Using machine learning to improve the diagnostic accuracy of the modified Duke/ESC 2015 criteria in patients with suspected prosthetic valve endocarditis - a proof of concept study.

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 [18F]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 [18F]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.

Cardiac [99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?

PURPOSE: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments. METHODS: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated. RESULTS: Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p < .001) in patients treated with patisiran for 29 [15-34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [ 3.39 to 5.80] (p = .010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p = .025). All other parameters did not change during treatment with a TTR-stabilizer. CONCLUSION: A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients.

Machine learning in the differentiation of follicular lymphoma from diffuse large B-cell lymphoma with radiomic [18F]FDG PET/CT features.

BACKGROUND: One of the challenges in the management of patients with follicular lymphoma (FL) is the identification of individuals with histological transformation, most commonly into diffuse large B-cell lymphoma (DLBCL). [18F]FDG-PET/CT is used for staging of patients with lymphoma, but visual interpretation cannot reliably discern FL from DLBCL. This study evaluated whether radiomic features extracted from clinical baseline [18F]FDG PET/CT and analyzed by machine learning algorithms may help discriminate FL from DLBCL. MATERIALS AND METHODS: Patients were selected based on confirmed histopathological diagnosis of primary FL (n=44) or DLBCL (n=76) and available [18F]FDG PET/CT with EARL reconstruction parameters within 6 months of diagnosis. Radiomic features were extracted from the volume of interest on co-registered [18F]FDG PET and CT images. Analysis of selected radiomic features was performed with machine learning classifiers based on logistic regression and tree-based ensemble classifiers (AdaBoosting, Gradient Boosting, and XG Boosting). The performance of radiomic features was compared with a SUVmax-based logistic regression model. RESULTS: From the segmented lesions, 121 FL and 227 DLBCL lesions were included for radiomic feature extraction. In total, 79 radiomic features were extracted from the SUVmap, 51 from CT, and 6 shape features. Machine learning classifier Gradient Boosting achieved the best discrimination performance using 136 radiomic features (AUC of 0.86 and accuracy of 80%). SUVmax-based logistic regression model achieved an AUC of 0.79 and an accuracy of 70%. Gradient Boosting classifier had a significantly greater AUC and accuracy compared to the SUVmax-based logistic regression (p≤0.01). CONCLUSION: Machine learning analysis of radiomic features may be of diagnostic value for discriminating FL from DLBCL tumor lesions, beyond that of the SUVmax alone.

Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0.

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [18F]FDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors. METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard. CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [18F]FDG PET/CT during immunotherapy. Local variations to this guideline should be taken into consideration. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.

Diagnostic value of [18F]FDG-PET/CT in polymyalgia rheumatica: a systematic review and meta-analysis.

PURPOSE: Polymyalgia rheumatica (PMR) can be difficult to diagnose. Whole-body [18F]FDG-PET/CT allows for a comprehensive evaluation of all relevant articular and extra-articular structures affected by PMR. We aimed to summarize current evidence on the diagnostic value of [18F]FDG-PET/CT for a diagnosis of PMR. METHODS: PubMed/MEDLINE and the Cochrane Library database were searched from inception through May 31, 2020. Studies containing patients with PMR who underwent [18F]FDG-PET/CT were included. Screening and full-text review were performed by 3 investigators and data extraction by 2 investigators. Risk of bias was examined with the QUADAS-2 tool. Diagnostic test meta-analysis was performed with a bivariate model. RESULTS: Twenty studies were included in the systematic review, of which 9 studies (n = 636 patients) were eligible for meta-analysis. [18F]FDG positivity at the following sites was associated with a diagnosis of PMR: interspinous bursae (positive likelihood ratio (LR+) 4.00; 95% CI 1.84-8.71), hips (LR+ 2.91; 95% CI 2.09-4.05), ischial tuberosities (LR+ 2.86; 95% CI 1.91-4.28), shoulders (LR+ 2.57; 95% CI 1.24-5.32) and sternoclavicular joints (LR+ 2.31; 95% CI 1.33-4.02). Negative likelihood ratios (LR-) for these sites, as well as the greater trochanters, were all less than 0.50. Composite [18F]FDG-PET/CT scores, as reported in 3 studies, provided a pooled LR+ of 3.91 (95% CI 2.42-6.32) and LR- of 0.19 (95% CI 0.10-0.36). Moderate to high heterogeneity was observed across the studies, mainly due to differences in patient selection, scanning procedures and/or interpretation criteria. CONCLUSION: Significant [18F]FDG uptake at a combination of anatomic sites is informative for a diagnosis of PMR. [18F]FDG-PET/CT might be an important diagnostic tool in patients with suspected PMR. This study also highlights the need for adherence to published procedural recommendations and standardized interpretation criteria for the use of [18F]FDG-PET/CT in PMR.

Diagnostic value of [18F]FDG-PET/CT for treatment monitoring in large vessel vasculitis: a systematic review and meta-analysis.

PURPOSE: Monitoring disease activity in patients with large vessel vasculitis (LVV) can be challenging. [18F]FDG-PET/CT is increasingly used to evaluate treatment response in LVV. In this systematic review and meta-analysis, we aimed to summarize the current evidence on the value of [18F]FDG-PET/CT for treatment monitoring in LVV. METHODS: PubMed/MEDLINE and the Cochrane library database were searched from inception through October 21, 2020. Studies containing patients with LVV (i.e. giant cell arteritis, Takayasu arteritis and isolated aortitis) that received treatment and underwent [18F]FDG-PET/CT were included. Screening, full-text review and data extraction were performed by 2 investigators. The risk of bias was examined with the QUADAS-2 tool. Meta-analysis of proportions and diagnostic test accuracy was performed by a random-effects model and bivariate model, respectively. RESULTS: Twenty-one studies were included in the systematic review, of which 8 studies were eligible for meta-analysis. Arterial [18F]FDG uptake decreased upon clinical remission in longitudinal studies. High heterogeneity (I2 statistic 94%) precluded meta-analysis of the proportion of patients in which the scan normalized during clinical remission. Meta-analysis of cross-sectional studies indicated that [18F]FDG-PET/CT may detect relapsing/refractory disease with a sensitivity of 77% (95%CI 57-90%) and specificity of 71% (95%CI 47-87%). Substantial heterogeneity was observed among the cross-sectional studies. Both variation in clinical aspects and imaging procedures contributed to the heterogeneity. CONCLUSION: Treatment of LVV leads to reduction of arterial [18F]FDG uptake during clinical remission. [18F]FDG-PET/CT has moderate diagnostic accuracy for detecting active LVV. [18F]FDG-PET/CT may aid treatment monitoring in LVV, but its findings should be interpreted in the context of the clinical suspicion of disease activity. This study underlines the relevance of published procedural recommendations for the use of [18F]FDG-PET/CT in LVV.

The value of 18F-FDG PET/CT for the diagnosis of device-related infections in patients with a left ventricular assist device: a systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used for the treatment of advanced heart failure. LVADs improve quality of life and decrease mortality, but the driveline carries substantial risk for major infections. These device-related LVAD and driveline infections are difficult to diagnose with conventional imaging. We reviewed and analysed the current literature on the additive value of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) imaging for the diagnosis of LVAD-related infections." MATERIALS/METHODS: We performed a systematic literature review using several databases from their inception until the 31st of December, 2019. Studies investigating the diagnostic performance of FDG-PET/CT in patients with suspected LVAD infection were retrieved. After a bias risk assessment using QUADAS-2, a study-aggregate meta-analysis was performed on a per examination-based analysis. RESULTS: A total of 10 studies were included in the systematic review, eight of which were also eligible for study-aggregate meta-analysis. For the meta-analysis, a total of 256 FDG-PET/CT scans, examining pump/pocket and/or driveline infection, were acquired in 230 patients. Pooled sensitivity of FDG-PET/CT was 0.95 (95% confidence interval (CI) 0.89-0.97) and pooled specificity was 0.91 (95% CI 0.54-0.99) for the diagnosis of device-related infection. For pump/pocket infection, sensitivity and specificity of FDG-PET/CT were 0.97 (95%CI 0.69-1.00) and 0.93 (95%CI 0.64-0.99), respectively. For driveline infection, sensitivity and specificity were 0.96 (95%CI 0.88-0.99) and 0.99 (95%CI 0.13-1.00) respectively. Significant heterogeneity existed across studies for specificity, mostly caused by differences in scan procedures. Predefined criteria for suspicion of LVAD and/or driveline infection were lacking in all included studies. CONCLUSIONS: FDG-PET/CT is a valuable tool for assessment of device-related infection in LVAD patients, with high sensitivity and high, albeit variable, specificity. Standardization of FDG-PET/CT procedures and criteria for suspected device-related LVAD infections are needed for consistent reporting of FDG-PET/CT scans.

18F-FDG PET/CT in Infective Endocarditis: Indications and Approaches for Standardization.

PURPOSE OF REVIEW: Additional imaging modalities, such as FDG-PET/CT, have been included into the workup for patients with suspected infective endocarditis, according to major international guidelines published in 2015. The purpose of this review is to give an overview of FDG-PET/CT indications and standardized approaches in the setting of suspected infective endocarditis. RECENT FINDINGS: There are two main indications for performing FDG-PET/CT in patients with suspected infective endocarditis: (i) detecting intracardiac infections and (ii) detection of (clinically silent) disseminated infectious disease. The diagnostic performance of FDG-PET/CT for intracardiac lesions depends on the presence of native valves, prosthetic valves, or implanted cardiac devices, with a sensitivity that is poor for native valve endocarditis and cardiac device-related lead infections, but much better for prosthetic valve endocarditis and cardiac device-related pocket infections. Specificity is high for all these indications. The detection of disseminated disease may also help establish the diagnosis and/or impact patient management. Based on current evidence, FDG-PET/CT should be considered for detection of disseminated disease in suspected endocarditis. Absence of intracardiac lesions on FDG-PET/CT cannot rule out native valve endocarditis, but positive findings strongly support the diagnosis. For prosthetic valve endocarditis, standard use of FDG-PET/CT is recommended because of its high sensitivity and specificity. For implanted cardiac devices, FDG-PET/CT is also recommended, but should be evaluated with careful attention to clinical context, because its sensitivity is high for pocket infections, but low for lead infections. In patients with prosthetic valves with or without additional aortic prosthesis, combination with CTA should be considered. Optimal timing of FDG-PET/CT is important, both during clinical workup and technically (i.e., post tracer injection). In addition, procedural standardization is key and encompasses patient preparation, scan acquisition, reconstruction, subsequent analysis, and clinical interpretation. The recommendations discussed here will hopefully contribute to improved standardization and enhanced performance of FDG-PET/CT in the clinical management of patients with suspected infective endocarditis.

Diagnostic performance of FDG-PET/CT of post-transplant lymphoproliferative disorder and factors affecting diagnostic yield.

PURPOSE: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, requiring a timely and accurate diagnosis. In this study, we evaluated the diagnostic performance of FDG-PET/CT in patients with suspected PTLD and examined if lactate dehydrogenase (LDH) levels, Epstein-Barr virus (EBV) load, or timing of FDG-PET/CT relate to detection performance of FDG-PET/CT. METHODS: This retrospective study included 91 consecutive patients with clinical suspicion of PTLD and a total of 97 FDG-PET/CT scans within an 8-year period. Pathology reports and a 2-year follow-up were used as the reference standard. Diagnostic performance of FDG-PET/CT for detection of PTLD as well as logistic regression analysis for factors expected to affect diagnostic yield were assessed. RESULTS: The diagnosis of PTLD was established in 34 patients (35%). Fifty-seven FDG-PET/CT scans (59%) were true negative, 29 (30%) were true positive, 6 (6%) false positive, and 5 (5%) false negative. Sensitivity of FDG-PET/CT for the detection of PTLD was 85%, specificity 90%, positive predictive value 83%, and negative predictive value 92%, with good inter-observer variability (k = 0.78). Of the parameters hypothesized to be associated with a true positive FDG-PET/CT result for the diagnosis of PTLD, only LDH was statistically significant (OR 1.03, p = 0.04). CONCLUSION: FDG-PET/CT has a good diagnostic performance in patients suspected of PTLD, with a good inter-observer agreement. Only LDH levels seemed to influence the detection performance of FDG-PET/CT. EBV-DNA load and timing of FDG-PET/CT after transplantation did not affect FDG-PET/CT diagnostic yield.

Molecular imaging in ovarian cancer.

Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer.

The value of PET/CT with FES or FDG tracers in metastatic breast cancer: a computer simulation study in ER-positive patients.

BACKGROUND: The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[(18)F]fluoro-17ß-oestradiol (FES) or 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms. METHODS: A published computer simulation model was adapted and validated. Three follow-up strategies were evaluated in a simulated cohort of women with primary breast cancer over a 5-year-time horizon: (1) the standard work-up, (2) upfront FES-PET/CT and (3) upfront FDG-PET/CT. The main outcome was the number of avoided biopsies to assess MBC. The costs for all three strategies were calculated based on the number of imaging tests and biopsies. The incremental cost-effectiveness ratio (ICER) to avoid a biopsy was calculated only based on the costs of initial imaging and staging tests. RESULTS: The FES-PET/CT strategy decreased the number of biopsies by 39 ± 9%, while upfront FDG-PET/CT increased the number of biopsies by 38 ± 15% when compared with the standard work-up. Both PET/CT strategies reduced the number of imaging tests and false positives when compared with the standard work-up. The number of false negatives decreased only in the FES-PET/CT strategy. The ICER in the FES-PET/CT strategy per avoided biopsy was 12.1 ± 3.4 thousand Euro. In the FDG-PET/CT strategy, the costs were higher and there were no avoided biopsies as compared with the standard work-up, hence this was an inferior strategy in terms of cost effectiveness. CONCLUSIONS: The number of performed biopsies was lower in the FES-PET/CT strategy at an ICER of 12.1 ± 3.4 thousand Euro per biopsy avoided, whereas the application of the FDG-PET/CT did not reduce the number of biopsies and was more expensive. Whether the FES-PET/CT strategy has additional benefits for patients in terms of therapy management has to be evaluated in clinical studies.

Challenges in diagnosing infection in the diabetic foot.

Diagnosing the presence of infection in the foot of a patient with diabetes can sometimes be a difficult task. Because open wounds are always colonized with microorganisms, most agree that infection should be diagnosed by the presence of systemic or local signs of inflammation. Determining whether or not infection is present in bone can be especially difficult. Diagnosis begins with a history and physical examination in which both classic and 'secondary' findings suggesting invasion of microorganisms or a host response are sought. Serological tests may be helpful, especially measurement of the erythrocyte sedimentation rate in osteomyelitis, but all (including bone biomarkers and procalcitonin) are relatively non-specific. Cultures of properly obtained soft tissue and bone specimens can diagnose and define the causative pathogens in diabetic foot infections. Newer molecular microbial techniques, which may not only identify more organisms but also virulence factors and antibiotic resistance, look very promising. Imaging tests generally begin with plain X-rays; when these are inconclusive or when more detail of bone or soft tissue abnormalities is required, more advanced studies are needed. Among these, magnetic resonance imaging is generally superior to standard radionuclide studies, but newer hybrid imaging techniques (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging) look to be useful techniques, and new radiopharmaceuticals are on the horizon. In some cases, ultrasonography, photographic and thermographic methods may also be diagnostically useful. Improved methods developed and tested over the past decade have clearly increased our accuracy in diagnosing diabetic foot infections.

Improved [18F]FDG PET/CT Diagnostic Accuracy for Infective Endocarditis Using Conventional Cardiac Gating or Combined Cardiac and Respiratory Motion Correction (CardioFreezeTM).

Infective endocarditis (IE) is a serious and diagnostically challenging condition. [18F]FDG PET/CT is valuable for evaluating suspected IE, but it is susceptible to motion-related artefacts. This study investigated the potential benefits of cardiac motion correction for [18F]FDG PET/CT. In this prospective study, patients underwent [18F]FDG PET/CT for suspected IE, combined with a conventional cardiac gating sequence, a data-driven cardiac and respiratory gating sequence (CardioFreezeTM), or both. Scans were performed in adherence to EANM guidelines and assessors were blinded to patients' clinical contexts. Final diagnosis of IE was established based on multidisciplinary consensus after a minimum of 4 months follow-up and surgical findings, whenever performed. Seven patients participated in the study, undergoing both an ungated [18F] FDG-PET/CT and a scan with either conventional cardiac gating, CardioFreezeTM, or both. Cardiac motion correction improved the interpretability of [18F]FDG PET/CT in four out of five patients with valvular IE lesions, regardless of the method of motion correction used, which was statistically significant by Wilcoxon's signed rank test: p = 0.046. In one patient the motion-corrected sequence confirmed the diagnosis of endocarditis, which had been missed on non-gated PET. The performance of the two gating sequences was comparable. In conclusion, in this exploratory study, cardiac motion correction of [18F]FDG PET/CT improved the interpretability of [18F]FDG PET/CT. This may improve the sensitivity of PET/CT for suspected IE. Further larger comparative studies are necessary to confirm the additive value of these cardiac motion correction methods.

Long axial field of view PET/CT in critically ill patients: lessons from a case report.

The introduction of new long axial field of view (LAFOV) scanners is a major milestone in positron emission tomography/computed tomography (PET/CT) imaging. With these new systems a revolutionary reduction in scan time can be achieved, concurrently lowering tracer dose. Therefore, PET/CT has come within reach for groups of patients in whom PET/CT previously was undesirable. In this case report we discuss the procedure of a continuous bed motion (CBM) total-body [18F]FDG PET/CT scan in an intensive care patient. We emphasize the clinical and technical possibilities with this new camera system, a matched clinical protocol, and the added value of a dedicated team.

Rationale for the use of radiolabelled peptides in diagnosis and therapy.

Nuclear medicine techniques are becoming more important in imaging oncological and infectious diseases. For metabolic imaging of these diseases, antibody and peptide imaging are currently used. In recent years peptide imaging has become important, therefore the rationale for the use of peptide imaging is described in this article. Criteria for a successful peptide tracer are a high target specificity, a high binding affinity, a long metabolic stability and a high target-to-background ratio. Tracer internalization is also beneficial. For oncological imaging, many tracers are available, most originating from regulatory peptides, but penetrating peptides are also being developed. Peptides for imaging inflammatory and infectious diseases include regulatory peptides, antimicrobial peptides and others. In conclusion, for the imaging of oncological, imflammatory and infectious diseases, many promising peptides are being developed. The ideal peptide probe is characterized by rapid and specific target localization and binding with a high tumour-to-background ratio.

Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors.

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [18F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0". These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.

Myocardial perfusion reserve compared with peripheral perfusion reserve: a [13N]ammonia PET study.

INTRODUCTION: [13N]ammonia PET allows quantification of myocardial perfusion. The similarity between peripheral flow and myocardial perfusion is unclear. We compared perfusion flow in the myocardium with the upper limb during rest and adenosine stress [13N]ammonia PET to establish whether peripheral perfusion reserve (PPR) correlates with MPR. METHODS: [13N]ammonia myocardial perfusion PET-scans of 58 patients were evaluated (27 men, 31 women, age 64 ± 13 years) and were divided in four subgroups: patients with coronary artery disease (CAD, n = 15), cardiac syndrome X (SX, n = 14), idiopathic dilating cardiomyopathy (DCM, n = 16), and normal controls (NC, n = 13). Peripheral limb perfusion was measured in the muscular tissue of the proximal upper limb and quantified through a 2-tissue-compartment model and the PPR was calculated (stress/rest ratio). MPR was also calculated by a 2-tissue-compartment model. The PPR results were compared with the MPR findings. RESULTS: Mean myocardial perfusion increased significantly in all groups as evidenced by the MPR (CAD 1.99 ± 0.47; SX 1.39 ± 0.31; DCM 1.72 ± 0.69; NC 2.91 ± 0.78). Mean peripheral perfusion also increased but not significantly and accompanied with great variations within and between groups (mean PPR: CAD 1.30 ± 0.79; SX 1.36 ± 0.71; DCM 1.60 ± 1.22; NC 1.27 ± 0.63). The mean difference between PPR and MPR for all subpopulations varied widely. No significant correlations in flow reserve were found between peripheral and myocardial microcirculatory beds in any of the groups (Total group: r = -0.07, SEE = 0.70, CAD: r = 0.14, SEE = 0.48, SX: r = 0.17, SEE = 0.30, DCM: r = -0.11, SEE = 0.71, NC: r = -0.19, SEE = 0.80). CONCLUSION: No correlations between myocardial and peripheral perfusion (reserve) were found in different patient populations in the same PET session. This suggests a functional difference between peripheral and myocardial flow in the response to intravenously administered adenosine stress.

Semi-Quantitative Characterization of Post-Transplant Lymphoproliferative Disorder Morphological Subtypes with [18F]FDG PET/CT.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation classified according to the WHO as nondestructive, polymorphic, monomorphic, and classic Hodgkin Lymphoma subtypes. In this retrospective study, we investigated the potential of semi-quantitative 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/computed tomography (CT)-based parameters to differentiate between the PTLD morphological subtypes. Methods: 96 patients with histopathologically confirmed PTLD and baseline [18F]FDG PET/CT between 2009 and 2019 were included. Extracted semi-quantitative measurements included: Maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean). Results: Median SUVs were highest for monomorphic PTLD followed by polymorphic and nondestructive subtypes. The median SUVpeak at the biopsy site was significantly higher in monomorphic PTLD (17.8, interquartile range (IQR):16) than in polymorphic subtypes (9.8, IQR:13.4) and nondestructive (4.1, IQR:6.1) (p = 0.04 and p ≤ 0.01, respectively). An SUVpeak ≥ 24.8 was always indicative of a monomorphic PTLD in our dataset. Nevertheless, there was a considerable overlap in SUV across the different morphologies. Conclusion: The median SUVpeak at the biopsy site was significantly higher in monomorphic PTLD than polymorphic and nondestructive subtypes. However, due to significant SUV overlap across the different subtypes, these values may only serve as an indication of PTLD morphology, and SUV-based parameters cannot replace histopathological classification.