern of maculopapular lesions (psoriasic eruption, lichenoid eruption, eczematous eruption, bullous eruption), LC-OCT and histopathological images have been compared based on specific characteristics (hyperkeratosis, acanthosis, spongiosis; papillomatosis; lichenoid inflammatory infiltrate; presence of intraepidermal/subepidermal cleavage plan with formation of a bulla)., Results: Eighteen patients were included in this study (11 males, 7 females, median age 64.5). LC-OCT demonstrated an overall concordance with histology of 77.8%, with a Cohen's Kappa of 0.69 (P < 0.0001). Sensitivity exceeded 70%, and specificity was ≥88.2%. The Area Under the Curve (AUC) ranged from 0.9 to 1 for psoriasis and lichenoid eruption and from 0.7 to 0.9 for eczematous and bullous eruption., Conclusions: LC-OCT appears to be a promising tool for the early differential diagnosis of adverse skin reactions related to targeted therapy and immunotherapy, offering the potential to avoid skin biopsies in fragile cancer patients., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: Despite advancements in psoriasis treatment, a gap remains in aligning patient satisfaction with clinical outcomes. Our study aimed to evaluate which clinical and psychological factors may impact treatment satisfaction in psoriatic patients undergoing long-term biological therapies., Methods: We performed an observational, cross-sectional, single-center study involving adult patients with moderate-to-severe psoriasis treated with biologics for at least 12 months. We collected sociodemographic characteristics and data on the course of the psoriasis. We also assessed the absolute (residual) Psoriasis Area and Severity Index (PASI), the site of the residual disease, and the severity of pruritus through the Visual Analogue Scale (VAS). Satisfaction was evaluated using the Treatment Satisfaction Questionnaire for Medication (TSQMv.II). The Type D Personality Scale (DS14 questionnaire and Patient Health Questionnaire-9 assessed the psychological profile., Results: Overall, 146 patients were included, and 82.1% were globally satisfied (global satisfaction TSQM score >75). Linear regression analysis showed a negative correlation between global satisfaction scoring and residual PASI. The multivariable analysis found a higher VAS-pruritus score (OR = 1.20, 95% CI = 1.01-1.44; P = 0.043) and not reaching a residual PASI < 2 (OR = 0.30, 95% CI = 0.09-0.94, P = 0.039) as the strongest predictors of global unsatisfied patients (TSQM < 75%). Other factors unrelated to residual disease, such as gender, class of biologic agent, and type D personality, have also been found to impact patient satisfaction., Conclusions: Our study's findings underscore the complexity of patient satisfaction in psoriasis management and highlight the multifactorial nature of treatment success beyond traditional clinical measures., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

[ 18 F]fluoro-2-deoxy-d-glucose PET/computed tomography has been implemented in the management of patients with lymphoma, offering real-time metabolic information on lymphoma with the promise of more accurate staging, treatment response assessment, prognostication, and early detection of disease recurrence. The clinical management of lymphoproliferative disease has recently, rapidly evolved from initial chemotherapeutic to the use of immunotherapy, targeted agents, and to the use of chimeric antigen receptor T-cell therapies. The implementation of these new systems and imaging protocols together with new tracer development creates, in the field of lymphoproliferative disease, both opportunities and challenges that will be detailed in this comprehensive literature review., Competing Interests: Discloure Research reported in this publication was supported by the National Institutes of Health, United States under award number R01CA249422. The study was also supported by the In Vivo Translational Imaging Shared Resources with funds from NCI P30CA093373 and by the Fred and Julia Rusch Foundation for Nuclear Medicine Research and Education. Dr H. Nalbant’s funding is partially provided by United Imaging Healthcare’s Fellowship Gift. L. Nardo is PI of service agreement with United Imaging Healthcare. L. Nardo is site PI of clinical trials supported by Novartis Pharmaceuticals Corporation, United States. L. Nardo is PI of a clinical trial supported by Telix Pharmaceuticals. L. Nardo is PI of a clinical trial supported by Lantheus Medical Imaging, United States. L. Nardo is PI of a clinical trial supported by GE Healthcare, United States. L. Nardo is Co-PI of a clinical trial supported by Lilly, United States. L. Nardo has a speaker engagement agreement with Lilly. UC Davis has a share revenue agreement with United Imaging Healthcare. H. Sari is a full-time employee of Siemens Healthcare AG, Switzerland. UC Davis has a revenue sharing agreement with United Imaging Healthcare. F. Sen is PI of clinical research sponsored by Biogen, United States. All other authors have no conflicts of interest to report., (Published by Elsevier Inc.)

Long-axial field-of-view (LAFOV) systems have changed the field of molecular imaging. Since their introduction, many PET centers have installed these next-generation digital systems to provide more detailed imaging and acquire PET images in a single bed position. Indeed, vertex to thigh imaging for oncological indications can be obtained in most of the population with the currently available LAFOV systems. Moreover, Total Body (TB) PET, a subtype of LAFOV, enables imaging the entire patient-from vertex through the toes-with one bed-position for most of the population. This review aims to identify possible challenges and opportunities for PET-centers working with TB and LAFOV systems. Emphasis is placed on the strength and weaknesses in clinical routine of currently available and upcoming TB and LAFOV PET systems., Competing Interests: Declaration of competing interest AR has received research support and speaker honoraria from Siemens. LN is principal investigator of several service agreements with United Imaging Healthcare. LN receives though UC Davis a recurrent gift from United Imaging Healthcare that support research (postdoctoral salary). LN is site PI of clinical trials supported by Novartis Pharmaceuticals Corporation. LN is PI of clinical trials supported by Telix Pharmaceuticals and Lantheus Medical Imaging and Curium Pharma Healthcare. LN is a co-investigator of a clinical trial supported by Lilly. UC Davis has a revenue sharing agreement with United Imaging Healthcare. Lorenzo Nardo has a speaking engagement agreement with Lilly. AP received consulting fees from GE. IA is PI of clinical trials supported by Alpha9 Oncology and has received speaker honoraria from Novartis outside of the present work. All other authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Immunotherapies, especially checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) antibodies, have transformed cancer treatment by enhancing the immune system's capability to target and kill cancer cells. However, predicting immunotherapy response remains challenging. 18 F-arabinosyl guanine ([ 18 F]F-AraG) is a molecular imaging tracer targeting activated T cells, which may facilitate therapy response assessment by noninvasive quantification of immune cell activity within the tumor microenvironment and elsewhere in the body. The aim of this study was to obtain preliminary data on total-body pharmacokinetics of [ 18 F]F-AraG as a potential quantitative biomarker for immune response evaluation. Methods: The study consisted of 90-min total-body dynamic scans of 4 healthy subjects and 1 non-small cell lung cancer patient who was scanned before and after anti-PD-1 immunotherapy. Compartmental modeling with Akaike information criterion model selection was used to analyze tracer kinetics in various organs. Additionally, 7 subregions of the primary lung tumor and 4 mediastinal lymph nodes were analyzed. Practical identifiability analysis was performed to assess the reliability of kinetic parameter estimation. Correlations of the SUV mean , the tissue-to-blood SUV ratio (SUVR), and the Logan plot slope ( K Logan ) with the total volume of distribution ( V T ) were calculated to identify potential surrogates for kinetic modeling. Results: Strong correlations were observed between K Logan and SUVR with V T , suggesting that they can be used as promising surrogates for V T , especially in organs with a low blood-volume fraction. Moreover, practical identifiability analysis suggested that dynamic [ 18 F]F-AraG PET scans could potentially be shortened to 60 min, while maintaining quantification accuracy for all organs of interest. The study suggests that although [ 18 F]F-AraG SUV images can provide insights on immune cell distribution, kinetic modeling or graphical analysis methods may be required for accurate quantification of immune response after therapy. Although SUV mean showed variable changes in different subregions of the tumor after therapy, the SUVR, K Logan , and V T showed consistent increasing trends in all analyzed subregions of the tumor with high practical identifiability. Conclusion: Our findings highlight the promise of [ 18 F]F-AraG dynamic imaging as a noninvasive biomarker for quantifying the immune response to immunotherapy in cancer patients. Promising total-body kinetic modeling results also suggest potentially wider applications of the tracer in investigating the role of T cells in the immunopathogenesis of diseases., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective. Penalty parameters in penalized likelihood positron emission tomography (PET) reconstruction are typically determined empirically. The cross-validation log-likelihood (CVLL) method has been introduced to optimize these parameters by maximizing a CVLL function, which assesses the likelihood of reconstructed images using one subset of a list-mode dataset based on another subset. This study aims to validate the efficacy of the CVLL method in whole-body imaging for cancer patients using a conventional clinical PET scanner. Approach. Fifteen lung cancer patients were injected with 243.7 ± 23.8 MBq of [ 18 F]FDG and underwent a 22 min PET scan on a Biograph mCT PET/CT scanner, starting at 60 ± 5 min post-injection. The PET list-mode data were partitioned by subsampling without replacement, with 20 minutes of data for image reconstruction using an in-house ordered subset expectation maximization algorithm and the remaining 2 minutes of data for cross-validation. Two penalty parameters, penalty strength β and Fair penalty function parameter δ , were subjected to optimization. Whole-body images were reconstructed, and CVLL values were computed across various penalty parameter combinations. The optimal image corresponding to the maximum CVLL value was selected by a grid search for each patient. Main results. The δ value required to maximize the CVLL value was notably small (⩽10 -6 in this study). The influences of voxel size and scan duration on image optimization were investigated. A correlation analysis revealed a significant inverse relationship between optimal β and scan count level, with a correlation coefficient of -0.68 ( p -value = 3.5 × 10 -5 ). The optimal images selected by the CVLL method were compared with those chosen by two radiologists based on their diagnostic preferences. Differences were observed in the selection of optimal images. Significance. This study demonstrates the feasibility of incorporating the CVLL method into routine imaging protocols, potentially allowing for a wide range of combinations of injected radioactivity amounts and scan durations in modern PET imaging., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Quantitative total-body PET imaging of blood flow can be performed with freely diffusible flow radiotracers such as 15 O-water and 11 C-butanol, but their short half-lives necessitate close access to a cyclotron. Past efforts to measure blood flow with the widely available radiotracer 18 F-fluorodeoxyglucose (FDG) were limited to tissues with high 18 F-FDG extraction fraction. In this study, we developed an early-dynamic 18 F-FDG PET method with high temporal resolution kinetic modeling to assess total-body blood flow based on deriving the vascular transit time of 18 F-FDG and conducted a pilot comparison study against a 11 C-butanol reference., Methods: The first two minutes of dynamic PET scans were reconstructed at high temporal resolution (60×1 s, 30×2 s) to resolve the rapid passage of the radiotracer through blood vessels. In contrast to existing methods that use blood-to-tissue transport rate ( K 1 ) as a surrogate of blood flow, our method directly estimates blood flow using a distributed kinetic model (adiabatic approximation to the tissue homogeneity model; AATH). To validate our 18 F-FDG measurements of blood flow against a flow radiotracer, we analyzed total-body dynamic PET images of six human participants scanned with both 18 F-FDG and 11 C-butanol. An additional thirty-four total-body dynamic 18 F-FDG PET scans of healthy participants were analyzed for comparison against literature blood flow ranges. Regional blood flow was estimated across the body and total-body parametric imaging of blood flow was conducted for visual assessment. AATH and standard compartment model fitting was compared by the Akaike Information Criterion at different temporal resolutions., Results: 18 F-FDG blood flow was in quantitative agreement with flow measured from 11 C-butanol across same-subject regional measurements (Pearson R=0.955, p<0.001; linear regression y=0.973x-0.012), which was visually corroborated by total-body blood flow parametric imaging. Our method resolved a wide range of blood flow values across the body in broad agreement with literature ranges (e.g., healthy cohort average: 0.51±0.12 ml/min/cm 3 in the cerebral cortex and 2.03±0.64 ml/min/cm 3 in the lungs, respectively). High temporal resolution (1 to 2 s) was critical to enabling AATH modeling over standard compartment modeling., Conclusions: Total-body blood flow imaging was feasible using early-dynamic 18 F-FDG PET with high-temporal resolution kinetic modeling. Combined with standard 18 F-FDG PET methods, this method may enable efficient single-tracer flow-metabolism imaging, with numerous research and clinical applications in oncology, cardiovascular disease, pain medicine, and neuroscience., Competing Interests: Disclosure The University of California, Davis has a research agreement and a revenue sharing agreement with United Imaging Healthcare. This work was supported in part by National Institutes of Health (NIH) grants R01 EB033435 and R61 AT012187. The image data of healthy participants were acquired under the support of NIH R01 CA206187 and P30 CA093373. The other authors declare no competing interests.

In the last decade, dupilumab, a monoclonal human antibody inhibiting IL-4/IL-13 signaling, has revolutionized the therapeutic management of moderate-to-severe atopic dermatitis (AD), permitting a long-term control of its signs and symptoms. The aim of this study was to identify histologic predictors of dupilumab efficacy after 16 weeks of treatment in a cohort of forty adult patients with moderate to severe AD who had undergone a skin biopsy for diagnostic purposes prior to treatment initiation. We found that EASI 75 and EASI 90 responses at week 16 were significantly associated with perivascular localization (OR=17.6, p=0.038) and lichenoid distribution (OR=31.8, p=0.025) of the immune infiltrate. Moreover, for each unit increase in the number (cells/m2) of CD4+ cells, the likelihood to achieve EASI75 response decreased by 1% (OR=0.99, p=0.037). In conclusion our study suggested a few pre-treatments qualitative and quantitative immunohistochemical features as promising markers predicting dupilumab response in AD patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To assess ChatGPT's ability as a resource for educating patients on various aspects of cardiac imaging, including diagnosis, imaging modalities, indications, interpretation of radiology reports, and management., Methods: 30 questions were posed to ChatGPT-3.5 and ChatGPT-4 three times in three separate chat sessions. Responses were scored as correct, incorrect, or clinically misleading categories by three observers-two board certified cardiologists and one board certified radiologist with cardiac imaging subspecialization. Consistency of responses across the three sessions was also evaluated. Final categorization was based on majority vote between at least two of the three observers., Results: ChatGPT-3.5 answered seventeen of twenty eight questions correctly (61 %) by majority vote. Twenty one of twenty eight questions were answered correctly (75 %) by ChatGPT-4 by majority vote. Majority vote for correctness was not achieved for two questions. Twenty six of thirty questions were answered consistently by ChatGPT-3.5 (87 %). Twenty nine of thirty questions were answered consistently by ChatGPT-4 (97 %). ChatGPT-3.5 had both consistent and correct responses to seventeen of twenty eight questions (61 %). ChatGPT-4 had both consistent and correct responses to twenty of twenty eight questions (71 %)., Conclusion: ChatGPT-4 had overall better performance than ChatGTP-3.5 when answering cardiac imaging questions with regard to correctness and consistency of responses. While both ChatGPT-3.5 and ChatGPT-4 answers over half of cardiac imaging questions correctly, inaccurate, clinically misleading and inconsistent responses suggest the need for further refinement before its application for educating patients about cardiac imaging., Competing Interests: Declaration of competing interest Lorenzo Nardo, MD PhD, is the principal investigator (PI) of a service agreement with United Imaging Healthcare, site PI of clinical trials supported by Novartis Pharmaceuticals Corporation, PI of a clinical trial supported by Telix Pharmaceuticals, PI of a clinical trial supported by Lantheus Medical Imaging, and PI of a clinical trial supported by GE Healthcare. None of the other authors have any disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different transport mechanisms. Our method uses high-temporal resolution dynamic imaging and kinetic modeling to jointly estimate cerebral blood flow and tracer-specific BBB transport rate from a single dynamic PET scan and measure the molecular permeability-surface area (PS) product of the radiotracer. We show our method can resolve BBB PS across three PET radiotracers with greatly differing permeabilities, measure reductions in BBB PS of 18 F-fluorodeoxyglucose (FDG) in healthy aging, and demonstrate a possible brain-body association between decreased FDG BBB PS in patients with metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to efficiently study the molecular permeability of the human BBB in vivo using the large catalogue of available molecular PET tracers., Competing Interests: Competing interests The University of California, Davis has a research agreement and a revenue sharing agreement with United Imaging Healthcare. The other authors declare no competing interests.

Standard Patlak plot is widely used to describe FDG kinetics for dynamic PET imaging. Whole-body Patlak parametric imaging remains constrained due to the need for a full-time input function. Here, we demonstrate the Relative Patlak (RP) plot, which eliminates the need for the early-time input function, for total-body parametric imaging and its application to clinical 20-min scan acquired in list-mode. We demonstrated that the RP intercept b' is equivalent to a ratio of standardized uptake value relative to the blood, while the RP slope Ki' is equal to the standard Patlak Ki multiplied by a global scaling factor for each subject. One challenge in applying RP to a short scan duration (20 min) is the high noise in parametric images. We applied a deep kernel method for noise reduction. Using the standard Patlak plot as the reference, the RP method was evaluated for lesion quantification, lesion-to-background contrast, and myocardial visualization in total-body parametric imaging with uEXPLORER in 22 human subjects who underwent a 1-h dynamic 18F-FDG scan. The RP method was also applied to the dynamic data regenerated from a clinical standard 20-min scan either at 1-h or 2-h post-injection for two cancer patients. We demonstrated that it is feasible to obtain high-quality parametric images from 20-min dynamic scans using the RP plot with a self-supervised deep-kernel noise reduction strategy. The RP Ki' highly correlated with Ki in lesions and major organs, demonstrating its quantitative potential across subjects. Compared to conventional SUVs, the Ki' images significantly improved lesion contrast and enabled visualization of the myocardium for potential cardiac assessment. The application of RP parametric imaging to two clinical scans also showed similar benefits. Total-body PET with the RP plot is feasible to generate parametric images from the dynamic data of a 20-min clinical scan.

Our aim was to define a lower limit of reduced injected activity in delayed [ 18 F]FDG total-body (TB) PET/CT in pediatric oncology patients. Methods: In this single-center prospective study, children were scanned for 20 min with TB PET/CT, 120 min after intravenous administration of a 4.07 ± 0.49 MBq/kg dose of [ 18 F]FDG. Five randomly subsampled low-count reconstructions were generated using ¼, ⅛, [Formula: see text], and [Formula: see text] of the counts in the full-dose list-mode reference standard acquisition (20 min), to simulate dose reduction. For the 2 lowest-count reconstructions, smoothing was applied. Background uptake was measured with volumes of interest placed on the ascending aorta, right liver lobe, and third lumbar vertebra body (L3). Tumor lesions were segmented using a 40% isocontour volume-of-interest approach. Signal-to-noise ratio, tumor-to-background ratio, and contrast-to-noise ratio were calculated. Three physicians identified malignant lesions independently and assessed the image quality using a 5-point Likert scale. Results: In total, 113 malignant lesions were identified in 18 patients, who met the inclusion criteria. Of these lesions, 87.6% were quantifiable. Liver SUV mean did not change significantly, whereas a lower signal-to-noise ratio was observed in all low-count reconstructions compared with the reference standard ( P < 0.0001) because of higher noise rates. Tumor uptake (SUV max ), tumor-to-background ratio, and total lesion count were significantly lower in the reconstructions with [Formula: see text] and [Formula: see text] of the counts of the reference standard ( P < 0.001). Contrast-to-noise ratio and clinical image quality were significantly lower in all low-count reconstructions than with the reference standard. Conclusion: Dose reduction for delayed [ 18 F]FDG TB PET/CT imaging in children is possible without loss of image quality or lesion conspicuity. However, our results indicate that to maintain comparable tumor uptake and lesion conspicuity, PET centers should not reduce the injected [ 18 F]FDG activity below 0.5 MBq/kg when using TB PET/CT in pediatric imaging at 120 min after injection., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background : Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods : This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results : Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions : This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.

Objective. This study investigates the potential of cloud-based serverless computing to accelerate Monte Carlo (MC) simulations for nuclear medicine imaging tasks. MC simulations can pose a high computational burden-even when executed on modern multi-core computing servers. Cloud computing allows simulation tasks to be highly parallelized and considerably accelerated. Approach. We investigate the computational performance of a cloud-based serverless MC simulation of radioactive decays for positron emission tomography imaging using Amazon Web Service (AWS) Lambda serverless computing platform for the first time in scientific literature. We provide a comparison of the computational performance of AWS to a modern on-premises multi-thread reconstruction server by measuring the execution times of the processes using between105and2·1010simulated decays. We deployed two popular MC simulation frameworks-SimSET and GATE-within the AWS computing environment. Containerized application images were used as a basis for an AWS Lambda function, and local (non-cloud) scripts were used to orchestrate the deployment of simulations. The task was broken down into smaller parallel runs, and launched on concurrently running AWS Lambda instances, and the results were postprocessed and downloaded via the Simple Storage Service. Main results. Our implementation of cloud-based MC simulations with SimSET outperforms local server-based computations by more than an order of magnitude. However, the GATE implementation creates more and larger output file sizes and reveals that the internet connection speed can become the primary bottleneck for data transfers. Simulating 10 9 decays using SimSET is possible within 5 min and accrues computation costs of about $10 on AWS, whereas GATE would have to run in batches for more than 100 min at considerably higher costs. Significance. Adopting cloud-based serverless computing architecture in medical imaging research facilities can considerably improve processing times and overall workflow efficiency, with future research exploring additional enhancements through optimized configurations and computational methods., (© 2024 IOP Publishing Ltd.)

Purpose: High blood glucose (hBG) in patients undergoing [ 18 F]FDG PET/CT scans often results in rescheduling the examination, which may lead to clinical delay for the patient and decrease productivity for the department. The aim of this study was to evaluate whether long-axial field-of-view (LAFOV) PET/CT can minimize the effect of altered bio-distribution in hBG patients and is able to provide diagnostic image quality in hBG situations., Materials and Methods: Oncologic patients with elevated blood glucose (≥ 8.0 mmol/l) and normal blood glucose (< 8.0 mmol/l, nBG) levels were matched for tumor entity, gender, age, and BMI. hBG patients were further subdivided into two groups (BG 8-11 mmol/l and BG > 11 mmol/l). Tracer uptake in the liver, muscle, and tumor was evaluated. Furthermore, image quality was compared between long acquisitions (ultra-high sensitivity mode, 360 s) on a LAFOV PET/CT and routine acquisitions equivalent to a short-axial field-of-view scanner (simulated (sSAFOV), obtained with high sensitivity mode, 120 s). Tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) were used as the main image quality criteria., Results: Thirty-one hBG patients met the inclusion criteria and were matched with 31 nBG patients. Overall, liver uptake was significantly higher in hBG patients (SUV mean , 3.07 ± 0.41 vs. 2.37 ± 0.33; p = 0.03), and brain uptake was significantly lower (SUV max , 7.58 ± 0.74 vs. 13.38 ± 3.94; p < 0.001), whereas muscle (shoulder/gluteal) uptake showed no statistically significant difference. Tumor uptake was lower in hBG patients, resulting in a significantly lower TBR in the hBG cohort (3.48 ± 0.74 vs. 5.29 ± 1.48, p < 0.001). CNR was higher in nBG compared to hBG patients (12.17 ± 4.86 vs. 23.31 ± 12.22, p < 0.001). However, subgroup analysis of nBG 8-11 mmol/l on sSAFOV PET/CT compared to hBG (> 11 mmol/l) patients examined with LAFOV PET/CT showed no statistical significant difference in CNR (19.84 ± 8.40 vs. 17.79 ± 9.3, p = 0.08)., Conclusion: While elevated blood glucose (> 11 mmol) negatively affected TBR and CNR in our cohort, the images from a LAFOV PET-scanner had comparable CNR to PET-images acquired from nBG patients using sSAFOV PET/CT. Therefore, we argue that oncologic patients with increased blood sugar levels might be imaged safely with LAFOV PET/CT when rescheduling is not feasible., (© 2024. The Author(s).)