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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.

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.

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Objective To construct a mediastinal-specific fluorine-18-fluorodeoxyglucose (F-18-FDG)-PET/MR protocol with high-quality MRI of minimal acquisition-time and comparable diagnostic value to F-18-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-18-FDG-PET/MRI immediately after F-18-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-18-FDG-PET/MRI was compared to F-18-FDG-PET/CT, in reference to histopathology/cytopathology.Results ECG-triggered T1-VIBE images showed the highest signal-to-noise ratio (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-18-FDG-PET/MR was not significantly different from F-18-FDG-PET/CT with comparable staging, standardized-uptake-values, and tumour-to-blood ratios. However, T-status was more often over-staged on F-18-FDG-PET/CT, while N-status was more frequently under-staged on F-18-FDG-PET/MR.Conclusion ECG-triggered T1-VIBE sequences acquired during short, multiple BHs are recommended for mediastinal imaging using F-18-FDG-PET/MR. With dedicated protocols, F-18-FDG-PET/MRI will be useful in thoracic oncology and aid in diagnostic evaluation and tailored treatment decision-making. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.

Background/Aims Giant cell arteritis (GCA) is a systemic vasculitis affecting the temporal arteries and large vessels, including the aorta, in 25% of cases. Incidence of vertebral artery involvement is unknown likely owing to the reliance on conventional diagnostics including temporal artery biopsy (TAB) and temporal/axillary ultrasound which evade the vertebral arteries. These tests lose sensitivity soon after steroid initiation. Early specialist assessment and diagnostics, as part of a fast track pathway (FTP), can overcome this challenge. We present the first 12 months data from our FTP. To our knowledge this is the first GCA-FTP in the UK to utilise positron emission tomography - computed tomography (PET-CT) as an early diagnostic tool so we present a unique cohort of patients. Methods Cohort 1: 40 patients, diagnosed between 2015-2019, before FTP implementation. Time from steroid initiation to temporal artery ultrasound (TAUS) and TAB was recorded. Cohort 2: 35 patients referred after pathway implementation. 21 had a positive diagnosis. Time from steroid initiation to diagnostic test was recorded. Results Cohort 1: 26 (65%) patients had TAB; 3 (7.5%) had TAUS. The average time from starting steroid to investigation was 6 and 2 days respectively. Cohort 2: 17 (48%) had TAB, 30 (86%) had TAUS, 28 (80%) had PET-CT. In confirmed diagnoses, time from steroid initiation to investigations was 6.6 days, 1 day and 2.5 days respectively. In negative diagnoses time frames were 11.5, 1.5 and 2.3 days respectively. Table 1 shows sensitivity and specificity of these tests. Table 1. Sensitivity and specificity comparison between diagnostic tests Conclusion Combining TAUS and PET-CT allows for high diagnostic accuracy without the need for invasive biopsy. 24% of patients had negative or inconclusive ultrasound and/ or negative biopsy but confirmed vasculitis on PET-CT. 50% of this cohort had vertebral involvement only. PET-CT has an important role in detecting extracranial particularly vertebral arteritis, where biopsy and ultrasound are unreliable. Our pathway design with the inclusion of PET-CT, enables us to capture all patients with GCA and satisfy NHS England criteria for tocilizumab use in refractory GCA. Continued evaluation of PET-CT and its role in predicting vascular complications is required. Disclosure D.R. Ludwig: None. V. Morris: None. A. Shashidhara: None. S. Voo: None. R. Reshat: None.

The aim of this study was to assess the temporal evolution of pulmonary

Background Haemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening syndrome characterised by hyperinflammation and macrophage activation. Viral infections such as Epstein-Barr virus (EBV) are a well-recognised trigger of HLH but the treatment of such cases is not well-defined. We present a case of primary EBV driven HLH that was successfully treated with the interleukin-1 inhibitor anakinra in addition to rituximab and high-dose steroids. Case A 22-year-old female with no past medical history developed a mononucleosis-like illness lasting five days characterised by fevers, sore throat and neck swelling. Two weeks following this she presented with fevers, night sweats, fatigue and right upper quadrant pain. She was diagnosed with HLH based on high fevers with hyperferritaemia, hypertriglyceridaemia, pancytopaenia, abnormal liver function tests and hepatosplenomegaly. Extensive investigation revealed an EBV viral load of 23,000,000 copies/ml with nil other obvious triggers. A diagnosis of primary-driven EBV HLH was made. She was treated with the interleukin-1 inhibitor anakinra, methylprednisolone and IVIG and a single dose of rituximab. Following the commencement of treatment, the patient made a dramatic improvement. Her EBV viral load reduced to 660 within nine days and her blood counts and liver function returned to normal. She was discharged from hospital on day sixteen. She continued the anakinra for 5 weeks at a weaning dose and completed a 12-week weaning dose of steroids. She has returned to her studies and has no lasting complications from her illness. Discussion This case highlights the potential of primary EBV infection to cause fulminant HLH. The prompt diagnosis and treatment of HLH using anakinra and rituximab in addition to conventional HLH treatment was safe, and associated with a dramatic clinical improvement. The use of anakinra has been documented in other cases of HLH but none, to our knowledge, of primary EBV-driven HLH with no underlying haematological or rheumatological condition.

Early recognition of treatment success or failure can impact on patient survival. Traditionally, this assessment relies upon the anatomical measurement of disease, such as CT evaluation using the Response Evaluation Criteria in Solid Tumors (RECIST). However, such measurements are of limited value following radiotherapy. The challenge of determining the presence or absence of viable tumor within residual masses following radiotherapy provides a convincing rationale for incorporating functional imaging into response assessment protocols. PET/CT employs radioactive tracers to assess molecular characteristics of tissues. PET/CT in radiotherapy response assessment is useful as a molecular response to radiotherapy, may precede anatomical response, and allows a more accurate estimate at an earlier stage. Besides the use of specific tracers, it will enable more reliable tumor discrimination from treatment-related inflammation or fibrosis. The chapter includes the advantages and limitations of conventional imaging and PET/CT in the postradiotherapy setting and discusses the potential benefits and pitfalls of image interpretation.

Simple Summary Ewing sarcoma (ES) is a rare primary bone cancer, usually found in children and adolescents, which can spread to the lungs, other bones and less commonly, the bone marrow. An accurate determination of the disease spread at baseline (staging) is important to establish prognosis, monitor treatment response and help with management decisions. There is no standard of care for staging ES, although the invasive bone marrow biopsy has traditionally been used to establish whether patients have bone marrow infiltration. Imaging techniques, including FDG-PET/CT and whole-body MRI (WB-MRI), have become established in staging other cancers with expanding use for staging ES. A number of studies have validated the accuracy, sensitivity and specificity of these modalities for detecting bone and bone marrow metastases in ES. The main aim of this review was to examine the current literature for the use of FDG-PET/CT and WB-MRI in staging ES to determine whether a bone marrow biopsy is still needed and would influence the management of patients. Hereafter, a new staging algorithm for ES recommends WB-MRI and/or FDG-PET/CT without bone marrow biopsy as the standard of care for staging localised and metastatic ES. Abstract 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.

Purpose To assess parameter agreement of volume transfer coefficient (Ktrans) between two vascular regions and to study the correlation with microvessel density on histology. The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter Ktrans is frequently used to study atherosclerotic plaque microvasculature. Ktrans has been reported using different descriptive statistics (mean, median, 75th percentile) either for the whole vessel wall or the adventitia in previous studies. Materials and Methods DCE-MRI parameter agreement was analyzed in 110 symptomatic patients with ≥2 mm carotid plaque that underwent a 3T carotid DCE-MRI examination. Ktrans was estimated in the entire vessel wall and adventitia. Twenty-three patients underwent carotid endarterectomy and were used for comparison with histological quantification of microvessel density of the plaque using CD31 immunohistochemistry. DCE-MRI parameters in the vessel wall regions were compared using Pearson's correlation coefficient, Bland–Altman analysis, and a two-sided paired samples t-test. Correlation of the DCE-MRI parameters with histology was studied using the Pearson's correlation coefficient. Results Median adventitial Ktrans was 5% higher (P = 0.003) than entire vessel wall Ktrans, with no differences for other descriptive statistics. Vessel wall and adventitial Ktrans showed similar moderately strong correlations with plaque microvessel density on histology (Pearson's ρ: 0.59–0.65 [P < 0.003] and 0.52–0.64 [P < 0.011], respectively). Conclusion The similar moderately strong correlations for vessel wall and adventitial Ktrans with microvessel density on histology suggested that both regions reflected plaque microvessel density. Care should to be taken when comparing absolute values between studies. Future studies incorporating thresholds for risk stratification need to agree upon standardization of DCE-MRI parameters. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1053–1059.

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.

18F-FDG PET/CT is currently the most useful and broadly used neuroimaging modality of global brain activity in neurologic patients. The images provide a tridimensional information on both cortical and subcortical structures allowing to consider brain activity in functional networks.

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. 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. 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). 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. 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).

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.

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.

European journal of nuclear medicine and molecular imaging 43(13), 2433-2447 (2016). doi:10.1007/s00259-016-3480-8, Published by Springer-Verl., Heidelberg [u.a.]

Purpose To examine the relationship between the extent of disease determined by [Ga-68]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. Methods We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [Ga-68]PSMA-HBED-CC PET/CT. Results PET/CT was positive in 44 %, 79 % and 89 % of patients with PSA levels of = 2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p

Background: :Giant Cell Arteritis (GCA) is a common primary systemic vasculitis (1). Its predilection for the temporal artery can result in permanent visual loss if left untreated. Over 25% of patients have involvement of large vessels, such as the aorta, resulting in an increased risk of aneurysm formation and dissection. (3)Diagnosis of GCA is largely clinical and temporal artery biopsy (TAB) has long been the gold standard for diagnosis. In recent years temporal artery ultrasound (TAUS) has emerged as an effective, non-invasive tool to aid diagnosis. Positron-emission tomography (PET) can also be utilised to detect the presence of large vessel involvement but is currently not used in many centres for diagnostic purposes and requires further standardisation and validation (2). The challenge arises from these investigations losing sensitivity in the days following steroid treatment, meaning that rapid access is key to confirm diagnosis.Objectives:To evaluate the impact of the introduction of a fast track pathway (FTP) on prompt diagnostics and treatment.To improve our understanding of the use of PET at diagnosis and compare this to the gold standard TAB, and to TAUS, in our institution.Methods:Cohort 1: 32 patients, all presenting before FTP implementation, identified from outpatient clinics and referrals to the Rheumatology team. Time taken from steroid initiation to TAUS/TAB was extracted from clinical records. Outcomes for this group included number of years on steroid (steroid burden).Cohort 2: 21 patients all referred after implementation of a new GCA FTP. This group contains all patients referred as query GCA, not just those with positive diagnoses. Time from steroid initiation to TAUS/TAB was recorded. The FTP included the addition of PET imaging within 72 hours.Results:Cohort 1: 20 (63%) patients had TAB and 3 (9%) had TAUS. The average time from starting steroid to investigation was 5.2 days and 2 days respectively. The average steroid burden in patients with no confirmatory test was 11 years. If patients had just a single diagnostic test this value dropped to 3 years.Cohort 2: 11 (52%) had TAB, 10 (48%) had TAUS and 11 (52%) had PET. In positive GCA diagnoses, time from steroid start to investigations was 7.2 days, 1 day and 3.2 days respectively. In patients with a negative diagnosis the time frames were 13 days, 1 day and 1.7 days respectively. Sensitivity for TAB was 45.5% and TAUS 40%. Specificity for TAB and TAUS was 100%. These results are comparable to similar studies (4). PET sensitivity was 63.6% and specificity 100%.Table 1.Sensitivity, specificity, predictive valuesTABTAUSPET CTSensitivity (%)45.540.063.6Specificity (%)100100100PPV (%)100100100NPV (%)33.357.155.6Conclusion:Prompt diagnostics, best facilitated through a FTP, can reduce steroid burden in GCA even if only one confirmatory test is available. Patients with a low clinical suspicion of GCA and negative TAUS or a high clinical suspicion and positive TAUS stand little to gain from TAB. These findings summarise the first 6 months of our GCA FTP. Continued evaluation of PET in our FTP is needed to understand its role in diagnosis, particularly in patients at risk of vascular complications.References:[1]Crowson CS, Matteson EL. Contemporary prevalence estimates for giant cell arteritis and polymyalgia rheumatica 2015. Semin Arthritis Rheum. 2017; 47 (2) 253–6[2]Camellino D, Dejaco C. Should 18 F FDG PET imaging be used in the diagnosis of GCA? Nature Reviews Rheumatology 2019; 15 (7) 388–90[3]Nuenninghoff DM et al. Incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large artery stenosis) in patients with giant cell arteritis: a population-based study over 50 years. Arthritis Rheum 2003; 48:3522-3531[4]Luqmani, R. et al. The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): A Diagnostic Accuracy and Cost-Effectiveness Study. Health Technol Assess 2016; 20 (90) 1-238Disclosure of Interests:None declared

Background:Giant cell arteritis (GCA) may affect both cranial and extra-cranial vessels; where the latter occurs, it can be termed large-vessel GCA (LV-GCA). Large vessel involvement is common: histological evidence has been seen in 80% of autopsies of patients with known GCA, and imaging studies suggest large vessel involvement in over 80%1. LV-GCA is important to diagnose due to the risks of vascular complications such as occlusion and ischaemic stroke. The clinical diagnosis can be challenging, and the American College of Rheumatology (ACR) GCA classification criteria often underperform in cases of LV-GCA1. F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been found to be useful in the detection of extra-cranial involvement to support the diagnosis of LV-GCA.2Objectives:To appreciate the variability in presentation of cases of LV-GCA, and to further characterise a subgroup of patients with vertebral arteritis.To explore the use of FDG-PET imaging in GCA patients in addition to or in place of traditional diagnostic tools (temporal artery ultrasound / biopsy).Methods:Through evaluation of the new GCA fast-track pathway implemented at UCLH, a subgroup of patients diagnosed with vertebral arteritis was identified. The history and presentation of these patients were analysed.Results:Three patients were diagnosed with vertebral arteritis. All three were male, Caucasian and aged over 70. All were investigated for GCA due to a history of severe headache (frontal in one, occipital in one, bi-temporal in one) with associated red flag symptoms. Two had a history of jaw claudication and visual disturbances (unilateral visual loss in one, transient diplopia in the other). Both of these patients had positive temporal artery biopsies. The third patient had no ischaemic symptoms but a strong history of prominent polymyalgic features and a positive temporal artery ultrasound. Inflammatory markers were raised in two, and normal in one, of the patients. Only one had systemic symptoms (weight loss). All three proceeded to FDG-PET scans which showed vertebral arteritis and were commenced on immunosuppressive treatment.Conclusion:The cases discussed illustrate the heterogeneity of the presentation of LV-GCA, and the diagnostic challenge this poses. FDG-PET imaging is useful in confirming extra-cranial involvement and therefore guiding treatment.References:[1]Large-vessel giant cell arteritis: diagnosis, monitoring and management.Matthew J Koster, Eric L Matteson, Kenneth J Warrington.2018, Rheumatology, Vol. 57, pp. 32-42.[2]EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice.Dejaco C, Ramiro S, Duftner C, et al.2018, Annals of the Rheumatic Diseases, Vol. 77, pp. 636-643.Disclosure of Interests: :None declared

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. 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. 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 6 years after surgery in 38.2% of patients. In 51.4% of patients, abnormal activity was seen in the adjacent segments 6 years after LSSS (p

We report a case where an integrated whole body F-18-fluorodeoxyglucose (F-18-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 F-18-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.

AIM: To evaluate diagnostic performance of gadofosveset ( GDF)-enhanced magnetic resonance imaging (MRI) in addition to T2-weighted (T2W) MRI for nodal (re) staging in newly diagnosed breast cancer patients. MATERIALS AND METHODS: Ninety patients underwent axillary T2W-and GDF-MRI. Two radiologists independently scored each lymph node; first on T2W-MRI, subsequently adjusting their score on GDF-MRI. Diagnostic performance parameters were calculated on node-by-node and patient-by-patient validation with histopathology as the reference standard. Furthermore, learning curve analysis for reading GDF-MRI was performed. RESULTS: In patient-by-patient validation, overall reader performances for T2W-and GDF-MRI were similar with area under the receiver operating characteristic curves (AUC) of 0.75 and 0.77 (p = 0.731) for reader 1 and 0.79 and 0.72 (p = 0.156) for reader 2. For node-by-node validation, AUC values of T2W-and GDF-MRI were 0.76 and 0.82 (p = 0.018) and 0.77 and 0.77 (p = 0.998) for reader 1 and 2. The AUC for reader 1 was 0.71 for first one-third of nodes evaluated, improving to 0.80 and 0.95 for the next and last one-third, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) improved from 38%, 89%, 56%, and 79% to 60%, 93%, 64%, and 92%. The AUC of reader 2 improved from 0.69 to 0.79. CONCLUSION: The present study confirmed that GDF-MRI, in addition to T2W-MRI, has potential as a non-invasive method for nodal (re) staging in breast cancer. (C) 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

BACKGROUND: Advanced stage cervical cancer is primarily treated by radiotherapy. Local tumor control is a prerequisite for cure. Imaging after treatment is controversial. Positron emission tomography (PET) combined with computer tomography (PET-CT) shows great promise for detecting metastases. On the other hand, magnetic resonance imaging (MRI) is superior in depicting anatomical details. The combination of PET-MRI could result in more accurate evaluation of cervical cancer treatment outcome. The aim of this pilot study is to share our initial experience with PET-MRI in the evaluation of treatment response in cervical cancer after radiation treatment. METHODS: Ten patients with cervical carcinoma (FIGO ≥IB2) were prospectively evaluated. Eleven weeks (median; range 8-15 weeks) after radiation therapy, treatment response was evaluated by PET-MRI. The PET, MRI, and combined PET-MRI images were evaluated for the presence of local residual tumor and metastasis. Diagnostic performance was assessed by area under the receiver operator characteristic (ROC) curve for evaluation of local residual tumor. The readers were blinded for outcome data. Local residual disease, metastasis, diagnostic confidence, and change of opinion were scored on a 5-point Likert scale. The reference standard consisted of pathology and/or follow-up according to the clinical guidelines. RESULTS: Three out of ten patients had local residual abnormalities suggestive for tumor residue after radiation treatment. The availability of both PET and MRI resulted in an increase in diagnostic confidence in 80-90% of all patients. Change of opinion was observed in 70% and change of policy in 50%, especially in the group with residual tumor. The diagnostic accuracy increased significantly for the radiologist if PET-MRI was combined (AUC .54 versus .83). CONCLUSIONS: PET-MRI shows promise for evaluation of treatment response after radiation for cervical cancer, especially increasing diagnostic confidence, while potentially increasing diagnostic performance. ispartof: EJNMMI RESEARCH vol:8 issue:1 ispartof: location:Germany status: published

European journal of nuclear medicine and molecular imaging 45(2), 179-186 (2018). doi:10.1007/s00259-017-3823-0, Published by Springer-Verl., Heidelberg [u.a.]

European journal of nuclear medicine and molecular imaging 42(9), 1423-1429 (2015). doi:10.1007/s00259-015-3081-y, Published by Springer-Verl., Heidelberg [u.a.]

Our purpose in this study was to assess the added clinical value of hybridIn this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed.A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed.Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients.

European journal of nuclear medicine and molecular imaging 44(7), 1234-1243 (2017). doi:10.1007/s00259-017-3675-7, Published by Springer-Verl., Heidelberg [u.a.]

European journal of nuclear medicine and molecular imaging 44(11), 1796-1805 (2017). doi:10.1007/s00259-017-3745-x, Published by Springer-Verl., Heidelberg [u.a.]

Background— 18 F-fluorocholine ( 18 F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that 18 F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation. Methods and Results— Ten consecutive stroke patients (90% men, median age 66.5 years, range, 59.4–69.7) with ipsilateral >70% carotid artery stenosis and who underwent carotid endarterectomy were included in the study. Before carotid endarterectomy, all patients underwent positron emission tomography to assess maximum 18 F-FCH uptake in ipsilateral symptomatic carotid plaques and contralateral asymptomatic carotid arteries, which was corrected for background activity, resulting in a maximum target-to-background ratio (TBRmax). Macrophage content was assessed in all carotid endarterectomy specimens as a percentage of CD68 + -staining per whole plaque area (plaqueCD68 + ) and as a maximum CD68 + percentage (maxCD68 + ) in the most inflamed section/plaque. Dynamic positron emission tomography imaging demonstrated that an interval of 10 minutes between 18 F-FCH injection and positron emission tomography acquisition is appropriate for carotid plaque imaging. TBRmax in ipsilateral symptomatic carotid plaques correlated significantly with plaqueCD68 + (Spearman’s ρ=0.648, P =0.043) and maxCD68 + (ρ=0.721, P =0.019) in the 10 corresponding carotid endarterectomy specimens. TBRmax was significantly higher ( P =0.047) in ipsilateral symptomatic carotid plaques (median: 2.0; interquartile range [Q1–Q3], 1.5–2.5) compared with the contralateral asymptomatic carotid arteries (median: 1.4; Q1–Q3, 1.3–1.6). TBRmax was not significantly correlated to carotid artery stenosis (ρ=0.506, P =0.135). Conclusions— In vivo uptake of 18 F-FCH in human carotid atherosclerotic plaques correlated strongly with degree of macrophage infiltration and recent symptoms, thus 18 F-FCH positron emission tomography is a promising tool for the evaluation of vulnerable plaques. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01899014.

Background Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT. Methods We included 33 patients (mean age 70 ± 7 years, mean left ventricular ejection fraction 55 ± 12 %) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3–7 spots/session, 100 impulses/spot, 0.09 mJ/mm2) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session. Results One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p

Aims: Transition metal ions have been implicated in atherosclerosis. The goal of this study was to investigate whether metal ion levels were higher in people with diabetes, in view of their increased risk of aggravated atherosclerosis. Methods and results: Absolute concentrations of iron, copper, zinc and calcium, and products of protein and lipid oxidation were quantified in atherosclerotic lesions from subjects with (T2DM, n = 27), without Type 2 diabetes (nonDM, n = 22), or hyperglycaemia (HG, n = 17). Iron (P

Non-small cell lung cancer (NSCLC) patients with a solitary metastasis are considered to have a more favourable prognosis compared to those with multiple metastases. This is also shown in the 8th tumor, node, metastases edition for lung cancer (TNM8): patients with M1b (single extrapulmonary metastasis) have a superior prognosis than those with M1c disease (multiple metastases). Although not described in the TNM8, site of single metastatic disease may reflect tumour biology and may be of important prognostic value. We report a case of a patient with squamous cell NSCLC and a single skeletal muscle metastasis with a remarkably aggressive disease course.

Metaiodobenzylguanidine (MIBG) is a tracer that selectively targets neuroendocrine cells. On this basis, radiolabeled iodinated-MIBG (I-131-MIBG) has been introduced as a molecular nuclear therapy in the management of neuroendocrine tumors, including neuroblastoma, pheochromocytoma, paraganglioma, neuroendocrine carcinomas, and other rare neuroendocrine tumors. Extensive work has been addressed to develop I-131-MIBG therapy: doses, therapeutic schemes, and efficiency. In this paper, we present an overview on I-131-MIBG therapy, with main focus on different aspects how to perform this treatment.

Monocyte recruitment into the vessel wall is a crucial initial step in vascular repair, arteriogenesis and atherogenesis. Two distinct human monocyte subpopulations can be classified according to their CD14/16 surface expression, namely CD14++CD16-monocytes (CD16-mo) and CD14+CD16+ monocytes (CD16+mo). We investigated different functional properties of the two monocyte subsets.CD16-/CD16+mo were isolated from human blood by an immunological selection. We assessed monocyte chemokinesis, chemotaxis, adhesion and Vascular-Endothelial Growth Factor (VEGF) receptor expression. Furthermore, generation of reactive oxygen species (ROS) as well as expression of antioxidant enzymes was investigated.Chemokinesis of CD16+mo was decreased compared to CD16-mo (p0.01). Likewise, adhesion capacity of CD16+mo was weaker (p0.05). CD16+mo chemotaxis towards the angiogenic ligands vascular endothelial growth factor-A (VEGF-A) and placenta growth factor-1 (PlGF-1) was reduced compared to CD16-mo. VEGFR-1 is the receptor for VEGF-A and PlGF-1 on monocytes. VEGFR-1 protein expression was lower in CD16+mo than in CD16-mo (p0.05). The impaired VEGF-A- and PlGF-1-induced CD16+mo chemotaxis might therefore be attributed to the reduced VEGFR-1 expression. CD16+mo exhibited less spontaneous ROS production than CD16-mo. Additionally, the antioxidant enzyme manganese superoxide dismutase was expressed at higher levels in CD16+mo (p0.05); this might partly explain the higher oxidative resistance of CD16+mo.These novel functional differences between CD16-mo and CD16+mo may predict different functional roles of both monocyte subsets in vascular repair, arteriogenesis and atherogenesis.

Background. Circulating progenitor cells (PC) can positively influence the healing of ischaemic myocardium. Cardiovascular risk factors including diabetes mellitus (DM) may have a negative influence on both number and recruitment of PC. Recent evidence suggests that less differentiated CD133+PC contribute to myocardial healing and are promising candidates for therapy. Therefore, we investigated whether DM affects CD133+PC. Methods. CD133+PC were analyzed in patients following acute myocardial infarction and successful reperfusion [acute myocardial infarction (AMI, n = 45) with/without non-insulin-requiring type 2 DM (T2DM)]. Stable coronary artery disease patients (CAD, n = 45) served as stable controls. Number and phenotype of CD133+PC were assessed by flow cytometry. CD133+PC chemotaxis was assessed towards vascular endothelial growth factor, an angiogenic stimulus upregulated in AMI. The expression of anti-oxidant enzymes in CD133+PC was detected by reverse-transcriptase PCR. Results. In non-DM patients, the number of CD133+PC increased on day 3 following AMI (P = 0.0001). In contrast, no changes were observed in AMI patients with T2DM. Regarding the function of CD133+PC, an enhanced chemotactic response was observed following AMI in both non-DM (P = 0.0001) and T2DM (P = 0.007). However, the AMI-related functional activation was significantly weaker in diabetic patients (P = 0.001). Moreover, the expression of catalase was lower in CD133+PC from T2DM. Conclusions. Our results show that T2DM not only limits the abundance of CD133+PC following AMI, but also limits their activation. This might be explained by a lower resistance of CD133+PC to oxidative stress. Our data provide a possible explanation for the delayed postischaemic vascular healing and myocardial recovery in DM.

Aims Circulating progenitor cells (PC) may contribute to myocardial recovery following infarction. Growth factors including VEGF are produced during ischaemia and stimulate PC release and activation. In this study, we focused on the functional chemotactic response of PC to VEGF in subjects early after myocardial ischaemia. Methods and results Number and phenotype of PC were characterized using flow-cytometry. CD133+PC were isolated from peripheral blood using positive MACS isolation. The chemotactic response towards members of the VEGF family (VEGF-A, PlGF-1, and VEGF-E) was analysed in three groups: (i) early period following acute myocardial infarction (days 2–4) treated with primary PCI (AMI) ( n = 35), (ii) stable coronary artery disease (CAD) ( n = 35), and (iii) controls (CTR) ( n = 20). CD133+PC number was 2-fold higher in AMI when compared with CAD and CTR ( P = 0.0001), whereas CAD was not different from CTR. The chemotactic response of CD133+PC to VEGF-A, PlGF-1, and VEGF-E was significantly enhanced (2-fold) in AMI when compared with CAD ( P = 0.0001). While the increase of the VEGFR-1-mediated/PlGF-triggered response was rapid (2 days following infarction), the VEGFR-2-mediated/VEGF-E-triggered response was maximally increased on day 4 post-AMI, thus correlating with the kinetics of maximal inflammatory activation reflected by increased CRP levels ( P = 0.019). Conclusion The enhanced chemotactic response of CD133+PC following myocardial infarction represents a novel principle potentially involved in cardiovascular repair early after myocardial infarction. Acute inflammatory processes are closely associated with this increased cellular function.

Purpose The objective of the study was to systematically assess aortic inflammation in patients with granulomatosis with polyangiitis (GPA) using 18F-2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/CT. Methods Aortic inflammation was studied in PET/CT scans obtained from 21 patients with GPA; 14 patients with sarcoidosis were included as disease controls, 7 patients with stage I or II head and neck carcinoma ascertained during routine clinical practice were used as healthy controls (HC) and 5 patients with large vessel vasculitis (LVV) were used as positive controls. Aortic 18F-FDG uptake was expressed as the blood-normalized maximum standardized uptake value (SUVmax), known as the target to background ratio (mean TBRmax). Results The mean TBRmax (interquartile range) of the aorta in patients with GPA, sarcoidosis, HC and LVV were 1.75 (1.32–2.05), 1.62 (1.54–1.74), 1.29 (1.22–1.52) and 2.03 (1.67–2.45), respectively. The mean TBRmax was significantly higher in patients suffering from GPA or LVV compared to HC (p 0.9). Conclusion Patients suffering from GPA show marked aortic FDG uptake. Electronic supplementary material The online version of this article (doi:10.1007/s00259-015-3081-y) contains supplementary material, which is available to authorized users.

Sarcoidosis is a multisystem disease of unknown etiology characterized by the formation of noncaseating epithelioid-cell granulomas. We present a black female patient with severe cutaneous and systemic sarcoidosis. In the diagnostic work-up a F-18 FDG PET scan demonstrated the extensiveness of the disease. The scan was combined with a low-dose CT for attenuation correction and improvement of the localization of the identified abnormalities. The presented case showed that F-18 FDG PET scan is useful not only in the diagnostic work-up and the assessment of the extent of sarcoidosis activity but also in the follow-up.

Summary Background Establishing inflammatory activity in sarcoidosis patients with persistent disabling symptoms is important. Whole body F 18 -FDG PET/CT (PET) appeared to be a sensitive method to detect inflammatory activity in newly diagnosed symptomatic sarcoidosis. The aim was to assess the presence of inflammatory activity using PET in sarcoidosis patients with unexplained persistent disabling symptoms and the association between PET findings and serological inflammatory markers. Methods Sarcoidosis patients who underwent a PET between June 2005 and June 2010 ( n = 89), were retrospectively included. All PET scans were examined and positive findings were classified as thoracic and/or extrathoracic. As serological markers of inflammatory activity angiotensine-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), and neopterine were considered. Results In 65/89 (73%) of the studied patients PET was positive, 52 of them (80%) had serological signs of inflammatory activity. In 14/15 patients with a Chest X-ray stage IV PET was positive. In 80% of the PET positive patients extrathoracic inflammatory activity was found. Sensitivity of combined serological inflammatory markers for the presence of inflammatory activity as detected by PET was 80%, specificity 100%, positive predictive value 100%, negative predictive value 65%. Conclusions The majority of sarcoidosis patients with persistent disabling symptoms, even those with radiological stage IV, had PET positive findings with remarkably 80% extrathoracic lesions. In 20% PET was positive without signs of serological inflammatory activity. PET appeared to be of additional value to assess inflammatory activity in patients with persistent symptoms in the absence of signs of serological inflammatory activity and to detect extrathoracic lesions.

Purpose of review Nuclear medicine techniques have the capacity to investigate neuronal dysfunction at the synapse level. For instance, metaiodobenzylguanidine (MIBG) shows a similar uptake, storage and release as norepinephrine. Intravenously injected radiolabeled MIBG is able to reflect neuronal damage induced by inflammation and tumors. The purpose of this review is to evaluate the results and the limitation of these neuronal imaging techniques in patients with pulmonary and cardiac diseases and to give an opinion about the clinical value of these new diagnostic tools. Recent findings MIBG neuronal images of the lungs and heart can show heterogeneous distribution patterns with either diminished or increased MIBG uptake and/or washout. These changes reflect changes in endothelial integrity, neuronal innervations and clearance of norepinephrine. Interest in the role of neurotransmitter involvement and the relation between endothelial cell integrity and vascularization is growing and of utmost importance to understand the effect on pathophysiology of diseases. Summary At this moment, there is no added clinical value to routinely use MIBG scanning of the lungs and the heart. This is partly due to the many unresolved questions such as what actually happens and which factors influence MIBG uptake and washout under normal physiological circumstances. But the technique, if standardized and when dynamic time acquisition is performed with the latest equipment, such as PET and single photon emission computed tomography-computed tomography (SPECT-CT), has a tremendous potential. It can unravel upto now unknown relationships between innervation, vascularization and endothelial integrity. Other diagnostic tools such as MRI and CT do not have this capacity, so the future looks bright for these new neuronal imaging techniques.