White Blood Cell Scintigraphy Research Articles

Relative contribution of imaging techniques for the contemporary diagnosis of infective endocarditis: a single-center experience

Abstract Introduction In developed countries, the incidence of infective endocarditis (IE) is up to 6 cases per 100,000 individuals and in-hospital mortality rates are reported to reach 30%. The diagnostic recommendations for IE have been revised in the new ESC guidelines emphasizing the use of transesophageal echocardiography (TEE) and advanced imaging techniques (computed tomography [CT], magnetic resonance [MR], positron emission tomography [PET] and white blood cell scintigraphy [WBC-SPECT]). Aims This research aims to investigate the practical applicability of established clinical guidelines in a real-world population with suspected IE. Methods We reviewed the hospital database from 06/2021 to 06/2023 using the international classification of disease codification (ICD-10) for IE. Only patients admitted to Cardiology or Cardiac Surgery departments were included. Diagnosis of IE was defined according to the modified Duke criteria. Firstly, we identified individuals in whom diagnosis was performed by clinical presentation, blood cultures and transthoracic echocardiogram (TTE). Subsequently, we identified those who required further imaging diagnostic investigation. Results A total of 63 patients were included [mean age 64 ±14 years; 76% male (n=48)]. Native IE was diagnosed in 53 (84%) patients, prosthetic IE in 7 (11%) and cardiac implantable electronic devices-related IE in 3 (5%). A total of 26 (41%) patients had at least one predisposing risk factor, 48 (76%) presented with fever, 24 (38%) suffered an embolic event and 1 (2%) had an immunological phenomenon. Out of 49 positive blood cultures (78%), typical microorganisms consistent with IE were isolated in 25 (78%) of samples: 13 (34%) staphylococcus aureus, 10 (26%) oral streptococci, 9 (24%) enterococcus faecalis, 5 (13%) streptococcus gallolyticus and 1 (3%) HACEK group. Overall, in 22 (34%) patients, a definitive diagnosis of IE was established by means of clinical presentation, blood cultures and TTE. In the remaining, TEE was performed in 86% (n=36). Of those, a definite diagnosis was established in 52% (n=22). Brain and whole-body imaging upgraded the diagnosis from possible to definite in 3 (5%) patients. In the one patient in which a comprehensive clinical evaluation including TTE and TEE rejected IE, the diagnosis was ultimately established by means of PET. The median time from admission to the definite/possible diagnosis of IE was 6 (IQR 2-17) days. A total of 47 (75%) patients underwent surgery, with the most frequent indications being heart failure 46% (n=21) and uncontrolled infection 28% (n=13). Time from diagnosis to surgery was 10 (2-19) days, hospital length of stay was 45 (35-70) days and in-hospital mortality 21%. Conclusion Clinical presentation, blood cultures and TTE plus TEE established the definite or possible diagnosis of IE in most patients with suspected IE. Advanced imaging techniques allowed the establishment of definite diagnosis in only 6% of patients.

Advancing infective endocarditis diagnosis: The promise and challenges of white blood cell scintigraphy in modern clinical practice

Advancing infective endocarditis diagnosis: The promise and challenges of white blood cell scintigraphy in modern clinical practice

Intra and Inter-Rater Variability in the Interpretation of White Blood Cell Scintigraphy of Hip and Knee Prostheses.

Background: White blood cell (WBC) scintigraphy plays a major role in the diagnostic approach to periprosthetic infections. Although the procedure has been standardized by the publication of several guidelines, the interpretation of this technique may be susceptible to intra and inter-variability. We aimed to assess the reproducibility of interpretation between nuclear medicine physicians and by the same physician and to demonstrate that Cohen's coefficient is more unstable than Gwet's coefficient, as the latter is influenced by the prevalence rates. Methods: We enrolled 59 patients who performed a Technetium-99m WBC (99mTc-WBC) scintigraphy for suspected hip or knee prosthesis infection. Three physicians, blinded to all patient clinical data, performed two image readings. Each WBC study was assessed both visually and semi-quantitatively according to the guidelines of the European Association of Nuclear Medicine (EANM). For semi-quantitative analysis, readers drew an irregular Region of Interest (ROI) over the suspected infectious lesion and copied it to the normal contralateral bone. The mean counts per ROI were used to calculate lesion-to-reference tissue (LR) ratios for both late and delayed images. An increase in LR over time (LRlate> LRdelayed) of more than 20% was considered indicative of infection. Agreement between readers and between readings was assessed by the first-order agreement coefficient (Gwet's AC1). Reading time for each scan was compared between the three readers in both the first and the second reading, using the Generalized Linear Mixed Model. Results: An excellent agreement was found among all three readers: 0.90 for the first reading and 0.94 for the second reading. Both inter- and intra-variability showed values ≥0.86. Gwet's method demonstrated greater robustness than the Cohen coefficient when assessing the intra and inter-rater variability, since it is not influenced by the prevalence rate. Conclusions: These studies can contribute to improving the reliability of nuclear medicine imaging techniques and to evaluating the effectiveness of trainee preparation.

[18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography and conventional imaging modalities in the diagnosis of diabetic foot osteomyelitis: a meta-analysis

This meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and conventional imaging, MRI, and white blood cell (WBC) scintigraphy in detecting foot osteomyelitis among diabetic patients. An exhaustive search was conducted within the PubMed and Embase databases to identify publications available up until February 2024. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET or the comparative diagnostic performance between PET and (MRI or WBC scintigraphy). Two researchers independently assessed the quality of the included studies, utilizing the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. Nine retrospective or prospective studies involving 605 patients were included in the meta-analysis. For [18F]FDG PET, the overall sensitivity was 0.83(95% CI: 0.69-0.94), while the overall specificity was 0.92(95% CI: 0.86-0.97). In the head-to-head comparison, no significant difference of sensitivity was found between [18F]FDG PET and MRI (0.72 vs. 0.68, P=0.81), as well as between [18F]FDG PET and WBC scintigraphy (0.57 vs. 0.66, P=0.64). In addition, specificity was also found to be no significant difference between [18F]FDG PET and MRI (0.90 vs. 0.82, P=0.27), as well as [18F]FDG PET and WBC scintigraphy (0.81 vs. 0.93, P=0.09). [18F]FDG PET demonstrates similar sensitivity and specificity to MRI and WBC scintigraphy in detecting foot osteomyelitis among diabetic patients. MRI, often cited as a primary choice in guidelines, might be preferred due to its lower cost and lower dose. Further larger sample prospective studies are needed to confirm these findings.

How to combine CTA, 99mTc-WBC SPECT/CT, and [18F]FDG PET/CT in patients with suspected abdominal vascular endograft infections?

PurposeWe aimed at comparing 99mTc-HMPAO white blood cells (99mTc-WBC) scintigraphy, 18fluorine-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and CT angiography (CTA) in patients with suspected abdominal vascular graft or endograft infection (VGEI). Moreover, we attempted to define a new visual score for interpreting [18F]FDG PET/CT scans aiming at increasing its specificity.MethodsWe prospectively compared 99mTc-WBC SPECT/CT, [18F]FDG PET/CT, and CTA in 26 patients with suspected abdominal VGEI. WBC scans were performed and interpreted according to EANM recommendations. [18F]FDG PET/CT studies were assessed with both qualitative (Sah’s scale and new visual score) and semi-quantitative analyses. CTA images were interpreted according to MAGIC criteria. Microbiology, histopathology or a clinical follow-up of at least 24 months were used to achieve final diagnosis.ResultsEleven out of 26 patients were infected. [18F]FDG PET/CT showed 100% sensitivity and NPV, with both scoring systems, thus representing an efficient tool to rule out the infection. The use of a more detailed scoring system provided statistically higher specificity compared to the previous Sah’s scale (p = 0.049). 99mTc-WBC SPECT/CT provided statistically higher specificity and PPV than [18F]FDG PET/CT, regardless the interpretation criteria used and it can be, therefore, used in early post-surgical phases or to confirm or rule out a PET/CT finding.ConclusionsAfter CTA, patients with suspected late VGEI should perform a [18F]FDG PET/CT given its high sensitivity and NPV. However, given its lower specificity, positive results should be confirmed with 99mTc-WBC scintigraphy. The use of a more detailed scoring system reduces the number of 99mTc-WBC scans needed after [18F]FDG PET/CT. Nevertheless, in suspected infections within 4 months from surgery, 99mTc-WBC SPECT/CT should be performed as second exam, due to its high accuracy in differentiating sterile inflammation from infection.

Multimodality radionuclide imaging in fever of unknown origin presenting with a solitary spleen lesion

BackgroundFever of unknown origin (FUO) still represents a serious challenge for clinicians, since it can be related to a wide spectrum of disorders, ranging from infections to malignancies. In this scenario, nuclear medicine can be of value to achieve a correct diagnosis both through positron emission computed tomography (PET/CT) and 99mTc labeled hexamethylpropylene amine oxime (HMPAO) white blood cell (WBC) scintigraphy.Case presentationWe are presenting the case of 65-year-old male, who was referred to our hospital due to prolonged unexplained fever. He was submitted to abdomen ultrasonography (US) that did not disclose relevant pathological findings. Subsequently, he underwent PET/CT scan with 18F-fluorodeoxyglucose (18F-FDG) that revealed an area of increased tracer uptake in splenic inferior pole. In order to solve differential diagnosis between tumor and infection, he was submitted to 99mTc-HMPAO WBC scintigraphy that resulted negative for sites of pathologic radiolabeled cells’ accumulation but revealed a photopenic area in the splenic inferior pole. The pattern of mismatched uptake between 18F-FDG PET/CT and 99mTc-HMPAO WBC scintigraphy was considered highly suspicious for spleen tumor localization. The patient was scheduled for splenectomy and histology resulted positive for non-Hodgkin lymphoma (NHL) of diffuse large B cell type. After splenectomy, a further 18F-FDG PET/CT revealed the appearance of hypermetabolic hepatic lesions. The patient underwent chemotherapy with complete remission.ConclusionNuclear medicine provides valuable tools for differential diagnosis in FUO. In case of patients presenting solitary lesion of the spleen, the combined use of 18F-FDG PET/CT and 99mTc-HMPAO WBC scintigraphy can provide relevant information to aid clinicians to a correct diagnosis.

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

PurposeConsensus 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.MethodsThis 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.ResultsSixty-six articles, published from January 2000 up to December 2021, were analysed and used for evidence-based recommendations.ConclusionComputed 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.PreambleThe 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.

Lack of Clinical Utility of Labeled White Blood Cell Scintigraphy in Patients With Fever of Unknown Origin.

BackgroundLabeled white blood cell scintigraphy (WBCS) has been used for over 40 years to localize an infection source in patients with fever of unknown origin (FUO). It continues to be in widespread use for such patients in modern times, despite the tremendous advances in modern radiological imaging and laboratory medicine.MethodsWe critically evaluated the clinical contribution of WBCS performed in 132 patients with FUO at 7 hospitals from mid-2015 to the end of 2019. For each patient, all radiographic and laboratory results and all electronic clinical notes were carefully evaluated as many days before and after the scan as necessary to arrive at a final diagnosis.ResultsAlthough 50 WBCS (38%) showed positive findings, the majority of these were false positive (FP). Of the 19 true-positive (TP) scans, most were already known or about to become known by tests already ordered at the time of the scan. Only 2 TP scans (1.5%) contributed to the final diagnosis, and these did so only indirectly. FP scans led to 7 unnecessary procedures.ConclusionsIn FUO patients for whom an infection source is not discovered following an appropriate radiographic and laboratory workup, WBCS is not a useful procedure.

The Role of a Virtual Noncalcium Dual-Energy CT Application in the Detection of Bone Marrow Edema in Peripheral Osteomyelitis.

Purpose: To determine the sensitivity and specificity of dual-energy CT (DECT) virtual noncalcium images (VNCa) with bone and soft tissue reconstructions in the diagnosis of osteomyelitis. Materials & Methods: Between December 1, 2014 to December 1, 2020, 91 patients who had 99 DECT performed for a clinical indication of osteomyelitis with corresponding MRI, triphasic bone scan and/or white blood cell scintigraphy with CT/SPECT performed either 2 weeks before or 1 month after the DECT were retrospectively identified. The presence or absence of osteomyelitis was established using a second imaging test, bone biopsy or surgery. Two radiologists interpreted VNCa images alone and with bone and soft tissue reconstructions for osteomyelitis. Fleiss k statistics was used to assess inter-level agreement. Results: Osteomyelitis was present in 26 cases (26.2%), of which 4 cases (4%) had co-existing septic arthritis. DECT was performed at the following sites: ankle/foot (n = 59), calf (n = 12), knee (n = 3), thigh (n = 7), hip (n = 9), pelvis (n = 6), wrist/hand (n = 1), and shoulder (n = 2). Sensitivity with VNCa images alone was 53.8% and 73.1% and specificity was 84.9% and 71.2%. Sensitivity with VNCa images and bone and soft tissue reconstructions was 80.8% and 80.8% and specificity was 80.8% and 72.6%. Interobserver agreement was 76.7% (76 of 99 cases), for VNCa images alone (k = .487), and 66.7% (66 of 99 patients) for bone and soft tissue reconstructions with VNCa images together (k = .390). Conclusion: When VNCa images were combined with bone and soft tissue reconstructions, there is improved sensitivity in the diagnosis of osteomyelitis.

Nuclear imaging does not have clear added value in patients with low a priori chance of periprosthetic joint infection. A retrospective single-center experience.

Background: A low-grade periprosthetic joint infection (PJI) may present without specific symptoms, and its diagnosis remains a challenge. Three-phase bone scintigraphy (TPBS) and white blood cell (WBC) scintigraphy are incorporated into recently introduced diagnostic criteria for PJI, but their exact value in diagnosing low-grade PJI in patients with nonspecific symptoms remains unclear. Methods: In this retrospective study, we evaluated patients with a prosthetic joint of the hip or knee who underwent TPBS and/or WBC scintigraphy between 2009 and 2016 because of nonspecific symptoms. We reviewed and calculated diagnostic accuracy of the TPBS and/or WBC scintigraphy to diagnose or exclude PJI. PJI was defined based on multiple cultures obtained during revision surgery. In patients who did not undergo revision surgery, PJI was ruled out by clinical follow-up of at least 2 years absent of clinical signs of infection based on MSIS 2011 criteria. Results: A total of 373 patients were evaluated, including 340 TPBSs and 142 WBC scintigraphies. Thirteen patients (3.5 %) were diagnosed with a PJI. TPBS sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were 71 %, 65 %, 8 % and 98 %, respectively. Thirty-five percent of TPBS showed increased uptake. Stratification for time intervals between the index arthroplasty and the onset of symptoms did not alter its diagnostic accuracy. WBC scintigraphy sensitivity, specificity, PPV and NPV were 30 %, 90 %, 25 % and 94 %, respectively. Conclusion: Nuclear imaging does not have clear added value in patients with low a priori chance of periprosthetic joint infection.

White Blood Cell Scintigraphy for Fracture-Related Infection: Is Semiquantitative Analysis of Equivocal Scans Accurate?

Purpose: White blood cell (WBC) scintigraphy is considered the gold-standard nuclear imaging technique for diagnosing fracture-related infection (FRI). Correct interpretation of WBC scans in FRI is important since a false positive or false negative diagnosis has major consequences for the patient in terms of clinical decision-making. The European Association of Nuclear Medicine (EANM) guideline for correct analysis and interpretation of WBC scans recommends semiquantitative analysis of visually equivocal scans. Therefore, this study aims to assess the diagnostic accuracy of semiquantitative analysis of visually equivocal WBC scans for diagnosing FRI. Methods: A retrospective single-center study was performed in consecutive patients who received WBC scintigraphy in the diagnostic work-up for FRI between February 2012 and January 2017. All the visually equivocal scans were analysed using semiquantitative analysis by comparing leukocyte uptake in the manually selected suspected infection focus with the contralateral bone marrow (L/R ratio). Cut-off points for a ‘positive’ scan result of >0%, >10% and >20% leukocyte increase between the early and late scans were used in separate analyses. The discriminative ability was quantified by calculating the sensitivity, specificity and diagnostic accuracy. Results: In total, 153 WBC scans were eligible for inclusion. After visual assessment of all the scans, 28 visually equivocal scans were included. Dichotomization of the ratios using the cut-off of >0% resulted in a sensitivity of 30%, a specificity of 45% and a diagnostic accuracy of 40%. The >10% cut-off point resulted in a sensitivity of 18%, a specificity of 82% and a diagnostic accuracy of 66%. The >20% cut-off point resulted in a sensitivity of 0%, a specificity of 89% and a diagnostic accuracy of 67%. Conclusion: Semiquantitative analysis of visually equivocal WBC scans is insufficient for correctly diagnosing FRI.

Metodología de la gammagrafía con leucocitos marcados en el diagnóstico de infección osteoarticular protésica/no protésica: ¿análisis visual o semicuantitativo? ¿Protocolo de uno o 2 días?

ObjectiveAs scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. Material and methodsProspective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. ResultsComparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (P<.01) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (P<.01). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (P<.01) than two-day-protocol (no significant results; P=.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; P<.01). ConclusionsMost accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

HMGB1 expression in leukocytes as a biomarker of cellular damage induced by [99mTc]Tc-HMPAO-labelling procedure: A quality control study

PurposeAutologous White Blood Cells (WBC) scintigraphy is based on a multi-step sequence of cell separation and radiolabelling. Besides in vivo imaging quality control, no molecular tool is available to evaluate WBC damage secondary to cell manipulation. High Mobility Group Box 1 (HMGB1) is a protein of the alarmins family, secreted by innate immune cells and released from the nucleus of damaged cells following different types of injury. Aim of this study was to evaluate HMGB1 levels in WBC cytosolic extracts (CE) before and after [99mTc]Tc-HMPAO labelling procedure, as a biomarker of induced WBC damage. ProceduresPatients with suspect of prosthetic joint infection were prospectively enrolled. HMGB1 levels were evaluated by immunoblotting analysis in plasma (t0), and in WBC-CE before (t1) and after (t2) [99mTc]Tc-HMPAO labelling. Blood samples from healthy subjects were evaluated under the same procedure. ResultsTwenty consecutive patients referred for WBC scintigraphy and ten controls were enrolled. HMGB1 levels were significantly upregulated both in plasma (t0) and in circulating WBC-CE (t1) from patients compared to controls (p < 0.0001). Otherwise, WBC-CE from [99mTc]Tc-HMPAO-labelled leukocyte concentrate (t2) did not show significant changes in HMGB1 levels compared to the cold leukocyte sample (t1). ConclusionsThe evaluation of HMGB1 levels in WBC-CE from each subject after radiolabelling with [99mTc]Tc-HMPAO did not show significant changes compared to the cold cellular sample. These results further prove the reliability of [99mTc]Tc-HMPAO leukocyte radiolabelling procedure in terms of cell viability and suggest that the monitoring of this alarmin may represent a specific tool to evaluate a secondary damage of WBC induced by radiolabelling procedure.In addition, significant upregulation of HMGB1 levels was found in WBC-CE and in plasma from patients with suspect of PJI - compared to healthy donors - reasonably related to their underlying inflammatory/infective condition.

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

Objectiveas scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. Material and methodsprospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. ResultsComparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (p<001) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (p<001). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (p<001) than two-day-protocol (no significant results; p=0.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; p<001). Conclusionsmost accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

The Role of Imaging Techniques to Define a Peri-Prosthetic Hip and Knee Joint Infection: Multidisciplinary Consensus Statements.

Diagnosing a peri-prosthetic joint infection (PJI) remains challenging despite the availability of a variety of clinical signs, serum and synovial markers, imaging techniques, microbiological and histological findings. Moreover, the one and only true definition of PJI does not exist, which is reflected by the existence of at least six different definitions by independent societies. These definitions are composed of major and minor criteria for defining a PJI, but most of them do not include imaging techniques. This paper highlights the pros and cons of available imaging techniques—X-ray, ultrasound, computed tomography (CT), Magnetic Resonance Imaging (MRI), bone scintigraphy, white blood cell scintigraphy (WBC), anti-granulocyte scintigraphy, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), discusses the added value of hybrid camera systems—single photon emission tomography/computed tomography (SPECT/CT), PET/CT and PET/MRI and reports consensus answers on important clinical questions that were discussed during the Third European Congress on Inflammation/Infection Imaging in Rome, December 2019.

Cardiovascular Imaging in Infective Endocarditis: A Multimodality Approach.

Multimodality imaging plays a pivotal role in the evaluation and management of infective endocarditis (IE)-a condition with high morbidity and mortality. The diagnosis of IE is primarily based on the modified Duke criteria with echocardiography as the first-line imaging modality. Both transthoracic and transesophageal echocardiography delineate vegetation location and size, assess for paravalvular extension of infection, and have the added advantage of defining the hemodynamic effects of valvular or device infection. Native and prosthetic valve IE, infections relating to cardiac implantable electronic devices, and indwelling catheters are effectively evaluated with echocardiography. However, complementary imaging is occasionally required when there remains diagnostic uncertainty following transesophageal echocardiography. Multidetector computed tomography and nuclear imaging techniques such as positron emission tomography and white blood cell scintigraphy have been shown to reduce the rate of misdiagnosed IE particularly in the setting of prosthetic valve endocarditis, paravalvular extension of infection, and cardiac implantable electronic devices. In this review, we describe a modern approach to cardiac imaging in native and prosthetic valve endocarditis, as well as cardiac implantable electronic devices including pacing devices and left ventricular assist devices. Current guidelines addressing the role of multimodality imaging in IE are discussed. The utility of imaging in the assessment of local and distant endocarditis complications such as pericardial sequelae, myocarditis, and embolic events is also addressed.

Comparison of White Blood Cell Scintigraphy, FDG PET/CT and MRI in Suspected Diabetic Foot Infection: Results of a Large Retrospective Multicenter Study.

Diabetic foot infections (DFIs) represent one of the most frequent and disabling morbidities of longstanding diabetes; therefore, early diagnosis is mandatory. The aim of this multicenter retrospective study was to compare the diagnostic accuracy of white blood cell scintigraphy (WBC), 18F-fluorodeoxyglucose positron emission tomography/computed tomography ((18F) FDG PET/CT), and Magnetic Resonance Imaging (MRI) in patients with suspected DFI. Images and clinical data from 251 patients enrolled by five centers were collected in order to calculate the sensitivity, specificity, and accuracy of WBC, FDG, and MRI in diagnosing osteomyelitis (OM), soft-tissue infection (STI), and Charcot osteoarthropathy. In OM, WBC acquired following the European Society of Nuclear Medicine (EANM) guidelines was more specific and accurate than MRI (91.9% vs. 70.7%, p < 0.0001 and 86.2% vs. 67.1%, p = 0.003, respectively). In STI, both FDG and WBC achieved a significantly higher specificity than MRI (97.9% and 95.7% vs. 83.6%, p = 0.04 and p = 0.018, respectively). In Charcot, both MRI and WBC demonstrated a significantly higher specificity and accuracy than FDG (88.2% and 89.3% vs. 62.5%, p = 0.0009; 80.3% and 87.9% vs. 62.1%, p < 0.02, respectively). Moreover, in Charcot, WBC was more specific than MRI (89.3% vs. 88.2% p < 0.0001). Given the limitations of a retrospective study, WBC using EANM guidelines was shown to be the most reliable imaging modality to differentiate between OM, STI, and Charcot in patients with suspected DFI.

Diagnostic Imaging In Vascular Graft Infection; A Meta-analysis. The Added Value of Nuclear Imaging Techniques and an Outdated Golden Standard

Introduction - Vascular graft infection (VGI), a serious complication in vascular surgery, has a high morbidity and mortality rate. Diagnosis is being complicated by nonspecific symptoms and challenged by variable accuracy of different imaging techniques. This systematic review and meta-analysis was conducted to evaluate the role of various diagnostic imaging modalities in patients suspected of VGI. Methods - A systematic review was conducted according to the PRISMA guidelines. Randomized controlled trials and observational cohort studies were included. Data sources included PubMed/Medline, Embase and Cochrane from January 1997 until October 2017. A meta-analysis was conducted on several imaging modalities: computed tomography with or without angiography (CT(A)), 18F-Fluoro-D-deoxyglucose positron emission tomography with or without low dose or contrast enhanced CT (FDG-PET(/CT)), and white blood cell scintigraphy with or without single photon emission computed tomography combined with low dose CT (WBC (SPECT/CT)). Results -Out of 4259 papers, 14 articles were included, which contained 8 prospective and 6 retrospective articles. CTA, FDG-PET and FDG-PET/CT showed negligible to moderate heterogeneity, while WBC scintigraphy ± SPECT/CT showed considerable heterogeneity. Pooled sensitivity for CTA was 0.67, in contrast to FDG-PET of 0.94, FDG-PET/CT of 0.95, WBC scintigraphy of 0.90 and WBC scintigraphy with SPECT/CT of 0.99. The pooled specificities were for CTA 0.63, FDG-PET 0.70, FDG-PET/CT 0.80, WBC scintigraphy 0.88 and WBC scintigraphy SPECT/CT 0.82. Pre- and posttest results showed that best probability per imaging modality is achieved by a combination of nuclear imaging and CT, where WBC SPECT/CT favors FDG-PET/CT with a positive posttest probability of 96% versus 83%. Conclusion - This meta-analysis suggests the diagnostic accuracy of WBC scintigraphy combined with SPECT/CT revealed the highest accuracy in diagnosing VGI. However it is a time consuming technique and not always available. Therefore FDG-PET/CT may be favorable as initial imaging technique. The use of solitary CTA in diagnosing VGI seems to be obsolete.

The role of 99mTc-HMPAO-labelled white blood cell scintigraphy in the diagnosis of cardiac device-related infective endocarditis.

The hybrid technique of single-photon emission tomography and computed tomography with technetium99m-hexamethylpropyleneamine oxime-labelled leucocytes (99mTc-HMPAO-SPECT/CT) is an emerging diagnostic technique in patients with cardiac device-related infective endocarditis (CDRIE). This prospective study assessed the 99mTc-HMPAO-SPECT/CT diagnostic profile and its added value to the modified Duke criteria (mDuke) in CDRIE diagnostic work-up. The study examined 103 consecutive patients with suspected CDRIE, who underwent 99mTc-HMPAO-SPECT/CT. Diagnostic accuracy was calculated based on a final clinical CDRIE diagnosis, including microbiology, echocardiography, and a 6-month follow-up. Subsequently, we compared the diagnostic value of the initial mDuke classification with a classification including 99mTc-HMPAO-SPECT/CT positive results as an additional major CDRIE criterion: mDuke-SPECT/CT.Overall, CDRIE was diagnosed in 31 (31%) patients, whereas 35 (34%) 99mTc-HMPAO-SPECT/CT were positive. 99mTc-HMPAO-SPECT/CT was characterized by 86% accuracy, 0.69 Cohen's kappa coefficient, 84% sensitivity, 88% specificity, 93% negative, and 74% positive predictive values. The original mDuke displayed 83% accuracy, 0.52 kappa, whereas mDuke-SPECT/CT had 88% accuracy, and 0.73 kappa. Compared with mDuke, mDuke-SPECT/CT showed significantly higher sensitivity (87% vs. 48%, P < 0.001). According to mDuke, 49.5% of patients had possible CDRIE, and after reclassification, that figure dropped to 37%. Furthermore, having assessed the diagnosis categorization improvement following the incorporation of 99mTc-HMPAO-SPECT/CT, the net reclassification index value was found to be 31.4%. In patients with CDRIE, 99mTc-HMPAO-SPECT/CT provides high diagnostic accuracy, whereas a negative scan excludes CDRIE with high probability. Inclusion of 99mTc-HMPAO-SPECT/CT into mDuke diagnostic criteria yields significantly higher sensitivity and a reduction in possible CDRIE diagnoses.

Imaging tests for the detection of osteomyelitis: a systematic review.

Osteomyelitis is an infection of the bone. Medical imaging tests, such as radiography, ultrasound, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET), are often used to diagnose osteomyelitis. To systematically review the evidence on the diagnostic accuracy, inter-rater reliability and implementation of imaging tests to diagnose osteomyelitis. We conducted a systematic review of imaging tests to diagnose osteomyelitis. We searched MEDLINE and other databases from inception to July 2018. Risk of bias was assessed with QUADAS-2 [quality assessment of diagnostic accuracy studies (version 2)]. Diagnostic accuracy was assessed using bivariate regression models. Imaging tests were compared. Subgroup analyses were performed based on the location and nature of the suspected osteomyelitis. Studies of children, inter-rater reliability and implementation outcomes were synthesised narratively. Eighty-one studies were included (diagnostic accuracy: 77 studies; inter-rater reliability: 11 studies; implementation: one study; some studies were included in two reviews). One-quarter of diagnostic accuracy studies were rated as being at a high risk of bias. In adults, MRI had high diagnostic accuracy [95.6% sensitivity, 95% confidence interval (CI) 92.4% to 97.5%; 80.7% specificity, 95% CI 70.8% to 87.8%]. PET also had high accuracy (85.1% sensitivity, 95% CI 71.5% to 92.9%; 92.8% specificity, 95% CI 83.0% to 97.1%), as did SPECT (95.1% sensitivity, 95% CI 87.8% to 98.1%; 82.0% specificity, 95% CI 61.5% to 92.8%). There was similar diagnostic performance with MRI, PET and SPECT. Scintigraphy (83.6% sensitivity, 95% CI 71.8% to 91.1%; 70.6% specificity, 57.7% to 80.8%), computed tomography (69.7% sensitivity, 95% CI 40.1% to 88.7%; 90.2% specificity, 95% CI 57.6% to 98.4%) and radiography (70.4% sensitivity, 95% CI 61.6% to 77.8%; 81.5% specificity, 95% CI 69.6% to 89.5%) all had generally inferior diagnostic accuracy. Technetium-99m hexamethylpropyleneamine oxime white blood cell scintigraphy (87.3% sensitivity, 95% CI 75.1% to 94.0%; 94.7% specificity, 95% CI 84.9% to 98.3%) had higher diagnostic accuracy, similar to that of PET or MRI. There was no evidence that diagnostic accuracy varied by scan location or cause of osteomyelitis, although data on many scan locations were limited. Diagnostic accuracy in diabetic foot patients was similar to the overall results. Only three studies in children were identified; results were too limited to draw any conclusions. Eleven studies evaluated inter-rater reliability. MRI had acceptable inter-rater reliability. We found only one study on test implementation and no evidence on patient preferences or cost-effectiveness of imaging tests for osteomyelitis. Most studies included < 50 participants and were poorly reported. There was limited evidence for children, ultrasonography and on clinical factors other than diagnostic accuracy. Osteomyelitis is reliably diagnosed by MRI, PET and SPECT. No clear reason to prefer one test over the other in terms of diagnostic accuracy was identified. The wider availability of MRI machines, and the fact that MRI does not expose patients to harmful ionising radiation, may mean that MRI is preferable in most cases. Diagnostic accuracy does not appear to vary with the potential cause of osteomyelitis or with the body part scanned. Considerable uncertainty remains over the diagnostic accuracy of imaging tests in children. Studies of diagnostic accuracy in children, particularly using MRI and ultrasound, are needed. This study is registered as PROSPERO CRD42017068511. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 61. See the NIHR Journals Library website for further project information.