The British nuclear medicine research strategy - the framework.

The British Nuclear Medicine Society (BNMS) has developed a Research Strategy framework led by the Research Champions of the BNMS and overseen by the BNMS Research and Innovation Committee. The objectives of the Research Strategy are to improve translation of cutting-edge nuclear medicine research from bench to bedside, the implementation of state-of-the-art multimodality technologies and to enhance multicentre radionuclide research in the UK. It strives to involve patients and the public in radionuclide research and to contribute to and work with the multi-professional national and international organisations involved in research with an ultimate aim to improve nuclear medicine services, and patients' outcomes and care.

Fast-track pathway for early diagnosis and management of giant cell arteritis: the combined role of vascular ultrasonography and [18F]-fluorodeoxyglucose PET-computed tomography imaging.

Giant cell arteritis (GCA) is a medical emergency, which can lead to irreversible blindness and other ischaemic vascular events if left untreated. Prompt access to specialist assessment, diagnostics in the form of a fast-track pathway (FTP) and access to appropriate treatment are key factors in preventing morbidity associated with this disease. Recent developments in vascular imaging prompted review of our management of GCA patients. Here, we present the newly implemented FTP in GCA at the University College London Hospital, with added vascular imaging in the form of temporal artery ultrasound (TAUS) and [18F]-fluorodeoxyglucose PET-computed tomography ( 18 F-FDG PET-CT) with temporal artery biopsy. The initial pilot data on the FTP showed a significant negative predictive value of the combined TAUS and 18 F-FDG PET-CT, and the vast majority of cases positive on imaging were confirmed by biopsy. Through the new FTP in GCA, the diagnosis was completed within 48-72 h, compared with the conventional pathway time of up to 2-3 weeks awaiting biopsy results. Prompt and accurate diagnosis of GCA enables commencement of corticosteroid (prednisolone) treatment in the appropriate patient population while avoiding unnecessary steroid exposure and toxicity in GCA-negative patients.

Evolution of 18F-FDG PET/CT Findings in Patients After COVID-19: An Initial Investigation.

The aim of this study was to assess the temporal evolution of pulmonary 18F-FDG uptake in patients with coronavirus disease 2019 (COVID-19) and post-COVID-19 lung disease (PCLD). Methods: Using our hospital's clinical electronic records, we retrospectively identified 23 acute COVID-19, 18 PCLD, and 9 completely recovered 18F-FDG PET/CT patients during the 2 peaks of the U.K. pandemic. Pulmonary 18F-FDG uptake was measured as a lung target-to-background ratio (TBRlung = SUVmax/SUVmin) and compared with temporal stage. Results: In acute COVID-19, less than 3 wk after infection, TBRlung was strongly correlated with time after infection (rs = 0.81, P < 0.001) and was significantly higher in the late stage than in the early stage (P = 0.001). In PCLD, TBRlung was lower in patients treated with high-dose steroids (P = 0.003) and in asymptomatic patients (P < 0.001). Conclusion: Pulmonary 18F-FDG uptake in COVID-19 increases with time after infection. In PCLD, pulmonary 18F-FDG uptake rises despite viral clearance, suggesting ongoing inflammation. There was lower pulmonary 18F-FDG uptake in PCLD patients treated with steroids.

Renal protection during 177lutetium DOTATATE molecular radiotherapy in children: a proposal for safe amino acid infusional volume during peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting. To protect the kidneys from PRRT-induced radiation nephropathy, basic amino acids are infused during PRRT as they competitively bind to the proximal tubular cells and prevent uptake of the radionuclide. In adults, 1 L of a basic amino acid solution consisting of arginine and lysine is infused over 4 h commencing 30 min prior to PRRT. However, this volume of amino acids infused over 4 h is excessive in small children and can result in hemodynamic overload. This is all the more relevant in paediatric oncology, as many of the children may have been heavily pretreated and so may have treatment-related renal and or cardiac impairment. We have therefore developed the following guidelines for safe paediatric dosing of renal protective amino acid infusions during PRRT. Our recommendations have been made taking into consideration the renal physiology in small children and the principles of safe fluid management in children.

Is It Time to Call Time on Bone Marrow Biopsy for Staging Ewing Sarcoma (ES)?

Primary malignant bone sarcomas are rare and Ewing sarcoma (ES), along with osteosarcoma, predominates in teenagers and young adults. The well-established multimodality treatment incorporates systemic chemotherapy with local control in the form of surgery, with or without radiation. The presence and extent of metastases at diagnosis remains the most important prognostic factor in determining patient outcome; patients with skeletal metastases or bone marrow infiltration having a significantly worse outcome than those with lung metastases alone. There is, however, no accepted staging algorithm for ES. Large cooperative groups and national guidelines continue to advocate bone marrow biopsy (BMB) for staging but functional imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with computerised tomography (CT) have been increasingly used for staging cancers and whole-body magnetic resonance imaging (WB-MRI) for staging skeletal metastases. This review outlines the current literature, from which we conclude that BMB is no longer required for the staging of ES as it does not influence the standard of care management. BMB may, however, provide prognostic information and insights into the biology of ES in selected patients on prospective clinical trials.

Revalidation of PET/computed tomography criteria (Hopkins criteria) for the assessment of therapeutic response in lung cancer patients: inter-reader reliability, accuracy and survival outcomes.

BACKGROUND/AIM: Systematic reporting using qualitative evaluation of PET/computed tomography (CT) results has been demonstrated to be very accurate and reproducible in posttherapy assessment of lung cancer (so-called Hopkins criteria). Our aim was to test, in a different cohort of patients, the Hopkins criteria for assessment of therapeutic response in lung cancer and to compare the results with those obtained using a semi-quantitative evaluation of uptake. METHODS: This is a retrospective study. A total of 85 patients with known lung cancer who underwent fluorine-18 fluorodeoxyglucose PET/CT assessment within 24 weeks (mean 7.9 weeks) of completion of treatment were included. Treatments included surgical resection, chemotherapy, radiation therapy, immunotherapy or combinations thereof. PET/CT interpretation was done by two nuclear medicine physicians, and discrepancies were resolved by a third interpreter. Studies were scored both according to the Hopkins criteria using qualitative assessment of tracer uptake for the primary tumour, locoregional disease in the mediastinum and distant metastatic sites and by applying the same five-point score using a semi-quantitative measure, maximum standardized uptake value. Overall scores of 1, 2 and 3 were considered negative for residual disease, while scores of 4 and 5 were considered positive. Patients were followed up for a median of 18.5 months (range 2-139 months). Kaplan-Meier plots with a Mantel-Cox log-rank test were performed, considering death as the endpoint. Inter-reader variability was assessed using percent agreement and kappa statistics. RESULTS: The Cohen κ coefficient analysis showed substantial agreement between the two interpreters on the five-point Hopkins criteria scoring, with a κ of 0.73. There was almost perfect agreement between the interpreters with respect to classification as positive or negative according to the Hopkins criteria, with a κ of 0.89. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the Hopkins criteria were 88.5% [95% confidence interval (CI) 80.6-96.5%), 79.2% (95% CI 63.2-95.1%), 91.5% (95% CI 84.4-98.6%), 73.1% (95% CI 61.8-84.4%) and 85.9% (95% CI 78.5-93.3%), respectively. There was almost perfect agreement between the qualitative and semi-quantitative scoring with a κ of 0.87, with sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the semi-quantitative Hopkin's criteria of 86.9% (95% CI 78.4-95.4%), 79.2% (95% CI 62.9-95.4%), 91.4% (95% CI 84.2-98.6%), 70.4% (95% CI 58.6-82.1%) and 84.7% (95% CI 80.8-92.4%), respectively. CONCLUSION: The use of Hopkins criteria for posttherapy assessment in patients with lung cancer represents an easy and reproducible method with substantial to almost perfect interobserver agreement and high positive predictive value and accuracy; moreover, it is easily understood by referring physicians. Additionally, there was no significant difference when applying a semi-quantitative measure to the same five-point score.

Performing clinical 18F-FDG-PET/MRI of the mediastinum optimising a dedicated, patient-friendly protocol.

OBJECTIVE: To construct a mediastinal-specific fluorine-18-fluorodeoxyglucose (F-FDG)-PET/MR protocol with high-quality MRI of minimal acquisition-time and comparable diagnostic value to F-FDG-PET/computed tomography (CT). MATERIALS AND METHODS: Fifteen healthy participants received PET/MRI and 10 patients with mediastinal tumours (eight non-small-cell lung, two oesophageal cancer) received F-FDG-PET/MRI immediately after F-FDG-PET/CT. Sequences volume interpolated breath-hold examination (T1-VIBE) and Half-Fourier acquisition single-shot turbo spin echo (T2-HASTE) were optimised by varying the parameters: breath-hold (BH, end-expiration), fat suppression (spectral adiabatic inversion recovery), and ECG-triggering (ECG, end-diastole). Image quality (IQ) of each sequence-variation was qualitatively scored by medical experts and quantitatively assessed by calculating signal-to-noise ratios, contrast relative to muscle, standardized-uptake-value, and tumour-to-blood ratios. Patient comfort was evaluated on patients' experience. Diagnostic accuracy of F-FDG-PET/MRI was compared to F-FDG-PET/CT, in reference to histopathology/cytopathology. RESULTS: ECG-triggered T1-VIBE images showed the highest signal-to-noise ratio (P < 0.01) and the largest contrast between mediastinal soft-tissues, regardless of BH or free-breathing acquisition. IQ of ECG-triggered T1-VIBE scans in BH were scored qualitatively highest with good reader agreement (κ = 0.62). IQ of T2-HASTE was not significantly affected by BH acquisition (P > 0.9). Qualitative IQ of T1-VIBE and T2-HASTE declined after spectral adiabatic inversion recovery fat-suppression. All patients could maintain BH at end-expiration and reported no discomfort. Diagnostic performance of F-FDG-PET/MR was not significantly different from F-FDG-PET/CT with comparable staging, standardized-uptake-values, and tumour-to-blood ratios. However, T-status was more often over-staged on F-FDG-PET/CT, while N-status was more frequently under-staged on F-FDG-PET/MR. CONCLUSION: ECG-triggered T1-VIBE sequences acquired during short, multiple BHs are recommended for mediastinal imaging using F-FDG-PET/MR. With dedicated protocols, F-FDG-PET/MRI will be useful in thoracic oncology and aid in diagnostic evaluation and tailored treatment decision-making.

Microvasculature and intraplaque hemorrhage in atherosclerotic carotid lesions: a cardiovascular magnetic resonance imaging study.

BACKGROUND: The presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events. However, the mechanisms leading to IPH are not fully understood. The dominant view is that IPH is caused by leakage of erythrocytes from immature microvessels. The aim of the present study was to investigate whether there is an association between atherosclerotic plaque microvasculature and presence of IPH in a relatively large prospective cohort study of patients with symptomatic carotid plaque. METHODS: One hundred and thirty-two symptomatic patients with ≥2 mm carotid plaque underwent cardiovascular magnetic resonance (CMR) of the symptomatic carotid plaque for detection of IPH and dynamic contrast-enhanced (DCE)-CMR for assessment of plaque microvasculature. Ktrans, an indicator of microvascular flow, density and leakiness, was estimated using pharmacokinetic modelling in the vessel wall and adventitia. Statistical analysis was performed using an independent samples T-test and binary logistic regression, correcting for clinical risk factors. RESULTS: A decreased vessel wall Ktrans was found for IPH positive patients (0.051 ± 0.011 min- 1 versus 0.058 ± 0.017 min- 1, p = 0.001). No significant difference in adventitial Ktrans was found in patients with and without IPH (0.057 ± 0.012 min- 1 and 0.057 ± 0.018 min- 1, respectively). Histological analysis in a subgroup of patients that underwent carotid endarterectomy demonstrated no significant difference in relative microvessel density between plaques without IPH (n = 8) and plaques with IPH (n = 15) (0.000333 ± 0.0000707 vs. and 0.000289 ± 0.0000439, p = 0.585). CONCLUSIONS: A reduced vessel wall Ktrans is found in the presence of IPH. Thus, we did not find a positive association between plaque microvasculature and IPH several weeks after a cerebrovascular event. Not only leaky plaque microvessels, but additional factors may contribute to IPH development. TRIAL REGISTRATION: NCT01208025 . Registration date September 23, 2010. Retrospectively registered (first inclusion September 21, 2010). NCT01709045 , date of registration October 17, 2012. Retrospectively registered (first inclusion August 23, 2011).

Quantitative SPECT: the time is now.

BACKGROUND: Quantification is one of the key benefits of nuclear medicine imaging. Recently, driven by the demand for post radionuclide therapy imaging, quantitative SPECT has moved from relative and semiquantitative measures to absolute quantification in terms of activity concentration, and yet further to normalised uptake using the standard uptake value (SUV). This expansion of quantitative SPECT has the potential to be a useful tool in the nuclear medicine armoury, but key factors must be addressed before it can meet its full potential. DISCUSSION: Quantitative SPECT should address an unmet clinical need and give metrics that are clinically meaningful. Using the technique in a similar manner to PET with longitudinal assessments of disease in terms of SUV is one example that meets these criteria. Having metrics that are evaluated to ensure that they are correct, that are optimised to maximise their sensitivity, and that are transferrable to allow multi-centre learning and applicability to all users of the technology are other areas of quantitative SPECT that need to be addressed and that have specific challenges associated with them. Finally, ensuring quantitative SPECT is cost-effective in times when healthcare budgets are being squeezed is also very important. CONCLUSION: Quantitative SPECT offers the possibility to continue and expand the potential of quantitative nuclear medicine applications. The time is now to ensure that our community works together to make this potential a reality.

Hybrid FDG-PET/MR imaging of chronic osteomyelitis: a prospective case series.

BACKGROUND: Magnetic resonance imaging (MRI) and 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography paired with computed tomography (PET/CT) are two commonly used imaging modalities in the complicated diagnostic workup of osteomyelitis. Diagnosis using these modalities relies on, respectively, anatomical (MRI) and metabolic (PET) signs. With hybrid PET/MRI being recently available, our goal is to qualitatively compare hybrid FDG PET/MRI to FDG PET/CT in the diagnosis and operative planning of chronic osteomyelitis. METHODS: Five patients with suspected chronic osteomyelitis in an extremity underwent an 18F-FDG single-injection/dual-imaging protocol with hybrid PET/CT and hybrid PET/MR. Images and clinical features were evaluated using a standardized assessment method. Standardized uptake value (SUV) measurements were performed on all images. Concordant and discordant findings between PET/MRI and PET/CT were analysed. RESULTS: The consensus diagnoses based on PET/MRI and PET/CT images were identical for all five patients. One discrepancy between PET/MRI and PET/CT was found in the assessment of the features in one patient. PET signal intensities and target-to-background ratios were on average highest for PET/MRI. On PET/MRI, the location of infection based on FDG uptake could clearly be correlated with certain soft tissue structures (oedema, fluid collection, or muscle), which is paramount for surgical planning. CONCLUSIONS: In the presented cases, FDG PET/MRI led to the same diagnosis and provided at least the same diagnostic information as PET/CT. PET/MRI was able to provide additional soft-tissue information for the physician planning treatment. Because of this, we suggest that PET/MRI could be used for osteomyelitis diagnosis and treatment planning.

Does quantification have a role to play in the future of bone SPECT?

Routinely, there is a visual basis to nuclear medicine reporting: a reporter subjectively places a patient's condition into one of multiple discrete classes based on what they see. The addition of a quantitative result, such as a standardised uptake value (SUV), would provide a numerical insight into the nature of uptake, delivering greater objectivity, and perhaps improved patient management.For bone scintigraphy in particular quantification could increase the accuracy of diagnosis by helping to differentiate normal from abnormal uptake. Access to quantitative data might also enhance our ability to characterise lesions, stratify and monitor patients' conditions, and perform reliable dosimetry for radionuclide therapies. But is there enough evidence to suggest that we, as a community, should be making more effort to implement quantitative bone SPECT in routine clinical practice?We carried out multiple queries through the PubMed search engine to facilitate a cross-sectional review of the current status of bone SPECT quantification. Highly cited papers were assessed in more focus to scrutinise their conclusions.An increasing number of authors are reporting findings in terms of metrics such as SUVmax. Although interest in the field in general remains high, the rate of clinical implementation of quantitative bone SPECT remains slow and there is a significant amount of validation required before we get carried away.

The role of bone SPECT/CT in patients with persistent or recurrent lumbar pain following lumbar spine stabilization surgery.

PURPOSE: Despite recent advances in lumbar spine stabilization surgery (LSSS), a high number of patients continue to complain of persistent/recurrent lumbar pain after LSSS. Conventional imaging (plain radiography, CT and MRI) is commonly performed to assess potential lumbar pain generators, but findings are equivocal in approximately 20% of patients. The purpose of this study was to assess the diagnostic performance of 99mTc-HDP bone SPECT/CT in identifying potential pain generators in patients with persistent/recurrent lumbar pain after LSSS but in whom conventional diagnostic imaging is inconclusive. METHODS: A total of 187 patients (median age 56 years, 70 men) with persistent/recurrent lumbar pain following LSSS with inconclusive conventional imaging (plain radiography, CT and/or MRI) underwent 99mTc-HDP bone SPECT/CT and were included in the study. Tracer uptake on SPECT/CT, as an indicator of ongoing or altered osteoblastic activity, was assessed in the lumbar spine stabilization segment(s) and in adjacent segments. Uptake intensity was graded as (1) high (the same as or more than iliac crest uptake), (2) mild (the same as or more than nondiseased vertebral uptake but less than iliac crest uptake), or (3) negative (normal scan). Mild and high uptake were regarded as positive. RESULTS: In 160 of the 187 patients (85.6%), SPECT/CT showed positive mild or high tracer uptake in the LSSS region. More than half of the patients had abnormal tracer uptake in the stabilized segments (56.7%) and/or in the adjacent segments (55.6%). Although positive stabilized segment findings were commonly seen at <2 years (70.3%) and the rate decreased with time after LSSS, they were seen at >6 years after surgery in 38.2% of patients. In 51.4% of patients, abnormal activity was seen in the adjacent segments <2 years after LSSS, suggesting early/accelerated degeneration after surgery. The proportion of patients with abnormal activity in the adjacent segments increased to 67.3% at >6 years after LSSS (p < 0.05). Positive SPECT/CT findings in the stabilized segments were more frequent in patients with three or more stabilized segments (p < 0.05), but were not more frequent in the adjacent segments. Overall, positive SPECT/CT guided therapy in 64% of patients, which included facet joint/nerve root injections or re-do surgery at active sites and/or adjacent sites. CONCLUSION: Bone SPECT/CT is a sensitive diagnostic tool for identifying altered osteoblastic activity, which might be a pain generator in patients with persistent/recurrent pain after lumbar surgery especially when conventional imaging is inconclusive.

18F-FDG PET/MRI in the diagnosis of an infected aortic aneurysm.

We report a case where an integrated whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) is performed in the diagnostic work-up of a saccular aortic aneurysm. The integrated whole body 18F-FDG PET/MRI study answered all relevant diagnostic questions, clearly marking an infected aortic aneurysm, depicting the extent of the infected area in relation to the aortic branch vessels, and indicating the aortic lesion as the primary site of infection. The patient was successfully treated by open type V TAAA repair and pericardial graft replacement. Aortic wall infection was proven in cultures of the surgical specimen.

Additional Clinical Value for PET/MRI in Oncology: Moving Beyond Simple Diagnosis.

Initial clinical research comparing the diagnostic performance of PET/MRI and PET/CT has largely shown equivalent diagnostic capabilities for these modalities in oncology. These uncertainties about the magnitude of diagnostic benefit are compounded by the considerable health economic challenges associated with clinical implementation. Therefore, there is a need to identify ways to extend the use of this technology beyond simple diagnosis so that PET/MRI can add sufficient clinical value beyond PET/CT or MRI alone and become a cost-effective imaging modality in clinical practice. A major advantage of PET/MRI over other imaging modalities is the ability to generate multiple quantitative images from a single examination. This article describes how a multiparametric PET/MRI approach not only can add clinical value through contributing to precision medicine but also can establish PET/MRI as a potentially cost-effective imaging modality in oncology.