Prosthetic joint replacements in hips and knees: pilot study for the development of a single imaging test in patients with painful prosthetic joint replacements. 18 F-Fluoride PET-CT and conventional radionuclide bone scans

An increasing number of annual joint replacement operations are performed. Prosthetic infection and aseptic loosening is very important and distinguishing between them allows prompt and accurate treatment but there is no consensus on how best to image these patients. I also reviewed the role of CT in prosthetic joint imaging with a spectrum of usual pathologic conditions and CT patterns. This showed that CT plays a significant role in detecting and demonstrating complications of joint prosthesis surgery but it may not be sufficient in itself. CT can be combined, in hybrid imaging, such as SPECT-CT and PET-CT. I assessed the magnitude of the problem with a retrospective study of painful prosthetic joints in UHCW from symptom onset to diagnosis. This demonstrated significant delays in diagnosis and the need for streamlined and reduced imaging tests with some patients undertaking multiple non-imaging and imaging tests. I performed a systematic review of the role of 18 F-NaF showed that sodium fluoride positron emission tomography (18 F-NaF-PET) is a promising tool with high sensitivity and specificity in the assessment of joint replacements after the ninth post-surgical month. A further study confirmed the practicality of performing dynamic 18 F NaF PET-CT in detecting aseptic loosening of lower limb prostheses but future research trials with larger patient populations are required. Beam hardening artefacts occur in CT and hybrid imaging of metallic prosthetic joints. A series of physics experiments to evaluate and correct beam hardening artefacts was performed to alleviate the problem. Beam hardening artefacts from prostheses reduce image quality on 18 F PET-CT. The experiments included pre-filtering with Aluminium; dual-energy CT and mathematical algorithms with MATLAB® filtered back projection. The results showed no significant difference in artefact reduction between the different methods. The artefact-reduction techniques introduce other secondary artefacts with subsequent image quality reduction. Analysis of data from the prospective dynamic 18 F-NaF PET-CT trial showed inconsistent results due to data corruption and dynamic 18 F-NaF data loss but quantitative methods with Time-Activity Curves and trend line assessment of 99m Tc-MDP 3-phase bone scans was more accurate. The trial problems were identified and suggestions were made for a larger study with opt-in methods for patient recruitment and more involved use of allied healthcare staff for patient recruitment. I designed and obtained funding for a study to use a novel radiopharmaceutical agent -99m Tc-Tilmanocept (Lymphoseek® ) to assess periprosthetic membranes in vivo. Lymphoseek® binds to the mannose receptor on the cell surface of macrophages and multinucleated giant cells which are likely to reflect wear particle aseptic loosening. Further in vitro periprosthetic membranes tests will also be performed using immunochemistry. This study has not yet been performed but it is hoped that a negative Tilmanocept scan would reassuringly make a diagnosis of wear particle induced aseptic loosening unlikely

The promising role of dynamic 18F-NaF PET-CT in diagnosing symptomatic joint prosthesis

Our purpose was to establish proof of principle case study for the use of dynamic 18F-NaF PET-CT in the assessment of knee and hip prostheses. Approval was granted by the research ethics committee and informed consent was obtained. This is a case study investigating the role of dynamic 18F NaF PET-CT in a patient with bilateral knee prostheses (1 symptomatic/painful and 1 asymptomatic). Both knees were studied with dynamic 18F-NaF PET-CT technique to demonstrate the different pattern of uptake in normal/asymptomatic joint as well as painful joints with aseptic loosening. In addition, a knee aspirate was obtained from the symptomatic knee and serum C-reactive protein and erythrocyte sediment rate levels as well as a peripheral white cell count were obtained in addition to 12 month clinical follow up. Images were obtained with multi-sequential dynamic image acquisition in list mode using GE Healthcare® volume imaging protocol (ViP) after an intravenous injection of 250 MBq 18F-NaF. The images were interpreted as normal, loosening or septic loosening based on the graphical pattern of tracer uptake produced at the bone-prosthesis interface. A final diagnosis was made by a combination of joint aspiration microbiology and clinical follow-up for 1 year; in addition to C-reactive protein and erythrocyte sediment rate levels as well as peripheral white cell count. NaF PET results were compared with 3-phase dynamic bone scan results and plain radiographs. The degree of uptake in the symptomatic joint exceeded background levels and also levels of uptake in the asymptomatic knee. The pattern of uptake and curve slope in both the asymptomatic and symptomatic joints matched the pattern of uptake in our hypothesis. Dynamic 18F-NaF PET-CT is a useful imaging modality for assessing painful joint prosthesis. It can differentiate between asymptomatic joints and aseptic loosening. However, more work is required for the detection of septic loosening

Brown fat depots in adult humans remain static in their locations on PET/CT despite changes in seasonality

Active brown adipose tissue (BAT) in humans has been demonstrated through use of positron emission tomography with 2-deoxy-2-(fluorine-18) fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) scans. The aim of our study was to determine whether active human BAT depots shown on 18F-FDG PET/CT scans remain static in their location over time. This was a retrospective study. Adult human subjects (n = 15) who had had 18F-FDG PET/CT imaging (n = 38 scans in total) for clinical reasons were included on the basis of 18F-FDG uptake patterns consistent with BAT activity. For each subject, 18F-FDG BAT uptake pattern on serial 18F-FDG PET/CT images was compared to an index 18F-FDG PET/CT image with the largest demonstrable BAT volume. Object-based colocalization was expressed as Mander's correlation coefficient (where 1 = 100% overlap, 0 = no overlap). Distribution of 18F-FDG BAT activity over time and across multiple 18F-FDG BAT scans was equivalent in 60% (n = 9) of the subjects. The degree of consistency in the pattern of 18F-FDG BAT uptake in each subject over time was greater than expected by chance in 87% (n = 13) of the subjects (pair-wise agreement 75–100%, Fleiss’ κ 0.4–1). The degree of BAT colocalization on serial scans was greater than that expected by chance in 93% (n = 14) of the subjects (mean Mander's coefficient 0.81 ± 0.21 [95% CI]). To our knowledge, our study provides the most conclusive evidence to date to support the notion that active BAT depots in humans (volumes and activities of which were measured through use of 18F-FDG PET/CT scans) remain static in location over sustained periods

Review of the role of dynamic 18F-NaF PET in diagnosing and distinguishing between septic and aseptic loosening in hip prosthesis

Joint replacements may fail due to infection, dislocation, peri-prosthetic fracture and loosening. Between 0.4 and 4% of joint replacements are known to be complicated by infection and aseptic loosening 2–18%. Differentiating between infection and aseptic loosening has an important bearing on the ongoing strategy for antimicrobial therapy and surgical intervention, but distinguishing one from the other can be difficult and will often require a battery of clinical and biochemical tests including the use of varying radiological modalities to accurately identify whether problematic joints are infected or aseptically loose. Prompt diagnosis is important due to the development of a biofilm on the surface of the infected prosthesis, which makes treatment difficult. There is no consensus among experts on the ideal imaging technique nor the methodology for image interpretation, but there is an increasing trend to apply hybrid imaging in the investigation of painful joint prosthesis and recent attempts have been made using PET-CT to identify aseptic loosening and infection with 18F-fluorodeoxyglucose (FDG) and sodium fluoride 18F-Na. The aim of this paper is to evaluate the role of 18F-NaF sodium fluoride (18F-NaF) positron emission tomography (PET) in distinguishing between septic and aseptic failure in hip and knee replacements, in addition to evaluating the feasibility of using multi-sequential 18F-NaF PET-CT for the assessment of painful lower limb prostheses

Identification of an optimal threshold for detecting human brown adipose tissue using receiver operating characteristic analysis of IDEAL MRI fat fraction maps

Purpose: Lower fat fraction (FF) in brown adipose tissue (BAT) than white adipose tissue (WAT) has been exploited using Dixon-based Magnetic Resonance Imaging (MRI) to differentiate these tissues in rodents, human infants and adults. We aimed to determine whether an optimal FF threshold could be determined to differentiate between BAT and WAT in adult humans in vivo. Methods: Sixteen volunteers were recruited (9 females, 7 males; 44.2 ± 19.2 years) based on BAT uptake on 18F-FDG PET/CT. Axial 3-echo TSE IDEAL sequences were acquired (TR(ms)/TE(ms)/matrix/NEX/FoV(cm) = 440/10.7–11.1/512 × 512/3/30–40), of the neck/upper thorax on a 3T HDxt MRI scanner (GE Medical Systems, Milwaukee, USA), and FF maps generated from the resulting water- and fat-only images. BAT depots were delineated on PET/CT based on standardized uptake values (SUV) >2.5 g/ml, and transposed onto FF maps. WAT depots were defined manually within subcutaneous fat. Receiver operating characteristic (ROC) analyses were performed, and optimal thresholds for differentiating BAT and WAT determined for each subject using Youden's J statistic. Results: There was large variation in optimal FF thresholds to differentiate BAT and WAT between subjects (0.68–0.85), with great variation in sensitivity (0.26–0.84) and specificity (0.62–0.99). FF was excellent or good at separating BAT and WAT in four cases (area under the curve [AUC] 0.84–0.92), but poor in 10 (AUC 0.25–0.68). Conclusion: Although this technique was effective at differentiating BAT and WAT in some cases, no universal cut-off could be identified to reliably differentiate BAT and WAT in vivo in adult humans on the basis of FF

Co-localisation analysis of brown adipose deposits on serial 18F-FDG PET/CT scans implies fixed deposits

Purpose: Brown adipose tissue (BAT) is the primary effector organ for non-shivering thermogenesis (NST), which positron emission tomography/computed tomography (PET/CT) studies have shown to be far more prevalent in adult humans than was hitherto believed. Research into weight loss by NST modulation through BAT manipulation requires a reliable imaging biomarker. This study evaluates patterns of BAT uptake on serial PET/CT scans to determine the degree of coincidence over time and the accuracy of PET/CT as a reference standard

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population