Publications by authors named "Lise Borgwardt"

36 Publications

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

Eur J Nucl Med Mol Imaging 2022 May 10. Epub 2022 May 10.

Nuclear Medicine Unit, Department of Medicine - DIMED, University Hospital of Padova, Padua, Italy.

Positron emission tomography (PET) has been widely used in paediatric oncology. 2-Deoxy-2-[F]fluoro-D-glucose ([F]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 [F]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 [F]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.
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http://dx.doi.org/10.1007/s00259-022-05817-6DOI Listing
May 2022

Transient congenital hyperinsulinism and hemolytic disease of a newborn despite rhesus D prophylaxis: a case report.

J Med Case Rep 2021 Nov 26;15(1):573. Epub 2021 Nov 26.

Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Background: In neonates, rhesus D alloimmunization despite anti-D immunoglobulin prophylaxis is rare and often unexplained. Rhesus D alloimmunization can lead to hemolytic disease of the newborn with anemia and unconjugated hyperbilirubinemia. In past reports, transient congenital hyperinsulinism has been described as a rare complication of rhesus D alloimmunization. Our case report illustrates that rhesus D alloimmunization can result in a pseudosyndrome with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia, despite correctly administered anti-D immunoglobulin prophylaxis.

Case Presentation: We report of a 36-year-old, Caucasian gravida 1, para 1 mother with A RhD negative blood type who received routine antenatal anti-D immunoglobulin prophylaxis. Her full term newborn boy presented with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia up to 295 µmol/L (ref. < 9), accounting for 64% of the total bilirubin. Syndromic congenital hyperinsulinism was suspected. Examinations showed a positive direct antiglobulin test, initially interpreted as caused by irregular antibodies; diffuse congenital hyperinsulinism by 18F-DOPA positron emission tomography/computed tomography scan; normal genetic analyses for congenital hyperinsulinism; mildly elevated liver enzymes; delayed, but present bile excretion by Tc99m-hepatobiliary iminodiacetic acid scintigraphy; and cholestasis and mild fibrosis by liver biopsy. The maternal anti-D titer was 1:16,000 day 20 postpartum. Y-chromosome material in the mother's blood could not be identified. This could, however, not exclude late intrapartum fetomaternal hemorrhage as the cause of immunization. No causative genetic findings were deetrmined by trio whole exome sequencing. The child went into clinical remission after 5.5 months.

Conclusion: Our case demonstrates that rhesus D alloimmunization may present as a pseudosyndrome with transient congenital hyperinsulinism, anemia, and inspissated bile syndrome with conjugated hyperbilirubinaemia, despite anti-D immunoglobulin prophylaxis, possibly due to late fetomaternal hemorrhage.
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http://dx.doi.org/10.1186/s13256-021-03167-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626963PMC
November 2021

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

Cochrane Database Syst Rev 2021 11 9;11:CD012325. Epub 2021 Nov 9.

Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.

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 (F-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. F-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 F-FDG-PET could replace other imaging modalities for the staging of distant metastases in RMS.

Objectives: To determine the diagnostic accuracy of F-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 F-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 F-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 F-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 F-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 F-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 F-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 F-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 F-FDG-PET/CT in the detection of distant metastases. Larger series evaluating the diagnostic accuracy of F-FDG-PET/CT for the detection of metastases in patients with RMS are necessary.
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http://dx.doi.org/10.1002/14651858.CD012325.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577863PMC
November 2021

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

Acta Oncol 2022 Feb 17;61(2):239-246. Epub 2021 Sep 17.

Section of Radiotherapy, Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

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 24 2016), the Danish Data Protection Agency (2012-58-0004, approved 1 January 2017). Registered retrospectively at clinicaltrials.gov (NCT03315546, 20 October 2017).
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http://dx.doi.org/10.1080/0284186X.2021.1974554DOI Listing
February 2022

Comparison of nuclear imaging techniques and volumetric imaging for the prediction of postoperative mortality and liver failure in patients undergoing localized liver-directed treatments: a systematic review.

EJNMMI Res 2021 Aug 21;11(1):80. Epub 2021 Aug 21.

Department of Nuclear Medicine, Aalborg University Hospital, Hobrovej 18-22, 9100, Aalborg, Denmark.

Background/aims: Although volumetric imaging by computed tomography (CT) is the gold standard for preoperative assessment of the future liver remnant, nuclear imaging studies have shown promising data. This systematic review summarized the results from trials investigating volumetric and nuclear medicine imaging for the prediction of postoperative mortality and liver failure (LF).

Methods: MEDLINE and Web of Science were searched for papers investigating nuclear imaging methods for the prediction of postoperative clinical outcomes in patients undergoing local, liver-directed treatments. Only papers investigating both preoperative nuclear imaging and CT or magnetic resonance imaging (MR) for the prediction of postoperative mortality and/or LF were included.

Results: Twenty-five trials were qualified for this review. All trials but two used technetium-based tracers for the nuclear imaging examination. Four papers used MR imaging and the remaining used CT for the volumetric evaluation. Overall, the studies were heterogeneous both in terms of methodology and imaging technique. Of the thirteen studies reporting on postoperative mortality, most were descriptive without detailed diagnostic data. A few with detailed data found that nuclear imaging had better predictive value than volumetric imaging. Nineteen studies investigated the prediction of postoperative LF of which seven papers investigated the predictive value of both modalities in multivariable regression analysis. Two papers found that only nuclear imaging parameters were predictive of LF, one paper found that the CT parameter was predictive, and four papers found that combined nuclear and CT/MR imaging parameters were predictive of LF.

Conclusion: Both methodologies were useful in the preoperative assessment of patients scheduled for liver interventions, especially in combination, but nuclear imaging demonstrated better predictive value for postoperative mortality and LF in a few trials. The overall technical and methodological heterogeneity of the included studies complicates the ability to directly compare the clinical utility of the two imaging techniques.
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http://dx.doi.org/10.1186/s13550-021-00816-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380203PMC
August 2021

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.

Pediatr Radiol 2021 09 17;51(10):1940-1951. Epub 2021 Jun 17.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

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.
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http://dx.doi.org/10.1007/s00247-021-05081-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426307PMC
September 2021

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

Acta Anaesthesiol Scand 2021 Oct 27;65(9):1254-1258. Epub 2021 May 27.

Children's Hospital Copenhagen and Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1111/aas.13851DOI Listing
October 2021

Eosinophilic Cystitis Presenting as Possible Pediatric Rhabdomyosarcoma in Conventional Imaging Including F-FDG-PET/CT/MRI-A Rare Case.

Diagnostics (Basel) 2021 Apr 8;11(4). Epub 2021 Apr 8.

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.

Eosinophilic cystitis (EC) is a relatively rare, but benign inflammatory bladder disease compared to that of the malignant pediatric rhabdomyosarcoma (RMS), in which it can be mimicking on initial suspicion. The origin, symptoms and findings of both EC and RMS are still discussed and hence, lead to the challenge in distinguishing them by cystoscopy and several image modalities. We present a case in which cross-sectional imaging modalities including fluorine-18-fluro-2-deoxy-D-glucose (F-FDG)-positron emission tomography (PET) / computed tomography (CT) / magnetic resonance imaging (MRI) (F-FDG-PET/CT/MRI (The imaging modality F-FDG-PET/CT/MRI referring to two continuous scans scanned on the same F-FDG-tracer dose for both the whole-body F-FDG-PET/CT and the regional F-FDG-PET/MRI of the pelvis.)) raised suspicion of RMS. Hence, the final diagnosis of EC was established by repeated histopathology. It is important to have EC in mind when seeking differential diagnosis of malignant diseases like RMS in order to provide the correct treatment for the patient and highly homogenously increased F-FDG-uptake should raise the suspicion of EC as a differential diagnosis. Furthermore, F-FDG-uptake rate is suggested as a future potential biomarker for monitoring of therapeutic response in eosinophilic inflammatory diseases, thus more research on this topic is needed.
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http://dx.doi.org/10.3390/diagnostics11040672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068401PMC
April 2021

Diagnostic accuracy and clinical impact of [18F]FET PET in childhood CNS tumors.

Neuro Oncol 2021 12;23(12):2107-2116

Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Background: Central nervous system (CNS) tumors cause the highest death rates among childhood cancers, and survivors frequently have severe late effects. Magnetic resonance imaging (MRI) is the imaging modality of choice, but its specificity can be challenged by treatment-induced signal changes. In adults, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET can assist in interpreting MRI findings. We assessed the clinical impact and diagnostic accuracy of adding [18F]FET PET to MRI in children with CNS tumors.

Methods: A total of 169 [18F]FET PET scans were performed in 97 prospectively and consecutively included patients with known or suspected childhood CNS tumors. Scans were performed at primary diagnosis, before or after treatment, or at relapse.

Results: Adding [18F]FET PET to MRI impacted clinical management in 8% [95% confidence interval (CI): 4%-13%] of all scans (n = 151) and in 33% [CI: 17%-53%] of scans deemed clinically indicated due to difficult decision making on MRI alone (n = 30). Using pathology or follow-up as reference standard, the addition of [18F]FET PET increased specificity (1.00 [0.82-1.00] vs 0.48 [0.30-0.70], P = .0001) and accuracy (0.91 [CI: 0.87-0.96] vs 0.81 [CI: 0.75-0.89], P = .04) in 83 treated lesions and accuracy in 58 untreated lesions (0.96 [CI: 0.91-1.00] vs 0.90 [CI: 0.82-0.92], P < .001). Further, in a subset of patients (n = 15) [18F]FET uptake correlated positively with genomic proliferation index.

Conclusions: The addition of [18F]FET PET to MRI helped discriminate tumor from non-tumor lesions in the largest consecutive cohort of pediatric CNS tumor patients presented to date.
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http://dx.doi.org/10.1093/neuonc/noab096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643444PMC
December 2021

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

Cardiol Young 2021 Nov 15;31(11):1796-1806. Epub 2021 Mar 15.

Department of Gastroenterology and Hepatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1017/S1047951121000901DOI Listing
November 2021

Interrater Reliability of Tc-DMSA Scintigraphy Performed as Planar Scan vs. SPECT/Low Dose CT for Diagnosing Renal Scarring in Children.

Diagnostics (Basel) 2020 Dec 17;10(12). Epub 2020 Dec 17.

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Tc-dimercaptosuccinic acid (DMSA) scintigraphy is currently the method of choice for assessing renal scarring in children, but it is not established whether conducting the scan as a single photon emission tomography combined with low-dose CT (SPECT/ldCT) scan provides additional diagnostic benefits when compared to conventional planar scintigraphy. In the present study, we evaluated the interrater reliability of DMSA SPECT/ldCT vs. planar DMSA scintigraphy for diagnosing renal scarring.

Methods: Two nuclear medicine physicians blinded to patient data retrospectively analysed all paediatric Tc-DMSA scintigraphes that were conducted in our department for the assessment of post pyelonephritis renal scarring between 2011 and 2016. All scintigraphies included both a planar scan and SPECT/ldCT, and were performed on either a Phillips Precedence 16 slice CT or a Siemens Symbia 16 slice CT. The readers were blinded to each other's readings and to patient data, and assessed all scans dichotomously for evidence of renal scarring. For each scan, the readers further noted if they were confident in their interpretation.

Results: A total of 46 pairs of planar SPECT/ldCT DMSA scans were included. The readers were unconfident about their interpretation of 40% of the planar scans and 5% of the SPECT/ldCT scans. The interrater agreement rate was 72% for planar scans and 91% for SPECT/ldCT, and the corresponding Cohen's kappa values were 0.38 and 0.79.

Conclusion: DMSA SPECT/ldCT is associated with higher reader confidence and interrater reliability than conventional planar DMSA scintigraphy for the assessment of post pyelonephritis renal scarring in children.
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http://dx.doi.org/10.3390/diagnostics10121101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766934PMC
December 2020

SNMMI Procedure Standard/EANM Practice Guideline on Pediatric F-FDG PET/CT for Oncology 1.0.

J Nucl Med 2021 01;62(1):99-110

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

PREAMBLEThe Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association founded in 1985 to facilitate communication worldwide among individuals pursuing clinical and academic excellence in nuclear medicine. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.The SNMMI and EANM will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process, entailing extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents, and are not inflexible rules or requirements of practice. They are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI and the EANM cautions against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question.The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that action differing from what is laid out in the standards/guidelines, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the standards/guidelines.The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/guidelines will not ensure a successful outcome. All that should be expected is that the practitioner follows a reasonable course of action, based on their level of training, the current knowledge, the available resources, and the needs/context of the particular patient being treated.PET and computerized tomography (CT) have been widely used in oncology. F-FDG is the most common radiotracer used for PET imaging. The purpose of this document is to provide imaging specialists and clinicians guidelines for recommending, performing, and interpreting F-FDG PET/CT in pediatric patients in oncology. There is not a high level of evidence for all recommendations suggested in this paper. These recommendations represent the expert opinions of experienced leaders in this field. Further studies are needed to have evidence-based recommendations for the application of F-FDG PET/CT in pediatric oncology. These recommendations should be viewed in the context of good practice of nuclear medicine and are not intended to be a substitute for national and international legal or regulatory provisions.
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http://dx.doi.org/10.2967/jnumed.120.254110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8679588PMC
January 2021

Nuclear imaging methods for the prediction of postoperative morbidity and mortality in patients undergoing localized, liver-directed treatments: a systematic review.

EJNMMI Res 2020 Sep 4;10(1):101. Epub 2020 Sep 4.

Department of Clinical Medicine, University of Aalborg, Sdr. Skovvej 15, DK-9000, Aalborg, Denmark.

Background: Several nuclear imaging methods may predict postoperative liver function and outcome, but none has achieved recommendations in clinical guidelines. The purpose of this systematic review was to summarize the existing knowledge on this topic.

Methods: MEDLINE and Web of Science were searched for studies investigating nuclear medicine imaging methods for the prediction of postoperative liver function in patients undergoing localized, liver-directed treatments. The postoperative endpoints were clinical outcome (morbidity and mortality) as well as measures of postoperative liver function, e.g., liver function assessed by biochemical tests or nuclear imaging.

Results: A total of 1352 references were identified, of which 82 fulfilled the eligibility criteria and were included in the review. Most studies (n = 63) were retrospective studies. The vast majority of studies assessed [Tc]Tc-galactosyl serum albumin (GSA) (n = 57) and [Tc]Tc-mebrofenin (n = 19). Liver resection was entirely or partly major (involved at least three segments) in 78 reports. There were notable variations in the research methodology, e.g., image acquisition, imaging variables, and endpoints. Thirty-seven studies reported on postoperative mortality, of which most reported descriptive data at the patient level. Of the four reports that performed multivariate analyses, two showed significant predictive results of isotope-based preoperative tests. Fifty-two papers presented data on postoperative liver failure. Multivariate predictive analyses were performed in eighteen trials, of which fifteen showed the significant value of nuclear medicine tests.

Conclusion: There is sparse evidence supporting the significant value of nuclear medicine imaging methods in predicting postoperative mortality. In contrast, a notable number of trials showed a significant prediction of liver failure in multivariate analyses. The research methodology was heterogeneous and exploratory in most trials. Documentation of nuclear medicine tests in this setting awaits the results of properly designed, prospective trials with the standardization of both the nuclear medicine test and endpoints.
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http://dx.doi.org/10.1186/s13550-020-00687-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474046PMC
September 2020

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

Eur J Nucl Med Mol Imaging 2020 03 15;47(3):729-733. Epub 2019 Nov 15.

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, København Ø, Denmark.

In the present study, we compared estimates of split renal function (SRF) in paediatric patients of various diagnostic subgroups by Tc-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 Tc-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.
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http://dx.doi.org/10.1007/s00259-019-04575-2DOI Listing
March 2020

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

Scand J Gastroenterol 2019 Apr 29;54(4):485-491. Epub 2019 Mar 29.

e Department of Clinical Physiology, Nuclear Medicine and PET , Copenhagen University Hospital, Rigshospitalet , Copenhagen Ø , Denmark.

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). 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. 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. 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.
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http://dx.doi.org/10.1080/00365521.2019.1591497DOI Listing
April 2019

Early Postoperative F-FET PET/MRI for Pediatric Brain and Spinal Cord Tumors.

J Nucl Med 2019 08 25;60(8):1053-1058. Epub 2019 Jan 25.

Department of Clinical Physiology, Nuclear Medicine, and PET, Copenhagen University Hospital, Rigshospitalet, Denmark.

Complete resection is the treatment of choice for most pediatric brain tumors, but early postoperative MRI for detection of residual tumor may be misleading because of MRI signal changes caused by the operation. PET imaging with amino acid tracers in adults increases the diagnostic accuracy for brain tumors, but the literature in pediatric neurooncology is limited. A hybrid PET/MRI system is highly beneficial in children, reducing the number of scanning procedures, and this is to our knowledge the first larger study using PET/MRI in pediatric neurooncology. We evaluated if additional postoperative F-fluoro-ethyl-tyrosine (F-FET) PET in children and adolescents would improve diagnostic accuracy for the detection of residual tumor as compared with MRI alone and would assist clinical management. Twenty-two patients (7 male; mean age, 9.5 y; range, 0-19 y) were included prospectively and consecutively in the study and had 27 early postoperative F-FET PET exams performed preferentially in a hybrid PET/MRI system (NCT03402425). Using follow-up (93%) or reoperation (7%) as the reference standard, PET combined with MRI discriminated tumor from treatment effects with a lesion-based sensitivity/specificity/accuracy (95% confidence intervals) of 0.73 (0.50-1.00)/1.00 (0.74-1.00)/0.87 (0.73-1.00) compared with MRI alone: 0.80 (0.57-1.00)/0.75 (0.53-0.94)/0.77 (0.65-0.90); that is, the specificity for PET/MRI was 1.00 as compared with 0.75 for MRI alone ( = 0.13). In 11 of 27 cases (41%), results from the F-FET PET scans added relevant clinical information, including one scan that directly influenced clinical management because an additional residual tumor site was identified. F-FET uptake in reactive changes was frequent (52%), but correct interpretation was possible in all cases. The high specificity for detecting residual tumor suggests that supplementary F-FET PET is relevant in cases where reoperation for residual tumor is considered.
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http://dx.doi.org/10.2967/jnumed.118.220293DOI Listing
August 2019

Prognostic molecular markers in pediatric liver disease - Are there any?

Biochim Biophys Acta Mol Basis Dis 2019 03 22;1865(3):577-586. Epub 2018 Dec 22.

Department of Hepatology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.

Pediatric liver disease (PLD) is a major cause of severe morbidity and prolonged hospitalizations in children. Stratifying patients in terms of prognosis remains challenging. The limited knowledge about molecular mechanisms causing and accompanying PLD remains the main obstacle in a search for reliable prognostic biomarkers. A systematic search of MEDLINE via PubMed and Embase via OVID was conducted on studies published between August 2007 and August 2017. Molecular markers with a prognostic potential in terms of survival, need for liver transplantation or disease progression/regression were selected. In general, identified studies were single center smaller case-control studies or case series with a low level of evidence and a high risk of bias. Only 23 studies comprising 898 patients could be included, mostly focusing on biliary atresia, non-alcoholic fatty liver disease, viral hepatitis, and LT; and markers related to morphogenesis and fibrosis. Furthermore, molecular markers in metabolic pathways and inflammation shown to be relevant, however requiring further validation. Hence, further biological and clinical studies are needed to gain greater molecular insight into PLD.
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http://dx.doi.org/10.1016/j.bbadis.2018.12.018DOI Listing
March 2019

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

Pediatr Transplant 2018 12 19;22(8):e13298. Epub 2018 Oct 19.

Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1111/petr.13298DOI Listing
December 2018

TEDDI: radiotherapy delivery in deep inspiration for pediatric patients - a NOPHO feasibility study.

Radiat Oncol 2018 Mar 27;13(1):56. Epub 2018 Mar 27.

Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Background: Radiotherapy (RT) delivered in deep inspiration breath-hold (DIBH) is a simple technique, in which changes in patient anatomy can significantly reduce the irradiation of the organs at risk (OARs) surrounding the treatment target. DIBH is routinely used in the treatment of some adult patients to diminish the risk of late effects; however, no formalized studies have addressed the potential benefit of DIBH in children.

Methods/design: TEDDI is a multicenter, non-randomized, feasibility study. The study investigates the dosimetric benefit of RT delivered in DIBH compared to free breathing (FB) in pediatric patients. Also, the study aims to establish the compliance to DIBH and to determine the accuracy and reproducibility in a pediatric setting. Pediatric patients (aged 5-17 years) with a tumor in the mediastinum or upper abdomen with the possible need of RT will be included in the study. Written informed consent is obligatory. Prior to any treatment, patients will undergo a DIBH training session followed by a diagnostic PET/CT- or CT-staging scan in both DIBH and FB. If the patient proceeds to RT, a RT planning CT scan will be performed in both DIBH and FB and two separate treatment plans will be calculated. The superior treatment plan, i.e. equal target coverage and lowest overall dose to the OARs, will be chosen for treatment. Patient comfort will be assessed daily by questionnaires and by adherence to the respiratory management procedure.

Discussion: RT in DIBH is expected to diminish irradiation of the OARs surrounding the treatment target and thereby reduce the risk of late effects in childhood cancer survivors.

Trial Registration: The Danish Ethical Committee (H-16035870, approved November 24th 2016, prospectively registered). The Danish Data Protection Agency (2012-58-0004, approved January 1st 2017, prospectively registered). Registered at clinicaltrials.gov ( NCT03315546 , October 20th  2017, retrospectively registered).
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http://dx.doi.org/10.1186/s13014-018-1003-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872576PMC
March 2018

An Uncommon Case of Pediatric Esthesioneuroblastoma Presenting as SIADH: F-FDG PET/CT in Staging and Post-Therapeutic Assessment.

Diagnostics (Basel) 2018 Jan 14;8(1). Epub 2018 Jan 14.

Department of Clinical Physiology, Nuclear Medicine & PET, Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark.

Esthesioneuroblastoma (ENB) is an uncommon neuroendocrine tumor originating from the olfactory neuroepithelium and accounts for 3-6% of all intranasal tumors [¹]. ENBs can be locally aggressive and cause invasion and destruction of surrounding structures. Histological grading and clinical stage at presentation are highly predictive of survival and especially presence of lymph node and distant metastases are determining prognostic factors [²,³,⁴,⁵]. Thus, reliable imaging is essential in these patients. Conventional imaging modalities for staging ENB are magnetic resonance imaging (MRI) and computed tomography (CT). However, fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/CT (F-FDG PET/CT) has been reported as a valuable adjunct and was found to upstage 36% of ENB patients compared to conventional imaging [6]. We present a case demonstrating the diagnostic work-up and follow-up with F-FDG PET/CT in a young patient with ENB with a highly atypical clinical presentation.
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http://dx.doi.org/10.3390/diagnostics8010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871991PMC
January 2018

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

J Arthroplasty 2018 05 5;33(5):1412-1420. Epub 2017 Dec 5.

Department of Orthopaedic Surgery, Bispebjerg and Frederiksberg University Hospital, Frederiksberg, Denmark.

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.
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http://dx.doi.org/10.1016/j.arth.2017.11.061DOI Listing
May 2018

Hepatobiliary scintigraphy for early diagnosis of biliary atresia.

Dan Med J 2016 Aug;63(8)

Introduction: The aim of this study was to evaluate the validity of (99m)Technetium-trimethylbromo-iminodiacetic acid hepatobiliary scintigraphy (HS) for the diagnosis of biliary atresia (BA).

Methods: From January 2005 to December 2009, a total of 47 infants with conjugated hyperbilirubinaemia (> 20 micromol/l total bilirubin of which 20% is conjugated) underwent HS. BA was suspected if no tracer was visualised in the gut 24 hours post-injection. The results of the HSs were compared with the gold standard, laparotomy with antegrade cholangiography findings.

Results: Considering the final diagnosis based on the gold standard, the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the HS in the diagnosis of BA was 100%, 63.6%, 53.8%, and 100%, respectively. The accuracy was 74.5%. BA patients with non-draining HS had significantly higher levels of gamma-glutamyl transpeptidase (GGTP) than non-BA patients with non-draining HS (p = 0.019) or draining HS (p = 0.0001).

Conclusions: HS plays an important role in the diagnostic strategy of infantile jaundice due to conjugated hyperbilirubinaemia. It is a non-invasive method that only seldomly calls for sedation. A high sensitivity and NPV prevent un-necessary surgery. Because of the low specificity of HS in diagnosing BA, it should be part of a multimodality imaging strategy when the result supports a clinical suspicion of BA. In cases with non-draining HS and normal GGTP blood levels, supplemental imaging modalities are especially needed.

Funding: none.

Trial Registration: not relevant.
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August 2016

Potential Pitfalls on the (99m)Tc-Mebrofenin Hepatobiliary Scintigraphy in a Patient with Biliary Atresia Splenic Malformation Syndrome.

Diagnostics (Basel) 2016 Jan 7;6(1). Epub 2016 Jan 7.

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9-KFNA 4011, DK-2100 Copenhagen, Denmark.

Biliary atresia (BA) is an obliterative cholangiopathy affecting 1:10.000-14.000 of newborns. Infants with Biliary Atresia Splenic Malformation syndrome (BASM) are a subgroup of BA patients with additional congenital anomalies. Untreated the disease will result in fatal liver failure within the first years of life. Kasai portoenterostomy restores bile flow and delay the progressive liver damage thereby postponing liver transplantation. An early diagnosis is of most importance to ensure the effectiveness of the operation. The (99m)Tc-Mebrofenin hepatobiliary scintigraphy is part of the diagnostic strategy when an infant presents jaundice due to conjugated hyperbilirubinemia (>20 µmol/L total bilirubin of which 20% is conjugated) with its high sensitivity of 97%-100% in refuting BA. Rapid extraction of tracer by the liver and no visible tracer in the small bowl after 24 h is indicative of BA. Laparotomy with antegrade cholangiography is then performed giving the final diagnosis when the remains of the obliterated biliary tree are revealed in the case of BA. We present a case demonstrating some of the challenges of interpreting the (99m)Tc-Mebrofenin hepatobiliary scintigraphy in an infant with BASM and stress the importance that the (99m)Tc-Mebrofenin hepatobiliary scintigraphy is part of a spectrum of imaging modalities in diagnosing BA.
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http://dx.doi.org/10.3390/diagnostics6010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808820PMC
January 2016

Clinical Performance of the ASR and ReCap Resurfacing Implants—7 Years Follow-Up.

J Arthroplasty 2015 Jun 23;30(6):993-7. Epub 2015 Jan 23.

Department of Orthopaedic Surgery, Frederiksberg University Hospital, Frederiksberg, Denmark.

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.
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http://dx.doi.org/10.1016/j.arth.2015.01.029DOI Listing
June 2015

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.

Pediatr Radiol 2015 Apr 7;45(4):570-81. Epub 2014 Nov 7.

Section of Radiotherapy, Department of Oncology, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark,

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.
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http://dx.doi.org/10.1007/s00247-014-3197-4DOI Listing
April 2015

[Acute, severe liver insufficiency caused by extrahepatic biliary atresia in a newborn].

Ugeskr Laeger 2013 Apr;175(17):1195-6

Klinik for Klinisk Fysiologi, Nuklearmedicin og PET, Righospitalet, Blegdamsvej 9, 2100 København Ø, Denmark.

A newborn female was hospitalized due to metabolic acidosis and conjugated hyperbilirubinaemia. Extrahepatic biliary atresia (EHBA) was suspected why a (99m)Tc-mebrofenin cholescintigraphy was performed. It showed poor hepatocyte tracer uptake and no drainage to the gut. The hepatocyte dysfunction was caused by an obstructing adrenal gland neuroblastoma later visualised by ultrasound and MRI. The cholescintigraphy is a non-invasive modality to exclude or confirm the suspicion of EHBA. Furthermore neonatal conjugated hyperbilirubinaemia demands the use of a multimodality imaging strategy for differential diagnosis to EHBA.
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April 2013

PET/MRI in cancer patients: first experiences and vision from Copenhagen.

MAGMA 2013 Feb 25;26(1):37-47. Epub 2012 Dec 25.

Department of Clinical Physiology, Nuclear Medicine & PET, University of Copenhagen, KF-4012 Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations.
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http://dx.doi.org/10.1007/s10334-012-0357-0DOI Listing
February 2013

First experiences from Copenhagen with paediatric single photon emission computed tomography/computed tomography.

Nucl Med Commun 2011 May;32(5):356-62

Department of Clinical Physiology, Nuclear Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark.

Objective: This study evaluates the diagnostic value of single photon emission computed tomographic (SPECT)/multislice computed tomographic (MSCT) fusion images compared with planar scintigraphy in children.

Methods: Fifteen children [eight girls, mean age 13 years (range 2-17 years)] who were examined in the SPECT/16-MSCT scanner at the Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet were included. The studies and clinical indications were eight Tc-hydroxymethane diphosphonate bone scintigraphies (three bone abnormalities, three osteomyelitis, two bone tumours), one bone scintigraphy combined with In-labelled leukocyte study (osteomyelitis), three I-meta-iodobenzylguanidine scintigraphies (neuroblastoma), three In-octreotide scintigraphies (two carcinoid tumours, one Langerhans cell histiocytosis) and one Tc-dimercaptosuccinic acid scintigraphy (suspected renal transplant infarction). At the evaluation of the planar scans, the decision to perform a SPECT/16-MSCT scan was taken. A specialist in nuclear medicine read the SPECT scans and the CT scans were, if performed as high resolution or when in doubt, read by the specialist in radiology, followed by a simultaneous reading. We categorized the additional information gained from the SPECT/MSCT scan into three groups: (i) structural information gained from the CT scan, (ii) additional nuclear medicine information gained from the SPECT scan and (iii) information used for biopsy guidance. Use of a CT scan of diagnostic quality was only allowed (n = 1) after referral from the clinicians, and read in collaboration with the specialist in radiology.

Results: Fourteen of the 15 planar scans gained additional structural information from SPECT/CT. Twelve of 15 planar scans gained additional nuclear medicine information. Six studies gained specific information for biopsy guidance.

Conclusion: SPECT/CT provided additional information in all cases. SPECT/CT in children seems to be a most valuable tool and it increases the certainty of the diagnostic work-up.
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http://dx.doi.org/10.1097/MNM.0b013e328342823dDOI Listing
May 2011

Fourteen-year-old girl with endobronchial carcinoid tumour presenting with asthma and lobar emphysema.

Clin Respir J 2010 Apr;4(2):120-4

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, København Ø, Denmark.

Introduction: Bronchial carcinoid tumours seldom occur in children, and represent a rare cause of pulmonary obstruction. Because of low clinical suspicion and the variable ways of presentation, diagnosis may be delayed.

Objectives: We report on a patient with this tumour. It is hoped that increased awareness of the tumour can lead to earlier diagnosis.

Methods: Report of a case.

Results: This case describes a 14-year-old previously healthy girl, presenting with asthma-like symptoms throughout 2 years, decreased lung function and emphysema in left lower lobe on chest x-ray. Computerized tomography (CT) showed an intraluminal process in the left main bronchus and emphysema in both the upper and lower left lobe and showed no signs of metastasis or spread to lung tissue. Bronchoscopy showed an inflammatory polyp. Surgical resection demonstrated a typical carcinoid tumour. Later control biopsy revealed no persisting malignant tissue. The asthma symptoms returned and a new bronchoscopy showed scarring and narrowing of the left bronchus. Treatment comprised of dilatation by bronchoscopy plus daily combination corticosteroids and beta-2-agonist inhalation and the symptoms improved. No signs of relapse 16 months postdiagnosis.

Conclusions: The case clearly shows the delay, which is common in the diagnosis of children with bronchial carcinoid tumours. Symptoms of the obstructive nature of the tumour are variable and might present as emphysema seen on x-ray and CT. Carcinoid tumour should be considered in children with longstanding pulmonary symptoms with no response to conventional treatment. Prognosis is good but long-term follow up is needed.
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http://dx.doi.org/10.1111/j.1752-699X.2009.00149.xDOI Listing
April 2010

When to image carotid plaque inflammation with FDG PET/CT.

Nucl Med Commun 2010 Sep;31(9):773-9

Department of Vascular Surgery, Rigshospitalet, University of Copenhagen, Denmark.

Objective: Quantification of 18-fluorodeoxyglucose (FDG) uptake in inflamed high-risk carotid atherosclerotic plaques is challenged by the spatial resolution of positron emission tomography (PET) and luminal blood activity. Late acquisition protocols have been used to overcome these challenges to enhance the contrast between the plaque and blood-pool FDG activity. However, for prospective studies the late acquisition is inconvenient for the patient and staff, and most retrospective studies of plaque uptake use data from early acquisition protocols. The objective was to evaluate changes in the quantification methods of FDG uptake in carotid artery plaques between early and late PET scans.

Methods: FDG uptake 1 and 3 h after tracer injection was compared in 19 carotid artery plaques. The average plaque maximum standardized uptake value (SUVmax) and a target to background ratio (TBR), using venous blood-pool activity as background, were evaluated at the two time points. These methods have been shown earlier to quantitate the degree of inflammation in late hour scans.

Results: A good individual plaque FDG uptake consistency was found between the two time points for SUVmax, r²=0.86. In contrast, the ratio method did not conserve the results between the two time points: TBR r²=0.34. For both methods, absolute values changed over time. TBR values generally increased as blood pool activity decreased, whereas the individual plaque SUVmax values showed both increases and decreases over time.

Conclusion: Identification of carotid plaque inflammation with PET can be performed 1 h after FDG injection using SUVmax for plaque FDG uptake quantification.
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http://dx.doi.org/10.1097/MNM.0b013e32833c365eDOI Listing
September 2010
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