MRI-based Zero Echo Time and Black Bone Pseudo-CT Compared with Whole-Body CT to Detect Osteolytic Lesions in Multiple Myeloma.

Background MRI is highly sensitive for assessing bone marrow involvement in multiple myeloma (MM) but does not enable detection of osteolysis. Purpose To assess the diagnostic accuracy, repeatability, and reproducibility of pseudo-CT MRI sequences (zero echo time [ZTE], gradient-echo black bone [BB]) in detecting osteolytic lesions in MM using whole-body CT as the reference standard. Materials and Methods In this prospective study, consecutive patients were enrolled in our academic hospital between June 2021 and December 2022. Inclusion criteria were newly diagnosed MM, monoclonal gammopathy of undetermined significance at high risk for MM, or suspicion of progressive MM. Participants underwent ZTE and BB sequences covering the lumbar spine, pelvis, and proximal femurs as part of 3-T whole-body MRI examinations, as well as clinically indicated fluorine 18 fluorodeoxyglucose PET/CT examination within 1 month that included optimized whole-body CT. Ten bone regions and two scores (categorical score = presence/absence of osteolytic lesion; semiquantitative score = osteolytic lesion count) were assessed by three radiologists (two experienced and one unfamiliar with pseudo-CT reading) on the ZTE, BB, and whole-body CT images. The accuracy, repeatability, and reproducibility of categorical scores (according to Gwet agreement coefficients AC1 and AC2) and differences in semiquantitative scores were assessed at the per-sequence, per-region, and per-patient levels. Results A total of 47 participants (mean age, 67 years ± 11 [SD]; 27 male) were included. In experienced readers, BB and ZTE had the same high accuracy (98%) in the per-patient analysis, while BB accuracy ranged 83%-100% and ZTE accuracy ranged 74%-94% in the per-region analysis. An increase of false-negative (FN) findings in the spine ranging from +17% up to +23%, according to the lumbar vertebra, was observed using ZTE (P < .013). Regardless of the region (except coxal bones), differences in the BB score minus the ZTE score were positively skewed (P < .021). Regardless of the sequence or region, repeatability was very good (AC1 ≥0.87 for all), while reproducibility was at least good (AC2 ≥0.63 for all). Conclusion Both MRI-based ZTE and BB pseudo-CT sequences of the lumbar spine, pelvis, and femurs demonstrated high diagnostic accuracy in detecting osteolytic lesions in MM. Compared with BB, the ZTE sequence yielded more FN findings in the spine. ClinicalTrials.gov Identifier: NCT05381077 Published under a CC BY 4.0 license. Supplemental material is available for this article.

EANM consensus document on the use of [18F]FDG PET/CT in fever and inflammation of unknown origin.

PURPOSE: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [18F]FDG-PET/CT in FUO and IUO based on current evidence. METHODS: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with "patients with FUO/IUO" as population, "[18F]FDG-PET/CT" as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness. RESULTS: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations. CONCLUSION: FUO and IUO remains a clinical challenge and [18F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50-60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients.

Hybrid cardiovascular imaging. A clinical consensus statement of the european association of nuclear medicine (EANM) and the european association of cardiovascular imaging (EACVI) of the ESC.

Hybrid imaging consists of a combination of two or more imaging modalities, which equally contribute to image information. To date, hybrid cardiovascular imaging can be performed by either merging images acquired on different scanners, or with truly hybrid PET/CT and PET/MR scanners. The European Association of Nuclear Medicine (EANM), and the European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology (ESC) aim to review clinical situations that may benefit from the use of hybrid cardiac imaging and provide advice on acquisition protocols providing the most relevant information to reach diagnosis in various clinical situations.

EANM/SNMMI guideline/procedure standard for [18F]FDG hybrid PET use in infection and inflammation in adults v2.0.

INTRODUCTION: Hybrid [18F]FDG PET imaging is currently the method of choice for a wide variety of infectious and inflammatory disorders and was recently adopted in several clinical guidelines. A large amount of evidence-based articles, guidelines and appropriate use criteria have been published since the first version of this guideline in 2013. PURPOSE: To provide updated evidence-based information to assist physicians in recommending, performing and interpreting hybrid [18F]FDG PET examinations for infectious and inflammatory disorders in the adult population. METHODS: A systematic literature search of evidence-based articles using whole-body [18F]FDG hybrid imaging on the indications covered within this guideline was performed. All systematic reviews and meta-analyses published within the last 10 years until January 2023 were identified in PubMed/Medline or Cochrane. For each indication covered in this manuscript, diagnostic performance was provided based on meta-analyses or systematic reviews. If not available, results from prospective or retrospective studies were considered based on predefined selection criteria. RESULTS AND CONCLUSIONS: Hybrid [18F]FDG PET is extremely useful in the work-up and management of adults with infectious and inflammatory diseases, as supported by extensive and rapidly growing evidence-based literature and adoption in clinical guidelines. Practical recommendations are provided describing evidence-based indications as well as interpretation criteria and pitfalls. Monitoring treatment response is the most challenging but insufficiently studied potential application in infection and inflammation imaging.

A systematic review for the evidence of recommendations and guidelines in hybrid nuclear cardiovascular imaging.

OBJECTIVES: This study aimed to evaluate the level of evidence of expert recommendations and guidelines for clinical indications and procedurals in hybrid nuclear cardiovascular imaging. METHODS: From inception to August 2023, a PubMed literature analysis of the latest version of guidelines for clinical hybrid cardiovascular imaging techniques including SPECT(/CT), PET(/CT), and PET(/MRI) was performed in two categories: (1) for clinical indications for all-in primary diagnosis; subgroup in prognosis and therapy evaluation; and for (2) imaging procedurals. We surveyed to what degree these followed a standard methodology to collect the data and provide levels of evidence, and for which topic systematic review evidence was executed. RESULTS: A total of 76 guidelines, published between 2013 and 2023, were included. The evidence of guidelines was based on systematic reviews in 7.9% of cases, non-systematic reviews in 47.4% of cases, a mix of systematic and non-systematic reviews in 19.7%, and 25% of guidelines did not report any evidence. Search strategy was reported in 36.8% of cases. Strengths of recommendation were clearly reported in 25% of guidelines. The notion of external review was explicitly reported in 23.7% of cases. Finally, the support of a methodologist was reported in 11.8% of the included guidelines. CONCLUSION: The use of evidence procedures for developing for evidence-based cardiovascular hybrid imaging recommendations and guidelines is currently suboptimal, highlighting the need for more standardized methodological procedures.

Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance.

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 [18F]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 [18F]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 [18F]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; [18F]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 [18F]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.

Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.

Evidence-based guideline of the European Association of Nuclear Medicine (EANM) on imaging infection in vascular grafts.

PURPOSE: Consensus on optimal imaging procedure for vascular graft/endograft infection (VGEI) is still lacking and the choice of a diagnostic test is often based on the experience of single centres. This document provides evidence-based recommendations aiming at defining which imaging modality may be preferred in different clinical settings and post-surgical time window. METHODS: This working group includes 6 nuclear medicine physicians appointed by the European Association of Nuclear Medicine, 4 vascular surgeons, and 2 radiologists. Vascular surgeons formulated 5 clinical questions that were converted into 10 statements and addressed through a systematic analysis of available literature by using PICOs (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 criteria. RESULTS: Sixty-six articles, published from January 2000 up to December 2021, were analysed and used for evidence-based recommendations. CONCLUSION: Computed tomography angiography (CTA) is the first-line imaging modality in suspected VGEI but nuclear medicine modalities are often needed to confirm or exclude the infection. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has very high negative predictive value but it should be performed preferably at least 4 months after surgery to avoid false positive results. Radiolabelled white blood cell (WBC) scintigraphy, given its high diagnostic accuracy, can be performed at any time after surgery. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional no-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. The EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The EANM recognizes that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the EANM suggests caution against the use of the current consensus document in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgement regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in the light of all the circumstances presented. Thus, there is no implication that an approach differing from the consensus document, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the consensus document when, in the reasonable judgement 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 consensus document. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to this consensus document will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient, to deliver effective and safe medical care. The sole purpose of this consensus document is to assist practitioners in achieving this objective.

The role of PET/CT in large vessel vasculitis and related disorders: diagnosis, extent evaluation and assessment of therapy response.

Large vessel vasculitides (LVV) are defined as chronic inflammatory disorders that affect the arteries with two major variants being distinguished: giant cell arteritis (GCA) and Takayasu's arteritis (TAK). These often present with nonspecific constitutional symptoms which makes an accurate diagnosis often challenging. Nevertheless, timely diagnosis is of utmost importance to initiate treatment and to avoid potential life-threatening complications. [18F]FDG-PET/CT is nowadays widely accepted as useful tool to aid in the diagnosis of large vessel vasculitis. However, its role to monitor disease activity and to predict disease relapse during follow-up is less obvious since vascular [18F]FDG uptake can be detected in the absence of clinical or biochemical signs of disease activity. In addition to the two major variants, [18F]FDG-PET/CT has shown promise in (peri-)aortitis and related disorders. This article aims to provide an update on the current knowledge and limitations of [18F]FDG-PET/CT for the diagnosis and assessment of treatment response in LVV. Furthermore, other radiopharmaceuticals targeting key components of the vascular immune system are being discussed which could provide an interesting alternative to image vascular inflammation in LVV.

Imaging of treatment response and minimal residual disease in multiple myeloma: state of the art WB-MRI and PET/CT.

Bone imaging has been intimately associated with the diagnosis and staging of multiple myeloma (MM) for more than 5 decades, as the presence of bone lesions indicates advanced disease and dictates treatment initiation. The methods used have been evolving, and the historical radiographic skeletal survey has been replaced by whole body CT, whole body MRI (WB-MRI) and [18F]FDG-PET/CT for the detection of bone marrow lesions and less frequent extramedullary plasmacytomas.Beyond diagnosis, imaging methods are expected to provide the clinician with evaluation of the response to treatment. Imaging techniques are consistently challenged as treatments become more and more efficient, inducing profound response, with more subtle residual disease. WB-MRI and FDG-PET/CT are the methods of choice to address these challenges, being able to assess disease progression or response and to detect "minimal" residual disease, providing key prognostic information and guiding necessary change of treatment.This paper provides an up-to-date overview of the WB-MRI and PET/CT techniques, their observations in responsive and progressive disease and their role and limitations in capturing minimal residual disease. It reviews trials assessing these techniques for response evaluation, points out the limited comparisons between both methods and highlights their complementarity with most recent molecular methods (next-generation flow cytometry, next-generation sequencing) to detect minimal residual disease. It underlines the important role of PET/MRI technology as a research tool to compare the effectiveness and complementarity of both methods to address the key clinical questions.

Antibiotic-Derived Radiotracers for Positron Emission Tomography: Nuclear or "Unclear" Infection Imaging?

The excellent features of non-invasive molecular imaging, its progressive technology (real-time, whole-body imaging and quantification), and global impact by a growing infrastructure for positron emission tomography (PET) scanners are encouraging prospects to investigate new concepts, which could transform clinical care of complex infectious diseases. Researchers are aiming towards the extension beyond the routinely available radiopharmaceuticals and are looking for more effective tools that interact directly with causative pathogens. We reviewed and critically evaluated (challenges or pitfalls) antibiotic-derived PET radiopharmaceutical development efforts aimed at infection imaging. We considered both radiotracer development for infection imaging and radio-antibiotic PET imaging supplementing other tools for pharmacologic drug characterization; overall, a total of 20 original PET radiotracers derived from eleven approved antibiotics.

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. PURPOSE: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. METHODS: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. RESULTS: We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. CONCLUSIONS: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM.

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.

Position paper of the EACVI and EANM on artificial intelligence applications in multimodality cardiovascular imaging using SPECT/CT, PET/CT, and cardiac CT.

In daily clinical practice, clinicians integrate available data to ascertain the diagnostic and prognostic probability of a disease or clinical outcome for their patients. For patients with suspected or known cardiovascular disease, several anatomical and functional imaging techniques are commonly performed to aid this endeavor, including coronary computed tomography angiography (CCTA) and nuclear cardiology imaging. Continuous improvement in positron emission tomography (PET), single-photon emission computed tomography (SPECT), and CT hardware and software has resulted in improved diagnostic performance and wide implementation of these imaging techniques in daily clinical practice. However, the human ability to interpret, quantify, and integrate these data sets is limited. The identification of novel markers and application of machine learning (ML) algorithms, including deep learning (DL) to cardiovascular imaging techniques will further improve diagnosis and prognostication for patients with cardiovascular diseases. The goal of this position paper of the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) is to provide an overview of the general concepts behind modern machine learning-based artificial intelligence, highlights currently prefered methods, practices, and computational models, and proposes new strategies to support the clinical application of ML in the field of cardiovascular imaging using nuclear cardiology (hybrid) and CT techniques.

Impact of left bundle branch block on myocardial perfusion and metabolism: A positron emission tomography study.

BACKGROUND: Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, 13N-NH3-derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates. METHODS: Twenty-five consecutive non-ischemic patients with LBBB underwent 18F-FDG and resting dynamic 13N-NH3 PET/CT prior to CRT implantation. Regional 18F-FDG uptake, absolute MBF, and late 13N-NH3 uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late 13N-NH3/18F-FDG uptake ratios. RESULTS: A significantly lower 18F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late 13N-NH3 uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). 13N-NH3/18F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively. CONCLUSIONS: Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static 13N-NH3 uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB.

Facial nerve palsy in giant-cell arteritis: case-based review.

Acute peripheral facial nerve palsy is most frequently idiopathic (Bell's palsy) or virally induced, but can also be due to several other conditions. A rare cause is underlying systemic or autoimmune disease. A 79-year-old man presented with peripheral facial nerve palsy, malaise, and fever. Physical examination revealed tenderness of the left temporal artery and reduced pulsatility. 18F-FDG-PET/CT and biopsy of the temporal artery confirmed the diagnosis of giant cell arteritis (GCA). Prompt institution of corticosteroid therapy produced rapid decrease in inflammatory markers and gradual improvement of the facial nerve palsy. We searched the MEDLINE, Embase, and Scopus databases to identify previous reports of peripheral nerve palsy in GCA, other vasculitides, and autoimmune diseases. Facial nerve palsy as the presenting symptom of GCA has very rarely been reported. Although temporal artery biopsy is the gold standard for diagnosis, it may be negative in up to one-third of cases. In doubtful cases, imaging can help establish the diagnosis. Ultrasound, 3 T MRI, and 18F-FDG-PET/CT have all been previously reported to be useful. Peripheral facial nerve palsy may very rarely be the presenting symptom of GCA. Early correct diagnosis is essential for starting appropriate therapy. In patients with atypical features, 18F-FDG-PET/CT may be useful for establishing the diagnosis.

In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma with an aggressive clinical course. To investigate the potential of immune-checkpoint therapy, we retrospectively studied the tumor microenvironment (TME) using high-plex immunohistochemistry in 22 PCNSL and compared to 7 secondary CNS lymphomas (SCNSL) and 7 "other" CNSL lymphomas with the presence of the Epstein-Barr virus and/or compromised immunity. The TME in PCNSL was predominantly composed of CD8+ cytotoxic T cells and CD163+ phagocytes. Despite molecular differences between PCNSL and SCNSL, the cellular composition and the functional spectrum of cytotoxic T cells were similar. But cytotoxic T cell activation was significantly influenced by pre-biopsy corticosteroids intake, tumor expression of PD-L1 and the presence of EBV. The presence of low numbers of CD8+ T cells and geographic-type necrosis each predicted inferior outcome in PCNSL. Both M1-like (CD68 + CD163low) and M2-like (CD68 + CD163high) phagocytes were identified, and an increased ratio of M1-like/M2-like phagocytes was associated with a better survival. PD-L1 was expressed in lymphoma cells in 28% of cases, while PD1 was expressed in only 0.4% of all CD8+ T cells. TIM-3, a marker for T cell exhaustion, was significantly more expressed in CD8posPD-1pos T cells compared to CD8posPD-1neg T cells, and a similar increased expression was observed in M2-like pro-tumoral phagocytes. In conclusion, the clinical impact of TME composition supports the use of immune-checkpoint therapies in PCNSL. Based on observed differences in immune-checkpoint expression, combinations that boost cytotoxic T cell activation (by blocking TIM-3 or TGFBR1) prior to the administration of PD-L1 inhibition could be of interest.

Prognostic value of cardiovascular magnetic resonance in patients with biopsy-proven systemic sarcoidosis.

OBJECTIVES: As prognosis in sarcoidosis is determined by cardiac involvement, the objective was to study the added value of cardiovascular magnetic resonance (CMR) in risk stratification. METHODS: In 114 patients (48 ± 12 years/52% male) with biopsy-proven sarcoidosis, we studied the value of clinical and CMR-derived parameters to predict future events, using sustained ventricular tachycardia, ventricular fibrillation, aborted cardiac death, implantable cardioverter-defibrillator (ICD) placement with appropriate shocks, hospitalization for heart failure, and death as composite endpoint. Median follow-up after CMR was 3.1 years (1.1-5.7 years). RESULTS: The ejection fraction (EF) was 58.2 ± 9.1% and 54.7 ± 10.8% for left ventricle (LV) and right ventricle (RV), respectively. LV late gadolinium enhancement (LGE) was present in 40 patients (35%) involving 5.1% of the LV mass (IQR, 3.0-12.0%), with concomitant RV involvement in 12 patients (11%). T2-weighting imaging and/or T2 mapping showed active disease in 14 patients. The composite endpoint was reached in 34 patients, with 7 deaths in the LGE-positive group (17.5%), versus two deaths in the LGE-negative group (2.7%) (p = 0.015). At univariate analysis, RVEF (p = 0.009), pulmonary arterial pressure (p = 0.002), and presence of LGE (p < 0.001) and LGE (% of LV) (p < 0.001) were significant. At multivariate analysis, only presence of LGE and LGE (% of LV) was significant (both p = 0.03). At Kaplan-Meier, presence of LGE and an LGE of 3% predicted event-free survival and patient survival. We found no difference in active versus inactive disease with regard to patient survival. CONCLUSION: Myocardial enhancement at LGE-CMR adds independent prognostic value in risk stratification sarcoidosis patients. In contrast, clinical as well as functional cardiac parameters lack discriminative power. KEY POINTS: • Sarcoidosis often affects the heart. • Comprehensive CMR, including T2 imaging and LGE enhancement CMR, allows to depict both active and inactive myocardial damage. • Patient prognosis in sarcoidosis is determined by the presence and severity of myocardial involvement at LGE CMR.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2-Diagnostic criteria and appropriate utilization.

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

Influence of pretreatment with everolimus or sunitinib on the subacute hematotoxicity of 177Lu-DOTATATE PRRT.

Background: Peptide receptor radionuclide therapy (PRRT) is a validated treatment for somatostatin receptor overexpressing neuroendocrine tumors (NETs). The NETTER-1 trial demonstrated a pronounced positive effect on progression-free-survival compared to high dose somatostatin analogs (SSAs), with a strong tendency toward overall survival benefit. Our aim was to investigate the influence of pretreatment with everolimus and/or sunitinib on subacute hematotoxicity of PRRT. To assess the influence of prior treatment with everolimus/sunitinib might be of clinical relevance due to the link between short-term hematotoxicity and increased incidence of late hematotoxicity.Material and methods: Our single-center retrospective study enrolled all patients treated with 177Lu-DOTATATE PRRT (1-4 cycles of 7.4 GBq), between November 2013 and July 2018. Patients were assigned to two groups according to their pretreatment: no targeted agents (N = 41), or targeted agents (everolimus, sunitinib or both; N = 41). The end point was subacute hematotoxicity, defined as the nadir value between the first administration until 3 months after the last administration, using the CTCAE 4.03 classification. The impact of splenectomy was also explored.Results: Eighty percent of patients had a primary gastroenteropancreatic NET. No statistically significant differences in severe subacute hematotoxicity were seen in the pretreated group vs. the naive group for hemoglobin (grade 3/4: 12% vs. 22%), neither for leucocytes (grade 3/4: 10% vs. 7%), neutrophils (grade 3/4: 5% vs. 7%), lymphocytes (grade 3/4: 49% vs. 37%) and platelets (grade 3/4: 15% vs. 15%). Furthermore, we observed significantly lower toxicity for total white blood cells, lymphocytes and platelets in the subgroup that had splenectomy (N = 12). Limitations of this study include the potential bias in lack of use of targeted agents in patients more susceptible to toxicity, and the limited number of patients and events.Conclusions: In a patient cohort with NET pretreated with everolimus and/or sunitinib, we could not demonstrate a significant effect of prior/pretreatment with everolimus and/or sunitinib on the subacute hematotoxicity of 177Lu-DOTATATE PRRT.