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Fibrosis is one of the key healing responses to injury, especially within the heart where it helps to maintain structural integrity following acute insults such as myocardial infarction. However, if it becomes dysregulated then fibrosis can become maladaptive leading to adverse remodelling, impaired cardiac function and heart failure. Fibroblast activation protein is exclusively expressed by activated fibroblasts, the key effector cells of fibrogenesis, and has a unique extracellular domain that is an ideal ligand for novel molecular imaging probes. Fibroblast activation protein inhibitor (FAPI) radiotracers have been developed for PET imaging, demonstrating high selectivity for activated fibroblasts across a range of different pathologies and disparate organ systems. In this review, we will summarize the role of fibroblast activation protein in cardiovascular disease and how FAPI radiotracers might improve the assessment and treatment of patients with cardiovascular diseases., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paolo Anna Erba reports a relationship with SIEMENS that includes: consulting or advisory and speaking and lecture fees. Paolo Anna Erba reports a relationship with Novartis Pharmaceuticals Corporation that includes: consulting or advisory, funding grants, and speaking and lecture fees. Paolo Anna Erba reports a relationship with Springer Healthcare Limited that includes: equity or stocks. Paolo Anna Erba reports a relationship with Pfizer that includes: funding grants. Antti Saraste reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and speaking and lecture fees. Antti Saraste reports a relationship with Pfizer that includes: consulting or advisory and funding grants. Antti Saraste reports a relationship with Abbott that includes: speaking and lecture fees. Antti Sarate reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Antti Saraste reports a relationship with Janssen Pharmaceuticals Inc that includes: speaking and lecture fees. Jan Bucerius reports a relationship with International Atomic Energy Agency that includes: funding grants, non-financial support, and travel reimbursement. Jan Bucerius reports a relationship with European Association of Nuclear Medicine that includes: board membership. Olivier Gheysens reports a relationship with General Electric Company that includes: speaking and lecture fees. Ronny Buechel reports a relationship with General Electric Company that includes: speaking and lecture fees. Ronny Buechel reports a relationship with Pfizer Inc that includes: speaking and lecture fees. Ronny Buechel reports a relationship with Gilead Sciences Inc that includes: speaking and lecture fees. 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.)

Aims: Calciprotein particles (CPPs) are circulating calcium and phosphate nanoparticles associated with the development of vascular calcification (VC) in chronic kidney disease (CKD). Although recent studies have been focusing on associations of CPPs with the presence of VC in CKD, insights in the underlying processes and mechanisms by which CPPs might aggravate VC and vascular dysfunction in vivo are currently lacking. Here, we assessed the overall burden of abdominal VC in healthy kidney donors and CKD patients and subsequently performed transcriptome profiling in the vascular tissue obtained from these subjects, linking outcome to CPP counts and calcification propensity., Methods and Results: Calcification scores were quantified in renal arteries, iliac arteries, and abdominal aorta using computed tomography (CT) scans of kidney donors and CKD patients. The vascular tissue was collected from kidney donors (renal artery) and CKD patients (iliac artery), after which bulk RNA sequencing and gene set enrichment analysis (GSEA) were performed on a subset of patients. Calcification propensity (crystallization time, T50) was measured using nephelometry and CPP counts with microparticle flow cytometric analysis. Increased calcification scores (based on CT) were found in CKD patients compared to kidney donors. Transcriptome profiling revealed enrichment for processes related to endothelial activation, inflammation, extracellular matrix (ECM) remodelling, and ossification in CKD vascular biopsies compared to kidney donors. Calcification propensity was increased in CKD, as well as CPP counts, with the latter being significantly associated with markers of vascular remodelling., Conclusion: Our findings reveal that CKD is characterized by systemic VC with increased calcification propensity and CPP counts. Transcriptome profiling showed altered vascular gene expression with enrichment for endothelial activation, inflammation, ECM remodelling, and ossification. Moreover, we demonstrate, for the first time, that vascular remodelling processes are associated with increased circulating CPP counts. Interventions targeting CPPs are promising avenues for alleviating vascular remodelling and VC in CKD., Competing Interests: Conflict of interest: A. Pasch is a founder and part-time employee of Calciscon AG, which commercializes the T50 test. E.R. Smith has received honoraria from CSL-Vifor, and is Scientific Advisor for Calciscon AG. G. Krenning is the Chief Scientific Officer of Sulfateq B.V. (Groningen, the Netherlands), a company that develops small-molecule therapeutics. Sulfateq B.V. was neither involved nor influenced the content of the manuscript. Astellas Pharma Europe was not involved in the design of the study, data analysis, or manuscript preparation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Kidney transplantation provides substantial benefits in extending survival and improving quality of life for patients with end-stage renal disease. The incidence of major adverse cardiac events (MACE) increases with a decline of kidney function in patients with chronic kidney disease. After kidney transplantation, the incidence of MACE remains high. The objective of this study was to assess the prognostic significance of pre-transplant single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in kidney transplant recipients., Methods: A systematic literature search was performed between January 1st 2015 and March 26th 2024 in PubMed, EMBASE, Web of Science and The Cochrane Library to identify the prognostic value of SPECT MPI for developing MACE (primary outcome) and mortality (secondary outcome) in kidney transplant recipients (PROSPERO CRD42020188610). Risk of bias was assessed. Meta-analyses and subgroup analyses were performed using random-effects models., Results: Six studies comprising 2090 SPECT MPI scans were included. Abnormal SPECT MPI scans were associated with an increased risk of MACE post-transplantation (HR 1.62, 95% CI 1.27-2.06, p < 0.001). Subgroup analyses showed consistent findings across various patient populations and methodological differences. Sensitivity analyses supported the robustness of our findings., Conclusions: Current evidence showed that pre-transplant SPECT MPI has significant prognostic value in identifying kidney transplant candidates at risk for MACE post-transplantation. Integrating SPECT MPI into preoperative assessments might enhance risk stratification and guide clinical decision-making. Prospective studies are needed to refine risk prediction models., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality., Methods: This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [ 99m Tc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied., Results: ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality., Conclusion: Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality., Competing Interests: Declarations. Informed consent: Requirement for consent was waived by the institutional review board of the University Medical Centre Groningen (Registration number: 202100405). Research involving human participants and/or animals: This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the institutional review board of the University Medical Centre Groningen (Registration number: 202100405). Conflicts of interest: H.S.A. Tingen no disclosures. D. Groothof no disclosures. A. Tubben no disclosures. J. Bijzet no disclosures. E.J. Houwerzijl no disclosures. F.L.H. Muntinghe no disclosures. P.A. van der Zwaag has received consultancy and speaker fees from Pfizer and Alnylam. P. van der Meer received grant support and/or consultancy fees from: Novartis, Pharma Nord, Pfizer, Ionis, Astra Zeneca, Vifor Pharma, Pharmacosmos, BridgeBio, NovoNordisk. B.P.C. Hazenberg no disclosures. R.H.J.A. Slart received independent grant support of Pfizer and Siemens Healthineers and is editor in the European Journal of Nuclear Medicine and Molecular Imaging. H.L.A. Nienhuis received consultancy and speaker fee from Pfizer and Alnylam., (© 2024. The Author(s).)

Aims: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an under-recognized aetiology of heart failure (HF), necessitating early detection for timely treatment. Our study aimed to differentiate patients with ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF patients by identifying and validating circulating protein biomarkers. In addition, we measured the same biomarkers in patients with cardiomyopathy due to light chain amyloidosis (AL)-CM to gain disease-specific insights., Methods and Results: In this observational study, serum concentrations of 363 protein biomarkers were measured in a discovery cohort consisting of 73 ATTRwt-CM, 55 AL-CM, and 59 ATTRwt-negative HFpEF/HFmrEF patients, using multiplex proximity extension assays. Sparse partial least squares analyses showed overlapping ATTRwt-CM and AL-CM biomarker profiles with clear visual differentiation from ATTRwt-negative patients. Pathway analyses with g:Profiler revealed significantly up-regulated proteoglycans (PG) and cell adhesion pathways in both ATTRwt-CM and AL-CM. Penalized regression analysis revealed that the proteoglycan decorin (DCN), lysosomal hydrolase alpha-L-iduronidase (IDUA) and glycosyl hydrolase galactosidase β-1 (GLB-1) most effectively distinguished ATTRwt-CM from ATTRwt-negative patients (R2 = 0.71). In a prospective validation cohort of 35 ATTRwt-CM patients and 25 ATTRwt-negative patients, DCN and IDUA significantly predicted ATTRwt-CM in the initial analysis (DCN: OR 3.3, IDUA: OR 0.4). While DCN remained significant after correcting for echocardiographic parameters, IDUA did not. DCN showed moderate discriminative ability (AUC, 0.74; 95% CI, 0.61-0.87; sensitivity, 0.91; specificity, 0.52) as did IDUA (AUC, 0.78; 95% CI, 0.65-0.91; sensitivity, 0.91; specificity, 0.61). A model combining clinical factors (AUC 0.92) outperformed DCN but not IDUA, a combination of the biomarkers was not significantly better. Neither DCN nor IDUA correlated with established disease markers., Conclusion: ATTRwt-CM has a distinctly different biomarker profile compared with HFpEF/HFmrEF, while ATTRwt-CM patients share a similar biomarker profile with AL-CM patients characterized by up-regulation of proteoglycans and cell-adhesion pathways. The biomarkers DCN and IDUA show the potential to serve as an initial screening tool for ATTTRwt-CM. Further research is needed to determine the clinical usefulness of these and other extracellular matrix components in identifying ATTRwt-CM., Competing Interests: Conflict of interest: Alwin Tubben: none. George Markousis-Mavrogenis: none. Laura M.G. Meems: none. Bart van Essen: none. Lukas Baumhove: none. Milou Berends: none. Hendrea S.A. Tingen: none. Johan Bijzet: none. Bouke P.C. Hazenberg: none. Adriaan A. Voors: The UMCG, which employs AAV, received consultancy fees or research support from Anacardio, AstraZeneca, BMS, Bayer, Boehringer Ingelheim, Cytokinetics, Corteria, EliLilly, Merck, Moderna, Novartis, NovoNordisk, Roche Diagnostics. Dirk-Jan van Veldhuisen: none. Riemer H.J.A. Slart: The UMCG, which employs RHJAS, received grant support of Pfizer and Siemens Healthineers. Hans L.A. Nienhuis: The UMCG, which employs HLAN, received consultancy fees and speaking honorarium from Pfizer and Alnylam. Peter van der Meer: PvdM is supported by a grant from the European Research Council (ERC CoG 101045236, DISSECT-HF). The UMCG, which employs PvdM, received consultancy fees and/or grants from Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Boehringer Ingelheim and Ionis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The aim of our current systematic dynamic phantom study was first, to optimize reconstruction parameters of coronary CTA (CCTA) acquired on photon counting CT (PCCT) for coronary artery calcium (CAC) scoring, and second, to assess the feasibility of calculating CAC scores from CCTA, in comparison to reference calcium scoring CT (CSCT) scans., Methods: In this phantom study, an artificial coronary artery was translated at velocities corresponding to 0, < 60, and 60-75 beats per minute (bpm) within an anthropomorphic phantom. The density of calcifications was 100 (very low), 200 (low), 400 (medium), and 800 (high) mgHA/cm 3 , respectively. CCTA was reconstructed with the following parameters: virtual non-iodine (VNI), with and without iterative reconstruction (QIR level 2, QIR off, respectively); kernels Qr36 and Qr44f; slice thickness/increment 3.0/1.5 mm and 0.4/0.2 mm. The agreement in risk group classification between CAC CCTA and CAC CSCT scoring was measured using Cohen weighted linear κ with 95% CI., Results: For CCTA reconstructed with 0.4 mm slice thickness, calcium detectability was perfect (100%). At < 60 bpm, CAC CCTA of low, and medium density calcification was underestimated by 53%, and 15%, respectively. However, CAC CCTA was not significantly different from CAC CSCT of very low, and high-density calcifications. The best risk agreement was achieved when CCTA was reconstructed with QIR off, Qr44f, and 0.4 mm slice thickness (κ = 0.762, 95% CI 0.671-0.853)., Conclusion: In this dynamic phantom study, the detection of calcifications with different densities was excellent with CCTA on PCCT using thin-slice VNI reconstruction. Agatston scores were underestimated compared to CSCT but agreement in risk classification was substantial., Clinical Relevance Statement: Photon counting CT may enable the implementation of coronary artery calcium scoring from coronary CTA in daily clinical practice., Key Points: Photon-counting CTA allows for excellent detectability of low-density calcifications at all heart rates. Coronary artery calcium scoring from coronary CTA acquired on photon counting CT is feasible, although improvement is needed. Adoption of the standard acquisition and reconstruction protocol for calcium scoring is needed for improved quantification of coronary artery calcium to fully employ the potential of photon counting CT., (© 2024. The Author(s).)

Introduction: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [ 18 F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms., Methods: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard., Results: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively., Discussion: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [ 18 F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE., (© 2024. The Author(s).)

Cardiovascular imaging has rapidly advanced over the past decades. Traditional imaging techniques such as echocardiography, computed tomography, and cardiovascular magnetic resonance are essential for assessing the structural and functional aspects of the cardiovascular system but often fall short in providing direct insights into disease activity. This gap is increasingly being bridged by molecular nuclear imaging techniques, including positron emission tomography and single-photon emission computed tomography, which enable the visualization of disease processes at the molecular and cellular levels. This review highlights the role of cardiovascular molecular imaging, emphasizing its current and potential applications in diagnosing and managing cardiovascular disease. With advancements in positron emission tomography scanners, novel radiotracers, and sophisticated imaging software, molecular imaging is set to play an essential role in precision medicine by enhancing our understanding of disease mechanisms, accelerating the development of targeted therapies, and facilitating personalized patient care., Competing Interests: None.

Methods to shorten [ 18 F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [ 18 F]FDG Patlak imaging at 55-65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30-60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30-60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value ( K i ) (mean difference ranging from -0.0022 to 0.0018 mL/[min × g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30-60 min after injection versus 55-65 min after injection, with 2.4% deviation in tumor K i (median difference, -0.0018 mL/[min × g]; range, -0.0047 to 0.0036 mL/[min × g]). For different maximum crystal ring difference settings using the scan time interval of 55-65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min × g]; range, -0.0004 to 0.0013 mL/[min × g]) in tumor K i was found. Conclusion: Ultrashort whole-body [ 18 F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision., Procedures: To this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[ 18 F]fluoro-D-glucose injection and underwent routine clinical ( ∼ 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon's signed rank test and the SUVs were statistically compared using a paired t-test., Results: Twenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra., Conclusion: This study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations., (© 2024. The Author(s).)

Positron emission tomography / computed tomography (PET/CT) plays a pivotal role in the assessment of cardiovascular diseases (CVD), particularly in the context of ischemic heart disease. Nevertheless, its application in other forms of CVD, such as infiltrative, infectious, or inflammatory conditions, remains limited. Recently, PET/CT systems with an extended axial field of view (LAFOV) have been developed, offering greater anatomical coverage and significantly enhanced PET sensitivity. These advancements enable head-to-pelvis imaging with a single bed position, and in systems with an axial field of view (FOV) of approximately 2 meters, even total body (TB) imaging is feasible in a single scan session. The application of LAFOV PET/CT in CVD presents a promising opportunity to improve systemic cardiovascular assessments and address the limitations inherent to conventional short axial field of view (SAFOV) devices. However, several technical challenges, including procedural considerations for LAFOV systems in CVD, complexities in data processing, arterial input function extraction, and artefact management, have not been fully explored. This review aims to discuss the technical aspects of LAFOV PET/CT in relation to CVD by highlighting key opportunities and challenges and examining the impact of these factors on the evaluation of most relevant CVD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Riemer H. J. A. Slart reports a relationship with Siemens Healthineers that includes: funding grants. Riemer H. J. A. Slart reports a relationship with Pfizer that includes: funding grants. Andor W. J. M. Glaudemans reports a relationship with Siemens Healthineers that includes: funding grants. Charalampos Tsoumpas reports a relationship with Siemens Healthineers that includes: funding grants. Charalampos Tsoumpas reports a relationship with Positrigo that includes: funding grants. Charalampos Tsoumpas reports a relationship with General Electric Healthcare that includes: funding grants. Charalampos Tsoumpas reports a relationship with Positrigo that includes: consulting or advisory. 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.)

The introduction of dual-energy X-ray absorptiometry (DXA) technology in the 1980s revolutionized the diagnosis, management and monitoring of osteoporosis, providing a clinical tool which is now available worldwide. However, DXA measurements are influenced by many technical factors, including the quality control procedures for the instrument, positioning of the patient, and approach to analysis. Reporting of DXA results may be confounded by factors such as selection of reference ranges for T-scores and Z-scores, as well as inadequate knowledge of current standards for interpretation. These points are addressed at length in many international guidelines but are not always easily assimilated by practising clinicians and technicians. Our aim in this report is to identify key elements pertaining to the use of DXA in clinical practice, considering both technical and clinical aspects. Here, we discuss technical aspects of DXA procedures, approaches to interpretation and integration into clinical practice, and the use of non-bone mineral density measurements, such as a vertebral fracture assessment, in clinical risk assessment., (© 2024. The Author(s).)

Purpose: Sodium[ 18 F]fluoride (Na[ 18 F]F) used in positron emission tomography (PET) binds to active calcification and correlates consistently with higher cardiovascular risk. This study aims to investigate the feasibility of aortic Na[ 18 F]F-PET in hybrid combination with low-dose computed tomography (CT) as a risk model for major adverse cardiovascular events (MACE)., Methods: Patient data and Na[ 18 F]F-PET/CT scans from January 2019 to February 2022 were retrospectively collected at the University Medical Center Groningen (UMCG), the Netherlands. MACE-outcome was a composite of time to first documented myocardial infarction, cerebral vascular accident (CVA), acute heart failure hospitalization, and aortic aneurysms. MACE dates were recorded from the day of the scan until follow-up in December 2023. The aorta was manually segmented in all low-dose CT scans. To minimize spill-over effects from the vertebrae, the vertebrae were automatically segmented using an open-source model, dilated with 10 mm, and subtracted from the aortic mask. The total aortic Na[ 18 F]F corrected maximum standardized uptake value (cSUV max ) and total aortic Agatston score were automatically calculated using SEQUOIA. Kaplan-Meier and Cox regression survival analysis were performed, stratifying patients into high, medium, and low cSUV max and Agatston categories. Cox regression models were adjusted for age., Results: Out of 280 identified scans, 216 scans of unique patients were included. During a median follow-up of 3.9 years, 12 MACE occurred. Kaplan-Meier survival analysis demonstrated a significant difference in MACE-free survival among the high cSUV max group compared to the medium and low groups (p = 0.03 and p < 0.01, respectively). Similarly, patients with high Agatston scores had a significantly lower MACE-free survival probability compared to those with medium and low scores (both p < 0.01)., Conclusion: This study highlights the potential clinical utility of Na[ 18 F]F-PET/CT as an imaging tool to predict the risk of MACE. Clinical validation of this novel proof-of-concept method is needed to confirm these results and expand the clinical context., (© 2024. The Author(s).)

Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome., 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 Inc. All rights reserved.)

Systemic vasculitides are autoimmune diseases characterized by inflammation of blood vessels. They are categorized based on the size of the preferentially affected blood vessels: large-, medium-, and small-vessel vasculitides. The main forms of large-vessel vasculitis include giant cell arteritis (GCA) and Takayasu arteritis (TAK). Depending on the location of the affected vessels, various imaging modalities can be employed for diagnosis of large vessel vasculitis: ultrasonography (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and [ 18 F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). These imaging tools offer complementary information about vascular changes occurring in vasculitis. Recent advances in PET imaging in large vessel vasculitis include the introduction of digital long axial field-of-view PET/CT, dedicated acquisition, quantitative methodologies, and the availability of novel radiopharmaceuticals. This review aims to provide an update on the current status of PET imaging in large vessel vasculitis and to share the latest developments on imaging vasculitides., 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: The study aimed, firstly, to validate automatically and visually scored coronary artery calcium (CAC) on low-dose computed tomography (CT) (LDCT) scans with a dedicated calcium scoring CT (CSCT) scan and, secondly, to assess the added value of CAC scored from LDCT scans acquired during [15O]-water-positron emission tomography (PET) myocardial perfusion imaging (MPI) on prediction of major adverse cardiac events (MACE)., Methods and Results: Five hundred seventy-two consecutive patients with suspected coronary artery disease, who underwent [15O]-water-PET MPI with LDCT and a dedicated CSCT scan were included. In the reference CSCT scans, manual CAC scoring was performed, while LDCT scans were scored visually and automatically using deep learning approach. Subsequently, based on CAC score results from CSCT and LDCT scans, each patient's scan was assigned to one out of five cardiovascular risk groups (0, 1-100, 101-400, 401-1000, >1000), and the agreement in risk group classification between CSCT and LDCT scans was investigated. MACE was defined as a composite of all-cause death, non-fatal myocardial infarction, coronary revascularization, and unstable angina. The agreement in risk group classification between reference CSCT manual scoring and visual/automatic LDCT scoring from LDCT was 0.66 [95% confidence interval (CI): 0.62-0.70] and 0.58 (95% CI: 0.53-0.62), respectively. Based on visual and automatic CAC scoring from LDCT scans, patients with CAC > 100 and CAC > 400, respectively, were at increased risk of MACE, independently of ischaemic information from the [15O]-water-PET scan., Conclusion: There is a moderate agreement in risk classification between visual and automatic CAC scoring from LDCT and reference CSCT scans. Visual and automatic CAC scoring from LDCT scans improve identification of patients at higher risk of MACE., Competing Interests: Conflict of interest: N.R.v.d.W. is an employee of Philips. I.I. received institutional research grants from Dutch Technology Foundation (P15–26) with participation of Philips Healthcare and Pie Medical Imaging BV and institutional research grant from Pie Medical Imaging BV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis., Methods: Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement., Results: Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4 kPa vs. 8.1 kPa; p = 0.001) and SAP scintigraphy (median 20.9 kPa vs. 6.2 kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4 kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard., Conclusion: Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement., (© 2024. The Author(s).)

Objectives: Cardiac motion artifacts hinder the assessment of coronary arteries in coronary computed tomography angiography (CCTA). We investigated the impact of motion compensation reconstruction (MCR) on motion artifacts in CCTA at various heart rates (HR) using a dynamic phantom., Materials and Methods: An artificial hollow coronary artery (5-mm diameter lumen) filled with iodinated contrast agent (400 HU at 120 kVp), positioned centrally in an anthropomorphic chest phantom, was scanned using a dual-layer spectral detector CT. The artery was translated at constant horizontal velocities (0-80 mm/s, increment of 10 mm/s). For each velocity, five CCTA scans were repeated using a clinical protocol. Motion artifacts were quantified using the in-plane motion area. Regression analysis was performed to calculate the reduction in motion artifacts provided by MCR, by division of the slopes of non-MCR and MCR fitted lines., Results: Reference mean (95% confidence interval) motion artifact area was 24.9 mm 2 (23.8, 26.0). Without MCR, motion artifact areas for velocities exceeding 20 mm/s were significantly larger (up to 57.2 mm 2 (40.1, 74.2)) than the reference. With MCR, no significant differences compared to the reference were shown for all velocities, except for 70 mm/s (29.0 mm 2 (27.0, 31.0)). The slopes of the fitted data were 0.44 and 0.04 for standard and MCR reconstructions, respectively, resulting in an 11-time motion artifact reduction., Conclusion: MCR may improve CCTA assessment in patients by reducing coronary artery motion artifacts, especially in those with elevated HR who cannot receive beta blockers or do not attain the targeted HR., Clinical Relevance Statement: This vendor-specific motion compensation reconstruction may improve coronary computed tomography angiography assessment in patients by reduction of coronary artery motion artifacts, especially in those with elevated various heart rates (HR) who cannot receive beta blockers or do not attain the targeted HR., Key Points: • Motion artifacts are known to hinder the assessment of coronary arteries on coronary CT angiography (CCTA), leading to more non-diagnostic scans. • This dynamic phantom study shows that motion compensation reconstruction (MCR) reduces motion artifacts at various velocities, which may help to decrease the number of non-diagnostic scans. • MCR in this study showed to reduce motion artifacts 11-fold., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR., Methods: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively., Results: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score., Conclusion: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Osteoporotic fractures, also known as fragility fractures, are reflective of compromised bone strength and are associated with significant morbidity and mortality. Such fractures may be clinically silent, and others may present clinically with pain and deformity at the time of the injury. Unfortunately, and even at the time of detection, most individuals sustaining fragility fractures are not identified as having underlying metabolic bone disease and are not evaluated or treated to reduce the incidence of future fractures. A multidisciplinary international working group with representation from international societies dedicated to advancing the care of patients with metabolic bone disease has developed best practice recommendations for the diagnosis and evaluation of individuals with fragility fractures. A comprehensive narrative review was conducted to identify key articles on fragility fractures and their impact on the incidence of further fractures, morbidity, and mortality. This document represents consensus among the supporting societies and harmonizes best practice recommendations consistent with advances in research. A fragility fracture in an adult is an important predictor of future fractures and requires further evaluation and treatment of the underlying osteoporosis. It is important to recognize that most fragility fractures occur in patients with bone mineral density T scores higher than -2.5, and these fractures confirm the presence of skeletal fragility even in the presence of a well-maintained bone mineral density. Fragility fractures require further evaluation with exclusion of contributing factors for osteoporosis and assessment of clinical risk factors for fracture followed by appropriate pharmacological intervention designed to reduce the risk of future fracture. Because most low-trauma vertebral fractures do not present with pain, dedicated vertebral imaging and review of past imaging is useful in identifying fractures in patients at high risk for vertebral fractures. Given the importance of fractures in confirming skeletal fragility and predicting future events, it is recommended that an established classification system be used for fracture identification and reporting., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings., Methods: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria., Results: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [ 18 F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [ 18 F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [ 18 F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [ 18 F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [ 18 F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging., Conclusion: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications., (© 2024. The Author(s).)