The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy.

BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Brain imaging in children with neonatal cholestatic liver disease: A systematic review.

AIM: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development. METHODS: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools. RESULTS: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation. CONCLUSION: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment.

Low skeletal muscle mass and liver fibrosis in children with cerebral palsy.

The purpose of the study was to conduct a nutritional and metabolic assessment of children with cerebral palsy, including an investigation of liver status, body composition, and bone mineral density. In this cross-sectional study we included 22 children with cerebral palsy. By using ultrasound, transient elastography, dual x-ray absorptiometry (DXA) scan, blood samples, anthropometric measurements, and a three-day diet registration, the nutritional and metabolic status was evaluated. Liver fibrosis and steatosis were found in four patients (18.2%), all with severe motor impairments, low skeletal muscle mass, and epilepsy. All patients with liver involvement had normal liver-related blood samples. Decreased bone mineral density was found in 26.3%, and 91.0% had low skeletal muscle mass. Fat mass and muscle mass were significantly lower in the patients with severe motor impairments compared to the patients with less severe motor impairments. Within the children classified as 'underweight' or 'normal' according to body mass index, body fat determined by DXA scan was normal or high in 50% of these patients. CONCLUSIONS: This study is the first to report liver fibrosis and steatosis in children with cerebral palsy. Possible causes of liver fibrosis and/or steatosis are altered body composition with low skeletal muscle mass, decreased mobility and medical drug intake. Further investigations of liver involvement and risk factors are needed. WHAT IS KNOWN: • Children and adolescents with cerebral palsy are at risk of malnutrition and altered body composition, both of which can lead to fatty liver disease. • It is unknown whether children with cerebral palsy are at increased risk of metabolic disturbances such as fatty liver disease. WHAT IS NEW: • Altered body composition and low skeletal muscle mass, regardless of ambulation is present in 91% of the children with cerebral palsy. • Liver fibrosis and/or steatosis were found in 18.2% of the patients. Possible causes are altered body composition, decreased mobility and medical drug intake.

Metabolic assessment in children with neuromuscular disorders shows risk of liver enlargement, steatosis and fibrosis.

AIM: The aim of this study was to conduct a metabolic and nutritional assessment of children with neuromuscular disorders, including the investigation of the liver and bone mineral density. METHODS: In this observational study, we included 44 children with neuromuscular disorders. The nutritional status, bone health and liver were assessed by ultrasound, transient elastography, dual X-ray absorptiometry scan, blood samples, anthropometric measurements and 3-day diet registration. RESULTS: Liver involvement was found in 31.0%: liver enlargement in 7.1%, steatosis in 4.8%, fibrosis in 14.3% and liver enlargement together with steatosis or fibrosis was found in 4.8%. These changes were found in 9/23 patients with Duchenne muscular dystrophy, 4/9 patients with spinal muscular atrophy type II and 0/12 patients with other neuromuscular diagnoses. Low bone mineral density was found in 44.0% of the patients, though the majority used daily vitamin D and calcium supplements. Vitamin D insufficiency or deficiency was found in 22.6%. CONCLUSION: The metabolic assessment in children with neuromuscular disorders shows an increased risk of liver enlargement, steatosis and fibrosis. Possible causes are obesity, decreased mobility, low skeletal muscle mass and for a subgroup the use of glucocorticoids. The findings suggest that monitoring liver function should be part of the nutritional assessment in patients with neuromuscular disorders.

Joint EANM/SIOPE/RAPNO practice guidelines/SNMMI procedure standards for imaging of paediatric gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0.

Positron emission tomography (PET) has been widely used in paediatric oncology. 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most commonly used radiopharmaceutical for PET imaging. For oncological brain imaging, different amino acid PET radiopharmaceuticals have been introduced in the last years. The purpose of this document is to provide imaging specialists and clinicians guidelines for indication, acquisition, and interpretation of [18F]FDG and radiolabelled amino acid PET in paediatric patients affected by brain gliomas. There is no high level of evidence for all recommendations suggested in this paper. These recommendations represent instead the consensus opinion of experienced leaders in the field. Further studies are needed to reach evidence-based recommendations for the applications of [18F]FDG and radiolabelled amino acid PET in paediatric neuro-oncology. These recommendations are not intended to be a substitute for national and international legal or regulatory provisions and should be considered in the context of good practice in nuclear medicine. The present guidelines/standards were developed collaboratively by the EANM and SNMMI with the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group and the Response Assessment in Paediatric Neuro-Oncology (RAPNO) working group. They summarize also the views of the Neuroimaging and Oncology and Theranostics Committees of the EANM and reflect recommendations for which the EANM and other societies cannot be held responsible.

Baseline FDG PET/CT in free breathing versus deep inspiration breath-hold for pediatric patients with mediastinal lymphoma.

INTRODUCTION: The prospective TEDDI protocol investigates the feasibility of radiotherapy delivery in deep inspiration breath-hold (DIBH) for pediatric patients. To secure optimal radiotherapy planning, a diagnostic baseline FDG PET/CT in free breathing (FB) and DIBH was acquired. The anatomical changes in the mediastinum and the effect on PET metrics between the two breathing conditions were assessed for pediatric patients with mediastinal lymphoma. MATERIAL AND METHODS: Ten patients aged 5-17 were included and had a PET/CT in FB and DIBH. Metabolic active lymphoma volumes were manually delineated with a visually based segmentation method and the PET metrics were extracted. The anatomical lymphoma, lung and heart volumes were delineated on CT. RESULTS: The lung volume increased while the heart was displaced caudally and separated from the lymphoma in DIBH compared to FB. Both the anatomical and the metabolically active lymphoma volumes appeared different regarding shape and configuration in the two breathing conditions. The image quality of the DIBH PET was equal to the FB PET regarding interpretation and delineation of lymphoma lesions. All PET metrics increased on the DIBH PET compared to the FB PET with the highest increase observed for the maximum standardized uptake value (33%, range 7-56%). CONCLUSION: Diminished respiratory motion together with anatomical changes within the lymphoma increased all PET metrics in DIBH compared to FB. The anatomical changes observed in DIBH compared to FB are expected to reduce radiation doses to the heart and lungs in pediatric patients with mediastinal lymphoma referred for radiotherapy delivery in DIBH and, thereby, reduce their risk of late effects. TRIAL REGISTRATION: The Danish Ethical Committee (H-16035870, approved November 24th 2016), the Danish Data Protection Agency (2012-58-0004, approved 1 January 2017). Registered retrospectively at clinicaltrials.gov (NCT03315546, 20 October 2017).

Markers of obesity in Danish pediatric liver transplantation recipients.

BACKGROUND: Long-time survivors of pediatric liver transplantation have an increased incidence of the metabolic syndrome. Adult recipients have an increased risk of post-transplantation obesity; however, pediatric data are limited. METHODS: The study included 42 recipients of pediatric liver transplantation in Denmark, transplanted between 1990 and 2014. The study participants were examined with anthropometric measures, dual-energy X-ray scans and blood samples. From the anthropometric measures, body mass index (BMI) and BMI standard deviation score (SDS) were calculated. From the dual-energy X-ray scans, fat percent was assessed, and body fat mass index (BFMI) was calculated. RESULTS: The median age was 17.4 years (range 4.1-38.9) at the time of the study, and the median time since transplantation was 8.5 years (range 0.4-23.9). The prevalence of overweight and obesity was 31.0% based on BMI SDS (age below 18) and BMI (age 18 and above). When compared to the participants with normal weight, the participants with overweight and obesity had a higher BFMI (9.29 vs 5.57 kg/m2 , p < .001) and fat percent (38.35% vs 29.50%, p = .006). They had higher levels of total cholesterol (4.3 vs 3.6 mmol/L, p = .023) and low-density lipoprotein (2.5 vs 1.7, p = .015), and had had longer time since transplantation (15.6 vs 8.5 years respectively, p = .045). CONCLUSIONS: Long-time survivors of pediatric liver transplantation have a higher BMI or BMI SDS than the general pediatric population. The obesity is characterized by a higher BFMI, fat percent, and cholesterols levels, when compared to recipients without overweight or obesity.

Unexplained fever in children-Benefits and challenges of FDG-PET/CT.

AIM: To explore [fluorine-18]-fluoro-2-deoxy-d-glucose positron-emission-tomography/computed tomography (18 FDG-PET/CT) in patients where standard investigations were non-diagnostic. METHODS: We reviewed medical records of previously healthy children who had 18 FDG-PET/CT performed at Copenhagen University Hospital in 2015-2020 due to unexplained fever. RESULTS: Thirty-five of 819 paediatric 18 FDG-PET/CT were performed due to unexplained fever. The final diagnoses were malignancy (11%), infections (23%), inflammatory diseases (43%) and miscellaneous (26%). 18 FDG-PET/CT was diagnostic in six cases with Takayasu's arteritis, tuberculosis, Langerhans cell histiocytosis and Ewing sarcoma. Sixteen cases had focal 18 FDG-uptake, but 18 FDG-PET/CT could only differentiate malignancy, infection and inflammation in three cases. In six cases with inflammatory diseases and no focal signs, PET/CT was normal except increased non-specific 18 FDG-uptake in bone marrow and spleen in five cases. One case was false positive (suspicion of appendicitis) and two false negative (leukaemia and inflammatory disease). CONCLUSION: 18 FDG-PET/CT was diagnostic, or contributed to the diagnosis, in several children with unexplained fever referred to a tertiary centre. Challenges comprised (i) only increased non-specific 18 FDG-uptake in bone marrow and spleen in half of cases with inflammatory diseases, (ii) no differentiation between complicated infections, malignancy and inflammation in most cases with focal processes and (iii) a small risk of false positive and false negative results.

Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT) for the detection of bone, lung, and lymph node metastases in rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma and can emerge throughout the whole body. For patients with newly diagnosed RMS, prognosis for survival depends on multiple factors such as histology, tumour site, and extent of the disease. Patients with metastatic disease at diagnosis have impaired prognosis compared to those with localised disease. Appropriate staging at diagnosis therefore plays an important role in choosing the right treatment regimen for an individual patient. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a functional molecular imaging technique that uses the increased glycolysis of cancer cells to visualise both structural information and metabolic activity. 18F-FDG-PET combined with computed tomography (CT) could help to accurately stage the extent of disease in patients with newly diagnosed RMS. In this review we aimed to evaluate whether 18F-FDG-PET could replace other imaging modalities for the staging of distant metastases in RMS. OBJECTIVES: To determine the diagnostic accuracy of 18F-FDG-PET/CT imaging for the detection of bone, lung, and lymph node metastases in RMS patients at first diagnosis. SEARCH METHODS: We searched MEDLINE in PubMed (from 1966 to 23 December 2020) and Embase in Ovid (from 1980 to 23 December 2020) for potentially relevant studies. We also checked the reference lists of relevant studies and review articles; scanned conference proceedings; and contacted the authors of included studies and other experts in the field of RMS for information about any ongoing or unpublished studies. We did not impose any language restrictions. SELECTION CRITERIA: We included cross-sectional studies involving patients with newly diagnosed proven RMS, either prospective or retrospective, if they reported the diagnostic accuracy of 18F-FDG-PET/CT in diagnosing lymph node involvement or bone metastases or lung metastases or a combination of these metastases. We included studies that compared the results of the 18F-FDG-PET/CT imaging with those of histology or with evaluation by a multidisciplinary tumour board as reference standard. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and methodological quality assessement according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We analysed data for the three outcomes (nodal involvement and lung and bone metastases) separately. We used data from the 2 × 2 tables (consisting of true positives, false positives, true negatives, and false negatives) to calculate sensitivity and specificity in each study and corresponding 95% confidence intervals. We did not consider a formal meta-analysis to be relevant because of the small number of studies and substantial heterogeneity between studies. MAIN RESULTS: Two studies met our inclusion criteria. The diagnostic accuracy of 18F-FDG-PET/CT was reported in both studies, which included a total of 36 participants. We considered both studies to be at high risk of bias for the domain reference standard. We considered one study to be at high risk of bias for the domain index test and flow and timing. Sensitivity and specificity of 18F-FDG-PET/CT for the detection of bone metastases was 100% in both studies (95% confidence interval (CI) for sensitivity was 29% to 100% in study one and 40% to 100% in study two; 95% CI for specificity was 83% to 100% in study one and 66% to 100% in study two). The reported sensitivity of 18F-FDG-PET/CT for the detection of lung metastases was not calculated since only two participants in study two showed lung metastases, of which one was detected by 18F-FDG-PET/CT. Reported specificity was 96% in study one (95% CI 78% to 100%) and 100% (95% CI 72% to 100%) in study two. The reported sensitivity for the detection of nodal involvement was 100% (95% CI 63% to 100% in study one and 40% to 100% in study two); the reported specificity was 100% (95% CI 78% to 100%) in study one and 89% (95% CI 52% to 100%) in study two. AUTHORS' CONCLUSIONS: The diagnostic accuracy of 18F-FDG-PET/CT for the detection of bone, lung, and lymph node metastases was reported in only two studies including a total of only 36 participants with newly diagnosed RMS. Because of the small number of studies (and participants), there is currently insufficient evidence to reliably determine the diagnostic accuracy of 18F-FDG-PET/CT in the detection of distant metastases. Larger series evaluating the diagnostic accuracy of 18F-FDG-PET/CT for the detection of metastases in patients with RMS are necessary.

Nonpharmacological interventions to reduce sedation/general anaesthesia in paediatric patients undergoing magnetic resonance imaging: A systematic review and meta-analysis protocol.

BACKGROUND: Magnetic resonance imaging is frequently used in paediatrics and requires the child/adolescent to remain still for 45 min or more. The long and narrow scanner gantry makes loud noises and may cause anxiety. To complete the procedure, children and adolescents are often sedated or receive general anaesthesia. Our primary aim is to determine whether nonpharmacological interventions designed to mentally prepare, support or distract children, and adolescents are effective in reducing the need for sedation and general anaesthesia. METHODS: We will conduct a systematic review with meta-analysis by searching the following electronic databases: Ovid MEDLINE, CINAHL, Embase and CENTRAL, as well as databases for ongoing trials. Eligibility criteria are based on the participants, intervention, comparator and outcome (PICO) framework. We will include intervention studies with comparator group(s) with no restriction on date. Two reviewers will independently screen titles/abstracts, and three reviewers will assess the full texts of potentially relevant studies. Data will be extracted, and the methodological quality will be assessed using Cochrane risk of bias tools. If the data allow, we will perform a meta-analysis using a random effects model on the primary outcome, sedation/general anaesthesia. A narrative synthesis will supplement the statistical analysis. Quality of evidence for the primary outcome will be assessed using the grading of recommendations, assessment, development and evaluations (GRADE) approach. DISCUSSION: Our findings will provide directions for future research and may guide clinicians in terms of which type(s) of intervention(s) to implement to reduce the use of sedation/general anaesthesia during paediatric magnetic resonance imaging.

European guideline for imaging in paediatric and adolescent rhabdomyosarcoma - joint statement by the European Paediatric Soft Tissue Sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society of Paediatric Radiology.

Appropriate imaging is essential in the treatment of children and adolescents with rhabdomyosarcoma. For adequate stratification and optimal individualised local treatment utilising surgery and radiotherapy, high-quality imaging is crucial. The paediatric radiologist, therefore, is an essential member of the multi-disciplinary team providing clinical care and research. This manuscript presents the European rhabdomyosarcoma imaging guideline, based on the recently developed guideline of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) Imaging Committee. This guideline was developed in collaboration between the EpSSG Imaging Committee, the Cooperative Weichteilsarkom Studiengruppe (CWS) Imaging Group, and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR). MRI is recommended, at diagnosis and follow-up, for the evaluation of the primary tumour and its relationship to surrounding tissues, including assessment of neurovascular structures and loco-regional lymphadenopathy. Chest CT along with [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT or PET/MRI are recommended for the detection and evaluation of loco-regional and distant metastatic disease. Guidance on the estimation of treatment response, optimal long-term follow-up, technical imaging settings and standardised reporting are described. This European imaging guideline outlines the recommendations for imaging in children and adolescents with rhabdomyosarcoma, with the aim to harmonise imaging and to advance patient care.

Liver fibrosis in patients with tetralogy of Fallot, an unrecognised complication?

OBJECTIVES: Improved survival has led to a growing population of adults with congenital heart disease (CHD), followed by numerous reports of late complications. Liver disease is a known complication in some patients, with most studies focusing on Fontan associated liver disease. Whether liver disease also exists in other patients with CHD is not fully investigated. Elevated central venous pressure is considered pivotal in the development of liver disease in Fontan associated liver disease, and other patients with alterations in central venous pressure may also be at risk for developing liver fibrosis. We wanted to see if liver fibrosis is present in patients with tetralogy of Fallot. Many patients with tetralogy of Fallot have severe pulmonary regurgitation, which can lead to elevated central venous pressure. Patients with tetralogy of Fallot may be at risk of developing liver fibrosis. MATERIALS AND METHODS: Ten patients (24-56 years) with tetralogy of Fallot and pulmonary regurgitation were investigated for liver fibrosis. All patients were examined with magnetic resonance elastography of liver, hepatobiliary iminodiacetic acid scan, indocyanine green elimination by pulse spectrophotometry, elastography via FibroScan, abdominal ultrasound including liver elastography, and blood samples including liver markers. RESULTS: Three out of ten patients had findings indicating possible liver fibrosis. Two of these had a liver biopsy performed, which revealed fibrosis stage 1 and 2, respectively. The same three patients had an estimated elevated central venous pressure in previous echocardiograms. CONCLUSIONS: Mild liver fibrosis was present in selected patients with tetralogy of Fallot and may be related to elevated central venous pressure.

Planar scan vs. SPECT/low-dose CT for estimating split renal function by 99mTc-DMSA scintigraphy in children.

In the present study, we compared estimates of split renal function (SRF) in paediatric patients of various diagnostic subgroups by 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy using either geometric mean (GM) based on planar scans or a volume of interest (VOI)-based analysis on single photon emission tomography combined with low-dose CT (SPECT/ldCT). Two experienced physicians blinded to patient diagnosis retrospectively analysed all paediatric 99mTc-DMSA scintigraphies that were conducted in our department between 2011 and 2016 and which included both a planar scan and SPECT/ldCT. All scintigraphies were performed on either a Phillips Precedence 16 slice CT or a Siemens Symbia 16 slice CT. SRF was estimated from planar scintigraphy using the geometric mean (GM), while the VOI-based analysis (VBA) was used for kidney segmentation on SPECT/ldCT. RESULTS: A total of 68 scintigraphies were included. A Bland-Altman plot-based analysis showed a bias for SRF of 2.1% with limits of agreement from - 7.5 to + 11.7% for the whole data set but showed larger differences between the two methods outside the normal range of 45-55%. In the GM-based SRF analyses, 29 cases were found to be outside the normal range, and in seven of these, VBA showed normal SRF. In the remaining 39 cases, VBA showed an abnormal SRF in only one case. CONCLUSION: Approximately a quarter of planar DMSA scintigraphies that show an abnormal SRF in paediatric patients may be normal when assessed by SPECT/ldCT, which likely reflects underestimation of the kidney with the poorest function when assessed by GM due to the lack of attenuation correction. Planar scans that show an abnormal SRF in paediatric patients should thus preferably be supplemented by SPECT/ldCT.

Minimally invasive assessment of hepatic function in children with indocyanine green elimination: a validation study.

Objectives: Pediatric liver disease (PLD) covers a variety of etiologies and severities, from mild temporary illness to diseases with fatal outcomes. There is a demand for minimally invasive and reliable measures for assessment of the severity of PLD. Indocyanine green (ICG) elimination kinetics to estimate hepatic function has been used in adults for decades, however, due to invasiveness, the use in PLD is still limited. The aim of the present study was to evaluate minimally invasive estimation of ICG elimination by pulse spectrophotometry (ICGLi), in comparison with traditional spectrophotometry using serial blood samples (ICGbs). Methods: One hundred children aged 0-18 years were included in the study. ICG elimination kinetics was measured with ICGLi and ICGbs, and results compared by failure rates, mean difference, limits of agreement, Bland Altman plots and linear regression analysis. Plasma disappearance rates (PDRLi and PDRbs) were used for comparison. Results: One hundred and twelve simultaneous measurements in 87 patients were performed successfully. Mean difference for PDR (%/min) was 3.58 (95% CI 2.69; 4.47). Limits of agreement were -5.06; 12.22. A linear correlation between the two methods with a regression coefficient of 0.83 (SE 0.02 95% CI 0.80; 0.87) was found. For conversion we computed the following equation; PDRbs = 0.83 × PDRLi. Conclusions: The present study shows that ICG PDR can be obtained by a minimally invasive method and thus replace measures by serial blood samples in children with liver disease of different etiologies and severities. However, a systematic relative difference between the two methods exists. Our proposed correction factor needs to be validated in larger cohorts.

Risk markers for later cardiovascular diseases in liver-transplanted children and adolescents.

BACKGROUND: Increased risk of cardiovascular diseases is well described after adult liver transplantation, whereas the risk in the pediatric population still is discussed. The aim of this study was to investigate the prevalence of metabolic syndrome in pediatric liver transplant recipients and whether measurements of carotid intima media thickness and pulse wave velocity were increased compared to healthy controls. METHODS: We included 42 pediatric liver transplantation recipients and examined them for markers of metabolic syndrome, liver fibrosis measured by shear wave velocity, body fat measured by DXA scans and carotid intima-media thickness, and pulse wave velocity (n = 41 for the carotid scans). The ultrasound measurements of carotid intima-media thickness and pulse wave velocity were also conducted on 82 healthy children and adolescents matched on height and age, respectively. RESULTS: Participants had a median age of 13.03 years, and median time since transplantation was 8.54 years. Compared to healthy controls, liver-transplanted patients had significantly increased intima-media thickness measurements in both control groups whereas there was no significant difference with regard to pulse wave velocity. Two patients (6.25%) were diagnosed with metabolic syndrome. Within the group of liver-transplanted pediatric patients, only elevated body mass index was associated with elevated carotid intima-media thickness measurement. Elevated pulse wave velocity was only associated with abdominal obesity. Factors not significantly correlated with either were age, sex, metabolic syndrome, hyperglycemia, triglycerides, years since transplantation, fibrosis of the liver, body fat content, smoking habits, HDL cholesterol levels, hypertension, and mono-drug versus multi-drug therapies. CONCLUSION: Pediatric liver transplant recipients do have an increased risk of increased carotid intima-media thickness.

A Randomized Seven-Year Study on Performance of the Stemmed Metal M2a-Magnum and Ceramic C2a-Taper, and the Resurfacing ReCap Hip Implants.

BACKGROUND: The large-diameter metal-on-metal hip prostheses were expected to have low wear and reduced dislocation rate compared to the traditional metal-on-polyethylene implants. We compare 2 such prostheses, the ReCap resurfacing implant and the M2a-Magnum stemmed implant, with the C2a ceramic-on-ceramic stemmed implant as to clinical performance, serum concentrations of prosthesis metals, and the durability of the implants in a randomized, controlled clinical trial at 7 years of follow-up. METHODS: All included patients had osteoarthritis. Preoperatively, the size of the implants was estimated from a magnetic resonance imaging (MRI) scan. Follow-up data included serum cobalt and chromium concentrations, Oxford and Harris Hip Scores, leg press and abduction force, 6-minute walk distance, WOMAC and SF-36 self-assessment scores, and from the 7th postoperative year also ultrasonography (US) examination of the soft tissue adjacent to the implant as well as MRI with metal artifact reduction sequence (MARS-MRI) when indicated. RESULTS: One hundred fifty-two hips in 146 patients were included. The serum cobalt and chromium concentrations were significantly higher for the 2 metal-on-metal prostheses than for the ceramic-on-ceramic, with the M2a-Magnum as the highest. No significant difference was found between the groups concerning physical performance measurements and scores as well as dislocations and prosthesis survival. Five revisions were done and concerned all groups, for reasons of pain, high serum cobalt and chromium concentrations, cystic fluid collection around the joint, and infection. Metal concentrations, US, and MARS-MRI contributed to the decision making regarding prosthesis revision. CONCLUSION: Metal concentrations were significantly higher for the metal-on-metal prostheses than for the ceramic-on-ceramic. The clinical performance was good in all 3 prosthesis groups. Metal concentrations, US, and MARS-MRI findings were of use to identify hips needing revision. ID Number in ClinicalTrials.gov PRS: NCT00284674.

Use of PET/CT instead of CT-only when planning for radiation therapy does not notably increase life years lost in children being treated for cancer.

BACKGROUND: PET/CT may be more helpful than CT alone for radiation therapy planning, but the added risk due to higher doses of ionizing radiation is unknown. OBJECTIVE: To estimate the risk of cancer induction and mortality attributable to the [F-18]2-fluoro-2-deoxyglucose (FDG) PET and CT scans used for radiation therapy planning in children with cancer, and compare to the risks attributable to the cancer treatment. MATERIALS AND METHODS: Organ doses and effective doses were estimated for 40 children (2-18 years old) who had been scanned using PET/CT as part of radiation therapy planning. The risk of inducing secondary cancer was estimated using the models in BEIR VII. The prognosis of an induced cancer was taken into account and the reduction in life expectancy, in terms of life years lost, was estimated for the diagnostics and compared to the life years lost attributable to the therapy. Multivariate linear regression was performed to find predictors for a high contribution to life years lost from the radiation therapy planning diagnostics. RESULTS: The mean contribution from PET to the effective dose from one PET/CT scan was 24% (range: 7-64%). The average proportion of life years lost attributable to the nuclear medicine dose component from one PET/CT scan was 15% (range: 3-41%). The ratio of life years lost from the radiation therapy planning PET/CT scans and that of the cancer treatment was on average 0.02 (range: 0.01-0.09). Female gender was associated with increased life years lost from the scans (P < 0.001). CONCLUSION: Using FDG-PET/CT instead of CT only when defining the target volumes for radiation therapy of children with cancer does not notably increase the number of life years lost attributable to diagnostic examinations.

Clinical Performance of the ASR and ReCap Resurfacing Implants­7 Years Follow-Up.

We perform a non-randomized, consecutive pilot study on the ASR and ReCap resurfacing hip implants and have completed 7 years follow-up. Forty-six non-osteoporotic patients with hip osteoarthritis and anatomical conditions suitable for resurfacing were divided into 2 equal groups and operated sequentially, starting with the ASR implants. Sixteen patients operated with ASR and 19 patients with ReCap have been followed-up. There were no significant differences between the two groups preoperatively as to physical function, pain, or femoral BMD. The serum concentrations of cobalt and chromium were higher in the ASR group from 1/2 to 7 years postoperatively. Five of 16 ASR implants have been revised, and none of the ReCap implants. BMD below the femoral component increased in both groups.

Performing [18F]MFBG Long-Axial-Field-of-View PET/CT Without Sedation or General Anesthesia for Imaging of Children with Neuroblastoma.

Meta-[123I]iodobenzylguanidine ([123I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [123I]MIBG with the new PET tracer meta-[18F]fluorobenzylguanidine ([18F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [18F]MFBG LAFOV PET/CT and compare it with [123I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [123I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [123I]MIBG scintigraphy and SPECT/low-dose CT, [18F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [123I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [18F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [18F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [123I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [18F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [18F]MFBG LAFOV PET/CT compared with [123I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [18F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma.