Publications by authors named "Henrik Petersen"

62 Publications

GMP production of 6-[F]Fluoro-L-DOPA for PET/CT imaging by different synthetic routes: a three center experience.

EJNMMI Radiopharm Chem 2021 Jun 12;6(1):21. Epub 2021 Jun 12.

Department of Nuclear Medicine, Copenhagen University Hospital Herlev and Gentofte, Borgmester Ib Juuls vej 31, DK-2730, Herlev, Denmark.

Background: The radiofluorinated levodopa analogue 6-[F]F-L-DOPA (3,4-dihydroxy-6-F-L-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site.

Methods: Data from four years of [F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two different nucleophilic approaches. Production failure rates, radiochemical yields, and molar activities are compared across sites and time. Additionally, the clinical use of the radiotracer over the time period considered at the different sites are presented and discussed.

Results: The electrophilic substitution route suffers from being demanding in terms of cyclotron operation and maintenance. This challenge, however, was found to be compensated by a production failure rate significantly below that of both nucleophilic approaches; a result of simpler chemistry. The five-step nucleophilic approach employed at HUH produces superior radiochemical yields compared to the three-step approach adopted at OUH but suffers from the need for more comprehensive synthesis equipment given the multi-step nature of the procedure, including HPLC purification. While the procedure at OUH furnishes the lowest radiochemical yield of the synthetic routes considered, it produces the highest molar activity. This is of importance across the clinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants.

Conclusion: For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use.
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http://dx.doi.org/10.1186/s41181-021-00135-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197687PMC
June 2021

The Utility of 18F-FDG PET/CT in Patients With Clinical Suspicion of Polymyalgia Rheumatica and Giant Cell Arteritis: A Prospective, Observational, and Cross-sectional Study.

ACR Open Rheumatol 2020 Aug 22;2(8):478-490. Epub 2020 Jul 22.

University of Southern Denmark, Odense, Denmark.

Objective: To define the proportions of agreement between fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), clinical diagnosis, and temporal artery biopsy (TAB) in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Furthermore, the association of 18F-FDG PET/CT uptake patterns and clinical presentation of newly diagnosed PMR and GCA was investigated.

Methods: Eighty patients newly suspected of having PMR, GCA, or concomitant PMR and GCA were included and followed for 40 weeks. Every patient underwent an 18F-FDG PET/CT scan before or within 3 days of initiation of steroids in case of GCA. FDG uptakes in 8 paired articular/periarticular sites and 14 arterial segments were evaluated based on a 4-point visual grading scale.

Results: Of the 80 patients (female: 50 [62.5%]; mean age ± SD: 72.0 ± 7.9), 64 (80.0%) patients were diagnosed with pure PMR, 3 (3.7%) with pure GCA, and 10 (12.5%) with concomitant PMR and GCA. Additionally, three (3.7%) patients were diagnosed with seronegative rheumatoid arthritis during the follow-up period. For the diagnosis of PMR, 18F-FDG PET/CT had a proportion of agreement of 75.3 (64.2-84.4), compared with clinical diagnosis. When comparing findings of 18F-FDG PET/CT with TAB, 18F-FDG PET/CT had a proportion of agreement of 93.0 (84.3-97.7) in all included patients and 69.2 (38.6-90.9) in the subgroup of patients with vasculitis. C-reactive protein was significantly higher in patients with PMR activity on 18F-FDG PET/CT compared with those without 18F-FDG PET/CT activity (P value = 0.006).

Conclusions: 18F-FDG PET/CT is a powerful imaging technique in PMR and GCA that was in good agreement with clinical diagnosis and TAB.
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http://dx.doi.org/10.1002/acr2.11163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437127PMC
August 2020

Prevalence of Newly Diagnosed Malignancies in Patients with Polymyalgia Rheumatica and Giant Cell Arteritis, Comparison of 18F-FDG PET/CT Scan with Chest X-ray and Abdominal Ultrasound: Data from a 40 Week Prospective, Exploratory, Single Centre Study.

J Clin Med 2020 Dec 4;9(12). Epub 2020 Dec 4.

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark.

The aim of the study was to identify the prevalence of newly diagnosed malignancies in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), with the aid of 18F-FDG PET/CT scan compared to conventional imaging techniques: Chest X-ray (CXR) and abdominal ultrasound (US). Secondarily, to examine the relative diagnostic accuracy of these two imaging modalities for the detection of cancer. Eighty consecutive patients with newly diagnosed PMR, GCA, or concomitant PMR and GCA, were included and followed up for 40 weeks. All patients underwent an 18F-FDG PET/CT scan, CXR, and abdominal US at diagnosis. Imaging findings were dichotomously categorized into malignant or benign. Among 80 patients, three patients were diagnosed with seronegative rheumatoid arthritis and were excluded from the analysis. Of the remaining 77, 64 (83.1%) patients were diagnosed with pure PMR, 3 (3.9%) with pure GCA, and 10 (13.0%) with concomitant PMR and GCA. Five types of cancer that were more prevalent than the one-year prevalence of 1.2% among the background population were found in four (5.2%; 95%CI: 1.4-12.8%) patients. CXR/abdominal US could detect the solid cancer in one patient, whereas 18F-FDG PET/CT could identify all four solid cancers. Furthermore, four (5.2%; 95%CI: 1.4-12.8%) cases of monoclonal gammopathy of undetermined significance (MGUS) were found. An increase in C reactive protein (CRP) implicated an increased risk for cancer of 2.4% (OR: 1.024, 95%CI: 1.001-1.047; = 0.041). 18F-FDG PET/CT can reveal occult cancers at an early stage with a high negative predictive value, and it is specifically beneficial in PMR/GCA patients with nonspecific symptoms.
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http://dx.doi.org/10.3390/jcm9123940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762038PMC
December 2020

Hybrid PET/MRI in non-small cell lung cancer (NSCLC) and lung nodules-a literature review.

Eur J Nucl Med Mol Imaging 2021 02 27;48(2):584-591. Epub 2020 Jul 27.

Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.

Background: The use of hybrid PET/MRI for clinical staging is growing in several cancer forms and, consequently, PET/MRI has also gained interest in the assessment of non-small cell lung cancer (NSCLC) and lung lesions. However, lung evaluation with PET/MRI is associated with challenges related to technical issues and diagnostic image quality. We, therefore, investigated the published literature on PET/MRI for clinical staging in NSCLC or lung nodule detection specifically addressing diagnostic accuracy and technical issues.

Methods: The data originates from a systematic search performed in PubMed/MEDLINE, Embase, and Cochrane Library on hybrid PET/MRI in patients with cancer for a scoping review published earlier ( https://doi.org/10.1007/s00259-019-04402-8 ). Studies in English and German evaluating the diagnostic performance of hybrid PET/MRI for NSCLC or lung nodule detection in cancer patients were selected. Data reported in peer-reviewed journals without restrictions to year of publication were included.

Results: A total of 3138 publications were identified from which 116 published 2012-2018 were included. Of these, nine studies addressed PET/MRI in NSCLC (4) or lung nodule detection (5). Overall, PET/MRI did not provide advantages in preoperative T- and N-staging in NSCLC compared to PET/CT. The data on M-staging were too few for conclusions to be drawn. The lung nodule detection rate of PET/MRI was comparable to that of PET/CT for FDG-avid nodules larger than 10 mm, but the sensitivity of PET/MRI for detection of non-FDG-avid nodules smaller than 5 mm was low.

Conclusion: PET/MRI did not provide advantages in T- and N-staging of NSCLC compared to PET/CT. PET/MRI had a comparable sensitivity for detection of FDG-avid lung nodules and nodules over 10 mm, but PET/CT yielded a higher detection rate in non FDG-avid lung nodules under 5 mm. With PET/MRI, the overall detection rate for lung nodules in various cancer types remains inferior to that of PET/CT due to the lower diagnostic performance of MRI than CT in the lungs.
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http://dx.doi.org/10.1007/s00259-020-04955-zDOI Listing
February 2021

The difficult management of persistent, non-focal congenital hyperinsulinism: A retrospective review from a single, tertiary center.

Pediatr Diabetes 2020 05 11;21(3):441-455. Epub 2020 Feb 11.

Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

Background/objective: Congenital hyperinsulinism (CHI) is a rare, heterogeneous disease with transient or persistent hypoglycemia. Histologically, focal, diffuse, and atypical forms of CHI exist, and at least 11 disease-causing genes have been identified.

Methods: We retrospectively evaluated the treatment and outcome of a cohort of 40 patients with non-focal, persistent CHI admitted to the International Hyperinsulinism Center, Denmark, from January 2000 to May 2017.

Results: Twenty-two patients (55%) could not be managed with medical monotherapy (diazoxide or octreotide) and six (15%) patients developed severe potential side effects to medication. Surgery was performed in 17 (43%) patients with resection of 66% to 98% of the pancreas. Surgically treated patients had more frequently K -channel gene mutations (surgical treatment 12/17 vs conservative treatment 6/23, P = .013), highly severe disease (15/17 vs 13/23, P = .025) and clinical onset <30 days of age (15/17 vs 10/23, P = .004). At last follow-up at median 5.3 (range: 0.3-31.3) years of age, 31/40 (78%) patients still received medical treatment, including 12/17 (71%) after surgery. One patient developed diabetes after a 98% pancreatic resection. Problematic treatment status was seen in 7/40 (18%). Only 8 (20%) had clinical remission (three spontaneous, five after pancreatic surgery). Neurodevelopmental impairment (n = 12, 30%) was marginally associated with disease severity (P = .059).

Conclusions: Persistent, non-focal CHI remains difficult to manage. Neurological impairment in 30% suggests a frequent failure of prompt and adequate treatment. A high rate of problematic treatment status at follow-up demonstrates an urgent need for new medical treatment modalities.
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http://dx.doi.org/10.1111/pedi.12989DOI Listing
May 2020

Hybrid PET/MRI in major cancers: a scoping review.

Eur J Nucl Med Mol Imaging 2019 Sep 2;46(10):2138-2151. Epub 2019 Jul 2.

Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.

Purpose: PET/MRI was introduced for clinical use in 2011 and is now an established modality for the imaging of brain and certain pelvic cancers, whereas clinical use for the imaging of other forms of cancer is not yet widespread. We therefore systematically investigated what has been published on the use of PET/MRI compared to PET/CT in the imaging of cancers outside the brain, focusing on clinical areas of application related to diagnosis, staging and restaging.

Methods: A systematic search of PubMed/MEDLINE, Embase and the Cochrane Library was performed. Studies evaluating the diagnostic performance of simultaneous PET/MRI in cancer patients were chosen.

Results: A total of 3,138 publications were identified and 116 published during the period 2012-2018 were included and were grouped according to the major cancer forms: 13 head and neck (HNC), 9 breast (BC), 21 prostate (PC), 14 gynaecological, 13 gastrointestinal (GIC), and 46 various cancers. Data from studies comparing PET/MRI and PET/CT for staging/restaging suggested the superiority of F-FDG PET/MRI for the detection of tumour extension and retropharyngeal lymph node metastases in nasopharyngeal cancer, and for the detection of liver metastases and possibly bone marrow metastases in high-risk BC. FDG PET/MRI tended to be inferior for the detection of lung metastases in HNC and BC. Ga-PSMA-11 PET/MRI was superior to PET/CT for the detection of local PC recurrence. FDG PET/MRI was superior to FDG PET/CT for the detection of local tumour invasion in cervical cancer and had higher accuracy for the detection of liver metastases in colorectal cancer.

Conclusion: The scoping review methodology resulted in the identification of a huge number of records, of which less than 5% were suitable for inclusion and only a limited number allowed conclusions on the advantages/disadvantages of PET/MRI compared to PET/CT in the oncological setting. There was evidence to support the use of FDG PET/MRI in staging of nasopharyngeal cancer and high-risk BC. Preliminary data indicate the superiority of PET/MRI for the detection of local recurrence in PC, local tumour invasion in cervical cancer, and liver metastases in colorectal cancer. These conclusions are based on small datasets and need to be further explored.
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http://dx.doi.org/10.1007/s00259-019-04402-8DOI Listing
September 2019

Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism.

Eur J Med Genet 2020 Jan 21;63(1):103632. Epub 2019 Feb 21.

Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark Odense, Odense, Denmark; Dept. of Pathology, Odense University Hospital, Odense, Denmark.

Mosaic genome-wide paternal uniparental disomy (GW-pUPD) is a rarely recognised disorder. The phenotypic manifestations of multilocus imprinting defects (MLIDs) remain unclear. We report of an apparently non-syndromic infant with severe congenital hyperinsulinism (CHI) and diffuse pancreatic labelling by 18F*-DOPA-PET/CT leading to near-total pancreatectomy. The histology was atypical with pronounced proliferation of endocrine cells comprising >70% of the pancreatic tissue and a small pancreatoblastoma. Routine genetic analysis for CHI was normal in the blood and resected pancreatic tissue. At two years' age, Beckwith-Wiedemann Syndrome (BWS) stigmata emerged, and at five years a liver tumour with focal nodular hyperplasia and an adrenal tumour were resected. pUPD was detected in 11p15 and next in the entire chromosome 11 with microsatellite markers. Quantitative fluorescent PCR with amplification of chromosome-specific DNA sequences for chromosomes 13, 18, 21 and X indicated GW-pUPD. A next generation sequencing panel with 303 SNPs on 21 chromosomes showed pUPD in both blood and pancreatic tissue. The mosaic distribution of GW-pUPD ranged from 31 to 35% in blood and buccal swap to 74% in the resected pancreas, 80% in a non-tumour liver biopsy, and 100% in the liver focal nodular hyperplasia and adrenal tumour. MLID features included transient conjugated hyperbilirubinaemia and lack of macrosomia from BWS (pUPD6); and behavioural and psychomotor manifestations of Angelman Syndrome (pUPD15) on follow-up. In conclusion, atypical pancreatic histology in apparently non-syndromic severe CHI patients may be the first clue to BWS and multi-syndromal CHI from GW-pUPD. Variations in the degree of mosaicism between tissues explained the phenotype.
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http://dx.doi.org/10.1016/j.ejmg.2019.02.004DOI Listing
January 2020

Intraoperative Ultrasound: A Tool to Support Tissue-Sparing Curative Pancreatic Resection in Focal Congenital Hyperinsulinism.

Front Endocrinol (Lausanne) 2018 22;9:478. Epub 2018 Aug 22.

Department of Paediatrics, Odense University Hospital, Odense, Denmark.

Focal congenital hyperinsulinism (CHI) may be cured by resection of the focal, but often non-palpable, pancreatic lesion. The surgical challenge is to minimize removal of normal pancreatic tissue. To evaluate the results of intraoperative ultrasound-guided, tissue-sparing pancreatic resection in CHI patients at an international expert center. Retrospective study of CHI patients treated at Odense University Hospital, Denmark, between January 2010 and March 2017. Of 62 consecutive patients with persistent CHI, 24 (39%) had focal CHI by histology after surgery. All patients had a paternal or mutation and a focal lesion by F-DOPA-PET/CT. Intraoperative ultrasound localized the focal lesion in 16/20 patients (sensitivity 0.80), including one ectopic lesion in the duodenal wall. Intraoperative ultrasound showed no focal lesion in 11/11 patients with diffuse CH (specificity 1.0). The positive predictive value for focal histology was 1.0, negative predictive value 0.73. Tissue-sparing pancreatic resection (focal lesion enucleation, local resection of tail or uncinate process) was performed in 67% ( = 16). In 11/12 having tissue-sparing resection and intraoperative ultrasound, the location of the focal lesion was exactly identified. Eight patients had resection of the pancreatic head or head/body, four with Roux-en-Y, three with pancreatico-gastrostomy and one without reconstruction. None had severe complications to surgery. Cure of hypoglycaemia was seen in all patients after one ( = 21) or two ( = 3) pancreatic resections. In focal CHI, tissue-sparing pancreatic resection was possible in 67%. Intraoperative ultrasound was a helpful supplement to the mandatory use of genetics, preoperative F-DOPA-PET/CT and intraoperative frozen sections.
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http://dx.doi.org/10.3389/fendo.2018.00478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113400PMC
August 2018

15-O-water myocardial flow reserve PET and CT angiography by full hybrid PET/CT as a potential alternative to invasive angiography.

Int J Cardiovasc Imaging 2018 Dec 31;34(12):2011-2022. Epub 2018 Jul 31.

Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, 5000, Odense, Denmark.

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89-97%) versus 76% (64-88%), p = 0.0004; positive predictive value 71% (55-86%) versus 51% (37-65%), p = 0.0001; accuracy 90% (84-95%) versus 77% (69-84%), p = 0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy.
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http://dx.doi.org/10.1007/s10554-018-1420-3DOI Listing
December 2018

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.

Eur J Nucl Med Mol Imaging 2018 02 8;45(2):250-261. Epub 2017 Nov 8.

Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

Purpose: Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI.

Methods: PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard.

Results: Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively.

Conclusion: 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.
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http://dx.doi.org/10.1007/s00259-017-3867-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745571PMC
February 2018

Can semiquantitative measurements of SUVmax and cut-off values differentiate colorectal malignant from benign lessions?

Hell J Nucl Med 2017 May-Aug;20(2):113-121. Epub 2017 Jul 12.

Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.

Objective: We investigated maximum standardized uptake value (SUVmax) and cut-off values for differentiation of malignant and benign lesions in colorectal cancer (CC) as multiple studies have questioned their validity. We also investigated more extended indices using common semi-quantification analysis in incidental colorectal findings (ICF).

Subjects And Methods: Fluorine-18-fluoro deoxy glucose positron emission tomography/computed tomography in 25 patients with a total of 30 focal ICF was retrospectively analysed using dedicated software. Method variability was tested through application of three common threshold-based lesion delineation techniques as well as a partial-volume correction (PVC). Lesion SUVmax, SUVmean, metabolically active volume (MAV) and mean total lesion glycolysis (TLG) were thereby extracted along with PVC corrected values (cSUVmean, cTLG) and SUVpeak.

Results: In all lesions, SUVmax was >5 and SUVmean≥2.7. Malignant SUVmax values (mean±SD: 16.5±6.2) were overall significantly higher than benign levels (9.8±3.6). There was a substantial overlap with values in polyps/adenomas (14.4±7.7). Both SUVpeak and SUVmean showed similar characteristics. Malignant MAV and TLG showed more distinct levels. Though different segmentation methods introduced variations, largest in MAV (-58.6%-141.5%), and PVC generally increased measures significantly by a factor of 1.2-2.7, neither changed relative levels much. SUVmax values were inadequate for aetiological differentiation of ICF, which also precludes a clinically significant cut-off value. The same applies to SUVpeak and SUVmean while TLG measures may be more indicative.

Conclusion: Semi-quantitative measurements of SUVmax and cut-off values proved inadequate for differentiating colorectal malignancies from benign findings. While integrated measures, e.g. cTLG, are potentially better indicators of disease severity and extent, more optimal segmentation and PVC methods are required.
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http://dx.doi.org/10.1967/s002449910551DOI Listing
October 2017

Activated Charcoal Haemoperfusion in the Treatment of Experimental Amitriptyline Poisoning in Pigs - The Effect on Amitriptyline Plasma Concentration and Haemodynamic Parameters.

Basic Clin Pharmacol Toxicol 2017 May 15;120(5):491-497. Epub 2017 Mar 15.

Department of Anaesthesiology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.

Coated activated charcoal haemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomized clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared with standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized, and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes after AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control groups were found when analysing for differences in AT levels in plasma at any time-point. Furthermore, significant differences between the control and intervention groups in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared with standard treatment alone. We suggest that the effect of modern CAC-HP as a treatment modality in AT-poisoned human patients may be inadequate.
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http://dx.doi.org/10.1111/bcpt.12704DOI Listing
May 2017

Clinical significance of incidental focal bowel uptake on F-FDG PET/CT as related to colorectal cancer.

Hell J Nucl Med 2016 Sep-Dec;19(3):245-249. Epub 2016 Nov 8.

Department of Nuclear Medicine, Odense University Hospital, 5000 Odense, Denmark.

Objective: Increased focal colorectal uptake of fluorine-18-fluorodeoxyglucose (F-FDG) is reported to occur in 1%-3% of patients undergoing F-FDG positron emission tomography/computed tomography (PET/CT) for disease outside the bowel. However, there is no consensus on how to deal with this finding in the clinic. Due to the non-specific appearance of such lesions and a certain rate of false positive findings, patients may by subjected to unnecessary invasive procedures or, conversely, cancers may be overlooked if the risk of malignancy is downplayed. The purpose of this study was to examine the incidence and clinical significance of focal colorectal incidentalomas (FCI) at our institution and to assess the potential benefit of using semi-quantitative measures instead of visual interpretation to discern malignant from benign lesions.

Subjects And Methods: We identified all patients in 2011 with a report of FCI. We reviewed patient charts with regard to basic characteristics, indications for and results of F-FDG-PET/CT and subsequent workup including colonoscopy and histopathological analyses, and applied post hoc semi-quantitative analysis. Out of 4,829 patients, twenty-five met the inclusion criteria (mean age 71 years, 13 females, 12 males).

Results: Of the 25 included patients, eight presented with no pathologic or non-malignant findings (e.g. inflammation), while ten had polyps/adenomas and seven a hitherto undiagnosed colorectal cancer. Semi-quantitative SUVmax values and ROC analysis based cut-off values could not reliably discriminate benign from premalignant or malignant disease.

Conclusion: It is the opinion of the authors that F-FDG PET/CT scan may identify incidentally sites of colorectal carcinoma but cannot discriminate them from polyps/adenomas. Nevertheless, incidental focal bowel uptake should always be reported and/or further evaluated.
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http://dx.doi.org/10.1967/s002449910407DOI Listing
June 2017

Local shape feature fusion for improved matching, pose estimation and 3D object recognition.

Springerplus 2016 8;5:297. Epub 2016 Mar 8.

Maersk Mc-Kinney Moller Institute, University of Southern Denmark, Odense, Denmark.

We provide new insights to the problem of shape feature description and matching, techniques that are often applied within 3D object recognition pipelines. We subject several state of the art features to systematic evaluations based on multiple datasets from different sources in a uniform manner. We have carefully prepared and performed a neutral test on the datasets for which the descriptors have shown good recognition performance. Our results expose an important fallacy of previous results, namely that the performance of the recognition system does not correlate well with the performance of the descriptor employed by the recognition system. In addition to this, we evaluate several aspects of the matching task, including the efficiency of the different features, and the potential in using dimension reduction. To arrive at better generalization properties, we introduce a method for fusing several feature matches with a limited processing overhead. Our fused feature matches provide a significant increase in matching accuracy, which is consistent over all tested datasets. Finally, we benchmark all features in a 3D object recognition setting, providing further evidence of the advantage of fused features, both in terms of accuracy and efficiency.
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http://dx.doi.org/10.1186/s40064-016-1906-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783326PMC
April 2016

[18F]Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) in Suspected Recurrent Breast Cancer: A Prospective Comparative Study of Dual-Time-Point FDG-PET/CT, Contrast-Enhanced CT, and Bone Scintigraphy.

J Clin Oncol 2016 06 21;34(16):1889-97. Epub 2016 Mar 21.

Malene Grubbe Hildebrandt, Oke Gerke, Christina Baun, Kirsten Falch, Jeanette Ansholm Hansen, Ziba Ahangarani Farahani, Henrik Petersen, Lisbet Brønsro Larsen, Sandra Duvnjak, Inguna Buskevica, Selma Bektas, Katrine Søe, Anne Marie Bak Jylling, Marianne Ewertz, and Poul Flemming Høilund-Carlsen, Odense University Hospital; Oke Gerke and Marianne Ewertz, University of Southern Denmark, Odense, Denmark; and Abass Alavi, University of Pennsylvania, Philadelphia, PA.

Purpose: To prospectively investigate the diagnostic accuracy of [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with dual-time-point imaging, contrast-enhanced CT (ceCT), and bone scintigraphy (BS) in patients with suspected breast cancer recurrence.

Patients And Methods: One hundred women with suspected recurrence of breast cancer underwent 1-hour and 3-hour FDG-PET/CT, ceCT, and BS within approximately 10 days. The study was powered to estimate the precision of the individual imaging tests. Images were visually interpreted using a four-point assessment scale, and readers were blinded to other test results. The reference standard was biopsy along with treatment decisions and clinical follow-up (median, 17 months).

Results: FDG-PET/CT resulted in no false negatives and fewer false positives than the other imaging techniques. Accuracy of results were similar for 1-hour and 3-hour FDG-PET/CT. For distant recurrence, the area under the receiver operating curve was 0.99 (95% CI, 0.97 to 1) for FDG-PET/CT, 0.84 (95% CI, 0.73 to 0.94) for ceCT, and 0.86 (95% CI, 0.77 to 0.94) for the combined ceCT+BS. Of 100 patients, 22 (22%) were verified with distant recurrence, and 18 of these had bone involvement. Nineteen patients (19%) had local recurrence only. In exploratory analyses, diagnostic accuracy of FDG-PET/CT was better than ceCT alone or ceCT combined with BS in diagnosing distant, bone, and local recurrence, shown by a greater area under the receiver operating curve and higher sensitivity, specificity, and superior likelihood ratios.

Conclusion: FDG-PET/CT was accurate in diagnosing recurrence in breast cancer patients. It allowed for distant recurrence to be correctly ruled out and resulted in only a small number of false-positive cases. Exploratory findings suggest that FDG-PET/CT has greater accuracy than conventional imaging technologies in this patient group.
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http://dx.doi.org/10.1200/JCO.2015.63.5185DOI Listing
June 2016

FDG PET/CT in cancer: comparison of actual use with literature-based recommendations.

Eur J Nucl Med Mol Imaging 2016 Apr 30;43(4):695-706. Epub 2015 Oct 30.

Department of Nuclear Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark.

Purpose: The Region of Southern Denmark (RSD), covering 1.2 of Denmark's 5.6 million inhabitants, established a task force to (1) retrieve literature evidence for the clinical use of positron emission tomography (PET)/CT and provide consequent recommendations and further to (2) compare the actual use of PET/CT in the RSD with these recommendations. This article summarizes the results.

Methods: A Work Group appointed a professional Subgroup which made Clinician Groups conduct literature reviews on six selected cancers responsible for 5,768 (62.6 %) of 9,213 PET/CT scans in the RSD in 2012. Rapid Evidence Assessment was applied, using the methodology of systematic reviews with predefined limitations to search PubMed, Embase and the Cochrane Library for articles published in English/Danish/Swedish/Norwegian since 2002. PICO questions were defined, data recorded and quality appraised and rated with regard to strength and evidence level. Consequent recommendations for applications of PET/CT were established. The actual use of PET/CT was compared with these, where grades A and B indicated "established" and "useful" and grades C and D "potentially useful" and "non-recommendable" indications, respectively.

Results: Of 11,729 citations, 1,729 were considered for review, and 204 were included. The evidence suggested usefulness of PET/CT in lung, lymphoma, melanoma, head and neck, and colorectal cancers, whereas evidence was sparse in gynaecological cancers. The agreement between actual use of PET/CT and literature-based recommendations was high in the first five mentioned cancers in that 96.2 % of scans were made for grade A or B indications versus only 22.2 % in gynaecological cancers.

Conclusion: Evidence-based usefulness was reported in five of six selected cancers; evidence was sparse in the sixth, gynaecological cancers. Actual use of PET/CT agreed well with recommendations.
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http://dx.doi.org/10.1007/s00259-015-3217-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764641PMC
April 2016

Planned FDG PET-CT Scan in Follow-Up Detects Disease Progression in Patients With Locally Advanced NSCLC Receiving Curative Chemoradiotherapy Earlier Than Standard CT.

Medicine (Baltimore) 2015 Oct;94(43):e1863

From the Southern Medical University (YP, Y-LW), Department of Radiation Oncology, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, P.R. China (YP), Department of Oncology, Odense University Hospital (YP, TS, OH), Institution of Clinical Research, University of Southern Denmark (YP, CB, TS, OH), Laboratory of Radiation Physics, Odense University Hospital (CB), Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark (HP); and Guangdong Lung Cancer Institute, Guangzhou, P.R. China (Y-LW).

The role of positron emission tomography-computed tomography (PET-CT) in surveillance of patients with nonsmall cell lung cancer (NSCLC) treated with curatively intended chemoradiotherapy remains controversial. However, conventional chest X-ray and computed tomography (CT) are of limited value in discriminating postradiotherapy changes from tumor relapse. The aim of this study was to evaluate the clinical value of PET-CT scan in the follow-up for patients with locally advanced (LA) NSCLC receiving concomitant chemoradiotherapy (CCRT).Between 2009 and 2013, eligible patients with stages IIB-IIIB NSCLC were enrolled in the clinical trial NARLAL and treated in Odense University Hospital (OUH). All patients had a PET-CT scan scheduled 9 months (PET-CT9) after the start of the radiation treatment in addition to standard follow-up (group A). Patients who presented with same clinical stage of NSCLC and received similar treatment, but outside protocol in OUH during this period were selected as control group (group B). Patients in group B were followed in a conventional way without PET-CT9. All patients were treated with induction chemotherapy followed by CCRT.Group A included 37 and group B 55 patients. The median follow-up was 16 months. Sixty-six (72%) patients were diagnosed with progression after treatment. At the time of tumor progression, patients in group A had better performance status (PS) than those in group B (P = 0.02). Because of death (2 patients), poor PS (3) or retreatment of relapse (9), only 23 patients had PET-CT9 in group A. Eleven (48%) patients were firstly diagnosed with progression by PET-CT9 without any clinical symptoms of progression. The median progression-free survival (PFS) was 8.8 months in group A and 12.5 months in group B (P = 0.04). Hazard function PFS showed that patients in group A had higher risk of relapse than in group B.Additional FDG PET-CT scan at 9 months in surveillance increases probability of early detection of disease progression in advanced NSCLC patients treated with curatively intended CCRT.
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http://dx.doi.org/10.1097/MD.0000000000001863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985411PMC
October 2015

Cardiac abnormalities assessed by non-invasive techniques in patients with newly diagnosed idiopathic inflammatory myopathies.

Clin Exp Rheumatol 2015 Sep-Oct;33(5):706-14. Epub 2015 Sep 7.

Department of Rheumatology, Copenhagen University Hospital, Copenhagen, Denmark.

Objectives: Knowledge of cardiac involvement in idiopathic inflammatory myopathies (IIM) is limited, especially in the early stage of disease. The objective of the present study was to perform a controlled evaluation of cardiac abnormalities in newly diagnosed, untreated patients with idiopathic inflammatory myopathies (IIM) by means of non-invasive techniques.

Methods: Fourteen patients with IIM (8 polymyositis, 4 dermatomyositis, 2 cancer-associated dermatomyositis) and 14 gender- and age- matched healthy control subjects were investigated. Participant assessments included a cardiac questionnaire, cardiac troponin-I (TnI), electrocardiogram (standard 12-lead and 48-h Holter monitoring), echocardiography with tissue Doppler measures, cardiac magnetic resonance (CMR) imaging with T2 mapping and semi-quantitative (99m)technetium pyrophosphate ((99m)Tc-PYP) scintigraphy.

Results: Dyspnoea was present in 8 (57%) of the patients compared to none of the controls (p<0.01). Median levels of TnI in patients and controls were 20 ng/L and 6 ng/L, respectively (p=0.06). QTc intervals were prolonged in the patient group (p=0.01). Two patients had systolic dysfunction, and one diastolic dysfunction. The myocardial (99m)Tc-PYP uptake and CMR results differed between patients and controls, albeit not with statistical significance. Overall, cardiac abnormalities were demonstrated in 9 (64%) of the patients versus 2 (14%) of the controls (p=0.02).

Conclusions: Cardiac abnormalities assessed by TnI, ECG or imaging modalities were significantly more common in newly diagnosed, treatment naïve patients with IIM compared to healthy control subjects. These abnormalities, although subclinical, may indicate that myocardial involvement is common in patients and calls for larger controlled studies and further investigations of the prognostic implications of this finding.
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December 2015

Clinical value of FDG-PET/CT in suspected paraneoplastic syndromes: a retrospective analysis of 137 patients.

Eur J Nucl Med Mol Imaging 2015 Dec 21;42(13):2056-63. Epub 2015 Jul 21.

Department of Nuclear Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark.

Purpose: Paraneoplastic syndromes (PNS) are relatively infrequent manifestations appearing before or after a cancer declares itself. Autoimmune mechanisms may be involved, but their cause and pathogenesis are often unknown. Due to disparity of symptoms, PNS remain a major diagnostic challenge. We examined the value of FDG-PET/CT for ruling in or out malignancy in a heterogeneous group of patients with suspected PNS.

Methods: We retrospectively extracted data from all patients referred 2009-2013 with suspected PNS. Data included age, sex, follow-up period, scan report, further diagnostic procedures, and final clinical diagnosis. Conclusions of the scan reports were compared to the final follow-up outcome as determined during an average follow-up of 31 months (range 6-51.5) in patients who were not diagnosed with cancer in immediate continuation of a positive PET/CT scan.

Results: A total of 137 patients were included. Main causes for referral were neurological (n = 67), rheumatological (n = 25), dermatological (n = 18), nephrological (n = 6), haematological (n = 2), abnormal biochemistry (n = 11), and others (n = 8). The cancer prevalence was 8.8%. The FDG-PET/CT results were as follows: nine true positives, 22 false positives, 103 true negatives, and three false negatives. Corresponding diagnostic values were: sensitivity 75%, specificity 82%, accuracy 82%, and positive and negative predictive values of 29% and 97%, respectively.

Conclusion: FDG-PET/CT has in patients with suspected PNS an impressively high negative predictive value and may be of value in ruling out PNS, the more so, the more the number of false positives can be minimized or used in differential diagnosis. We believe that FDG-PET/CT may become an important adjunct to the work-up and triage of patients with suspected PNS.
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http://dx.doi.org/10.1007/s00259-015-3126-2DOI Listing
December 2015

FDG in Urologic Malignancies.

PET Clin 2014 Oct 30;9(4):457-68, vi. Epub 2014 Jul 30.

Institute of Clinical Research, University of Southern Denmark, Winsløwparken 19, DK-5000, Odense, Denmark; Department of Urology, Odense University Hospital, Sønder Boulevard 29, Odense DK-5000, Denmark.

Kidney, bladder, and prostate cancer account for more than one-eighth of new cancer cases worldwide. Imaging in kidney cancer is dominated by computed tomography (CT). Positron emission tomography (PET) imaging of bladder cancer is hampered by the urinary excretion of the most common PET tracer, 18F-fluoro-deoxy-glucose (FDG). PET imaging has been applied more often in prostate cancer. FDG-PET/CT is claimed to have a high frequency of false-negative results in urologic cancers; however, this finding may instead reflect correctly the state of disease being due to slow-growing cancers with a good prognosis and without a need of therapy.
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http://dx.doi.org/10.1016/j.cpet.2014.07.003DOI Listing
October 2014

Quantitative myocardial perfusion by O-15-water PET: individualized vs. standardized vascular territories.

Eur Heart J Cardiovasc Imaging 2015 Sep 5;16(9):970-6. Epub 2015 May 5.

Department of Nuclear Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.

Aims: Reporting of quantitative myocardial blood flow (MBF) is typically performed in standard coronary territories. However, coronary anatomy and myocardial vascular territories vary among individuals, and a coronary artery may erroneously be deemed stenosed or not if territorial demarcation is incorrect. So far, the diagnostic consequences of calculating individually vs. standardly assessed MBF values have not been reported. We examined whether individual reassignment of vascular territories would improve the diagnostic accuracy of MBF with regard to the detection of significant coronary artery disease (CAD).

Methods And Results: Forty-four patients with suspected CAD were included prospectively and underwent coronary CT-angiography and quantitative MBF assessment with O-15-water PET followed by invasive, quantitative coronary angiography, which served as reference. MBF was calculated in the vascular territories during adenosine stress according to a standardized 17-segment American Heart Association model and an individualized model, using CT-angiography to adjust the coronary territories to their feeding vessels. Individually defined territories deviated from standard territories in 52% of patients. However, MBF in the three coronary territories defined by standard and individualized models did not differ significantly, except in one patient, in whom the MBF of an individualized coronary territory deviated sufficiently as to change the test from a false positive to a true negative result in this particular territory.

Conclusion: Disparity between standardized and individualized vascular territories was present in half of the patients, but had little clinical impact. Still, caution should be taken not always to rely on standard territories, as this may at times cause misinterpretation.
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http://dx.doi.org/10.1093/ehjci/jev111DOI Listing
September 2015

Chemical purity and toxicology of pigments used in tattoo inks.

Curr Probl Dermatol 2015 26;48:136-41. Epub 2015 Mar 26.

MT.DERM GmbH, Berlin, Germany.

The safety of tattoo inks has obviously increased in Europe since the existence of European Union Resolution ResAP(2008)1, which resulted in the improved quality control of pigment raw materials due to the definition of impurity limits that manufacturers can refer to. High-performance pigments are mostly used in tattoo inks, and these pigments are supposed to be chemically inert and offer high light fastness and low migration in solvents. However, these pigments were not developed or produced for applications involving long-term stay in the dermis or contact with bodily fluids. Therefore, these pigments often do not comply with the purity limits of the resolution; however, it is required that every distributed tattoo ink does not contain aromatic amines and not exceed the limits of heavy metals or polycyclic aromatic hydrocarbons. Current toxicity studies of pigments underline that no ecotoxicological threat to human health or to the environment should be expected. However, the pigment as well as its impurities and coating materials must be considered. In order to evaluate the safety of pigments according to their impurities, two different validated sample preparation methods are necessary: (1) simulation of their long-term stay in the bodily fluid of the dermis and (2) simulation of cleavage due to laser removal or ultraviolet exposure. The development of standardized, validated and well-adapted methods for this application has to be part of prospective efforts. Concerning legislation, it might be appropriate that the first regulative approaches be based on those of cosmetics.
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http://dx.doi.org/10.1159/000369647DOI Listing
February 2016

Tailored surface engineering of pigments by layer-by-layer coating.

Curr Probl Dermatol 2015 26;48:128-35. Epub 2015 Mar 26.

Surflay Nanotec GmbH, Berlin, Germany.

We have evaluated the feasibility of layer-by-layer encapsulation technology for the improvement of dye pigments used for tattoos or permanent make-up. The formation of core-shell structures is possible by coating pigments with thin films of several different polyelectrolytes using this technology. The physicochemical surface properties, such as charge density and chemical functionality, can be reproducibly varied in a wide range. Tailoring the surface properties independently from the pigment core allows one to control the rheological behaviour of pigment suspensions, to prevent aggregation between different pigments, to reduce the cytotoxicity, and to influence the response of phagocytes in order to have similar or the same uptake and bioclearance for all pigments. These properties determine the durability and colour tone stability of tattoos and permanent make-up.
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http://dx.doi.org/10.1159/000369195DOI Listing
February 2016

Traditional cardiovascular risk factors and coronary artery calcification in adults with polymyositis and dermatomyositis: a Danish multicenter study.

Arthritis Care Res (Hoboken) 2015 May;67(6):848-54

Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objective: To determine the occurrence of traditional cardiovascular (CV) risk factors and coronary artery calcification (CAC) in adults with polymyositis (PM) or dermatomyositis (DM) compared to healthy controls and to assess the association between CV risk factors, PM/DM, and CAC score.

Methods: Traditional CV risk factors were assessed in a cross-sectional, observational study of 76 patients with PM/DM and in 48 sex- and age-matched healthy controls. CAC was quantified by means of cardiac computed tomography scan and expressed in Agatston units. The associations between CV risk factors, PM/DM, and CAC were studied by multivariate analyses.

Results: Thirty-three percent of the patients were obese compared to 11% of the controls (P = 0.005). Hypertension and diabetes mellitus were more frequent in patients (71% versus 42%; P = 0.002, and 13% versus 0%; P = 0.007), and patients had higher levels of triglycerides (P = 0.0009). High CAC score occurred more frequently in patients (20% versus 4%; P = 0.04). In multivariate analysis of patient factors associated with CAC were age (P = 0.02) and smoking (P = 0.02).

Conclusion: In this study, traditional CV risk factors and severe CAC were commonly found in patients with PM/DM. However, severe CAC was not associated with PM/DM per se, but rather with age and smoking in these patients.
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http://dx.doi.org/10.1002/acr.22520DOI Listing
May 2015

Answer to the letter to the editor of L. Uhrenholt et al. concerning "do X-ray-occult fractures play a role in chronic pain following a whiplash injury?" by Hertzum-Larsen R, Petersen H, Kasch H, Bendix T, Eur Spine J, 2014; DOI 10.1007/s00586-014-3362-3.

Eur Spine J 2014 Oct 15;23(10):2225. Epub 2014 Aug 15.

Back Research Unit, Center for Rheumatology and Spinal Diseases, Glostrup University Hospital, Nordre Ringvej 57, 2600, Glostrup, Denmark,

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http://dx.doi.org/10.1007/s00586-014-3493-6DOI Listing
October 2014

Do X-ray-occult fractures play a role in chronic pain following a whiplash injury?

Eur Spine J 2014 Aug 28;23(8):1673-9. Epub 2014 May 28.

Back Research Unit, Center for Rheumatology and Spinal diseases, Glostrup University Hospital, Nordre. Ringvej 57, 2600, Glostrup, Denmark,

Purpose: Whiplash trauma in motor vehicle accidents (MVA) may involve various painful soft tissue damages, but weeks/months later a minority of victims still suffers from various long-lasting and disabling symptoms, whiplash-associated disorders (WAD). The etiology is currently unknown, but X-ray-occult fractures may be one cause in some cases. The purpose of this prospective study was to examine the association between occult fractures, as seen on bone single photon emission computed tomography (SPECT), with neck-, head- and arm pain.

Methods: An inception cohort of 107 patients presenting with acute whiplash symptoms following an MVA was invited to have a cervical SPECT shortly post injury and again 6 months later. Associations between occult fractures and pain levels at baseline, 6 and 12 months of follow-up were analyzed.

Results: Eighty-eight patients had baseline SPECT performed at median 15 days (range 3-28) post injury, but only 49 patients accepted to have the follow-up SPECT at 6 months. Abnormal SPECT, defined as minimum one area of focal uptake, was seen in 32 patients at baseline, reflecting an occult fracture. Occult fractures were not associated with pain levels, neither at baseline nor at follow-up.

Conclusion: Occult fractures do not seem to play a role for development of chronic pain after whiplash.
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http://dx.doi.org/10.1007/s00586-014-3362-3DOI Listing
August 2014

FDG-PET/CT can rule out malignancy in patients with vocal cord palsy.

Am J Nucl Med Mol Imaging 2014 20;4(2):193-201. Epub 2014 Mar 20.

Department of Nuclear Medicine, Odense University Hospital Denmark.

The aim was to investigate the performance of (18)F-fluorodeoxyglucose PET/CT to rule out malignancy in patients with confirmed vocal cord palsy (VCP). Between January 2011 and June 2013, we retrospectively included consecutive patients referred to PET/CT with paresis or paralysis of one or both vocal cords. PET/CT results were compared to clinical workup and histopathology. The study comprised 65 patients (32 females) with a mean age of 66±12 years (range 37-89). Eleven patients (17%) had antecedent cancer. Twenty-seven (42%) were diagnosed with cancer during follow-up. The palsy was right-sided in 24 patients, left-sided in 37, and bilateral in 4. Median follow-up was 7 months (interquartile range 4-11 months). Patients without cancer were followed for at least three months. PET/CT suggested a malignancy in 35 patients (27 true positives, 8 false positives) and showed none in 30 (30 true negatives, 0 false negatives). Thus, the sensitivity, specificity, positive and negative predictive values, and accuracy were (95% confidence intervals in parenthesis): 100% (88%-100%), 79% (64%-89%), 77% (61%-88%), 100% (89%-100%), and 88% (78%-94%), respectively. Sixteen patients had palliative treatment, while 11 were treated with curative intent, emphasising the severity of VCP and the need for a rapid and accurate diagnostic work-up. In this retrospective survey, biopsy proven malignancy (whether newly diagnosed or relapsed) was the cause of VCP in almost half of patients (42%). PET/CT had a high sensitivity (100%) with a relatively high false positive rate, but was excellent in ruling out malignancy (negative predictive value 100%).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992212PMC
April 2014

Spine metastases in prostate cancer: comparison of technetium-99m-MDP whole-body bone scintigraphy, [(18) F]choline positron emission tomography(PET)/computed tomography (CT) and [(18) F]NaF PET/CT.

BJU Int 2014 Dec 22;114(6):818-23. Epub 2014 May 22.

Research Unit of Urology, Department of Urology, Odense University Hospital, Odense, Denmark.

Objective: To compare the diagnostic accuracy of the following imaging techniques in the detection of spine metastases, using magnetic resonance imaging (MRI) as a reference: whole-body bone scintigraphy (WBS) with technetium-99m-MDP, [18F]-sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) and [(18) F]-fluoromethylcholine (FCH) PET/CT.

Patients And Methods: The study entry criteria were biopsy-proven prostate cancer, a positive WBS consistent with bone metastases, and no history of androgen deprivation. Within 30 days of informed consent, trial scans were performed in random order. Scans were interpreted blindly for the purpose of a lesion-based analysis. The primary target variable was bone lesion (malignant/benign) and the 'gold standard' was MRI.

Results: A total of 50 men were recruited between May 2009 and March 2012. Their mean age was 73 years, their median PSA level was 84 ng/mL, and the mean Gleason score of the tumours was 7.7. A total of 46 patients underwent all four scans, while four missed one PET/CT scan. A total of 526 bone lesions were found in the 50 men: 363 malignant and 163 non-malignant according to MRI. Sensitivity, specificity, positive and negative predictive values and accuracy were: WBS: 51, 82, 86, 43 and 61%; NaF-PET/CT: 93, 54, 82, 78 and 81%; and FCH-PET/CT: 85, 91, 95, 75 and 87%, respectively.

Conclusions: We found that FCH-PET/CT and NaF-PET/CT were superior to WBS with regard to detection of prostate cancer bone metastases within the spine. The present results call into question the use of WBS as the method of choice in patients with hormone-naïve prostate cancer.
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http://dx.doi.org/10.1111/bju.12599DOI Listing
December 2014

Hybrid CT angiography and quantitative 15O-water PET for assessment of coronary artery disease: comparison with quantitative coronary angiography.

Eur J Nucl Med Mol Imaging 2013 Dec 28;40(12):1894-904. Epub 2013 Aug 28.

Department of Nuclear Medicine, OUH, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark,

Purpose: CT angiography (CTA) can rule out significant stenoses with a very high reliability, whereas its ability to confirm significant stenoses is suboptimal. In contrast, measurements of myocardial blood flow (MBF) provide information on the haemodynamic consequences of stenoses. Therefore, a combination of the two might improve diagnostic accuracy. We conducted a head-to-head comparison of CTA, measurement of MBF by (15)O-water PET, and hybrid PET/CTA for the detection of significant coronary artery stenoses.

Methods: The study group comprised 44 outpatients scheduled for invasive coronary angiography (ICA) with an intermediate pretest likelihood of coronary artery disease. The patients underwent 64-slice CTA and baseline and hyperaemic PET before ICA with quantitative coronary angiography analysis.

Results: On a per-patient basis, the negative predictive values (NPV; 95% confidence intervals in parentheses) were 88 % (64 - 97%) for CTA, 90% (71 - 97%) for PET and 92% (74 - 98%) for PET/CTA, and the positive predictive values (PPV) were 71% (53 - 85%) for CTA, 87% (68 - 95%) for PET and 100% (84 - 100%) for PET/CTA. Similarly, on a per-vessel basis the NPVs (which were generally high) were 97% (94 - 100%) for CTA, 95 % (90 - 99%) for PET and 97% (95 - 100%) for PET/CTA, and the PPVs (which were lower, but higher with PET/CTA) were 53% (39 - 66%) for CTA, 53 % (40 - 66%) for PET and 85 % (73 - 97%) for PET/CTA. In six patients, CTA analysis was hampered by the presence of severe calcifications. However, with the addition of the PET data, all six patients were correctly categorized.

Conclusion: Cardiac quantitative hybrid PET/CTA imaging has better diagnostic accuracy than CTA alone and PET alone. CTA has a suboptimal PPV, suggesting that hybrid PET/CTA imaging should be used to assess the significance of coronary stenoses diagnosed by CTA.
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http://dx.doi.org/10.1007/s00259-013-2519-3DOI Listing
December 2013
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