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  • 51.
    Eklöf, Hampus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Hägg, A.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Outcome after endovascular revascularization of atherosclerotic renal artery stenosis2009In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 50, no 3, p. 256-64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: With an aging population, more patients might be treated for atherosclerotic renal artery stenosis (ARAS). The goal of this treatment is to achieve a dialysis-free life or a well-controlled blood pressure with reduced risks of cardiovascular complications. PURPOSE: To analyze the clinical outcome of percutaneous transluminal renal artery angioplasty without stenting (PTRA) or with stenting (PTRS) for ARAS at one center. MATERIAL AND METHODS: The study group comprised 152 patients who underwent 203 PTRA/PTRS. All had hypertension, and 45% had azotemia. A retrospective collection of baseline and postprocedural number of antihypertensive drugs, blood pressure, and serum creatinine were analyzed during a follow-up of 3-18 months. RESULTS: Technical success rate was 95%, and clinical benefit was seen in 63% of patients. Complications included a 30-day mortality rate of 1.5%, a total complication rate of 35%, and major adverse events in 13%. The major adverse events were highly related to azotemia. Major adverse events within 30 days, with permanent disability, were seen in 5% and almost exclusively in patients with moderate or severe renal impairment. A subgroup analysis of 28 patients with renal duplex resistive index (RI) pre-PTRA/S and 6 months' follow-up showed a benefit of PTRA/PTRS in 17 (68%) of the 25 patients with RI <80 and in all three (100%) of the patients with RI >or=80. CONCLUSION: Endovascular treatment of ARAS has an excellent technical success rate, with a clinical improvement rate of >60%. However, it is associated with a considerable complication rate. Serious complications are seen mainly in azotemic patients. Predictors of clinical response could not be identified. Renal duplex RI is questioned as a predictor of clinical outcome.

  • 52.
    Eklöf, Hampus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Hägg, Anders
    Gottsäter, Anders
    Kahan, Thomas
    Dimény, Emöke
    Berggren, Bosse
    Jensen, Gert
    Herlitz, Hans
    Eliasson, Keith
    Hedin, Ulf
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    ASTRAL-studiens konklusion ifrågasätts: Experter eniga om indikationer för behandling av njurartärstenos2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 36, p. 2102-2104Article in journal (Refereed)
  • 53.
    Eklöf, Hampus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Radecka, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Teleradiology Uppsala-Sydney for nighttime emergencies: preliminary experience2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 8, p. 851-853Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The development of digital imaging systems for radiology in combination with the possibility to transfer large quantities of data over the Internet has increased the interest in teleradiology. Transferring nighttime examinations to an evaluation center in a daytime zone may provide improved patient security, better working hours for radiologists, and reduced costs for emergency radiological services. PURPOSE: To evaluate the time required for transferring radiological information from Uppsala (Sweden) to Sydney (Australia). MATERIAL AND METHODS: A radiologist in Sydney reported on radiological examinations performed in Uppsala. The time required for downloading 75 examinations and returning 24 reports was registered. RESULTS: Downloading was completed in <60 min for all conventional radiological examinations, but only 44% of computed tomography (CT) examinations with >65 images. Reports were completed in <10 min. Turnaround time was directly related to the time required for downloading the images. The Sydney report was available in Uppsala within 30 min of the in-house report in 79% of examinations. CONCLUSION: The main challenge for emergency teleradiology is the time required for downloading large volumes of data over the Internet.

  • 54. Eriksson, Jan W.
    et al.
    Jansson, Per-Anders
    Carlberg, Bo
    Hägg, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kurland, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svensson, Maria K.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ström, Conny
    Lönn, Lars
    Öjbrandt, Kristina
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study2008In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 52, no 6, p. 1030-1037Article in journal (Refereed)
    Abstract [en]

    Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P<or=0.01). Liver fat content was higher (P<0.05) following H than both P and C. The subcutaneous to visceral abdominal adipose tissue ratio was reduced following H versus C and P (P<0.01). Glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein levels were higher (P<0.05) after H, but not C, versus P. There were no changes in body fat, intramyocellular lipid, extramyocellular lipid, or first-phase insulin secretion. Blood pressure was reduced similarly by C and H versus P. In conclusion, visceral fat redistribution, liver fat accumulation, low-grade inflammation, and aggravated insulin resistance were demonstrated after hydrochlorothiazide but not candesartan treatment. These findings can partly explain the diabetogenic potential of thiazides.

  • 55.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Krause, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lundberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgery and radiofrequency ablation for treatment of liver metastases from midgut and foregut carcinoids and endocrine pancreatic tumors2008In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 32, no 5, p. 930-938Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Many neuroendocrine tumors (NETs) have a tendency to metastasize to the liver. In case of limited number of metastases, liver surgery or radiofrequency ablation (RFA) may result in apparently total clearance of metastases. However, it is not clear whether such therapy will provide symptom reduction or increased survival.

    METHODS:

    Seventy-three patients with foregut (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two patients with NETs without discernable origin were studied. Symptoms were evaluated using a Symptom Severity Score. Liver surgery was performed in 42 operations and RFA on 205 lesions.

    RESULTS:

    Apparently total clearance of liver metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of 17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no improvement of symptoms after surgical/RFA liver treatment, but eight patients had functioning EPT, and four of these reduced their biochemical markers by at least 50%. NETs with higher Ki67 index tended to recur more often. Complications occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.

    CONCLUSIONS:

    Treatment of liver metastases is successful in midgut carcinoid patients with limited liver metastases. Patients with foregut carcinoid and EPTs recur more often, possibly related to higher Ki67 index, and treatment of liver lesions less often reduces symptoms. Liver resections and RFA may be safely performed, and RFA is associated with few complications.

  • 56.
    Eriksson, Lars-Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ljungdahl, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Transcatheter arterial embolization versus surgery in the treatment of upper gastrointestinal bleeding after therapeutic endoscopy failure2008In: Journal of Vascular and Interventional Radiology, ISSN 1051-0443, E-ISSN 1535-7732, Vol. 19, no 10, p. 1413-8Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To retrospectively compare the outcome of transcatheter arterial embolization (TAE) and surgery as salvage therapy of upper gastrointestinal bleeding after failed endoscopic treatment. MATERIALS AND METHODS: From January 1998 to December 2005, 658 patients were referred to diagnostic/therapeutic emergency endoscopy and diagnosed with upper gastrointestinal bleeding. Ninety-one of these 658 patients (14%) had repeat bleeding or continued to bleed. Forty of those 91 patients were treated with TAE and 51 were treated with surgery. From the medical records, the following variables were recorded: demographic data, endoscopic diagnoses, comorbidities, lowest hemoglobin levels, total transfusion requirements, lengths of hospitalization stays, postprocedure complications, and mortality rates. The relative survival rate was calculated, and survival probability was calculated with the Kaplan-Meier technique. RESULTS: Patients treated with TAE were older (mean age, 76 years; age range, 40-94 years) and had slightly more comorbidities compared to patients who underwent surgery (mean age, 71 years; age range, 45-89 years). The 30-day mortality rate in patients treated with TAE was one of 40 (3%) compared to seven of 51 (14%) in patients treated with surgery (P < .07). Most repeat bleeding could be effectively treated with TAE, both in the surgical and TAE groups. CONCLUSIONS: The results of this study suggest that, after failure of therapeutic endoscopy for upper gastrointestinal bleeding, TAE should be the treatment of choice before surgery and that TAE can also be used to effectively control bleeding after failed surgery or TAE. There was a clear trend to lower 30-day mortality with use of TAE instead of surgery.

  • 57.
    Eriksson, Lars-Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lutvica-Mulic, Ajlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jangland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Massive Postpartum Hemorrhage Treated with Transcatheter Arterial Embolization: Technical aspects and long-term effects on fertility and menstrual cycle2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 6, p. 635-642Article in journal (Refereed)
    Abstract [en]

    Background: Transcatheter arterial embolization (TAE) is considered a safe, life-saving procedure in postpartum hemorrhage (PPH), but its long-term effect on menstruation and fertility is unclear. Purpose: To investigate technical aspects and the evaluation of complications, focused on menstrual cycle and fertility, using TAE in patients with PPH. Material and Methods: A retrospective study including 20 patients (seven with vaginal and 13 with cesarean delivery) with severe PPH treated with bilateral TAE of the uterine artery was carried out. All patients were asked to answer a questionnaire regarding their post-embolization history. In six patients, the radiation dose was measured. Results: All 20 cases underwent bilateral TAE of the uterine artery. Gelfoam was used as the embolic agent. However, after cesarean delivery in six patients who had clear contrast medium extravasation and/or pseudoaneurysm-like lesion, metallic coils had to be used in order to achieve hemostasis. No major short- or long-term complications were registered. Normal menses resumed in all patients. Four patients had a total of five full-term and two preterm pregnancies, and all delivered healthy infants by cesarean section with no recurrence of PPH. The mean radiation dose to the ovaries was 586 mGy (range 204-729 mGy). Conclusion: TAE in patients with PPH is safe and has no major short- or long-term side effects. A patient managed with TAE can expect return of normal menses and preservation of future fertility and successful pregnancies. PPH after cesarean section might need to be embolized with metallic coils in addition to Gelfoam in order to achieve secure hemostasis.

  • 58.
    Eriksson, Lars-Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sundbom, Magnus
    Gustavsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Endoscopic marking with metallic clip facilitates transcatheter arterial embolization in upper peptic ulcer bleeding.2006In: Journal of Vascular and Interventional Radiology, ISSN 1051-0443, E-ISSN 1535-7732, Vol. 17, no 6, p. 959-964Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To enable accurate transcatheter arterial embolization (TAE) of the target vessel, a new technique to localize the exact position of a bleeding ulcer was tested that involves endoscopic marking of the ulcer with a metallic clip. MATERIALS AND METHODS: In 13 patients (mean age, 75 years) with acute bleeding ulcers (11 duodenal ulcers, two malignant ulcers), a metallic clip was placed at gastroscopy followed or preceded by routine endoscopic treatment. The metallic clip was placed in the fibrous edge of the ulcer adjacent to the bleeding point. In 10 patients, TAE was indicated as a result of continued or recurrent bleeding. The artery was embolized with microcoils as close as possible to the clip. In three patients, there was no indication for TAE, so plain abdominal radiography was performed to determine whether the marking clip was still in place. RESULTS: In 11 patients, the clip was still in place on radiography; in two, it had disappeared. Hemostasis was achieved in eight of 10 patients after TAE. In six patients, the clip was essential to identify the bleeding vessel. CONCLUSION: Marking of the bleeding ulcer with a clip before TAE enhances the possibility that the correct vessel is embolized. This will most likely minimize the risk of recurrent bleeding after embolization, especially in patients who do not show contrast medium extravasation.

  • 59.
    Eriksson, Mats-Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Intravascular Ultrasound with a Vector Phased-Array Probe (AcuNav) Is Feasible in Endovascular Abdominal Aortic Aneurysm Repair2009In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 50, no 8, p. 870-875Article in journal (Refereed)
    Abstract [en]

    Background: The ideal imaging method for endovascular aneurysm repair (EVAR) should provide all data regarding diagnosis, measurements, and guiding of stent-graft deployment. Contrast-enhanced computed tomography (CT) is used for preoperative EVAR planning, together with intraoperative angiography. However, the administered contrast volume might result in contrast-induced nephropathy (CIN). Purpose: To develop a technique for aortic measurements, vessel wall evaluation, and stent-graft positioning by using a vector phased-array intravascular ultrasound probe with color Doppler function (AcuNav) in elective EVAR. Material and Methods: Thirteen elective EVAR patients were included. AcuNav was compared to pre- and postoperative CT examinations, perioperative angiography, and postoperative duplex. Results: Measurements for stent-graft sizing were easily obtained and facilitated by the color Doppler function and corresponded well with CT and angiography. The combined information from AcuNav and fluoroscopy provided exact positioning of the stent graft. An aortic placement of the probe provided superior imaging results compared to an inferior vena cava approach. Detection of endoleak was found to be difficult. No complications were registered. Conclusion: The use of AcuNav combined with fluoroscopy in EVAR was found to be safe, effective, and feasible in planning and guiding EVAR procedures. Best results were seen with the probe placed in the artery. AcuNav might be used to replace contrast-enhanced CT and angiography, hence reducing the risk of CIN, especially in high-risk patients.

  • 60.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Imaging Islets of Langerhans by Positron Emission Tomography: Quantification of Beta-Cell Mass in the Native Pancreas and the Islet Graft2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 and 2 Diabetes Mellitus are a growing health problem throughout the world. There is an increasing  need for methodologies, which are both reliable and non-invasive to measure the amount of insulin-producing tissue (Beta-cell mass, or BCM), as well as rapidly quantify changes in the BCM due to the onset of disease, beta-cell replacement therapy, or other treatments.

    Positron Emission Tomography (PET) is a non-invasive, quantitative functional imaging technique which can be used to study dynamical or static processes inside the body.

    In this thesis, we present a study protocol for in vivo imaging of the most common form of beta- cell replacement therapy; islet transplantation. Islets were labeled with the PET tracer, 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG), and administered intra-portally, while the recipient was monitored by PET/CT. The hepatic distribution of the islets was highly heterogeneous, and around 25% (human) or 50% (porcine) of the administered islets could not be found in the liver after completed transplantation, confirming previous reports of considerable cell injury during the procedure leading to low hepatic engraftment.

    Native BCM in the pancreas can potentially be quantified using a PET tracer with sufficiently high specificity, but the major obstacle is the relative low amounts of insulin producing tissue (only 1-2% of the pancreatic volume). Two tetrabenazine analogues, [18F]FE-(+)-DTBZ and [18F]FE-(+)-DTBZ-d4, are ligands to VMAT2, which is expressed in islet tissue. Both analogues were investigated and characterized as potential BCM imaging agents both in vitro and in vivo.  Both tracers exhibited high preferential binding to islet tissue compared to exocrine pancreatic tissue. However, the specificity was not high enough to overcome the obscuring exocrine signal in vivo (7-10% of the signal originating from specific islet tracer uptake).

    This thesis demonstrates that it is possible to quantitatively assess islet transplantation by PET imaging. In vivo determination of native pancreatic BCM is, in theory, possible with both [18F]FE-(+)-DTBZ and [18F]FE-(+)-DTBZ-d4, but tracer analogues with higher islet specificity is needed for quantification of smaller BCM changes with physiological impact.

    List of papers
    1. Positron emission tomography: A real-time tool to quantify early islet engraftment in a preclinical large animal model
    Open this publication in new window or tab >>Positron emission tomography: A real-time tool to quantify early islet engraftment in a preclinical large animal model
    Show others...
    2007 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 84, no 7, p. 893-898Article in journal (Refereed) Published
    Abstract [en]

    Background. Clinical islet transplantation is currently being explored as a therapeutic option for persons with type I diabetes and hypoglycemic unawareness. Techniques to monitor graft survival are urgently needed to optimize the procedure. Therefore, the objective of the present study was to develop a technique for imaging survival of transplanted islets in the peritransplant and early posttransplant phase.

    Methods. Isolated porcine islets were labeled in vitro with 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) and infused intraportally into anesthetized pigs (n=10). Dynamic examination was performed on a positron emission tomography/computed tomography hybrid system.

    Results. More than 95% of the radioactivity was confined to the islets at the time of transplantation. The peak percentage of infused radioactivity within the liver, quantified at the end of the islet infusion, was only 54±5.1%. The distribution of the radioactivity in the liver was found to be heterogeneous. A whole-body examination showed no accumulation in the lungs or brain; extrahepatic radioactivity was, except urinary excretion, evenly distributed in the pig body.

    Conclusions. Our results imply that almost 50% of the islets were damaged to the extent that the FDG contained was release within minutes after intraportal transplantation. The distribution of radioactivity without accumulation in the brain indicates that the activity is released from lysed islet cells in the form of [18F]FDG-6P rather than native [18F]FDG. The presented technique shows promise to become a powerful and quantitative tool, readily available in the clinic, to evaluate initial islet engraftment and survival.

    Keywords
    Imaging, Islets, PET scanning, Transplantation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-14994 (URN)10.1097/01.tp.0000284730.86567.9f (DOI)000250232600014 ()17984843 (PubMedID)
    Available from: 2008-06-05 Created: 2008-06-05 Last updated: 2017-12-11Bibliographically approved
    2. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography
    Open this publication in new window or tab >>Visualization of early engraftment in clinical islet transplantation by positron-emission tomography
    2007 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 356, no 26, p. 2754-2755Article in journal, Letter (Refereed) Published
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-103621 (URN)000247564500035 ()17596618 (PubMedID)
    Available from: 2009-05-20 Created: 2009-05-20 Last updated: 2017-12-13Bibliographically approved
    3. Positron emission tomography in clinical islet transplantation
    Open this publication in new window or tab >>Positron emission tomography in clinical islet transplantation
    Show others...
    2009 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 9, no 12, p. 2816-2824Article in journal (Refereed) Published
    Abstract [en]

    The fate of islets in clinical transplantation is unclear. To elude on this positron emission tomography combined with computed tomography (PET/CT) was performed for 60 min during islet transplantation in five patients receiving six transplants. A fraction of the islets (23%) were labeled with 18F-fluorodeoxyglucose ([(18)F]FDG) and carefully mixed with unlabeled islets just prior to intraportal transplantation. The peak radioactivity concentration in the liver was found at 19 min after start of islet infusion and corresponded to only 75% of what was expected, indicating that islets are lost during the transplantation procedure. No accumulation of radioactivity was found in the lungs. A nonphysiological peak of C-peptide was found in plasma during and immediately after transplantation in all subjects. Distribution in the liver was heterogeneous with wide variations in location and concentration. Islets found in areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32% of the graft in different subjects. No side effects attributed to the PET/CT procedure were found. Clinical outcome in all patients was comparable to that previously observed indicating that the [(18)F]FDG labeling procedure did not harm the islets. The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-111860 (URN)10.1111/j.1600-6143.2009.02844.x (DOI)000272127600023 ()19845588 (PubMedID)
    Available from: 2009-12-28 Created: 2009-12-28 Last updated: 2017-12-12Bibliographically approved
    4. In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass
    Open this publication in new window or tab >>In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass
    Show others...
    2010 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 37, no 3, p. 357-363Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: The positron emission tomography (PET) tracer 9-[(18)F]fluoroethyl-(+)-dihydrotetrabenazine ([(18)F]-FE-(+)-DTBZ) is a potential candidate for quantifying beta-cell mass in vivo. The purpose was to investigate in vitro and in vivo utility of this tracer for the assessment of beta-cell mass.

    METHODS: Three pigs were intravenously administered [(18)F]-FE-(+)-DTBZ and examined by PET/computed tomography. Binding parameters were estimated by kinetic modeling. In vitro k(D) and B(max) were determined by saturation binding studies of endocrine and exocrine human tissue homogenates. In vitro pancreatic uptake was determined by tissue autoradiography with pancreases from patients with types 1 (T1DM) and 2 diabetes mellitus (T2DM) and healthy controls.

    RESULTS: [(18)F]-FE-(+)-DTBZ had a k(D) of 3.5+/-1.0 nM, a B(max) of 382+/-108 fmol/mg protein and a specificity of 89+/-1.8% in islet homogenates. The total exocrine uptake was lower and 65% was nondisplaceable. No uptake difference was observed in pancreatic tissue slices from patients with T1DM, T2DM or healthy controls. The in vivo porcine pancreatic uptake reached a peak of standardized uptake value (SUV) of 2.8 with a low distribution volume ratio in all animals. Moderate to high tracer uptake was identified in the bile system and in bone.

    CONCLUSIONS: [(18)F]-FE-(+)-DTBZ binds to vesicular monoamine transporter 2 (VMAT2) with high specificity in pure islet tissue in vitro. However, there is high nondisplaceable binding to exocrine tissue. In addition, in vivo tracer metabolism and dehalogenation result in severe underestimation of porcine pancreatic VMAT2 expression and BCM. The results do not support [(18)F]-FE-(+)-DTBZ as a suitable tracer for in vivo beta-cell imaging.

    Keywords
    Positron emission tomography, DTBZ, Beta-cell mass, VMAT2
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-136369 (URN)10.1016/j.nucmedbio.2009.12.004 (DOI)000276551800013 ()20346875 (PubMedID)
    Available from: 2010-12-12 Created: 2010-12-12 Last updated: 2017-12-11Bibliographically approved
    5. Decreased defluorination by using the novel beta cell imaging agent [18F]FE-DTBZ-d4 in pigs examined by PET
    Open this publication in new window or tab >>Decreased defluorination by using the novel beta cell imaging agent [18F]FE-DTBZ-d4 in pigs examined by PET
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: Fluorine-18 DTBZ-analogues, which selectively targets the vesicular monoamine transporter 2 (VMAT2), have been extensively studied for in vivo quantification of beta cell mass by positron emission tomography (PET).  This study describes a novel deuterated radioligand [18F]FE-(+)-DTBZ-d4, aimed to increase the stability against in vivo defluorination previously observed for [18F]FE-(+)-DTBZ.

    Methods: [18F]FE-(+)-DTBZ-d4 was synthesized by alkylation of desmethyl -(+)-DTBZ precursor with deuterated  [18F]fluoroethyl bromide ([18F]FCD2CD2Br). Radioligand affinity and specificity to VMAT2 was assessed by an in vitro saturation homogenate binding assay using human endocrine and exocrine pancreatic tissues. In vivo PK/PD was studied in a porcine model by PET/CT. The rate of defluorination was quantified by compartmental modeling and contrasted against defluorination of the non-deuterated analogue.

    Results: [18F]FE-DTBZ-d4 was produced in good radiochemical yield (3.0-1.7 GBq) in 100 min. Radiochemical purity of the formulated product was > 98% for up to 5h. The in vitro Binding Potential (BP) for VMAT2 in islet tissue was 27.0±8.8. The BP was lower in exocrine tissue (1.7±1.0) in addition to a close to three-fold decrease in specificity. The rate of in vivo defluorination was decreased significantly (kdefluorination= 0.0016±0.0007) compared to the non-deuterated analogue (kdefluorination= 0.012±0.002), resulting in a more than six-fold increase in half-life stability.

    Conclusion: [18F]FE-(+)-DTBZ-d4 has favorable pharmacokinetic (PK) properties for VMAT2 imaging, in addition to gaining significantly increased stability against defluorination. The in vitro islet BP and specificity was lower compared to a non-deuterated analogue but the islet/exocrine BP ratio was unchanged, potentially allowing for improved target tissue discrimination.

    National Category
    Immunology in the medical area
    Identifiers
    urn:nbn:se:uu:diva-136370 (URN)
    Available from: 2010-12-12 Created: 2010-12-12 Last updated: 2018-01-12
  • 61.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Eich, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tibell, Annika
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Andersson, H.
    Felldin, M.
    Foss, A.
    Kyllönen, L.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Lundgren, Torbjörn
    Positron emission tomography in clinical islet transplantation2009In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 9, no 12, p. 2816-2824Article in journal (Refereed)
    Abstract [en]

    The fate of islets in clinical transplantation is unclear. To elude on this positron emission tomography combined with computed tomography (PET/CT) was performed for 60 min during islet transplantation in five patients receiving six transplants. A fraction of the islets (23%) were labeled with 18F-fluorodeoxyglucose ([(18)F]FDG) and carefully mixed with unlabeled islets just prior to intraportal transplantation. The peak radioactivity concentration in the liver was found at 19 min after start of islet infusion and corresponded to only 75% of what was expected, indicating that islets are lost during the transplantation procedure. No accumulation of radioactivity was found in the lungs. A nonphysiological peak of C-peptide was found in plasma during and immediately after transplantation in all subjects. Distribution in the liver was heterogeneous with wide variations in location and concentration. Islets found in areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32% of the graft in different subjects. No side effects attributed to the PET/CT procedure were found. Clinical outcome in all patients was comparable to that previously observed indicating that the [(18)F]FDG labeling procedure did not harm the islets. The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation.

  • 62.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Jahan, Mahabuba
    Johnström, Peter
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Halldin, Christer
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass2010In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 37, no 3, p. 357-363Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The positron emission tomography (PET) tracer 9-[(18)F]fluoroethyl-(+)-dihydrotetrabenazine ([(18)F]-FE-(+)-DTBZ) is a potential candidate for quantifying beta-cell mass in vivo. The purpose was to investigate in vitro and in vivo utility of this tracer for the assessment of beta-cell mass.

    METHODS: Three pigs were intravenously administered [(18)F]-FE-(+)-DTBZ and examined by PET/computed tomography. Binding parameters were estimated by kinetic modeling. In vitro k(D) and B(max) were determined by saturation binding studies of endocrine and exocrine human tissue homogenates. In vitro pancreatic uptake was determined by tissue autoradiography with pancreases from patients with types 1 (T1DM) and 2 diabetes mellitus (T2DM) and healthy controls.

    RESULTS: [(18)F]-FE-(+)-DTBZ had a k(D) of 3.5+/-1.0 nM, a B(max) of 382+/-108 fmol/mg protein and a specificity of 89+/-1.8% in islet homogenates. The total exocrine uptake was lower and 65% was nondisplaceable. No uptake difference was observed in pancreatic tissue slices from patients with T1DM, T2DM or healthy controls. The in vivo porcine pancreatic uptake reached a peak of standardized uptake value (SUV) of 2.8 with a low distribution volume ratio in all animals. Moderate to high tracer uptake was identified in the bile system and in bone.

    CONCLUSIONS: [(18)F]-FE-(+)-DTBZ binds to vesicular monoamine transporter 2 (VMAT2) with high specificity in pure islet tissue in vitro. However, there is high nondisplaceable binding to exocrine tissue. In addition, in vivo tracer metabolism and dehalogenation result in severe underestimation of porcine pancreatic VMAT2 expression and BCM. The results do not support [(18)F]-FE-(+)-DTBZ as a suitable tracer for in vivo beta-cell imaging.

  • 63.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Josephsson, Ray
    Långström, Bengt
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Positron emission tomography and target-controlled infusion for precise modulation of brain drug concentration2008In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 35, no 3, p. 299-303Article in journal (Refereed)
    Abstract [en]

    Introduction: There are several instances when it is desirable to control brain concentration of pharmaceuticals, e.g., to modulate the concentration of anesthetic agents to different desired levels fitting to different needs during the course of surgery. This has so far only been possible using indirect estimates of drug concentration such as assuming constant relation between tissue and blood including extrapolations from animals. Methods: A system for controlling target tissue concentration (UIPump) was used to regulate whole-brain concentrations of a central benzodiazepine receptor antagonist at therapeutic levels with input from brain kinetics as determined with PET. The system was tested by using pharmacological doses of flumazenil mixed with tracer amounts of [C-11]flumazenil. Flumazenil was used as a model compound for anesthesia. An infusion scheme to produce three different steady-state levels in sequence was designed based on kinetic curves obtained after bolus injection. The subjects (Sprague-Dawley rats, n = 6) were monitored in a microPET scanner during the whole experiment to verify resulting brain kinetic curves. Results: A steady-state brain concentration was rapidly achieved corresponding to a whole-brain concentration of 118 +/- 6 ng/ml. As the infusion rate decreased to lower the exposure by a factor of 2, the brain concentration decreased to 56 +/- 4 ng/ml. A third increased steady-state level of anesthesia corresponding to a whole-brain concentration of 107 +/- 7 ng/ml was rapidly achieved. Conclusion: The experimental setup with computerized pump infusion and PET supervision enables accurate setting of target tissue drug concentration.

  • 64.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wallberg, Andreas
    Syvänen, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Josephsson, Raymond
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    A computerized Infusion Pump for control of tissue tracer concentration during Positron Emission Tomography in vivo Pharmacokinetic/Pharmacodynamic measurements2008In: BMC Medical Physics, ISSN 1756-6649, E-ISSN 1756-6649, Vol. 8, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    A computer controlled infusion pump (UIPump) for regulation of target tissue concentration of radioactive compounds was developed for use in biological research and tracer development for PET.

    METHODS:

    Based on observed tissue or plasma kinetics after a bolus injection of the tracer an algorithm calculates the infusion needed to obtain a specified target kinetic curve. A computer feeds this infusion scheme into an infusion pump connected to an animal via a venous catheter. The concept was validated using [11C]Flumazenil administrated to Sprague-Dawley rats where the whole brain distribution and kinetic of the tracer was measured over time using a microPET-scanner. The accuracy and precision of the system was assessed by producing steady-state levels of the tracer and by mimicking kinetics after oral administration.

    RESULTS:

    Various kinetic profiles could be generated, including rapid achievement of constant levels, or step-wise increased levels. The resulting tissue curves had low deviation from the target curves according to the specified criteria: AUC (%): 4.2 +/- 2.8, Maximal deviation (%): 13.6 +/- 5.0 and R2: 0.95 +/- 0.02.

    CONCLUSION:

    The UIPump-system is suitable for use in PET-research for assessment of PK/PD properties by simulation of different tracer tissue kinetics in vivo.

  • 65.
    Eriksson, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Karlsson, Jan Olof G.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Contrast enhancement of manganese-hydroxypropyl-tetraacetic acid, an MR contrast agent with potential for detecting differences in myocardial blood flow2006In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 24, no 4, p. 858-863Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine whether the contrast agent MnHPTA has potential for detecting differences in myocardial blood flow.

    Materials and Methods: R1 in the myocardium was calculated from MR signal intensity measurements in 18 pigs after intravenous injection of 5, 15, or 25 mu mol MnHPTA/kg body weight. Measurements were made in each animal after administration at rest and during dobutamine-induced stress.

    Results: A difference of approximately 0.1 see(-1) in the R1 increase between rest and stress still remained 31 minutes after administration of 25 mu mol MnHPTA/kg body weight. When two consecutive MnHPTA injections were performed, the second injection induced a lower R1 increase than the corresponding first injection.

    Conclusion: MnHPTA at a dose of 25 mu mol/kg body weight (b.w.) has the potential to detect perfusion differences in myocardium. When two consecutive injections of MnHPTA were administered, the RI change after the second injection was affected by the earlier administration. Therefore, a protocol including more than one administration is not ideal for this contrast agent.

  • 66. Finnbogason, T.
    et al.
    Jorulf, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Söderman, E.
    Rehnberg, L.
    Anterior dynamic ultrasound and Graf's examination in neonatal hip instability2008In: Acta radiologica (Stockholm, Sweden : 1987), ISSN 1600-0455, Vol. 49, no 2, p. 204-11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Discrepancy between neonatal hip morphology and stability has been reported in the literature. Comparative ultrasound studies on this issue are limited. PURPOSE: To compare neonatal hip instability, as assessed by dynamic ultrasound and clinical examination, with acetabular morphology, as assessed by Graf's method. MATERIAL AND METHODS: 536 newborn infants with clinical signs of hip instability, ambiguous findings at clinical hip examination, or positive risk factors for DDH were investigated with two ultrasound methods, the Graf method and anterior dynamic ultrasound, at an average age of 12 days. The hips were allocated to three groups according to the Graf result: A, normal (type Ia and b); B, borderline or immature (type IIa); and C, pathologic (type IIc and worse). Graf examination was compared with two diagnostic tests for instability, namely clinical examination by senior pediatric orthopedists and anterior dynamic ultrasound. RESULTS: According to Graf's method, 77% of the hips were normal, 20% borderline/immature, and 3% pathologic. On clinical hip examination, 82% were stable, 14% unstable, and 4% dislocatable. The dynamic ultrasound outcome was 88% stable hips, 10% unstable, and 2% dislocatable. Of the hips considered unstable or dislocatable on dynamic ultrasound, 21% had normal (type I) and 66% immature acetabular morphology according to the Graf method. Of the hips that were stable on dynamic ultrasound, only one (0.1%) was dysplastic according to the Graf method. Graf's examination showed the smallest number of normal hips, but also the fewest pathologic hips, with many indeterminate results that needed follow-up. CONCLUSION: Acetabular morphology correlated better to stability as assessed by dynamic ultrasound than to the clinical examination results, with fair to moderate agreement. Graf's examination resulted in a large number of indeterminate results that needed follow-up, but when used as the sole criterion for deciding treatment did not lead to a higher treatment rate than when the decision was based on clinical hip examination.

  • 67. Finnbogason, T.
    et al.
    Jorulf, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Söderman, E.
    Rehnberg, L.
    Neonatal hip instability: a prospective comparison of clinical examination and anterior dynamic ultrasound2008In: Acta radiologica (Stockholm, Sweden : 1987), ISSN 1600-0455, Vol. 49, no 2, p. 212-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ultrasound is increasingly being used to complement the clinical examination in assessing neonatal hip instability. The clinical examination, although highly sensitive in detecting hip instability, can lead to considerable overtreatment. PURPOSE: To compare anterior dynamic ultrasound and clinical examination in the assessment of neonatal hip instability and regarding treatment rates. MATERIAL AND METHODS: 536 newborn infants (out of a population of 18,031) were selected, on the basis of a combination of risk factors, clinical signs of hip instability or ambiguous clinical findings, to undergo an anterior dynamic ultrasound examination of the hip, by a method developed by our group. This examination, performed by one out of seven experienced examiners, was compared with the standard clinical hip examination conducted by one of four pediatric orthopedic surgeons. The clinical examination was carried out both prior to and within a few hours after the ultrasound examination. RESULTS: The clinical examination diagnosed 81.7% of the hips as normal, 14.5% as unstable, and 3.8% as dislocatable or dislocated. With the dynamic ultrasound method, the corresponding figures were 87.8%, 10.4%, and 1.8%, respectively. Use of the criteria of the clinical examination resulted in treatment of 147 infants. Using the dynamic ultrasound examination as a criterion meant that 87 infants would receive treatment. The calculated treatment rate was 0.85% when based on the clinical stress test and 0.49% when based on the dynamic ultrasound. CONCLUSION: The dynamic ultrasound results reduced the treatment rate by over 40% when used as a basis for the decision regarding treatment.

  • 68.
    Forsberg, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Agartz, Ingrid
    Department of Clinical Neuroscience, Karolinska Institutet and Hospital.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Henriksson, Karin
    Department of Laboratory Medicine, Lund University.
    Landmark-Based Software for Anatomical Measurements: A Precision Study2009In: Clinical anatomy (New York, N.Y. Print), ISSN 0897-3806, E-ISSN 1098-2353, Vol. 22, no 4, p. 456-462Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to develop a software program, called Landmarker, which would aid studies of complex anatomical morphometry by simplifying the manual identification of landmarks in 3D images. We also tested its precision on routine magnetic resonance imaging (MRI) scans. To understand human biological variation, there is a need to identify morphological characteristics from the exterior and the interior of human anatomy. MRI, as opposed to other radiographic methods (mainly based on X-ray techniques), supplies good soft tissue contrast, which allows for more complex assessments than what bony landmarks can provide. Because automation of this assessment is highly demanding, one of the primary goals for the new software was to enable more rapid identification of landmark sets in 3D image data. Repeat acquisition of head MRIs having a resolution of 0.94 x 0.94 x 1.20 mm3 were performed on 10 volunteers. Intra- and interoperator, as well as interacquisition variations of manual identification of exterior, craniofacial interior, and brain landmarks were studied. The average distances between landmarks were <1.8 mm, <2.3 mm, and <2.0 mm in the intra- and interoperator, and interacquisition evaluations, respectively. This study presents new software for time efficient identification of complex craniofacial landmarks in 3D MRI. To the best of our knowledge, no evaluation of software for rapid landmark-based analysis of complex anatomies from 3D MR data has yet been presented. This software may also be useful for studies in other anatomical regions and for other types of image data.

  • 69. Frennby, Bo
    et al.
    Almén, Torsten
    Lilja, Bo
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hellsten, Sverker
    Lindblad, Bengt
    Nilsson, Mats
    Nyman, Uif
    Törnquist, Carl
    Determination of the relative glomerular filtration rate of each kidney in man: Comparison between iohexol CT and 99mTc-DTPA scintigraphy1995In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 36, no 4, p. 410-417Article in journal (Refereed)
    Abstract [en]

    Iohexol and 99mTc-DTPA were used in 43 patients to determine the relative glomerular filtration rate (GFR), i.e., the GFR of each kidney in percent of total GFR. The amount of any GFR marker accumulating in Bowman's space, tubuli and renal pelvis within a few minutes after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was determined by CT using 10 slices of 8-mm thickness 1 to 4 minutes after injection. The renal accumulation of 99mTc-DTPA was determined with a gamma camera within 2 minutes after injection. The correlation coefficient between the two methods was 0.98. Due to the higher radiation dose from CT than from 99mTc-DTPA injection, relative GFR determination with CT should be performed when there is also a diagnostic need to reveal morphology.

  • 70.
    Friederich, Malou
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Olerud, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fasching, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Uncoupling protein-2 in diabetic kidneys: increased protein expression correlates to increased non-transport related oxygen consumption2008In: Oxygen Transport to Tissue XXIX, Springer Berlin/Heidelberg, 2008, Vol. 614, p. 37-43Chapter in book (Refereed)
    Abstract [en]

    Diabetic patients have an elevated risk to develop renal dysfunction and it has been postulated that altered energy metabolism is involved. We have previously shown that diabetic rats have markedly decreased oxygen availability in the kidney, resulting from increased oxygen consumption. A substantial part of the increased oxygen consumption is unrelated to tubular transport, suggesting decreased mitochondrial efficiency. In this study, we investigated the protein expression of mitochondrial uncoupling protein (UCP)-2 in kidney tissue from control and streptozotocin (STZ)-induced diabetic rats. Protein levels of UCP-2 were measured in adult male control and STZ-diabetic Wistar Furth as well as Sprague Dawley rats in both the kidney cortex and medulla by Western blot technique. Two weeks of hyperglycemia resulted in increased protein levels of UCP-2 in kidneys from both Wistar Furth and Sprague Dawley rats. Both cortical and medullary UCP-2 levels were elevated 2-3 fold above control levels. We conclude that sustained STZ-induced hyperglycemia increases the kidney levels of mitochondrial UCP-2, which could explain the previously reported increase in non-transport related oxygen consumption in diabetic kidneys. The elevated UCP-2 levels may represent an effort to reduce the increased production of superoxide radicals which is evident during diabetes.

  • 71.
    Frimmel, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Näppi, Janne
    Yoshida, Hiroyuki
    Centerline-based colon segmentation for CT colonography2005In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 32, p. 2665-2672Article in journal (Refereed)
  • 72. Glaessgen, Axel
    et al.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Norberg, Mona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, Bo
    Egevad, Lars
    Prediction of percent Gleason grade 4/5 by multiple core biopsies2006In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 40, no 6, p. 465-471Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate whether percent Gleason grade 4/5 (i.e. the proportion of a tumor occupied by high-grade cancer) can be predicted by multiple needle biopsies. Material and methods. In 115 men, 8-14 (mean 10) biopsies were taken, including eight from standardized positions (apex, mid-medial, mid-lateral and base). Biopsies were reviewed and cancer lengths measured. All men underwent radical prostatectomy. The prostatectomy specimens were totally embedded and tumor volume measured planimetrically. Gleason scores and percent Gleason grade 4/5 were assessed for both biopsy and prostatectomy specimens. Results. Percent Gleason grade 4/5 in prostatectomy specimens was predicted correctly in 34% of cases and within 10%, 20% and 30% in 55%, 64% and 73% of cases, respectively. Biopsies had a sensitivity, specificity and accuracy for Gleason grade 4/5 of 62%, 87% and 69%, respectively. Positive and negative predictive values were 93% and 45%, respectively. The weighted kappa value for agreement was slightly higher for Gleason score (0.685) than for percent Gleason grade 4/5 (0.573). The univariate correlation for percent Gleason grade 4/5 in biopsies and the main tumor was r = 0.62, r(2) = 0.39 (p < 0.001). In univariate logistic regression, percent Gleason grade 4/5 on biopsies predicted the presence of any Gleason grade 4/5 cancer in the main tumor (p = 0.009). Conclusions. Gleason grade 4/5 in prostatectomy specimens correlates with findings in preoperative biopsies. Whether this measure will be used in routine practice remains to be seen.

  • 73.
    Granberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kindmark, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Liver embolization with trisacryl gelatin microspheres (embosphere) in patients with neuroendocrine tumors2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 2, p. 180-185Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To report our experience of liver embolization with trisacryl gelatin microspheres (Embospheretrade mark) in patients with metastatic neuroendocrine tumors.

    MATERIAL AND METHODS:

    Fifteen patients underwent selective embolization of the right or left hepatic artery with Embosphere. One lobe was embolized in seven patients and both lobes, on separate occasions, in eight patients. Seven patients had midgut carcinoids, two had lung carcinoids, one suffered from a thymic carcinoid, and five had endocrine pancreatic tumors. Eight patients suffered from endocrine symptoms, seven of whom had carcinoid syndrome and one WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome.

    RESULTS:

    Partial radiological response was seen after eight embolizations (in six different patients), stable disease was observed after 13 embolizations (after three of these, necroses occurred), while radiological progression was noted after only two embolizations. Only two patients experienced a biochemical response. Clinical improvement of carcinoid syndrome was observed after five embolizations. There were no major complications. Fever >38 degrees C was seen after all but four embolizations, and urinary tract infections were diagnosed after eight embolizations.

    CONCLUSION:

    Selective hepatic artery embolization with Embosphere particles is a safe treatment for patients with metastatic neuroendocrine tumors and may lead to partial radiological response as well as symptomatic improvement of disabling endocrine symptoms.

  • 74.
    Granberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Garske, Ulrike
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kindmark, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Selective internal radiation therapy in patients with carcinoid liver metastases2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 6, p. 1169-1171Article in journal (Refereed)
  • 75.
    Hagen, Gaute
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wadström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Magnusson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Outcome after percutaneous transluminal angioplasty of arterial stenosis in renal transplant patients2009In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 50, no 3, p. 270-275Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ensuring graft survival in renal transplant patients is of paramount importance. Early detection and treatment of complications such as transplant renal artery stenosis (TRAS) are essential. PURPOSE: To evaluate the technical and clinical success rate of renal transplant patients with stenosis in the transplant renal artery or in the iliac artery after percutaneous transluminal angioplasty (PTA). MATERIAL AND METHODS: PTA was carried out on 24 patients with TRAS or iliac artery stenosis. Altogether, 28 stenoses were treated with PTA. The immediate technical result and the clinical outcomes after 1 and 3 months were assessed as well as clinical adverse events. A reduction in serum creatinine and/or a reduction in the number of antihypertensive drugs were criteria for clinical success. RESULTS: The immediate technical success rate after PTA was 93%. The clinical success rate after 1 month was 58%, increasing to 75% after 3 months. CONCLUSION: The technical success rate is not equivalent to the clinical success rate when treating TRAS with PTA. Furthermore, there is a delay in clinical response, sometimes of 3 months, after a technically successful PTA.

  • 76. Hahn, Gabriele
    et al.
    Sorge, Ina
    Gruhn, Bernd
    Glutig, Katja
    Hirsch, Wolfgang
    Bhargava, Ravi
    Furtner, Julia
    Born, Mark
    Schröder, Cornelia
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kaiser, Sylvie
    Moritz, Jörg Detlev
    Kunze, Christian Wilhelm
    Shroff, Manohar
    Stokland, Eira
    Trnkova, Zuzana Jirakova
    Schultze-Mosgau, Marcus
    Reif, Stefanie
    Bacher-Stier, Claudia
    Mentzel, Hans-Joachim
    Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in pediatric patients2009In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 44, no 12, p. 776-783Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This clinical study investigated the pharmacokinetics and safety of gadobutrol, a magnetic resonance (MR) imaging extracellular contrast agent, in pediatric patients aged 2 to 17 years. MATERIALS AND METHODS: In this open-label, multicenter study, patients scheduled for routine contrast-enhanced MR imaging of the brain, spine, liver or kidney, or MR angiography received a single intravenous injection of gadobutrol (0.1 mmol/kg/0.1 mL/kg). Patients were stratified by age groups (2-6, 7-11, and 12-17 years). Blood and urine samples were collected at prespecified time points and analyzed for gadolinium concentrations. Plasma data were evaluated by means of a nonlinear mixed effects model, and urine data were analyzed using descriptive statistics. In addition, the safety of gadobutrol was evaluated. RESULTS: A total of 130 patients (2-6 years, n = 45; 7-11 years, n = 39; 12-17 years, n = 46) were included in the final population pharmacokinetic analysis. Gadobutrol pharmacokinetics in children aged 2 to 17 years were adequately described by an open 2-compartment model with elimination from the central compartment. The median estimates (2.5th percentile, 97.5th percentile) of body weight-normalized total body clearance (L/h/kg) per age group were 0.10 (0.05, 0.17) for all ages, 0.13 (0.09, 0.17) in the 2 to 6 year age group, 0.10 (0.05, 0.17) in the 7 to 11 year age group and 0.09 (0.05, 0.10) in the 12 to 17 year age group. The body weight-normalized median estimates of total volume of distribution (L/kg) were 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6 year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group. Median gadolinium plasma concentrations at 20 minutes postinjection were simulated using the population pharmacokinetic model and ranged from 414 (13 kg subject) to 518 micromol/L (65 kg subject). Body weight was identified as the major covariate influencing the pharmacokinetic parameters of total body clearance and central volume of distribution. Age was not found to be an additional independent parameter. The median amount of renally excreted gadolinium was 77.0% of the administered dose within 6 hours postinjection, indicating that gadobutrol was renally excreted in this pediatric population aged 2 to 17 years. Gadobutrol was well tolerated, with drug-related adverse events of mild intensity reported for 8 (5.8%) of 138 patients. CONCLUSIONS: Observed differences in pharmacokinetics were attributed to body weight, with no additional independent effect of age. Thus, no dose adjustment from the standard dose of gadobutrol in adults based on body weight (0.1 mmol/kg) is necessary in pediatric patients aged 2 to 17 years. Gadobutrol was safe and well tolerated in the pediatric population in this study.

  • 77. Haldorsen, I. S.
    et al.
    Espeland, A.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Central Nervous System Lymphoma: Characteristic Findings on Traditional and Advanced Imaging2011In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 32, no 6, p. 984-992Article in journal (Refereed)
    Abstract [en]

    SUMMARY: CNS lymphoma consists of 2 major subtypes: secondary CNS involvement by systemic lymphoma and PCNSL. Contrast-enhanced MR imaging is the method of choice for detecting CNS lymphoma. In leptomeningeal CNS lymphoma, representing two-thirds of secondary CNS lymphomas, imaging typically shows leptomeningeal, subependymal, dural, or cranial nerve enhancement. Single or multiple periventricular and/or superficial contrast-enhancing lesions are characteristic of parenchymal CNS lymphoma, representing one-third of secondary CNS lymphomas and almost 100% of PCNSLs. New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions. Advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis. Furthermore, these imaging techniques may play a pivotal role in planning targeted therapies, prognostication, and monitoring treatment response.

  • 78. Haller, Olle
    et al.
    Karlsson, Lars
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Can low-dose abdominal CT replace abdominal plain film in evaluation of acute abdominal pain?2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 2, p. 113-120Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Non-contrast computed tomography (NCT) has become an important diagnostic tool in acute abdominal pain, but the drawback is the increased radiation dose compared to abdominal plain film (APF). PURPOSE: To evaluate whether NCT, including low-dose computed tomography (LDCT, using 50 mAs), provides more diagnostic information than APF in patients presenting with acute non-traumatic abdominal pain and if the use of CT can reduce the total number of additional radiograms. A second aim was to compare the diagnostic outcome between standard-dose computed tomography (SDCT) and LDCT. MATERIAL AND METHODS: During 2000, 2002, and 2004 a total of 222 patients were retrospectively reviewed, and 86 patients had APF, 60 had SDCT, and 76 had LDCT. The radiological report of each patient was compared with the final diagnosis obtained from the medical record within 30 days. Additional radiograms were registered, and a total radiation dose excluding or including APF or NCT was calculated. RESULTS: NCT gave a correct diagnosis in 50%, compared to 20% with APF (P < 0.001). The total number of additional radiograms was substantially lower in the computed tomography (CT) group compared to the APF group (P < 0.001), and the average sum of radiation dose was similar for APF and LDCT. CONCLUSION: NCT was found to be significantly better at providing diagnostic information than APF in patients presenting with acute abdominal pain. It reduced the number of additional radiograms, but the total patient dose remained somewhat higher in the CT group even when using LDCT with 50 mAs.

  • 79.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Whole-body screening of atherosclerosis with magnetic resonance angiography.2007In: Topics in Magnetic Resonance Imaging (TMRI), ISSN 0899-3459, E-ISSN 1536-1004, Vol. 18, no 5, p. 329-337Article in journal (Refereed)
    Abstract [en]

    With whole-body magnetic resonance angiography (WBMRA), it is possible to examine the whole arterial tree except intracranial and coronary vessels in a single examination without the risks involved in ionizing radiation or arterial cannulation. Whole-body magnetic resonance angiography is well suited for repeated clinical examinations in patients with systemic diseases such as vasculitis or atherosclerosis and can also be used for scientific purposes. On the basis of the WBMRA overview, a possible further development of the WBMRA concept can be to perform further acquisitions at sites with atherosclerotic plaques with higher-resolution scans to determine the degree of stenosis more accurately or to achieve plaque characterization. A total validation of WBMRA compared with digital subtraction angiography (DSA) is not possible owing to the hazards of ionizing radiation. Studies have shown a high sensitivity and specificity for the pelvic and lower limb arteries in comparison with DSA. No systematic validation against DSA has been performed for the renal, aortic, and carotid arteries. Various methods have been used, however, for confirmation of vascular abnormalities found on WBMRA such as ultrasonography, dedicated MRA, or DSA, with reasonably high agreement. The WBMRA method has not been studied with regard to prediction of future cardiovascular (CV) events, as have intima media thickness, coronary artery calcium scoring, and the ankle-brachial index. The full usefulness of WBMRA in an epidemiological setting and as a complementary screening tool for assessing CV risk still needs to be validated against future CV events.

  • 80.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Söderberg, S.
    Hulthe, J.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population2009In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 205, no 1, p. 163-167Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS: Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS: VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

  • 81.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    A total atherosclerotic score for whole-body MRA and its relation to traditional cardiovascular risk factors2008In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 18, no 6, p. 1174-1180Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to create a scoring system for whole-body magnetic resonance angiography (WBMRA) that allows estimation of atherosclerotic induced luminal narrowing, and determine whether the traditional cardiovascular (CV) risk factors included in the Framingham risk score (FRS) were related to this total atherosclerotic score (TAS) in an elderly population. A group of 306 subjects, aged 70, were recruited from the general population and underwent WBMRA in a 1.5-T scanner. Three-dimensional sequences were acquired after administration of one i.v. injection of 40 ml gadodiamide. The arterial tree was divided into five territories (carotid, aorta, renal, upper and lower leg) comprising 26 vessel segments, and assessed according to its degree of stenosis or occlusion. FRS correlated to TAS (r=0.30, P < 0.0001), as well as to the atherosclerotic score for the five individual territories. Of the parameters included in the FRS, male gender (P < 0.0001), systolic blood pressure (P=0.0002), cigarette pack-years (P=0.0008) and HDL cholesterol (P=0.008) contributed to the significance. A scoring system for WBMRA was created. The significant relation towards traditional CV risk factors indicates that the proposed scoring system could be of value for assessing atherosclerotically induced luminal narrowing.

  • 82.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Eriksson, Mats-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lundberg, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ljungman, Christer
    Hoogeven, Romhild
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Whole-body magnetic resonance angiography of patients using a standard clinical scanner.2006In: European Radiology, ISSN 0938-7994, Vol. 16, p. 147-153Article in journal (Refereed)
  • 83.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    The Prevalence and Quantification of Atherosclerosis in an Elderly Population Assessed by Whole-Body Magnetic Resonance Angiography2007In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 27, no 3, p. 649-654Article in journal (Refereed)
    Abstract [en]

    Objective-The principal aim of the present study was to explore the feasibility of using whole-body magnetic resonance angiography to assess atherosclerosis in different vascular territories in a cohort of elderly. Methods and Results-Three hundred six 70-year-old subjects (145 women, 161 men) recruited from a population-based cohort study (Prospective Investigation of the Vasculature in Uppsala Seniors, ie, the PIVUS study) underwent 1.5-T whole-body magnetic resonance angiography with gadodiamide. The arteries were divided into 26 segments. In total, 7956 vessel segments were evaluated with 7900 segments (99.3%) possible to evaluate. Of these, 7186 segments (91%) were normal. Luminal narrowing of ≥50% was observed in 9 (1.5%) of the renal arteries, 12 (1.8%) of the carotid arteries, in 31 segments (1.1%) of the pelvic/upper leg territories, and in 136 segments (6.2%) of territories in the lower leg. Approximately one-third of the sample had no vascular abnormalities, one-third had stenoses of <50%, and the remainder had stenoses ≥50% or occlusions. Six subjects (2%) had aortic aneurysms. In subjects without evident vascular disease, 26% had significant vascular abnormalities. Conclusions-Whole-body magnetic resonance angiography performed with a clinical scanner can be used for quantifying atherosclerosis in different vascular territories in a single examination in an elderly population.

  • 84. Hedström, Erik
    et al.
    Arheden, Håkan
    Eriksson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Importance of perfusion in myocardial viability studies using delayed contrast-enhanced magnetic resonance imaging2006In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 24, no 1, p. 77-83Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate whether an extracellular gadolinium-(Gd)-based contrast agent (CA) enters nonperfused myocardium during acute coronary occlusion, and whether nonperfused myocardium presents as hyperintense in delayed contrast-enhanced (DE) MR images in the absence of CA in that region. MATERIALS AND METHODS: The left anterior descending coronary artery (LAD) was occluded for 200 minutes in six pigs. The longitudinal relaxation rate (R(1)) in blood, perfused myocardium, and nonperfused myocardium was repeatedly measured using a Look-Locker sequence before and during the first hour after administration of Gd-DTPA-BMA. RESULTS: While blood and perfused myocardium showed a major increase in R(1) after CA administration, nonperfused myocardium did not. R(1) in nonperfused myocardium was significantly lower than in blood and perfused myocardium during the first hour after CA administration. When the signal from perfused myocardium was nulled, demarcation of the hyperintense nonperfused myocardium was achieved in all of the study animals. CONCLUSION: Gd-DTPA-BMA does not enter ischemic myocardium within one hour after administration during acute coronary occlusion. The ischemic region with complete absence of CA still appears bright when the signal from perfused myocardium is nulled using inversion-recovery DE-MRI. This finding is important for understanding the basic pathophysiology of inversion-recovery viability imaging, as well as for imaging of acute coronary syndromes.

  • 85.
    Hellgren, Laila
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Landelius, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kvidal, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Severe mitral regurgitation: relations between magnetic resonance imaging, echocardiography and natriuretic peptides2008In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 42, no 1, p. 48-55Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Assessment of the severity of mitral regurgitation by echocardiography can be technically demanding in certain patients and supplementary methods are therefore desirable. This study addressed the agreement between magnetic resonance imaging (MRI) and echocardiography, and their relations to natriuretic peptides (NT-proANP and NT-proBNP), in quantifying severe mitral regurgitation.

    METHODS:

    Eighteen patients with severe mitral regurgitation scheduled for surgery underwent MRI, echocardiography and assay of natriuretic peptides preoperatively for clinical assessment.

    RESULTS:

    MRI and echocardiography were comparable in measuring severity of regurgitation qualitatively but not quantitatively, mitral regurgitant fraction (mean difference 27.5 (11) ml). There was a correlation between increasing regurgitant fraction on MRI and increased levels of plasma NT-proANP and NT-proBNP. In echocardiography, increasing vena contracta width and increasing PISA correlated to increased levels of plasma NT-proANP and NT-proBNP. No other correlation was found between measures on MRI and echocardiography and natriuretic peptides.

    CONCLUSIONS:

    MRI and echocardiography were comparable grading the severity of mitral regurgitation with qualitative measures but not with quantitative measures. MRI might be a complement to echocardiography when a more distinct measure of the regurgitant volume is needed, as in paravalvular leakage.

  • 86.