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  • 251.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Simon, Tabassome
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kotti, Salma
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Machecourt, Jacques
    Ninio, Ewa
    Tedgui, Alain
    Danchin, Nicolas
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Mallat, Ziad
    Circulating levels of secretory- and lipoprotein-associated phospholipase A2 activities: relation to atherosclerotic plaques and future all-cause mortality2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no 23, p. 2946-54Article in journal (Refereed)
    Abstract [en]

    Aims

    Secretory- and lipoprotein-associated phospholipases A2 (sPLA2 and Lp-PLA2) are enzymes both suggested to be of importance for atherosclerosis. We investigated relationships between the activities of these enzymes in the circulation and atherosclerosis as well as future clinical events.

    Methods and results

    The population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study included 1016 randomly selected subjects, all aged 70. The prevalence of carotid artery plaques was recorded by ultrasound (n= 954), and arterial stenosis was assessed by whole-body magnetic resonance angiography (WBMRA, n= 302). Secretory-associated phospholipase A2 [odds ratio 1.23 for 1 SD increase, 95% confidence interval (CI): 1.05-1.44, P= 0.007], but not Lp-PLA2 (P= 0.26), activity was significantly related to carotid atherosclerosis and to the amount of stenosis at WBMRA (P= 0.006) following adjustment for multiple risk factors (waist circumference, serum triglycerides, body mass index, C-reactive protein, high density lipoprotein-C, low density lipoprotein-C, triglycerides, GFR, fasting glucose, blood pressure, statin use, and exercise habits). Secretory-associated phospholipase A2 [hazard ratio (HR) 1.45 for 1 SD increase, 95% CI: 1.15-1.84, P= 0.001], but not Lp-PLA2 (HR 0.95, P= 0.55), activity was a significant risk factor for all-cause mortality (114 had died) during 7.0 years follow-up after adjustment for the risk factors described above. In a sample of 1029 post-myocardial infarction (MI) patients (French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction), sPLA2 (adjusted HR 1.32 for 1 unit increase, 95% CI: 1.02-1.71, P= 0.036), but not Lp-PLA2 (HR 1.03, P= 0.90), activity predicted death or recurrent MI during 1-year follow-up (n= 136 cases).

    Conclusion

    sPLA2 activity was related to atherosclerosis and predicted all-cause mortality in a sample of elderly subjects, as well as death or MI in post-MI patients.

  • 252.
    Lind, P. Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Roos, Vendela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Rönn, Monika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women2012In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 11, no 1, p. 21-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used.

    METHODS:

    1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements.

    RESULTS:

    In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p < 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men.

    CONCLUSIONS:

    The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.

  • 253.
    Lindblom, Rickard P F
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Department of Cardiothoracic Surgery and Anesthesia, Uppsala University Hospital, Uppsala, Sweden.
    Zemgulis, Vitas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Department of Cardiothoracic Surgery and Anesthesia, Uppsala University Hospital, Uppsala, Sweden.
    Lilieqvist, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Department of Cardiothoracic Surgery and Anesthesia, Uppsala University Hospital, Uppsala, Sweden.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Even small aneurysms can bleed: a ruptured small idiopathic aneurysm of the internal thoracic artery2013In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 17, no 3, p. 583-585Article in journal (Refereed)
    Abstract [en]

    Internal thoracic artery (ITA) aneurysms are rare, but a rupture is potentially fatal. Most cases of ITA aneurysms are iatrogenic, caused by, for instance, previous sternotomy or pacemaker implantation. Other known aetiologies are vasculopathies, either of inflammatory origin or as part of connective tissue disorders like Marfan's syndrome, Ehler-Dahnlos syndrome or neurofibromatosis Type 1. Idiopathic ITA aneurysms are exceedingly scarce. The present case illustrates an unusual scenario, which posed diagnostic challenges, where spontaneous rupture of an idiopathic or possibly very late post-traumatic aneurysm of the left ITA led to a life-threatening bleeding, successfully treated by endovascular coiling with standby preparation for conversion to open surgery. This case demonstrates the importance of the careful interpretation of radiological findings and the significance of multidisciplinary collaboration between radiologist and clinician.

  • 254. Lindgren, Cecilia
    et al.
    Hultin, Magnus
    Koskinen, Lars-Owe D.
    Lindvall, Peter
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Naredi, Silvana
    ADMA Levels and Arginine/ADMA Ratios Reflect Severity of Disease and Extent of Inflammation After Subarachnoid Hemorrhage2014In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 21, no 1, p. 91-101Article in journal (Refereed)
    Abstract [en]

    Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome. Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0-240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3-5 and less severe clinical condition H&H 1-2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome. Compared to admission, 0-48 h after SAH, the following was observed 49-240 h after SAH; (a) ADMA was significantly increased at 97-240 h (highest 217-240 h), (b) CRP was significantly increased at 49-240 h (highest 73-96 h), (c) interleukin-6 (IL-6) was significantly lower at 97-240 h (highest 49-96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1-2 compared to patients with H&H 3-5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55 %) or without (45 %) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1-3 and patients with GOS 4-5. ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.

  • 255.
    Lindner, Karl-Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Hartvig, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Åkesson, Christina
    Tyrefors, Niklas
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Långström, Bengt
    Analysis of l-[methyl-11C]methionine and metabolites in human plasma by an automated solid-phase extraction and a high-performance liquid chromatographic procedure1996In: Journal of Chromatography B: Biomedical Sciences and Applications, ISSN 1387-2273, E-ISSN 1878-5603, Vol. 679, no 1-2, p. 13-19Article in journal (Refereed)
    Abstract [en]

    A fully automated method for separation of l-[methyl-11C]Methionine from metabolites in patient plasma was developed. l-[methyl-11C]Methionine was isolated from plasma by solid-phase extraction (SPE). The radioactivity retained on the SPE column was eluted and injected onto the HPLC system for separation of in vivo formed l-[methyl-11C]methionine radiolabeled metabolites. The yield through the isolation procedure and HPLC analysis was greater than 95% with a precision better than 5% (R.S.D.). The calculated rate of l-[methyl-11C]methionine transport into tumor tissue was markedly different with and without compensation for radiolabeled metabolises in patient plasma.

  • 256.
    Lindqvist, Ulla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Westerberg, G
    Bergström, M
    Torsteindottir, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Gustafson, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lööf, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. University Hospital, Uppsala, Sweden.
    Långström, Bengt
    [11C]Hyaluronan uptake with positron emission tomography in liver disease2000In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 30, no 7, p. 600-607Article in journal (Other academic)
    Abstract [en]

    Background

    A hyaluronan-loading test has been developed for assessment of hyaluronan kinetics and applied in patients with liver and joint diseases. This test describes the metabolic process of hyaluronan but cannot define the specific contribution of different organs. A method for labelling of hyaluronan with the short-lived positron-emitting radionuclide 11C has been published and in this study applied in healthy subjects and liver diseases.

    Materials and methods

    Positron emission tomography (PET) was used for the regional assessment and quantification of [11C]hyaluronan uptake in three healthy subjects, four patients with alcoholic liver cirrhosis, one with alcoholic hepatitis and one with liver steatosis. After intravenous administration of 60 MBq of 11C-labelled hyaluronan, a 55-min PET scan was performed over the liver and plasma radioactivity was analysed. Rate constants describing the transport of the [11C]hyaluronan tracer from plasma to the liver were calculated.

    Results

    High uptake was observed in the liver combined with a rapid elimination of tracer from plasma. The liver uptake rate (k1) was significantly lower in patients (0.018 min−1) than in healthy subjects (0.043 min−1, P = 0.002). The rate constants seem to be related to the severity of the disease as defined by the Child–Pugh score.

    Conclusions

    The study suggests that PET with [11C]hyaluronan could be an accurate method by which to assess liver dysfunction, in conditions where endothelial cell function is impaired. The possibility of quantification over extended portions of the body also opens up possibilities to explore regional differences in liver function and to assess other elimination routes of hyaluronan.

  • 257.
    Lindskog, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Jan W
    Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Danielsson, Angelika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Novel pancreatic beta cell-specific proteins: Antibody-based proteomics for identification of new biomarker candidates2012In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 75, no 9, p. 2611-2620Article in journal (Refereed)
    Abstract [en]

    Beta cell-specific surface targets are required for non-invasive monitoring of beta cell mass, which could be used for evaluation of new diabetes treatments as well as to help unravel pathogenic mechanisms underlying beta cell dysfunction. By antibody-based proteomics, we have identified and explored a set of islet cell-specific proteins. A search algorithm in the Human Protein Atlas was set up for identification of islet-specific proteins that yielded 27 hits, of which twelve showed a clear membranous expression pattern or had predicted transmembrane regions. The specificity of the identified proteins was investigated by immunohistochemical staining of pancreas sections from diabetic and non-diabetic subjects. No expression of these antigens could be detected in the exocrine pancreas. Colocalization with insulin and glucagon was further determined by confocal microscopy using isolated human islets. All antibodies specifically stained human islets and colocalization analysis revealed that four proteins were exclusively expressed in beta cells. Importantly, these antibodies were negative in sections from subjects with long-standing type 1 diabetes. In the present study, we present four proteins; DGCR2, GBF1, GPR44 and SerpinB10, the expression of which has not previously been described in beta cells.

  • 258. Lindvall, Peter
    et al.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Department of Neurosurgery, Umeå University Hospital, Umeå, Sweden.
    Birgander, Richard
    Jonasson, Per
    Ridderheim, Per-Åke
    Long-term follow-up of intracranial aneurysms treated with endovascular coiling: experience from one institution2012In: Vascular and endovascular surgery, ISSN 1938-9116, Vol. 46, no 4, p. 325-328Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Our aim was to evaluate the long-term treatment results in patients with intracranial aneurysms treated with endovascular techniques.

    METHODS:

    Forty-four patients treated due to intracranial aneurysms between 1996 and 2002 were investigated with a time-of-flight sequence magnetic resonance angiography (TOF MRA).

    RESULTS:

    Depending on the assessment, 47% to 51% of the treated aneurysms had a residual neck at the last digital subtraction angiography follow-up. There was filling of the aneurysm base (2%) in only 1 patient, whereas the remaining aneurysms were totally occluded. A TOF MRA performed 6 to 14 (mean 9.68) years after the last procedure showed a stable result in 93.9% of the treated aneurysms. There were no de novo aneurysms and previously untreated aneurysms were unchanged in size.

    CONCLUSION:

    Our long-term follow-up showed a stable result in previously coiled intracranial aneurysms.

  • 259.
    Liss, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Cox, Eleanor F.
    Eckerbom, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Francis, Sue T.
    Imaging of intrarenal haemodynamics and oxygen metabolism2013In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 40, no 2, p. 158-167Article, review/survey (Refereed)
    Abstract [en]

    The interruption of blood flow results in impaired oxygenation and metabolism. This can lead to electrophysiological changes, functional impairment and symptoms in quick succession. Quantitative measures of organ perfusion, perfusion reserve and tissue oxygenation are crucial to assess normal tissue metabolism and function. Magnetic resonance imaging (MRI) provides a number of quantitative methods to assess physiology in the kidney. Blood oxygenation level-dependent (BOLD) MRI provides a method for the assessment of oxygenation. Blood flow to the kidney can be assessed using phase contrast MRI. Dynamic contrast-enhanced MRI and arterial spin labelling (ASL) provide methods to assess tissue perfusion, ASL using the magnetization of endogenous water protons and thus providing a non-invasive method to assess perfusion. The application of diffusion-weighted MRI allows molecular motion in the kidney to be measured. Novel techniques can also be used to assess oxygenation in the renal arteries and veins and, combined with flow measures, provide an estimation of oxygen metabolism. Magnetic resonance imaging provides a synergy of non-invasive techniques to study renal function and the demand for these techniques is likely to be driven by the incentive to avoid the use of contrast media, to avoid radiation and to avoid complications with intervention procedures.

  • 260.
    Ljunggren, Östen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Bolinder, J.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wilding, J.
    Langkilde, A. M.
    Sjostrom, C. D.
    Sugg, J.
    Parikh, S.
    Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin2012In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 14, no 11, p. 990-999Article in journal (Refereed)
    Abstract [en]

    Aims Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50?weeks of dapagliflozin treatment. Methods This international, multi-centre, randomized, parallel-group, double-blind, placebo-controlled study (ClinicalTrials.gov NCT00855166) enrolled patients with T2DM (women 5575?years and men 3075?years; HbA1c 6.58.5%; BMI?=?25?kg/m2; body weight?=?120?kg) whose T2DM was inadequately controlled on metformin. One hundred and eighty-two patients were randomly assigned 1:1 to receive dapagliflozin 10?mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 50, serum markers of bone formation (procollagen type 1 N-terminal propeptide; P1NP) and resorption (C-terminal cross-linking telopeptides of type I collagen; CTX), bone mineral density (BMD) as assessed by standardized Dual-Energy X-ray Absorptiometry (DXA) measurements and adverse events of fracture were evaluated as safety objectives. Results One hundred and sixty-five patients (90.7%) completed the first 50 weeks. Compared with placebo, no significant changes from baseline in P1NP, CTX or BMD were identified over 50 weeks of dapagliflozin treatment, with no significant treatment-by-gender interactions. No fractures were reported. Conclusions Dapagliflozin had no effect on markers of bone formation and resorption or BMD after 50 weeks of treatment in both male and post-menopausal female patients whose T2DM was inadequately controlled on metformin.

  • 261. Loizou, L
    et al.
    Albiin, Nils
    Ansorge, C
    Andersson, M
    Segersvärd, R
    Leidner, Bertil
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Department of Radiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Lundell, L
    Kartalis, N
    Computed tomography staging of pancreatic cancer: a validation study addressing interobserver agreement2013In: Pancreatology (Print), ISSN 1424-3903, E-ISSN 1424-3911, Vol. 13, no 6, p. 570-575Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES:

    Ductal adenocarcinoma in the head of the pancreas (PDAC) is usually unresectable at the time of diagnosis due to the involvement of the peripancreatic vessels. Various preoperative classification algorithms have been developed to describe the relationship of the tumor to these vessels, but most of them lack a surgically based approach. We present a CT-based classification algorithm for PDAC based on surgical resectability principles with a focus on interobserver variability.

    METHODS:

    Thirty patients with PDAC undergoing pancreaticoduodenectomy were examined by using a standard CT protocol. Nine radiologists, representing three different levels of expertise, evaluated the CT examinations and the tumors were classified into four categories (A-D) according to the proposed system. For the interobserver agreement, the Intraclass Correlation Coefficient (ICC) was estimated.

    RESULTS:

    The overall ICC was 0.94 and the ICCs among the trainees, experienced radiologists, and experts were 0.85, 0.76, and 0.92, respectively. All tumors classified as category A1 showed no signs of vascular invasion at surgery. In category A2, 40% of the tumors had corresponding infiltration and required resection of the superior mesenteric vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in category C required SMV/PV resection. All six patients in category D had both arterial and venous involvement.

    CONCLUSION:

    There is almost perfect agreement among radiologists with different levels of expertise in regards to the local staging of PDAC. For tumors in a more advanced preoperative category, an increased risk for vascular involvement was noticed at surgery.

  • 262.
    Loskog, Angelica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Maleka, Aglaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mangsbo, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Svensson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Krause, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Agnarsdottir, Margret
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tötterman, Thomas H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    AdCD40L Immunostimulatory Gene Therapy in Combination with Cyclophosphamide Prolongs 6-Months Survival in a Phase I/II Trial for Malignant Melanoma2014In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 22, p. S247-S247Article in journal (Other academic)
  • 263.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Tovedal, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Golla, Sandeep
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Asplund, Veronika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Myrdal, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Measurement of absolute cerebral blood flow during cardiopulmonary bypass and selective cerebral perfusion using [O-15]water and PET2012In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 32, no S1, p. S157-S158Article in journal (Other academic)
  • 264.
    Lundberg, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. AstraZeneca R&D, Mölndal, Sweden.
    The relationship between carotid intima-media thickness and global atherosclerosis2014In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, no 6, p. 457-462Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of this study was to investigate the relationship between (i) carotid intima-media thickness (CIMT) at baseline as well as (ii) change in CIMT over 5 years (ΔCIMT) and atherosclerotically induced luminal narrowing in non-coronary arterial territories assessed by whole-body magnetic resonance angiography (WBMRA).

    METHODS AND RESULTS:

    In subgroups of the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) study, US measurements of CIMT in the common carotid arteries were analysed at 70 and 75 years and ΔCIMT was calculated (n = 272). WBMRA, assessing arterial stenosis in five different territories by which also a total atherosclerotic score (TAS) was calculated, was performed at 70 years (n = 306).

    RESULTS:

    Carotid intima-media thickness in the carotid artery at baseline was correlated with TAS (P = 0·0001) when adjusted to a set of traditional risk factors for atherosclerosis, as well as to stenosis in two of the different investigated territories (aorta and lower leg, P = 0·013 and P = 0·004), but there was no significant correlation between ΔCIMT and TAS (P = 0·41).

    CONCLUSIONS:

    In the present study, CIMT, but not ΔCIMT over 5 years, in the carotid artery was related to overall stenoses in the body, as assessed by WBMRA. These findings support CIMT as a general marker for atherosclerosis.

  • 265.
    Lundberg, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Total atherosclerotic burden by whole body magnetic resonance angiography predicts major adverse cardiovascular events2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, no 1, p. 148-152Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The purpose of the present study was to investigate the relationship between the Total Atherosclerotic Score (TAS), a measurement of the overall atherosclerotic burden of the arterial tree by whole body magnetic resonance angiography (WBMRA), and the risk of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, stroke and/or coronary revascularization, assuming that TAS predicts MACE.

    METHODS AND RESULTS:

    305 randomly selected 70 year-old subjects (47% women) underwent WBMRA. Their atherosclerotic burden was evaluated and TAS > 0, that is atherosclerotic changes, were found in 68% of subjects. During follow-up (mean 4.8 years), MACE occurred in 25 subjects (8.2%). Adjusting for multiple risk factors, TAS was associated with MACE (OR 8.86 for any degree of vessel lumen abnormality, 95%CI 1.14-69.11, p = 0.037). In addition, TAS improved discrimination and reclassification when added to the Framingham risk score (FRS), and ROC (Receiver Operator Curve) increased from 0.681 to 0.750 (p = 0.0421).

    CONCLUSION:

    In a population-based sample of 70 year old men and women WBMRA, with TAS, predicted MACE independently of major cardiovascular risk factors.

  • 266. Lundblad, Henrik
    et al.
    Maguire, Gerald Q
    Olivecrona, Henrik
    Jonsson, Cathrine
    Jacobsson, Hans
    Noz, Marilyn E
    Zeleznik, Michael P
    Weidenhielm, Lars
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Can Na18F PET/CT Be Used to Study Bone Remodeling in the Tibia When Patients Are Being Treated with a Taylor Spatial Frame?2014In: Scientific World Journal, ISSN 1537-744X, E-ISSN 1537-744X, Vol. 2014, p. 249326-Article in journal (Refereed)
    Abstract [en]

    Monitoring and quantifying bone remodeling are of interest, for example, in correction osteotomies, delayed fracture healing pseudarthrosis, bone lengthening, and other instances. Seven patients who had operations to attach an Ilizarov-derived Taylor Spatial Frame to the tibia gave informed consent. Each patient was examined by Na(18)F PET/CT twice, at approximately six weeks and three months after the operation. A validated software tool was used for the following processing steps. The first and second CT volumes were aligned in 3D and the respective PET volumes were aligned accordingly. In the first PET volume spherical volumes of interest (VOIs) were delineated for the crural fracture and normal bone and transferred to the second PET volume for SUVmax evaluation. This method potentially provides clinical insight into questions such as, when has the bone remodeling progressed well enough to safely remove the TSF? and when is intervention required, in a timelier manner than current methods? For example, in two patients who completed treatment, the SUVmax between the first and second PET/CT examination decreased by 42% and 13%, respectively. Further studies in a larger patient population are needed to verify these preliminary results by correlating regional Na(18)F PET measurements to clinical and radiological findings.

  • 267.
    Lundqvist, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Segelsjö, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Andersson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Measurement of transplanted pancreatic volume using computed tomography: reliability by intra- and inter-observer variability2012In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 9, p. 966-972Article in journal (Refereed)
    Abstract [en]

    Background

    Unlike other solid organ transplants, pancreas allografts can undergo a substantial decrease in baseline volume after transplantation. This phenomenon has not been well characterized, as there are insufficient data on reliable and reproducible volume assessments. We hypothesized that characterization of pancreatic volume by means of computed tomography (CT) could be a useful method for clinical follow-up in pancreas transplant patients.

    Purpose

    To evaluate the feasibility and reliability of pancreatic volume assessment using CT scan in transplanted patients.

    Material and Methods

    CT examinations were performed on 21 consecutive patients undergoing pancreas transplantation. Volume measurements were carried out by two observers tracing the pancreatic contours in all slices. The observers performed the measurements twice for each patient. Differences in volume measurement were used to evaluate intra- and inter-observer variability.

    Results

    The intra-observer variability for the pancreatic volume measurements of Observers 1 and 2 was found to be in almost perfect agreement, with an intraclass correlation coefficient (ICC) of 0.90 (0.77-0.96) and 0.99 (0.98-1.0), respectively. Regarding inter-observer validity, the ICCs for the first and second measurements were 0.90 (range, 0.77-0.96) and 0.95 (range, 0.85-0.98), respectively.

    Conclusion

    CT volumetry is a reliable and reproducible method for measurement of transplanted pancreatic volume.

  • 268.
    Lundqvist, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ureteroperitoneostomy: a rare complication after kidney transplantation2011In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, no 9, p. e75-e76Article in journal (Refereed)
  • 269.
    Lundqvist, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lövqvist, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Beshara, Soheir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bruskin, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Westlin, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Positron emission tomography and radioimmunotargeting: general aspects1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 335-341Article in journal (Refereed)
    Abstract [en]

    To optimize radioimmunotherapy, in vivo information on individual patients, such as radionuclide uptake, kinetics, metabolic patterns and optimal administration methods, is important. An overriding problem is to determine accurately the absorbed dose in the target organ as well as critical organs. Positron Emission Tomography (PET) is a superior technique to quantify regional kinetics in vivo with a spatial resolution better than 1 cm3 and a temporal resolution better than 10 s. However, target molecules often have distribution times of several hours to days. Conventional PET nuclides are not applicable and alternative positron-emitting nuclides with matching half-lives and with suitable labelling properties are thus necessary. Over many years we have systematically developed convenient production methods and labelling techniques of suitable positron nuclides, such as 110In(T(1/2) = 1.15 h), 86Y(T(1/2) = 14 h), 76Br(T(1/2) = 16 h) and 124I(T(1/2) = 4 days). 'Dose planning' can be done, for example, with 86Y- or 124I-labelled ligands before therapy, and 90Y- and 131I-labelled analogues and double-labelling, e.g. with a 86Y/90Y-labelled ligand, can be used to determine the true radioactivity integral from a pure beta-emitting nuclide. The usefulness of these techniques was demonstrated in animal and patient studies by halogen-labelled MAbs and EGF-dextran conjugates and peptides chelated with metal ions.

  • 270. Lundqvist, Roger
    et al.
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Thomas, Benjamin A
    Lötjönen, Jyrki
    Villemagne, Victor L
    Rowe, Christopher C
    Thurfjell, Lennart
    Implementation and validation of an adaptive template registration method for 18F-flutemetamol imaging data.2013In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, no 8, p. 1472-8Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: The spatial normalization of PET amyloid imaging data is challenging because different white and gray matter patterns of negative (Aβ-) and positive (Aβ+) uptake could lead to systematic bias if a standard method is used. In this study, we propose the use of an adaptive template registration method to overcome this problem.

    METHODS: Data from a phase II study (n = 72) were used to model amyloid deposition with the investigational PET imaging agent (18)F-flutemetamol. Linear regression of voxel intensities on the standardized uptake value ratio (SUVR) in a neocortical composite region for all scans gave an intercept image and a slope image. We devised a method where an adaptive template image spanning the uptake range (the most Aβ- to the most Aβ+ image) can be generated through a linear combination of these 2 images and where the optimal template is selected as part of the registration process. We applied the method to the (18)F-flutemetamol phase II data using a fixed volume of interest atlas to compute SUVRs. Validation was performed in several steps. The PET-only adaptive template registration method and the MR imaging-based method used in statistical parametric mapping were applied to spatially normalize PET and MR scans, respectively. Resulting transformations were applied to coregistered gray matter probability maps, and the quality of the registrations was assessed visually and quantitatively. For comparison of quantification results with an independent patient-space method, FreeSurfer was used to segment each subject's MR scan and the parcellations were applied to the coregistered PET scans. We then correlated SUVRs for a composite neocortical region obtained with both methods. Furthermore, to investigate whether the (18)F-flutemetamol model could be generalized to (11)C-Pittsburgh compound B ((11)C-PIB), we applied the method to Australian Imaging, Biomarkers and Lifestyle (AIBL) (11)C-PIB scans (n = 285) and compared the PET-only neocortical composite score with the corresponding score obtained with a semimanual method that made use of the subject's MR images for the positioning of regions.

    RESULTS: Spatial normalization was successful on all scans. Visual and quantitative comparison of the new PET-only method with the MR imaging-based method of statistical parametric mapping indicated that performance was similar in the cortical regions although the new PET-only method showed better registration in the cerebellum and pons reference region area. For the (18)F-flutemetamol quantification, there was a strong correlation between the PET-only and FreeSurfer SUVRs (Pearson r = 0.96). We obtained a similar correlation for the AIBL (11)C-PIB data (Pearson r = 0.94).

    CONCLUSION: The derived adaptive template registration method allows for robust, accurate, and fully automated quantification of uptake for (18)F-flutemetamol and (11)C-PIB scans without the use of MR imaging data.

  • 271.
    Långström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Grahnen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Honoré, Per Hartvig
    Borlak, Jürgen
    Bergström, Mats
    Nielsen, Bengt
    Vanderheyden, Jeanluc
    Watanabe, Yasuyoshi
    Josephsson, Raymond
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Høilund-Carlsen, Poul F
    Schwaiger, Markus
    Larson, Steven M
    Goldenberg, David M
    Melzer, Andreas
    Engler, Henry
    Hicks, Rodney
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Seppänen, Marko
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nordberg, Agneta
    Brooks, David
    The risk of exaggerated risk aversion: a life and death struggle for molecular imaging2009In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 36, no 10, p. 1693-1694Article in journal (Refereed)
  • 272.
    Långström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Bergström, Mats
    [Positron emission tomography in oncology--an introduction]1998In: Nordisk Medicin, ISSN 0029-1420, Vol. 113, no 9, p. 299-300Article in journal (Refereed)
    Abstract [sv]

    Positron emission tomography has developed very much since the start in the late 1970s, especially with the development of new labelling procedures for PET-tracers. With the development of whole body imaging and the discovery that 18F-FDG allows a high sensitivity for the detection of soft tissue tumors, the clinical use has increased remarkably. The cost-effectiveness of this modality, when properly used, has been demonstrated and 18F-FDG-PET should be considered as an early alternative in patient evaluation.

  • 273.
    Lönnemark, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Oral contrast media in CT of the abdomen. A double-blind randomized study comparing an aqueous solution of amidotrizoate, an aqueous solution of iohexol and a viscous solution of iohexol1993In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 34, no 5, p. 517-519Article in journal (Refereed)
    Abstract [en]

    In a double-blind randomized study 3 different preparations of oral contrast media for bowel opacification at CT of the abdomen have been compared. Plain aqueous solutions of amidotrizoate (9 mg I/ml) and iohexol (9 mg I/ml) were used as well as a preparation of iohexol (9 mg I/ml) to which a viscosity-increasing agent had been added. The distribution of the contrast media in the intestine, transit time and patient tolerance were evaluated. No significant differences were found regarding the distribution between the 3 preparations of contrast media, while there was a tendency for the transit time to be increased when the viscous preparation of iohexol was used. The aqueous solution of iohexol had the best taste, while the viscous preparation was markedly more difficult to drink. Aqueous solutions of iohexol and amidotrizoate were equal for bowel opacification and the addition of the viscosity-increasing agent did not improve the distribution of the contrast medium in the intestine.

  • 274.
    Lövqvist, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Sundín, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    76Br-labeled monoclonal anti-CEA antibodies for radioimmuno positron emission tomography1995In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 22, no 1, p. 125-131Article in journal (Refereed)
    Abstract [en]

    For the application of anti-tumor monoclonal antibodies (MAbs) in positron emission tomography (PET), labeling radionuclides with half-lives allowing a suitable time frame for imaging are required. The anti-CEA MAb 38S1 was labeled with the positron emitting nuclide 76Br (t1/2 16 h) using bromoperoxidase (BPO), and subsequently affinity purified. A procedure was devised to allow reproducible production of MAb-preparations of high immunoreactivity and with acceptable bromination yield. The biological activity of 76Br-38S1 was retained and comparable to that of chloramine-T labeled 125I-38S1, as tested in vitro.

  • 275. Lövqvist, Anna
    et al.
    Sundín, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Pharmacokinetics and experimental PET imaging of a bromine-76-labeled monoclonal anti-CEA antibody1997In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 38, no 3, p. 395-401Article in journal (Refereed)
    Abstract [en]

    Bromine-76 is potentially useful as a radiolabel for monoclonal antibodies (MAbs) in PET imaging. The purpose of the present study was to evaluate the 76Br-labeled anticarcinoembryonic antigen (-CEA) MAb 38S1 as a tumor imaging agent in an experimental tumor model and to study the pharmacokinetics of 76Br-38S1 in comparison with 125I-38S1.

    METHODS:

    Nude rats carrying human colon carcinoma xenografts were co-injected with directly labeled 76Br-38S1 and 125I-38S1. Biodistribution of labeled 38S1 was monitored for 4 days after administration, in the case of 76Br activity, including PET imaging. In addition, catabolism of radiolabeled MAbs was analyzed by gel filtration chromatography of blood plasma and homogenized tissues.

    RESULTS:

    Tumor sites could be readily identified by PET imaging from 46 hr after administration of 76Br-38S1 and onwards. The concentration of 76Br activity in tumors, blood and most normal tissues was higher than the corresponding 125I concentration at all time points. This was mainly due to catabolism of radiolabeled MAb, resulting in free radiohalides, of which 76Br- was retained in contrast to the rapidly excreted 125I- ion.

    CONCLUSION:

    Bromine-76-labeled anti-CEA MAbs may be applied for experimental tumor imaging with PET.

  • 276. Lövqvist, Anna
    et al.
    Sundín, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Roberto, Amilcar
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Comparative PET imaging of experimental tumors with bromine-76-labeled antibodies, fluorine-18-fluorodeoxyglucose and carbon-11-methionine1997In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 38, no 7, p. 1029-1035Article in journal (Refereed)
    Abstract [en]

    The potential of a 76Br-labeled anti-carcinoembryonic antigen monoclonal antibody (MAb), 38S1, as tumor-imaging agent for PET was investigated in a comparative experimental study with [18F]fluorodeoxyglucose ([18F]FDG) and L-[methyl-11C]methionine ([11C]Met).

    METHODS:

    The three radiotracers were administered to nude rats carrying subcutaneous xenografts or liver metastases from a human colonic carcinoma. Tracer biodistribution was evaluated by PET imaging and radioactivity measurement of dissected tissues and also by whole-body autoradiography for subcutaneous xenografts.

    RESULTS:

    For PET imaging of subcutaneous tumors, 76Br-38S1 proved superior to the other radiotracers. Tumor-to-tissue ratios were, except for the tumor-to-blood ratio, generally higher for 76Br-labeled MAb than for [18F]FDG and [11C]Met. Liver metastases were imaged with PET using both 76Br-38S1 and [18F]FDG, and the metastases-to-liver ratios of dissected samples were not significantly different for the two radiotracers.

    CONCLUSION:

    The tumor-imaging capacity of 76Br-labeled MAb 38S1 was superior to [18F]FDG and [11C]Met in the subcutaneous tumor model, whereas 76Br-38S1 and [18F]FDG were equally successful for the identification of liver metastases.

  • 277.
    Magnusson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Geterud, Kjell
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lindqvist, Klas
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nyman, Ulf
    Hellström, Mikael
    Ultraljud vs DT vid uretärsten: svenska rutiner gäller2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 49-50, p. 2236-2237Article in journal (Other academic)
  • 278.
    Magnusson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Förändrad teknik förbättrar behandlingen med prostataspiral1991In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 88, no 16, p. 1485-Article in journal (Refereed)
  • 279.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, B S
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    5-FU uptake in liver metastases after intravenous and intraperitoneal administration: an autoradiographic study in the rat1998In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 18, no 2A, p. 943-949Article in journal (Refereed)
    Abstract [en]

    AIM:

    To analyse 5-fluorouracil (5-FU) uptake in hepatic metastases and normal tissues after intravenous (i.v.), intraperitoneal (i.p.e.) and intraportal (IPO) administration.

    METHODS AND RESULTS:

    A total of 18 inbred rats with hepatic metastases were injected with 14C-labelled 5-FU either through the i.v. (n = 7), i.p.e (n = 7) or IPO (n = 4) route. Radioactivity was visualised autoradiographically and quantified by computer-based image analysis. After 20 minutes, 10 i.v. injected tumours showed a higher amount of radioactivity (mean +/- SD) 23.8 +/- 7.8 than 6 i.p.e. injected (16.5 +/- 5.1, P = 0.06). At 2 hours, 9 i.v. injected metastases contained more radioactivity (49.6 +/- 9.2) than 19 i.p.e. injected tumours (28.2 + 11.3, P = 0.00003). After 24 hours, 2 i.p.e. injected tumours had higher radioactivity (mean 25.2) compared with 7 i.v. injected (7.6 +/- 4.1). IPO administration did not confer higher radioactivity at any time point. When the calculations were based on average metastatic radioactivity of individual rats, the difference between i.v. and i.p.e. injected rats was still present at 2 hours.

    CONCLUSION:

    These results indicate that early tumour 5-FU uptake after intraperitoneal and intraportal administration may be inferior to that after intravenous injection. Deposition of the drug in the peritoneal cavity may, however, act as a slow release preparation giving continuous drug exposure for prolonged periods of time. These results suggest a role for combined intravenous and intraperitoneal adjuvant therapy.

  • 280.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lövqvist, A
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Adjuvant 131I-anti-CEA-antibody radioimmunotherapy inhibits the development of experimental colonic carcinoma liver metastases1998In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 18, no 2A, p. 843-848Article in journal (Refereed)
    Abstract [en]

    Adjuvant radioimmunotherapy (RIT) for human colonic cancer was performed in a nude rat model of experimental liver metastases. Thirty-three rats were injected intraportally through a mesenteric vein with 5 x 10(6) cells from the human colonic cancer cell line LS174T. Within half an hour, 20 MBq (n = 2), 75 MBq (n = 5), or 150 MBq (n = 10) of the 131I-labelled anti- carcinoembryonic antigen (CEA) monoclonal antibody (MAb) 38S1 was administered intravenously (i.v.), whereas control groups received either i.v. saline injections (n = 12) or 150 MBq of the irrelevant 131I-labelled MAb 79C (n = 4). Decay corrected whole-body data showed that more than 80% of the initially MAb-bound radioiodine was excreted during the first 2 weeks. Whole- body clearance and blood clearance of 131I-38S1 and 131I-79C were essentially similar. At sacrifice 5-7 weeks after administration, neither 20 MBq nor 75MBq 131I-38S1 significantly prevented the development of liver metastases. By contrast, with 150 MBq, no metastases formed in the animals treated with MAb 131I-38S1 or 131I-79C. A radiation induced effect on the haematopoietic system was found in the 150MBq dosage groups. It is concluded that the inhibition of tumour induction was not strictly dependent on a radiation dose delivered by a tumour-specific MAb. Since a non-tumour-specific 131I-MAb, in a smaller group of animals, proved equally efficacious in preventing tumour growth, the total body 131I dose was probably the major contributing factor.

  • 281.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Bengt
    Khamis, Harry
    Arow, Kiril
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction: an autoradiographic study in the rat2005In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 25, no 2A, p. 917-922Article in journal (Refereed)
    Abstract [en]

    This study was conducted to test if tumour drug uptake could be increased in experimental colorectal cancer peritoneal metastases, by using pretreatment with peritoneal vasoconstriction or radioimmunotherapy. A total of 29 nude rats with peritoneal metastases were injected intraperitoneally (i.p.) with 14C-labelled 5-FU. The animals were randomly allocated to 5 groups. Six days prior to 5-FU, group I (control) received i.p. NaCl, group II was subjected to i.p. radioimmunotherapy (RIT) 131I-labelled anti-CEA monoclonal antibody (150 MBq) and group III received i.p. Norbormide 10 minutes before 5-FU. Two days prior to 5-FU group IV and V received i.p. NaCl (control) and RIT, respectively. 5-FU uptake was visualised with autoradiography and quantified by computer-based image analysis. Tumours in group III showed a higher uptake (mean+/-SD, 21.4+/-17) than in group I (11.8+/-10, p=0.04). This was also true when the analysis was restricted to larger tumours (> or = median 627 pixels) group III (23.2+/-19) vs. group I (11.8+/-7, p=0.002). Peritoneal tumours in group II were of smaller size (median area 308 pixels) than in group I (619 pixels), in group III (901 pixels), in group IV (769 pixels) and in group V (808 pixels). RIT decreased the tumour size whereas it did not affect 5-FU uptake. The uptake of 5-FU was potentiated by pretreating the animals with Norbormide. These results demonstrate that 5-FU uptake in experimental peritoneal metastases is increased when the peritoneal absorption of the drug is blocked using pretreatment with a vasoconstrictive agent. This principle may also be relevant when treating patients with colorectal cancer peritoneal metastases.

  • 282.
    Malmberg, Filip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    SmartPaint: a tool for interactive segmentation of medical volume images2017In: Computer Methods In Biomechanics And Biomedical Engeineering-Imaging And Visualization, ISSN 2168-1163, Vol. 5, no 1, p. 36-44Article in journal (Refereed)
    Abstract [en]

    We present SmartPaint, a general-purpose method and software for interactive segmentation of medical volume images. SmartPaint uses a novel paint-brush interaction paradigm, where the user segments objects in the image by 'sweeping' over them with the mouse cursor. The key feature of SmartPaint is that the painting tools adapt to the image content, selectively sticking to objects of interest while avoiding other structures. This behaviour is achieved by modulating the effect of the tools by both the Euclidean distance and the range distance (difference in image intensity values) from the mouse cursor. We evaluate SmartPaint on three publicly available medical image datasets, covering different image modalities and segmentation targets. The results show that, with a limited user effort, SmartPaint can produce segmentations whose accuracy is comparable to both the state-of-the-art automatic segmentation methods and manual delineations produced by expert users. The SmartPaint software is freely available, and can be downloaded from the authors' web page (http://www.cb.uu.se/similar to filip/SmartPaint/).

  • 283.
    Malmberg, Filip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Smart Paint: A New Interactive Segmentation Method\\ Applied to MR Prostate Segmentation2012In: Prostate MR Image Segmentation Grand Challenge (PROMISE'12), a MICCAI 2012 workshop, 2012Conference paper (Refereed)
    Abstract [en]

    This paper describes a general method for interactive segmentation, Smart Paint. The user interaction is inspired by the way an airbrush is used, objects are segmented by "sweeping" with the mouse cursor in the image. The user adds or removes details in 3D by the proposed segmentation tool and the user interface shows the segmentation result in 2D slices through the object. We use the novel method for prostate segmentation in transversal T2-weighted MR images from multiple centers and vendors and with differences in scanning protocol.

    The method was evaluated on the training set obtained from http://promise12.grand-challenge.org. In the first round, all 50 volumes were segmented and the mean of Dice's coefficient was 0.82 with standard deviation 0.09. In a second round, the first 30 volumes were re-segmented by the same user and the result was slightly improved -- Dice's coefficient 0.86 $\pm$ 0.05 was obtained. For the training data, the mean time to segment a volume was 3 minutes and 30 seconds.

    The proposed method is a generic tool for interactive image segmentation and this paper illustrates that it is well-suited for prostate segmentation.

  • 284.
    Malmberg, Filip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    An interactive tool for deformable registration of volume images2014In: Symposium of the Swedish Society for Automated Image Analysis (SSBA), 2014Conference paper (Other academic)
  • 285.
    Malmberg, Filip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Seeded Segmentation Based on Object Homogeneity2012In: Proceedings of the 21st International Conference on Pattern Recognition (ICPR), 2012, p. 21-24Conference paper (Refereed)
    Abstract [en]

    Seeded segmentation methods attempt to solve the segmentation problem in the presence of prior knowledge in the form of a partial segmentation, where a small subset of the image elements (seed-points) have been assigned correct segmentation labels. Common for most of the leading methods in this area is that they seek to find a segmentation where the boundaries of the segmented regions coincide with sharp edges in the image. Here, we instead propose a method for seeded segmentation that seeks to divide the image into areas of homogeneous pixel values. The method is based on the computation of minimal cost paths in a discrete representation of the image, using a novel path-cost function. The utility of the proposed method is demonstrated in a case study on segmentation of white matter hyperintensitities in MR images of the human brain.

  • 286. Mannerås-Holm, Louise
    et al.
    Leonhardt, Henrik
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Jennische, Eva
    Odén, Anders
    Holm, Göran
    Hellström, Mikael
    Lönn, Lars
    Olivecrona, Gunilla
    Stener-Victorin, Elisabet
    Lönn, Malin
    Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, But Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance2011In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 96, no 2, p. E304-E311Article in journal (Refereed)
    Abstract [en]

    Context: Comprehensive characterization of the adipose tissue in women with polycystic ovary syndrome (PCOS), over a wide range of body mass indices (BMIs), is lacking. Mechanisms behind insulin resistance in PCOS are unclear. Objective: To characterize the adipose tissue of women with PCOS and controls matched pair-wise for age and BMI, and to identify factors, among adipose tissue characteristics and serum sex steroids, that are associated with insulin sensitivity in PCOS. Design/Outcome Measures: Seventy-four PCOS women and 31 controls were included. BMI was 18-47 (PCOS) and 19-41 kg/m(2) (controls). Anthropometric variables, volumes of subcutaneous/visceral adipose tissue (magnetic resonance imaging; MRI), and insulin sensitivity (clamp) were investigated. Adipose tissue biopsies were obtained to determine adipocyte size, lipoprotein lipase (LPL) activity, and macrophage density. Circulating testosterone, free testosterone, free 17β-estradiol, SHBG, glycerol, adiponectin, and serum amyloid A were measured/calculated. Results: Comparison of 31 pairs revealed lower insulin sensitivity, hyperandrogenemia, and higher free 17β-estradiol in PCOS. Abdominal adipose tissue volumes/distribution did not differ in the groups, but PCOS women had higher waist-to-hip ratio, enlarged adipocytes, reduced adiponectin, and lower LPL activity. In regression analysis, adipocyte size, adiponectin, and waist circumference were the factors most strongly associated with insulin sensitivity in PCOS (R(2)=0.681, P < 0.001). Conclusions: In PCOS, adipose tissue has aberrant morphology/function. Increased waist-to-hip ratio indicates abdominal/visceral fat accumulation, but this is not supported by MRI. Enlarged adipocytes and reduced serum adiponectin, together with a large waistline, rather than androgen excess, may be central factors in the pathogenesis/maintenance of insulin resistance in PCOS.

  • 287. Meaney, James F M
    et al.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Prince, M R
    Pulmonary magnetic resonance angiography1999In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 10, no 3, p. 326-338Article in journal (Refereed)
    Abstract [en]

    Early attempts to image the pulmonary vasculature with spin-echo magnetic resonance (MR) imaging were hampered by severe image degradation related to respiratory and cardiac pulsation artifact, susceptibility at interfaces between lung parenchyma and vessel wall, and poor contrast between flowing blood and intravascular filling defects of emboli. With the development of gradient-echo MR angiographic techniques some of these limitations were overcome; however, the need for multiple breath-holds and the frequent occurrence of flow-related artifacts that could simulate pulmonary emboli diminished their clinical utility. With the development of contrast-enhanced MR angiography, many of the limitations of earlier techniques were addressed. Images of both lungs with high signal-to-noise ratios and high contrast between flowing blood and pulmonary emboli could be acquired in a single breath-hold, during "first-pass" imaging with extracellular contrast agents in the coronal plane. However, subsegmental vessels could not be assessed with this approach. The technique has been refined further by imaging each lung separately in the sagittal plane; this offers higher resolution and total lung coverage and requires a shorter breath-hold. Finally, several investigators have reported preliminary data on imaging of the pulmonary vasculature with blood pool agents, exploiting respiratory triggering or navigator echoes to eliminate the need for breath-holding for the detection of pulmonary emboli.

  • 288.
    Melberg, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    White matter disorders with autosomal dominant heredity2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, no 1, p. 71-72Article in journal (Refereed)
  • 289.
    Melhus, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burman, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Use of novel bone biopsy system to study molecular effects of growth hormone in human bone: a pilot study1999In: IUBMB Life - A Journal of the International Union of Biochemistry and Molecular Biology, ISSN 1521-6543, E-ISSN 1521-6551, Vol. 48, no 2, p. 175-178Article in journal (Refereed)
    Abstract [en]

    In this study, we have examined whether a novel bone biopsy system combined with reverse transcription-polymerase chain reaction (RT-PCR) or differential display PCR (ddPCR) can be used to detect specific mRNAs induced by growth hormone (GH) in human bone. In a 58-year-old man with complete GH deficiency as a result of empty sella, bone biopsies were taken before, and 5 and 24 h after administration of 24 recombinant human GH. Insulin-like growth factor binding protein-3 (IGFBP-3) mRNA levels in this patient, measured in a semiquantitative RT-PCR assay, increased about 40% 24 h after GH administration. This increase was not seen in a healthy control who did not receive GH, suggesting that the increase was an effect of GH rather than of the biopsy itself. Several differentially expressed mRNAs were detected by ddPCR. Thus, this pilot study suggests that our novel bone biopsy system may be suitable for in vivo studies of the molecular effects of substances with essential functions in human bone.

  • 290. Meppelink, Anne Marthe
    et al.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    van Laar, Teus
    Drent, Martje
    Prins, Ted
    Leenders, Klaus Leonhard
    Transcutaneous Port for Continuous Duodenal Levodopa/Carbidopa Administration in Parkinson's Disease2011In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 26, no 2, p. 331-334Article in journal (Refereed)
    Abstract [en]

    Motor fluctuations in Parkinson's disease (PD) can be reduced by intraduodenal infusion of levodopa-carbidopa (Duodopa®) via percutaneous endoscopic gastrojejunostomy (PEG). We applied the transcutaneous soft-tissue anchored titanium port (T-port) in 15 PD patients with motor fluctuations; 7 Duodopa-naive (non-PEG), and 8 previously receiving Duodopa (former-PEG). Motor scores (UPDRS-III) and quality of life (QOL, PDQ-8) were assessed at baseline and 6 month follow-up. Six patients had local irritation shortly after implantation, persisting in one patient at 6 month follow-up, which led to explantation. After having finished the protocol, four T-ports were explanted in total. UPDRS-III and PDQ-8 scores improved moderately in the non-PEG patients, but remained similar in the former-PEG users. Two former-PEG users developed polyneuropathy. No obstructions, retractions, or leakages occurred. Technical and hygienic properties of the T-port were preferred by most patients. The T-port seems to be suitable for most PD patients qualifying for Duodopa therapy, although local infection may lead to explantation during longer-term follow-up.

  • 291. Meyer, Sofie
    et al.
    Valdemarsson, Stig
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Classification of pituitary growth hormone producing adenomas according to SIPAP: application in clinical practice2011In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 52, no 7, p. 796-801Article in journal (Refereed)
    Abstract [en]

    Background In 1997, the SIPAP classification was introduced, a guide designed for MRI, to characterize pituitary adenomas with emphasis on extrasellar extensions and impact on adjacent structures. To our knowledge no previous evaluation of the inter-observer agreement of the SIPAP classification has been performed.

    Purpose To evaluate the inter-observer agreement of the SIPAP classification.

    Material and Methods Sixty patients operated on for growth hormone producing pituitary adenomas at Lund University Hospital 1991-2007 had an assessable preoperative MRI scan. Forty-five of them also had an assessable postoperative MRI scan. The mean time between surgery and postoperative MRI scans was 11 months. Two observers evaluated all the MRI scans independently. The outcome of the evaluation is presented as the percentage of concordance in each of the evaluated directions and the degree of discrepancy for each of the directions evaluated.

    Results In 284 (79%) of 360 preoperative gradings both observers agreed completely. In 17 of the 60 preoperative MRI scans, both observers made identical assessments according to the SIPAP classification in all the six different directions of tumor extension. In 76 gradings the results differed between the observers. The difference was 1 grade (or less) in 69 cases. In 230 (85%) of 270 postoperative gradings the results were identical for both observers. In 18 of the 45 postoperative MRI scans, both observers made the same assessments according to the SIPAP classification in all the six different directions of tumor extension. In 40 gradings the results differed between the observers. The difference was 1 grade (or less) in all 40 cases.

    Conclusion We found a relatively high inter-observer agreement both pre- and postoperatively, supporting the usefulness and easy applicability of the SIPAP system for grading of pituitary adenomas pre- as well as postoperatively.

  • 292.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Quantitative Tracer Based MRI Perfusion: Potentials and Limitations2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tracer based MRI perfusion measurements is a clinically useful tool to assess regional distributions of tissue blood flow and volume. The method may be based on any of the three relaxation mechanisms T1, T1 and T2*, the latter denoted DSC-MRI being the most common. The primary aim of this work was to study the feasibility of obtaining quantitative estimates using these methods.

    1) Feasibility of DSC-MRI for kidneys using an iron oxide based contrast agent and the influence of secondary relaxation effects on the results, part of a clinical phase II trial: The method proved feasible and the underestimation induced by secondary relaxation can be corrected for by using a double echo sequence.

    2) Influence of blood flow rate on risk factors for developing cerebral ischemia during cardio pulmonary bypass, measurements in pig with gadolinium based DSC-MRI: The results indicated an ischemic threshold level at a blood flow rate of approximately 6 ml/kg/min.

    3) The ability of gadolinium based DSC-MRI to detect changes in global blood flow, experimental measurements in pig and numerical simulations: The results support that DSC-MRI can discriminate between global flow levels in the same subject given that all other parameters are kept constant. The results also indicate that calculated perfusion values are highly sensitive to the arterial deconvolution procedure.

    4) Influence of differences in blood/tissue relaxivity and secondary relaxation for a gadolinium based contrast agent, measurements in pig and numerical simulations: The blood/tissue relaxivity ratio is not unity and the situation is complicated by secondary relaxation effects. Deconvolution regularization appears to partly counteract the overestimation induced by difference in blood/tissue relaxivity for DSC-MRI.

    In summary, the fundamental assumption of equal blood and tissue relaxivity is experimentally shown to be invalid and the influence of this discrepancy is substantial. Several factors contribute to measurement errors, a combination of these factors can incidentally lead to additive errors or error cancellation based on a variety of experimental and analysis conditions. Given that the differences in blood/tissue relaxivity cannot readily be accounted for in a clinical setting, absolute perfusion quantification by tracer based MRI remains challenging if not impossible.

    List of papers
    1. Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of T1 shortening
    Open this publication in new window or tab >>Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of T1 shortening
    Show others...
    2008 (English)In: Acta radiologica (Stockholm, Sweden : 1987), ISSN 1600-0455, Vol. 49, no 8, p. 955-62Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Using conventional contrast agents, the technique of quantitative perfusion by observing the transport of a bolus with magnetic resonance imaging (MRI) is limited to the brain due to extravascular leakage. PURPOSE: To perform quantitative perfusion measurements in humans with an intravascular contrast agent, and to estimate the influence of the T1 relaxivity of the contrast agent on the first-pass response. MATERIAL AND METHODS: Renal cortical perfusion was measured quantitatively in six patients with unilateral renal artery stenosis using a rapid gradient double-echo sequence in combination with an intravenous bolus injection of NC100150 Injection, an intravascular contrast agent based on iron-oxide nanoparticles. The influence of T1 relaxivity was measured by comparing perfusion results based on single- and double-echo data. RESULTS: The mean values of cortical blood flow, cortical blood volume, and mean transit time in the normal kidneys were measured to 339+/-60 ml/min/100 g, 41+/-8 ml/100 g, and 7.3+/-1.0 s, respectively, based on double-echo data. The corresponding results based on single-echo data, which are not compensated for the T1 relaxivity, were 254+/-47 ml/min/100 g, 27+/-3 ml/100 g, and 6+/-1.2 s, respectively. CONCLUSION: The use of a double-echo sequence enabled elimination of confounding T1 effects and consequent systematic underestimation of the perfusion.

    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Research subject
    Radiology
    Identifiers
    urn:nbn:se:uu:diva-103263 (URN)10.1080/02841850802227139 (DOI)000260046200017 ()18615336 (PubMedID)
    Available from: 2009-05-18 Created: 2009-05-18 Last updated: 2012-08-01Bibliographically approved