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  • 201.
    Helenius, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Investigation of Bladder Tumors with CT Urography in Patients Presenting with Gross Hematuria2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bladder tumor is the most common tumor detected in patients presenting with gross hematuria. Early detection and treatment is crucial for good prognosis, however, delay in diagnosis and treatment is common. Routine work-up of gross hematuria includes cystoscopy and Computed Tomography Urography (CTU). If CTU has a high detection rate of bladder tumor, it can be used to direct further investigation of the patient, hopefully reducing delay to diagnosis and treatment. There is no consensus on which phase the bladder should be assessed at CTU. Assessment of the bladder in an early contrast-enhancing phase requires contrast material enhancement in bladder tumors and a bladder that is properly distended with urine. For patients younger than 50 years, the routine CTU protocol used for examining gross hematuria patients included unenhanced (UE), corticomedullary phase (CMP), and excretory phase (EP), with the start of the scan being enhancement triggered: patients aged 50 years or older followed the same protocol plus a nephrographic phase (NP).

    The CTU protocol was compared with flexible cystoscopy for detecting bladder tumors. Sensitivity for bladder cancer detection was equal for CTU and cystoscopy (0.87).

    Patients diagnosed with bladder cancer (n=50) were examined during UE, CMP, and EP, and 21 patients were additionally examined in NP. The highest mean tumor contrast enhancement was seen in CMP (37 HU).

    The CMP, NP, and EP in 106 patients were randomized into an evaluation order (n=318 different phases) and blindly reviewed by two uroradiologists. In CMP, sensitivity (0.95) and negative predictive value (0.99) were higher than in NP and EP.

    Four different preparation protocols for achieving bladder distension were compared. The protocol that included drinking 1 l of fluid during a two-hour period prior to examination without voiding during that period, gave satisfactory bladder distension without causing unacceptable patient discomfort and having the lowest compliance.

     

    Gross hematuria patients should be primarily examined with CTU including UE, CMP and EP to direct further investigation of the patients. The patients should follow a preparation protocol including drinking 1 l of fluid during a two-hour period before examination and not voiding during that period.

     

    List of papers
    1. Bladder cancer detection in patients with gross haematuria: Computed tomography urography with enhancement triggered scan versus flexible cystoscopy
    Open this publication in new window or tab >>Bladder cancer detection in patients with gross haematuria: Computed tomography urography with enhancement triggered scan versus flexible cystoscopy
    Show others...
    2015 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 5, p. 377-381Article in journal (Refereed) Published
    Abstract [en]

    Objective

    Computed tomography urography (CTU) can be used to direct further investigation of patients if the bladder tumour detection rate is high. The aim of this study was to compare a CTU protocol including an enhancement-triggered scan and flexible cystoscopy for detecting bladder tumours.

    Materials and methods

    Patients with gross haematuria undergoing CTU during 2005–2008 were included. For patients younger than 50 years the CTU protocol included unenhanced, enhancement-triggered corticomedullary, and excretory phases. Patients older than 50 years followed the same protocol plus a nephrographic phase. The entire urinary tract was examined in all phases.

    Results

    Of 435 patients, 55 patients were diagnosed with bladder tumour. CTU detected bladder tumour in 48 patients (87%). Five CTU examination reports were false positive. With CTU, sensitivity for finding bladder tumour was 0.87, specificity 0.99, positive predictive value (PPV) 0.91 and negative predictive value (NPV) 0.98. Cystoscopy detected bladder tumour in 48 patients (87%) and had one false-positive finding, resulting in sensitivity of 0.87, specificity 1.0, PPV 0.98 and NPV 0.98.

    Conclusions

    The detection rate of bladder tumours for the CTU protocol including an enhancement-triggered scan was high and comparable to flexible cystoscopy. Hence, this protocol could be used to assess the bladder as the primary investigation and direct further investigation of the patient.

    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Research subject
    Radiology
    Identifiers
    urn:nbn:se:uu:diva-221283 (URN)10.3109/21681805.2015.1026937 (DOI)000364428800006 ()
    Available from: 2014-03-27 Created: 2014-03-27 Last updated: 2017-12-05Bibliographically approved
    2. Contrast enhancement in bladder tumors examined with CT urography using traditional scan phases
    Open this publication in new window or tab >>Contrast enhancement in bladder tumors examined with CT urography using traditional scan phases
    Show others...
    2014 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 55, no 9, p. 1129-1136Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Bladder assessment in an early contrast-enhancing computed tomography urography (CTU) phase requires that bladder tumors be enhanced using contrast material.

    PURPOSE:

    To investigate the enhancement pattern in bladder tumors using a CTU protocol where the scan is enhancement triggered.

    MATERIAL AND METHODS:

    Fifty patients diagnosed with bladder cancer were examined during the unenhanced (UP), corticomedullary (CMP), and excretory phases (EP). Twenty-one patients, all aged 50 years or older, were also examined during the nephrographic phase (NP). A ROI placed in the aorta was used to start the scan during the CMP when the attenuation reached 200 Hounsfield units (HU). The NP and EP were started with a 40 s and 300 s delay, respectively, after the CMP was finished. Attenuation and size measurements were made in the axial plane.

    RESULTS:

    Mean contrast enhancement of bladder tumors was 37, 25, and 17 HU in the CMP, NP, and EP, respectively. The differences in contrast enhancement were significant across all three phases. Eighty-eight percent of patients showed the highest contrast enhancement in the CMP. In 96% of the cases, contrast enhancement >20 HU was seen. The mean value of the shortest dimension of the bladder tumors was 22 ± 12 mm.

    CONCLUSION:

    The contrast enhancement is significantly higher in the CMP than in the NP and EP, suggesting that the CMP is preferable when assessing the bladder in the early contrast enhancing phase.

    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-212552 (URN)10.1177/0284185113513762 (DOI)000343887800015 ()24277884 (PubMedID)
    Available from: 2013-12-11 Created: 2013-12-11 Last updated: 2017-12-06Bibliographically approved
    3. Comparison of post contrast CT urography phases in bladder cancer detection
    Open this publication in new window or tab >>Comparison of post contrast CT urography phases in bladder cancer detection
    Show others...
    2016 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 26, no 2, p. 585-591Article in journal (Refereed) Published
    Abstract [en]

    Objectives The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. Methods The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. Results Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). Conclusion In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment.

    Keywords
    Multidetector computed tomography; Urography; Urinary bladder neoplasms; Haematuria; Early detection of cancer
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Research subject
    Radiology
    Identifiers
    urn:nbn:se:uu:diva-221282 (URN)10.1007/s00330-015-3844-7 (DOI)000368639200034 ()26002135 (PubMedID)
    Available from: 2014-03-27 Created: 2014-03-27 Last updated: 2017-12-05Bibliographically approved
    4. Comparison of four different preparation protocols to achieve bladder distension in patients with gross haematuria undergoing a CT urography
    Open this publication in new window or tab >>Comparison of four different preparation protocols to achieve bladder distension in patients with gross haematuria undergoing a CT urography
    2012 (English)In: Radiography, ISSN 1078-8174, E-ISSN 1532-2831, Vol. 18, no 3, p. 206-211Article in journal (Refereed) Published
    Abstract [en]

    Introduction

    CT examination has been shown to be effective in detecting bladder cancer. Proper evaluation of the bladder requires it to be well distended. The purpose of the present study was to establish a preparation protocol to achieve satisfactory bladder distension without causing unacceptable patient discomfort.

    Material and method

    We used four different preparation protocols (1: 0.5 L of fluid intake during a 1-h period, 2: Same as 1 with the addition of IV diuretics when the patient was examined, 3: 1 L of fluid intake during a 2-h period, 4: Same as 3 with the additional instruction to empty the bladder after 1 h. In protocols 1–3, the patients were asked not to empty their bladder during the preparation time). Bladder volume was calculated and bladder distension was judged as satisfactory or not by the radiologist. The patients answered questions about their ability to follow the preparation protocol and were requested to rate their need to empty the bladder pre-, during and post-examination.

    Results

    Protocol 1 had the lowest bladder volume. Protocols 2, 3 and 4 were similar in bladder volume. However, Protocol 2 caused unacceptable patient discomfort, and the compliance was lowest in Protocol 4.

    Conclusion

    Protocol 3, drinking 1 L of fluid during a 2-h period, gave satisfactory bladder distension, did not cause unacceptable discomfort in patients and did not have the lowest compliance.

    Keywords
    Bladder cancer, CT, Haematuria, Urography, Distension
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-183661 (URN)10.1016/j.radi.2012.02.004 (DOI)
    Available from: 2012-10-31 Created: 2012-10-31 Last updated: 2017-12-07Bibliographically approved
  • 202.
    Helenius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bladder cancer detection in patients with gross haematuria: Computed tomography urography with enhancement triggered scan versus flexible cystoscopy2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 5, p. 377-381Article in journal (Refereed)
    Abstract [en]

    Objective

    Computed tomography urography (CTU) can be used to direct further investigation of patients if the bladder tumour detection rate is high. The aim of this study was to compare a CTU protocol including an enhancement-triggered scan and flexible cystoscopy for detecting bladder tumours.

    Materials and methods

    Patients with gross haematuria undergoing CTU during 2005–2008 were included. For patients younger than 50 years the CTU protocol included unenhanced, enhancement-triggered corticomedullary, and excretory phases. Patients older than 50 years followed the same protocol plus a nephrographic phase. The entire urinary tract was examined in all phases.

    Results

    Of 435 patients, 55 patients were diagnosed with bladder tumour. CTU detected bladder tumour in 48 patients (87%). Five CTU examination reports were false positive. With CTU, sensitivity for finding bladder tumour was 0.87, specificity 0.99, positive predictive value (PPV) 0.91 and negative predictive value (NPV) 0.98. Cystoscopy detected bladder tumour in 48 patients (87%) and had one false-positive finding, resulting in sensitivity of 0.87, specificity 1.0, PPV 0.98 and NPV 0.98.

    Conclusions

    The detection rate of bladder tumours for the CTU protocol including an enhancement-triggered scan was high and comparable to flexible cystoscopy. Hence, this protocol could be used to assess the bladder as the primary investigation and direct further investigation of the patient.

  • 203.
    Helenius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Comparison of post contrast CT urography phases in bladder cancer detection2016In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 26, no 2, p. 585-591Article in journal (Refereed)
    Abstract [en]

    Objectives The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. Methods The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. Results Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). Conclusion In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment.

  • 204.
    Helenius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Mats
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Contrast enhancement in bladder tumors examined with CT urography using traditional scan phases2014In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 55, no 9, p. 1129-1136Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Bladder assessment in an early contrast-enhancing computed tomography urography (CTU) phase requires that bladder tumors be enhanced using contrast material.

    PURPOSE:

    To investigate the enhancement pattern in bladder tumors using a CTU protocol where the scan is enhancement triggered.

    MATERIAL AND METHODS:

    Fifty patients diagnosed with bladder cancer were examined during the unenhanced (UP), corticomedullary (CMP), and excretory phases (EP). Twenty-one patients, all aged 50 years or older, were also examined during the nephrographic phase (NP). A ROI placed in the aorta was used to start the scan during the CMP when the attenuation reached 200 Hounsfield units (HU). The NP and EP were started with a 40 s and 300 s delay, respectively, after the CMP was finished. Attenuation and size measurements were made in the axial plane.

    RESULTS:

    Mean contrast enhancement of bladder tumors was 37, 25, and 17 HU in the CMP, NP, and EP, respectively. The differences in contrast enhancement were significant across all three phases. Eighty-eight percent of patients showed the highest contrast enhancement in the CMP. In 96% of the cases, contrast enhancement >20 HU was seen. The mean value of the shortest dimension of the bladder tumors was 22 ± 12 mm.

    CONCLUSION:

    The contrast enhancement is significantly higher in the CMP than in the NP and EP, suggesting that the CMP is preferable when assessing the bladder in the early contrast enhancing phase.

  • 205.
    Helenius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Segelsjö, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Comparison of four different preparation protocols to achieve bladder distension in patients with gross haematuria undergoing a CT urography2012In: Radiography, ISSN 1078-8174, E-ISSN 1532-2831, Vol. 18, no 3, p. 206-211Article in journal (Refereed)
    Abstract [en]

    Introduction

    CT examination has been shown to be effective in detecting bladder cancer. Proper evaluation of the bladder requires it to be well distended. The purpose of the present study was to establish a preparation protocol to achieve satisfactory bladder distension without causing unacceptable patient discomfort.

    Material and method

    We used four different preparation protocols (1: 0.5 L of fluid intake during a 1-h period, 2: Same as 1 with the addition of IV diuretics when the patient was examined, 3: 1 L of fluid intake during a 2-h period, 4: Same as 3 with the additional instruction to empty the bladder after 1 h. In protocols 1–3, the patients were asked not to empty their bladder during the preparation time). Bladder volume was calculated and bladder distension was judged as satisfactory or not by the radiologist. The patients answered questions about their ability to follow the preparation protocol and were requested to rate their need to empty the bladder pre-, during and post-examination.

    Results

    Protocol 1 had the lowest bladder volume. Protocols 2, 3 and 4 were similar in bladder volume. However, Protocol 2 caused unacceptable patient discomfort, and the compliance was lowest in Protocol 4.

    Conclusion

    Protocol 3, drinking 1 L of fluid during a 2-h period, gave satisfactory bladder distension, did not cause unacceptable discomfort in patients and did not have the lowest compliance.

  • 206.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergström, M
    Sundín, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Westerberg, G
    Juhlin, C
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, J
    Positron emission tomography with 11C-methionine in hyperparathyroidism1994In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 116, no 6, p. 974-981Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism.

    METHODS:

    Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained.

    RESULTS:

    Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET.

    CONCLUSIONS:

    The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism.

  • 207. Hellquist, Barbro Numan
    et al.
    Duffy, Stephen W.
    Abdsaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Björneld, Lena
    Bordas, Pål
    Tabar, Laszlo
    Vitak, Bedrich
    Zackrisson, Sophia
    Nyström, Lennarth
    Jonsson, Håkan
    Effectiveness of Population-Based Service Screening With Mammography for Women Ages 40 to 49 Years Evaluation of the Swedish Mammography Screening in Young Women (SCRY) Cohort2011In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, no 4, p. 714-722Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted. METHODS: Breast cancer mortality was compared between women who were invited to service screening at ages 40 to 49 years (study group) and women in the same age group who were not invited during 1986 to 2005 (control group). Together, these women comprise the Mammography Screening of Young Women (SCRY) cohort, which includes all Swedish counties. A prescreening period was defined to facilitate a comparison of mortality in the absence of screening. The outcome measure was refined mortality, ie, breast cancer death for women who were diagnosed during follow-up at ages 40 to 49 years. Relative risks (RRs) with 95% confidence intervals (Os) were estimated. RESULTS: There was no significant difference in breast cancer mortality during the prescreening period. During the study period, there were 803 breast cancer deaths in the study group (7.3 million person-years) and 1238 breast cancer deaths in the control group (8.8 million person-years). The average follow-up was 16 years. The estimated RR for women who were invited to screening was 0.74 (95% Cl, 0.66-0.83), and the RR for women who attended screening was 0.71 (95% CI, 0.620.80). CONCLUSIONS: In this comprehensive study, mammography screening for women ages 40 to 49 years was efficient for reducing breast cancer mortality.

  • 208.
    Hemmingsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ericsson, A
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Contrast agents in acute myocardial infarction2001In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 12, no 2-3, p. 96-98Article in journal (Refereed)
    Abstract [en]

    The experimental design in examination of acute myocardial infarctions should be valid in terms of flow, perfusion and re-flow after intervention. The contrast agents concentration in experimental studies can be measured by microdialysis. We have assessed the usefulness of different extracellular and blood pool contrast agents for visualization of the area at risk in coronary artery occlusions. The double contrast technique, where Dy-DTPA-BMA was combined with Gd-DTPA-BMA yielded a superior infarct visualization. Blood pool agents for example NC100/150 injection is also promising in first path myocardial perfusion imaging.

  • 209. Henriksson, Lars
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Smedby, Örjan
    Albrektsson, Per
    Assessment of congestive heart failure in chest radiographs: Observer performance with two common film-screen systems1990In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 31, no 5, p. 469-471Article in journal (Refereed)
    Abstract [en]

    The effect of observer variations and film-screen quality on the diagnosis of congestive heart failure based on chest radiographs was studied in 27 patients. For each patient, two films were exposed, one with the Kodak Lanex Medium system and one with the Agfa MR 400 system. The films were presented to three observers who assessed the presence of congestive heart failure on a three-graded scale. The results showed no significant difference between the two systems but large systematic differences between the observers. There were also differences between the two ratings by the same observer that could not be explained by the film-screen factor. It is concluded that the choice between these two systems is of little importance in view of the interobserver and intraobserver variability that can exist within the same department.

  • 210. Heradstveit, Bård E
    et al.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Skeidsvoll, Håvard
    Hammersborg, Stig-Morten
    Wentzel-Larsen, Tore
    Guttormsen, Anne Berit
    Heltne, Jon-Kenneth
    Repeated magnetic resonance imaging and cerebral performance after cardiac arrest: a pilot study2011In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 82, no 5, p. 549-555Article in journal (Refereed)
    Abstract [en]

    AIM OF THE STUDY:

    Prognostication may be difficult in comatose cardiac arrest survivors. Magnetic resonance imaging (MRI) is potentially useful in the prediction of neurological outcome, and it may detect acute ischemia at an early stage. In a pilot setting we determined the prevalence and development of cerebral ischemia using serial MRI examinations and neurological assessment.

    METHODS:

    Ten witnessed out-of-hospital cardiac arrest patients were included. MRI was carried out approximately 2h after admission to the hospital, repeated after 24h of therapeutic hypothermia and 96 h after the arrest. The images were assessed for development of acute ischemic lesions. Neurophysiological and cognitive tests as well as a self-reported quality-of-life questionnaire, Short Form-36 (SF-36), were administered minimum 12 months after discharge.

    RESULTS:

    None of the patients had acute cerebral ischemia on MRI at admission. Three patients developed ischemic lesions after therapeutic hypothermia. There was a change in the apparent diffusion coefficient, which significantly correlated with the temperature (p < 0.001). The neurophysiological tests appeared normal. The patients scored significantly better on SF 36 than the controls as regards both bodily pain (p = 0.023) and mental health (p = 0.016).

    CONCLUSIONS:

    MRI performed in an early phase after cardiac arrest has limitations, as MRI performed after 24 and 96 h revealed ischemic lesions not detectable on admission. ADC was related to the core temperature, and not to the volume distributed intravenously. Follow-up neurophysiologic tests and self-reported quality of life were good.

  • 211. Hjelmgren, O.
    et al.
    Holdfeldt, P.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fagerberg, B.
    Prahl, U.
    Schmidt, C.
    Bergstrom, G. M. L.
    Identification of Vascularised Carotid Plaques Using a Standardised and Reproducible Technique to Measure Ultrasound Contrast Uptake2013In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 46, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    Objectives: Contrast-enhanced ultrasonography (CEUS) has been used to assess the vascularisation of carotid plaques. Our aim was to develop and validate a standardised semi-automated method for CEUS examination of plaques, and test if the technique could be used to identify vulnerable plaques. Methods: Study participants were a mixed population of symptomatic and asymptomatic subjects, selected if they had a plaque with height >2.5 mm and <10% acoustic shadowing. Participants received a bolus of ultrasound contrast agent and a 90-s cine-loop was captured. A Contrast Quantification Program (CQP) was developed and trained to identify extent of contrast uptake after motion correction and application of a noise reduction algorithm. The technique was validated by comparing CQP values with visual assessment of contrast uptake. CQP values were also compared with plaque echogenicity and history of clinical events. Results: CQP values correlated with a visual, 5-scale classification of contrast uptake by two blinded, experienced sonographers. Repeated contrast injections showed high reproducibility. Participants with a history of ipsilateral stroke/TIA had significantly higher CQP values than asymptomatic participants. Conclusion: We present a reproducible, semi-automatic method to identify vascularisation of carotid plaques, which could be used in prospective studies to determine the clinical value of plaque vascularisation. 

  • 212. Hjelmgren, Ola
    et al.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Prahl, Ulrica
    Schmidt, Caroline
    Freden-Lindqvist, Johan
    Bergstrom, Goran M. L.
    A study of plaque vascularization and inflammation using quantitative contrast-enhanced US and PET/CT2014In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 83, no 7, p. 1184-1189Article in journal (Refereed)
    Abstract [en]

    Background: Contrast-enhanced ultrasound (CEUS) is an in vivo methodology to quantify carotid plaque vascularization. Increased metabolism in plaques, measured as FDG uptake in PET/CT examination, has been associated with markers of inflammation in histological samples. In this study, we tested the association between FDG uptake and vascularization measured by CEUS to assess whether CEUS can be used as an in vivo marker of plaque vulnerability. Methods: After informed consent, subjects aged >60 years with carotid plaque height exceeding 2.5 mm were recruited. CEUS was performed and analyzed using earlier described protocol and software, Contrast Quantification Program, which calculates the fraction of the plaque being contrast positive (CQP value). PET/CT examination was performed within 3 months of CEUS (median time 7 days). PET/CT images were acquired 90 min after FDG injection (2.7 MBq/kg). FDG uptake was measured as tissue background index (TBI), calculated using Spearman's rho as mean standard uptake value (SUV) of the plaque divided by mean Shy in the jugular vein (mean of 7 measuring points). Local ethics committee approved the study. Results: We recruited 13 subjects (5 women) with a mean age of 71 years, 6 had a history of stroke or TIA, 1 had a history of ipsilateral stroke. CQP values showed a significant, positive correlation with TBI of carotid plaques, r= 0.67, p <0.02. Conclusions: Plaque vascularization measured by CEUS correlates positively with FDG uptake measured by PET/CT in humans. This indicates an association between vascularization and inflammation and/or hypoxia, supporting the use of CEUS as a non-invasive method to detect plaque vulnerability. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

  • 213. Holm, Jon
    et al.
    Loizou, Louiza
    Albiin, Nils
    Kartalis, Nikolaos
    Leidner, Bertil
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Department of Radiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Low tube voltage CT for improved detection of pancreatic cancer: detection threshold for small, simulated lesions2012In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 12, p. 20-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Pancreatic ductal adenocarcinoma is associated with dismal prognosis. The detection of small pancreatic tumors which are still resectable is still a challenging problem.The aim of this study was to investigate the effect of decreasing the tube voltage from 120 to 80 kV on the detection of pancreatic tumors.

    METHODS:

    Three scanning protocols was used; one using the standard tube voltage (120 kV) and current (160 mA) and two using 80 kV but with different tube currents (500 and 675 mA) to achieve equivalent dose (15 mGy) and noise (15 HU) as that of the standard protocol.Tumors were simulated into collected CT phantom images. The attenuation in normal parenchyma at 120 kV was set at 130 HU, as measured previously in clinical examinations, and the tumor attenuation was assumed to differ 20 HU and was set at 110HU. By scanning and measuring of iodine solution with different concentrations the corresponding tumor and parenchyma attenuation at 80 kV was found to be 185 and 219 HU, respectively.To objectively evaluate the differences between the three protocols, a multi-reader multi-case receiver operating characteristic study was conducted, using three readers and 100 cases, each containing 0-3 lesions.

    RESULTS:

    The highest reader averaged figure-of-merit (FOM) was achieved for 80 kV and 675 mA (FOM=0,850), and the lowest for 120 kV (FOM=0,709). There was a significant difference between the three protocols (p<0,0001), when making an analysis of variance (ANOVA). Post-hoc analysis (students t-test) shows that there was a significant difference between 120 and 80 kV, but not between the two levels of tube currents at 80 kV.

    CONCLUSION:

    We conclude that when decreasing the tube voltage there is a significant improvement in tumor conspicuity.

  • 214.
    Hänni, Mari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Leppänen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Smedby, Örjan
    Postangioplasty restenosis followed with magnetic resonance imaging in an atherosclerotic rabbit model2012In: International Journal of Biomedical Imaging, ISSN 1687-4188, E-ISSN 1687-4196, Vol. 2012, p. 747264-Article in journal (Refereed)
    Abstract [en]

    Rationale and Objectives. Testing a quantitative, noninvasive method to assess postangioplasty vessel wall changes in an animal model. Material and Methods. Six New Zealand white rabbits were subjected to atherosclerotic injury, including cholesterol-enriched diet, deendothelialization, and percutaneous transluminal angioplasty (PTA) in the distal part of abdominal aorta (four weeks after deendothelialization). The animals were examined with a 1.5T MRI scanner at three times as follows: baseline (six weeks after diet start and two days after PTA) and four weeks and 10 weeks after-PTA. Inflow angiosequence (M2DI) and proton-density-weighted sequence (PDW) were performed to examine the aorta with axial slices. To identify the inner and outer vessel wall boundaries, a dynamic contour algorithm (Gradient Vector Flow Snakes) was applied to the images, followed by calculation of the vessel wall dimensions. The results were compared with histopathological analysis. Results. The wall thickness in the lesion was significantly higher than in the control region at 4 and 10 weeks, reflecting induction of experimentally created after-angioplasty lesion. At baseline, no significant difference between the two regions was present. Conclusions. It is possible to follow the development of vessel wall changes after-PTA with MRI in this rabbit model.

  • 215. Håkansson, A
    et al.
    Rantatalo, M
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Patient specific biomodel of the whole aorta: the importance of calcified plaque removal2011In: VASA, ISSN 0301-1526, E-ISSN 1664-2872, Vol. 40, no 6, p. 453-459Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The use of anatomical models produced by 3D printing technique (rapid prototyping, RP) is gaining increased acceptance as a complementary tool for planning complex surgical interventions. This paper describes a method for creating a patient specific replica of the whole aorta.

    METHODS: Computed tomography angiography (CTA) DICOM-data was converted to a three-dimensional computer aided design-model (CAD) of the inner wall of the aorta representing the lumen where the calcified plaque contribution was removed in a multi-step editing-manoeuvre. The edited CAD-model was used for creating a physical plaster model of the true lumen in a 3D-printer. Elastic and transparent silicon was applied onto the plaster model, which was then removed leaving a silicon replica of the aorta.

    RESULTS: The median (interquartile range) difference between diameters obtained from CTA- and RP plaster-model at 19 predefined locations was 0.5 mm (1 mm) which corresponds to a relative median difference of 4.6% (7.0%). The average wall thickness of the silicone model was 3.5 mm. The elasticity property and performance during intervention was good with an acceptable transparency.

    CONCLUSIONS: The integration of RP-techniques with CAD based reconstruction of 3D-medical imaging data provides the needed tools for making a truly patient specific replica of the whole aorta with high accuracy. Plaque removal postprocessing is necessary to obtain a true inner wall configuration.

  • 216.
    Ilan, Ezgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Garske-Román, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE2015In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 56, no 2, p. 177-182Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE.

    METHODS: Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density sphere model from OLINDA was used for absorbed dose calculations. The absorbed doses were corrected for partial-volume effect based on phantom measurements. On the basis of these results, only tumors larger than 2.2 cm in diameter at any time during the treatment were included for analysis. To further decrease the effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors.

    RESULTS: Tumor-absorbed doses until best response ranged approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the data, and a significant correlation between the absorbed dose and tumor reduction was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy.

    CONCLUSION: The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.

  • 217.
    Jacobsson, Josefin A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sällman Almén, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hedberg, Lilia A.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 5, p. e20158-Article in journal (Refereed)
    Abstract [en]

    Background

     The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution.

    Objective

    To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.

    Design

    Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.

    Results

     Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.

    Conclusions

    Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

  • 218. Jahan, Mahabuba
    et al.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johnström, Peter
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Halldin, Christer
    Decreased defluorination using the novel beta-cell imaging agent [18F]FE-DTBZ-d4 in pigs examined by PET2011In: EJNMMI research, ISSN 2191-219X, Vol. 1, no 1, p. 33-Article in journal (Refereed)
    Abstract [en]

    Background

    Fluorine-18 dihydrotetrabenazine [DTBZ] analogues, which selectively target 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]fluoroethyl [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 9-O-desmethyl-(+)-DTBZ precursor with deuterated [18F]FE bromide ([18F]FCD2CD2Br). Radioligand binding potential [BP] was assessed by an in vitro saturation homogenate binding assay using human endocrine and exocrine pancreatic tissues. In vivo pharmacokinetics and pharmacodynamics [PK/PD] was studied in a porcine model by PET/computed tomography, and the rate of defluorination was quantified by compartmental modeling.

    Results

    [18F]FE-DTBZ-d4 was produced in reproducible good radiochemical yield in 100 ± 20 min. Radiochemical purity of the formulated product was > 98% for up to 5 h with specific radioactivities that ranged from 192 to 529 GBq/μmol at the end of the synthesis. The in vitro BP for VMAT2 in the islet tissue was 27.0 ± 8.8, and for the exocrine tissue, 1.7 ± 1.0. The rate of in vivo defluorination was decreased significantly (kdefluorination = 0.0016 ± 0.0007 min-1) compared to the non-deuterated analogue (kdefluorination = 0.012 ± 0.002 min-1), resulting in a six fold increase in half-life stability.

    Conclusions

    [18F]FE-DTBZ-d4 has similar PK and PD properties for VMAT2 imaging as its non-deuterated analogue [18F]FE-DTBZ in addition to gaining significantly increased stability against defluorination. [18F]FE-DTBZ-d4 is a prime candidate for future preclinical and clinical studies on focal clusters of beta cells, such as in intramuscular islet grafts.

  • 219. Jameel, Muhammad
    et al.
    Klar, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tariq, Muhammad
    Moawia, Abubakar
    Altaf Malik, Naveed
    Seema Waseem, Syeda
    Abdullah, Uzma
    Naeem Khan, Tahir
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Baig, Shahid Mahmood
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency2014In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 15, p. 133-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family.

    METHODS:

    We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP4M1 mRNA was performed using quantitative real-time PCR on total RNA from cultured fibroblasts. The brothers were investigated clinically and by MRI.

    RESULTS:

    We identified a novel homozygous AP4M1 mutation c.194_195delAT, p.Y65Ffs*50 in the affected brothers. Quantitative RT-PCR analysis showed markedly reduced AP4M1 mRNA levels suggesting partial non-sense mediated mRNA decay. Several clinical and MRI features were consistent with AP-4 complex deficiency. However, in contrast to previously reported cases with AP4M1 mutations our patients show an aggressive behavior and a relatively late onset of disease.

    CONCLUSION:

    This study shows an AP4M1 mutation associated with aggressive behavior in addition to mild dysmorphic features, intellectual disability, spastic paraparesis and reduced head circumference. Our findings expand the clinical spectrum associated with AP-4 complex deficiency and the study illustrates the importance of MRI and WES in the diagnosis of patients with CP and intellectual disability.

  • 220.
    Janson, Eva Tiensuu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sorbye, Halfdan
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Federspiel, Birgitte
    Grønbæk, Henning
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ladekarl, Morten
    Langer, Seppo W
    Mortensen, Jann
    Schalin-Jäntti, Camilla
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundlöv, Anna
    Thiis-Evensen, Espen
    Knigge, Ulrich
    Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 10, p. 1284-1297Article, review/survey (Refereed)
    Abstract [en]

    Background

    The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine tumours (NETs) including G1 (Ki67 index ≤ 2%) and G2 (Ki67 index 3-20%) tumours and neuroendocrine carcinomas (NECs) with Ki67 index > 20%, G3. Aim. These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients.

  • 221.
    Janson, Eva Tiensuu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Sørbye, Halfdan
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Federspiel, Birgitte
    Grønbaek, Henning
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Mathisen, Oystein
    Mortensen, Jann
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Thiis-Evensen, Espen
    Välimäki, Matti J
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Knigge, Ulrich
    Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 6, p. 740-756Article in journal (Refereed)
    Abstract [en]

    The diagnostic work-up and treatment of patients with neuroendocrine tumours has undergone a major change during the last decade. New diagnostic possibilities and treatment options have been developed. These Nordic guidelines, written by a group with a major interest in the subject, summarises our current view on how to diagnose and treat these patients. The guidelines are meant to be useful in the daily practice for clinicians handling patients with neuroendocrine tumours.

  • 222. Jansson, T
    et al.
    Westlin, J E
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lilja, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Bergh, J
    Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation?1995In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 13, no 6, p. 1470-1477Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To investigate if sequential positron emission tomographic (PET) scans with the glucose analog 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and/or L-methyl-11C-methionine (11C-methionine) in patients with breast cancer could provide early information on the efficacy of polychemotherapy.

    PATIENTS AND METHODS:

    Sixteen patients with breast cancer (11 with locally advanced tumors, three with recurrent disease in the contralateral breast, two of them with distant and regional metastases, and two with distant metastases) underwent a baseline and two follow-up PET scans after the first and third/fourth polychemotherapy course. Tumor response was determined clinically/radiographically after three/four polychemotherapy courses.

    RESULTS:

    Five patients were investigated with 18FDG, seven with both 11C-methionine and 18FDG, and four with only 11C-methionine before polychemotherapy. 11C-methionine presented a more distinct visualization of primary/contralateral breast cancers in five of seven patients when compared with 18FDG. Twelve of 16 patients demonstrated a response using conventional methods after the third/fourth course of polychemotherapy. Eight of these 12 clinical responders had a significant decrease in tracer uptake at the first PET scan performed 6 to 13 days after the first polychemotherapy course, and these reductions were further augmented after the third/fourth course and corresponded to the conventional therapy evaluation (clinical examination, computed tomography [CT], ultrasonography, and mammography).

    CONCLUSION:

    Our data indicate that PET may be of clinical value in predicting response to chemotherapy in patients with locally advanced breast cancer and/or metastatic disease earlier than any other method used.

  • 223.
    Johansson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Correlation between dose rate and T1 in blood at Gd-enhanced MR angiography1998In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 39, no 5, p. 579-582Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To determine the correlation between dose rate and T1 in blood at Gd-enhanced MR angiography (MRA).

    MATERIAL AND METHODS:

    A test dose of contrast agent was used to calculate the time delay between injection and arrival in the abdominal aorta. The dose rate was expressed as ml.kg b.w.-1.s-1. The correlation between dose rate and T1 was determined by varying the dose rate while keeping the scanning and infusion times constant. The signal intensity in the abdominal aorta was measured during the first pass of Gd and compared with markers of known T1 values.

    RESULTS:

    A correlation between dose rate and T1 in blood was obtained.

    CONCLUSION:

    A Gd dose rate of 0.01 ml.kg b.w.-1.s-1 gives a T1 in blood of 100 ms. This can be used to calculate the optimal pulse sequence for contrast-enhanced MRA.

  • 224.
    Johansson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjornerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tarlo, Kirk S
    Lorenz, Christine H
    Utility of NC100150 injection in cardiac MRI2002In: Academic Radiology, ISSN 1076-6332, E-ISSN 1878-4046, Vol. 9, no Suppl 1, p. S79-S81Article in journal (Refereed)
  • 225.
    Johansson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Björnerud, Atle
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ladd, D L
    Fujii, D K
    A targeted contrast agent for magnetic resonance imaging of thrombus: implications of spatial resolution2001In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 13, no 4, p. 615-8Article in journal (Refereed)
  • 226.
    Johansson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johnsson, Cecilia
    Penno, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Björnerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Acute cardiac transplant rejection: detection and grading with MR imaging with a blood pool contrast agent - experimental study in the rat2002In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 225, no 1, p. 97-103Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To investigate the possibility of detecting cardiac transplant rejection and determining its degree of severity with magnetic resonance (MR) imaging with a blood pool contrast agent.

    MATERIALS AND METHODS:

    Rat allogeneic (PVG to Wistar/Kyoto, n = 9) and syngeneic (Wistar/Kyoto to Wistar/Kyoto, n = 6) heterotopic heart transplantations were performed. On the 2nd and 6th postoperative days, an ultrasmall superparamagnetic iron oxide, or USPIO, contrast agent was injected intravenously at a dose of 2 mg of iron per kilogram of body weight. The injection was followed by three-dimensional T1-weighted MR imaging of the heart grafts with an imaging time of approximately 2 minutes for each image for 44 minutes. The signal intensity (SI) was measured in the myocardium over time, and the relative enhancement was calculated. After the 6th day, the rats were sacrificed, and the morphology of the transplanted hearts was assessed histologically. The CIs for the difference of the means on day 2 and day 6 were calculated by using a bootstrap technique, and the correlation between the relative SI change and the histologically determined degree of rejection were calculated with the Spearman rank order correlation coefficient.

    RESULTS:

    On day 6, a statistically significant difference between the groups was found at 4 minutes after injection of the contrast agent and increased with increasing time after injection. The mean percentage change in SI at the last time point for the allogeneic group on day 2 was -8.7% (SD, 8.5) and for the syngeneic group was -6.6% (SD, 6.0). On day 6, the allogeneic group had a relative SI change of 17.7% (SD, 8.7), whereas the syngeneic group had a change of -7.4% (SD, 2.6). There was a significant difference between only the two groups on day 6 (P <.001). Furthermore, in the allogeneic group the histologically determined degree of rejection correlated positively with the relative SI enhancement (r = 0.89, P <.005).

    CONCLUSION:

    Acutely rejecting heart transplants can be distinguished from nonrejecting ones in an animal model with MR imaging and a blood pool contrast agent. In addition, the relative SI enhancement reflects the histologically determined degree of rejection.

  • 227.
    Johansson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kirchin, Miles A
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Gadobenate dimeglumine (MultiHance) in MR angiography: an in-vitro phantom comparison with gadopentetate dimeglumine (Magnevist) at different concentrations2012In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 10, p. 1112-1117Article in journal (Refereed)
    Abstract [en]

    Background

    Numerous clinical studies suggest that gadobenate dimeglumine is diagnostically superior to other gadolinium chelates for MR imaging applications, including contrast-enhanced MR angiography (CE-MRA). However, confirmatory in-vitro phantom studies have thus far been lacking.

    Purpose

    To evaluate the difference in signal intensity achieved with the high-relaxivity MR contrast agent gadobenate dimeglumine (MultiHance) relative to that achieved with the standard-relaxivity non-specific agent gadopentetate dimeglumine (Magnevist) at different concentrations using an in-vitro phantom study design.

    Material and Methods

    Test tubes with whole human blood were prepared with concentrations of gadobenate dimeglumine or gadopentetate dimeglumine ranging from 0 to 12 mM. A three-dimensional (3D) T1-weighted gradient echo sequence normally used for CE-MRA of the renal arteries was performed at flip angles of 25° and 35°. The signal-to-noise ratio (SNR) was calculated for all concentrations of both contrast agents. Furthermore a Look-Locker sequence was used and quantitative T1 mapping was performed for all the test tubes. The contrast agent concentration in the aorta was simulated using previously published data on T1 in the aorta during the first pass of a contrast agent. The differences between gadobenate dimeglumine and gadopentetate dimeglumine were compared at the simulated concentrations.

    Results

    The SNR achieved with gadobenate dimeglumine was consistently greater than that achieved with gadopentetate dimeglumine at all concentrations. An improvement of 15-25% in SNR was obtained when increasing the flip angle from 25° to 35°. The relative improvement in SNR with gadobenate dimeglumine relative to gadopentetate dimeglumine ranged from 25-72% and was markedly greater at lower concentrations with a flip angle of 35°.

    Conclusion

    Our findings suggest that the relative benefit of gadobenate dimeglumine over gadopentetate dimeglumine for CE-MRA applications is greater at lower concentrations.

  • 228.
    Jonsson, Ove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Zemgulis, Vitas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Lundström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tovedal, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Myrdal Einarsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Björnerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade2011In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 91, no 4, p. 1198-1205Article in journal (Refereed)
    Abstract [en]

    Background

    Selective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig.

    Methods

    Two groups of pigs were subjected to SACP at 20°C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg−1 · min−1 and in group 2 (n = 5), flow was kept constant at 6 mL · kg−1 · min−1. Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100β was measured in peripheral blood.

    Results

    Decreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg−1 · min−1. No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100β were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP.

    Conclusions

    The findings suggest an ischemic threshold close to 6 mL · kg−1 · min−1 in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.

  • 229. Juhlin, C
    et al.
    Törnblom, S
    Rastad, J
    Bergström, Mats
    Bonasera, T
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Långström, Bengt
    [Differential diagnosis in adrenal gland tumors using PET and 11C-metomidate]1998In: Nordisk Medicin, ISSN 0029-1420, Vol. 113, no 9, p. 306-307Article in journal (Refereed)
    Abstract [sv]

    We have investigated 13 patients with incidentaloma using PET with 11C-metomidate. The patients included six adrenocortical adenomas, one adrenal cancer, two pheochromocytomas, one myelolipoma, one benign cyst and two metastases. A very high tracer uptake was observed in all tumors originating from the adrenal cortex, allowing excellent visualisation, whereas all other processes were negative. PET with 11C-metomidate is a very promising method for the characterisation of incidentalomas and is suggested to be included very early in the evaluation of these patients.

  • 230. Järnum, Hanna
    et al.
    Eskildsen, Simon F
    Steffensen, Elena G
    Lundbye-Christensen, Søren
    Simonsen, Carsten W
    Thomsen, Ib S
    Fründ, Ernst-Torben
    Théberge, Jean
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder2011In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 124, no 6, p. 435-446Article in journal (Refereed)
    Abstract [en]

    Objective:  To determine whether patients with major depressive disorder (MDD) display morphologic, functional, and metabolic brain abnormalities in limbic-cortical regions at a baseline magnetic resonance (MR) scan and whether these changes are normalized in MDD patients in remission at a follow-up scan.

    Method:  A longitudinal 3.0-Tesla (T) magnetic resonance imaging (MRI) study was carried out with cortical thickness measurements with a surface-based approach, perfusion measurements with three-dimensional (3D) pseudo-continuous arterial spin labeling (pCASL), and spectroscopy (1H-MRS) measurements in the anterior cingulate cortex (ACC) with water as an internal reference adjusted for cerebrospinal fluid content. We examined 23 MDD patients and 26 healthy controls. MDD patients underwent a baseline MRI at inclusion and were invited to a follow-up scan when they were in remission or after a 6-month follow-up period.

    Results:  Major findings were a significantly thinner posterior cingulate cortex in non-remitters than in remitters, a significant decrease in perfusion in the frontal lobes and the ACC in non-remitters compared with healthy controls at baseline and significantly reduced N-acetylaspartate, myo-inositol, and glutamate levels in MDD patients compared with healthy controls at baseline.

    Conclusion:  Using novel MRI techniques, we have found abnormalities in cerebral regions related to cortical-limbic pathways in MDD patients.

  • 231. Järnum, Hanna
    et al.
    Knutsson, Linda
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Brain tumours: evaluation of perfusion using 3D-FSE-pseudocontinuous arterial spin labelling2011In: Tumors of the Central Nervous system / [ed] M A Hayat, Dordrecht: Springer, 2011, vol 3, part 2, p. 135-142Chapter in book (Refereed)
  • 232.
    Karacagil, Sadettin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljungman, C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Boström, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hellberg, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Logason, K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Extra-anatomic bypass from the ascending aorta for treatment of critical lower limb ischaemia2000In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 20, no 6, p. 579-580Article in journal (Refereed)
  • 233.
    Karacagil, Sadettin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    A long distal prosthetic bypass grafting from descending aorta to distal peroneal artery: Sometimes it works!2000In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 19, no 1, p. 92-93Article in journal (Refereed)
  • 234. Karlsson, Ann-Katrine
    et al.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stokland, Eira
    Allvin, Kerstin
    Gronowitz, Eva
    Svensson, Pär-Arne
    Dahlgren, Jovanna
    Measurements of total and regional body composition in preschool children: a comparison of MRI, DXA and anthropometric data2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 5, p. 1018-1024Article in journal (Refereed)
    Abstract [en]

    The presence of adipose tissue in the abdominal area in particular is associated with unfavourable metabolic changes. Furthermore, there are clear sex differences in the distribution of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in adults, with males having more VAT and less SAT than females. The present study assessed whether these differences between the sexes were already present in preschool children. It also evaluated which measures of body composition were most appropriate for assessing abdominal obesity in this age group. One-hundred and five children (57 boys, 48 girls) participated in the study. Body composition was measured using dual-energy X-ray absorptionetry (DXA). Weight, height and waist circumference (WC) were also recorded. Magnetic resonance imaging (MRI) of the entire abdomen using sixteen 10 mm thick T1-weighted slices was performed in a subgroup of 48 children (30 boys, 18 girls); SAT and VAT volumes were measured using semi-automated segmentation.

    Boys had significantly more VAT than girls (0.17 versus 0.10 L, p<0.001). Results showed that VAT correlated significantly with all measurements of anthropometry (p<0.01) after adjusting for SAT and for total fat mass measured with DXA. The mean limits of agreement between DXA and MRI regarding truncal FM were calculated to -11.4 (range -17.8 to -3.6), using a Bland-Altman plot.

    In conclusion, sex differences in adipose tissue distribution are apparent at an early age. MRI is the best method with which to study abdominal fat distribution in young children.

  • 235.
    Karlsson, Britt-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Andersson Forsman, Catarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindgren, Per-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Jacobson, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Efficiency of percutaneous core biopsy in pancreatic tumor diagnosis1996In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 120, no 1, p. 75-79Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Radiologic diagnosis of pancreatic tumors exhibits limited precision. The aim of this study was to investigate the outcome and complications of pancreatic core biopsy in patients with suspected pancreatic neoplasms.

    METHODS:

    One hundred patients underwent ultrasonography-guided core biopsy of 1.2 mm external diameter. Medical charts were examined for biochemical and clinical signs of complications. Final diagnosis was settled by operation, autopsy, and clinical signs of the disease including survival with at least 2.3 years of follow-up.

    RESULTS:

    Histopathologic biopsy evaluation showed correct discrimination between exocrine and endocrine tumors and nonneoplastic conditions in 89 patients. No false-positive cancer diagnosis was found, and guidance on nature of primary tumors was obtained for eight of eight metastases. The sensitivity was 91% for exocrine and 87% for endocrine pancreatic tumors, and negative predictive values of these diagnoses were 83% and 97%, respectively. No clinically significant complications were noted.

    CONCLUSIONS:

    Core biopsy is an attractive alternative to diagnostic laparotomy in unresectable pancreatic cancer and efficiently provides diagnosis of endocrine tumors and pancreatic metastases in conjunction with rare complications. Benign biopsy findings cannot be used to exclude presence of primary or metastatic pancreatic neoplasms.

  • 236.
    Kartalis, Nikolaos
    et al.
    Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden; Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden.
    Mucelli, Raffaella Maria Pozzi
    Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden; Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Recent developments in imaging of pancreatic neuroendocrine tumors2015In: Annals of Gastroenterology, ISSN 1108-7471, E-ISSN 1792-7463, Vol. 28, no 2, p. 193-202Article in journal (Refereed)
    Abstract [en]

    Pancreatic neuroendocrine tumors (PNETs) are very rare, accounting for 1-2% of all pancreatic neoplasms. They are classified into functioning and non-functioning and their behavior varies widely from benign to highly malignant. For their investigation, a variety of anatomical and functional imaging methods are available. Anatomical methods include computed tomography (CT), magnetic resonance imaging, and ultrasonography. Functional methods include scintigraphy and positron emission tomography (PET). A combination of anatomical and morphological methods results in the so-called hybrid imaging, such as PET/CT. We herein discuss the currently available imaging modalities for the investigation of PNETs and, more specifically, their applications in tumor detection and staging as well as in choice of therapy, imaging follow up and prediction of response, with emphasis on the recent developments.

  • 237. Kasza, Zsolt
    et al.
    Fredlund Fuchs, Peder
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Tamm, Christoffer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Eriksson, Anna S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    O'Callaghan, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Heindryckx, Femke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Spillmann, Dorothe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Larsson, Erik
    Le Jan, Sebastien
    Eriksson, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kjellen, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kreuger, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    MicroRNA-24 Suppression of N-Deacetylase/N-Sulfotransferase-1 (NDST1) Reduces Endothelial Cell Responsiveness to Vascular Endothelial Growth Factor A (VEGFA)2013In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 36, p. 25956-25963Article in journal (Refereed)
    Abstract [en]

    Heparan sulfate (HS) proteoglycans, present at the plasma membrane of vascular endothelial cells, bind to the angiogenic growth factor VEGFA to modulate its signaling through VEGFR2. The interactions between VEGFA and proteoglycan co-receptors require sulfated domains in the HS chains. To date, it is essentially unknown how the formation of sulfated protein-binding domains in HS can be regulated by microRNAs. In the present study, we show that microRNA-24 (miR-24) targets NDST1 to reduce HS sulfation and thereby the binding affinity of HS for VEGFA. Elevated levels of miR-24 also resulted in reduced levels of VEGFR2 and blunted VEGFA signaling. Similarly, suppression of NDST1 using siRNA led to a reduction in VEGFR2 expression. Consequently, not only VEGFA binding, but also VEGFR2 protein expression is dependent on NDST1 function. Furthermore, overexpression of miR-24, or siRNA-mediated reduction of NDST1, reduced endothelial cell chemotaxis in response to VEGFA. These findings establish NDST1 as a target of miR-24 and demonstrate how such NDST1 suppression in endothelial cells results in reduced responsiveness to VEGFA.

  • 238. Kechagias, Stergios
    et al.
    Zanjani, Sepehr
    Gjellan, Solveig
    Dahlqvist Leinhard, Olof
    Kihlberg, Johan
    Smedby, Örjan
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindström, Torbjörn
    Nystrom, Fredrik H
    Effects of moderate red wine consumption on liver fat and blood lipids: a prospective randomized study2011In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 43, no 7, p. 545-554Article in journal (Refereed)
    Abstract [en]

    Background: There have been no human prospective randomized studies of the amount of alcohol that can induce hepatic steatosis.

    Methods: Thirty-two healthy women and twelve healthy men (34 ± 9 years of age) were randomized to consume 150 ml of red wine/day for women (16 g ethanol/day) or double that amount for men (33 g ethanol/day), or to alcohol abstention for 90 days. Participants underwent proton-nuclear magnetic-resonance spectroscopy for measurement of hepatic triglyceride content (HTGC). Blood samples for assessment of cardiovascular risk were drawn before and after the intervention.

    Results: After exclusion of three subjects with steatosis at baseline a trend towards increased HTGC was apparent for red wine (before median: 1.1%, range 0.2-3.9%, after median: 1.1%, range 0.5-5.2 %, P = 0.059) a difference that was statistically significant compared with abstainers (p = 0.02). However, no subject developed hepatic steatosis. Low-density lipoprotein (LDL)-cholesterol was lowered by red wine (-0.3 mmol/l, SE -0.1, 95% CI -0.6 to -0.04).

    Conclusions: Moderate consumption of red wine during three months increased HTGC in subjects without steatosis at baseline. However, since not a single participant developed steatosis we suggest that the threshold of alcohol consumption to define nonalcoholic fatty liver disease should not be lower than the amount in our study.

  • 239.
    Khoschnau, Shwan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milosavljevic, Jugoslav
    Radiology department, Västerås central hospital.
    Sahlstedt, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rylance, Rebecca
    The southern Sweden musculoskeletal research center, department of orthopedics, Lund, Sweeden.
    Rahme, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    High prevalence of rotator cuff tears ina population who never sought for shoulder problems: a clinical, ultrasonographic and radiographic screening study2012In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500Article in journal (Refereed)
  • 240.
    Kilarski, Witold W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Petersson, Ludvig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fuchs, Peder Fredlund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zielinski, Marcin S
    Institute of Bioengineering and Swiss Institute of Experimental, Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne (EPFL).
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    An in vivo neovascularization assay for screening regulators of angiogenesis and assessing their effects on pre-existing vessels2012In: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 15, no 4, p. 643-655Article in journal (Refereed)
    Abstract [en]

    Therapeutic regulation of tissue vascularization has appeared as an attractive approach to treat a number of human diseases. In vivo neovascularization assays that reflect physiological and pathological formation of neovessels are important in this effort. In this report we present an assay where the effects of activators and inhibitors of angiogenesis can be quantitatively and qualitatively measured. A provisional matrix composed of collagen I and fibrin was formed in a plastic cylinder and implanted onto the chick chorioallantoic membrane. A nylon mesh separated the implanted matrix from the underlying tissue to distinguish new from pre-existing vessels. Vascularization of the matrix in response to fibroblast growth factor-2 or platelet-derived growth factor-BB was scored in a double-blinded manner, or vessel density was measured using a semi-automated image analysis procedure. Thalidomide, fumagillin, U0126 and TGFβ inhibited neovessel growth while hydrocortisone exerted a negative and wortmannin a toxic effect on the pre-existing vasculature. This quantitative, inexpensive and rapid in vivo angiogenesis assay might be a valuable tool in screening and characterizing factors that influence wound or tumor induced vascularization and in assessing their effects on the normal vasculature.

  • 241.
    Knutson, Tina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Fridblom, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tannergren, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Increased understanding of intestinal drug permeability determined by the LOC-I-GUT approach using multislice computed tomography2009In: Molecular pharmaceutics, ISSN 1543-8384, Vol. 6, no 1, p. 2-10Article in journal (Refereed)
    Abstract [en]

    This study further evaluated the in vivo single-pass perfusion technique (LOC-I-GUT) in three different ways. First, the intestinal radius of the human small intestinal segment was measured on plain X-ray films; second, evaluation was performed by applying multislice computed tomography investigations; and third, furosemide was used as model drug in a transport study. In total 17 (6 + 4 +7) intubation/perfusion studies were performed in healthy volunteers. Mixobar was used as a positive radiographic contrast agent in the first six volunteers when plain film examination was made, followed by four studies using multislice computed tomography. Mantel area calculations of the perfused segment after X-ray investigations using barium as contrast were determined to be 101.0 +/- 2.9 cm2. Maximal dilatation of the closed segment with room air as contrast and using MSCT revealed a mantel area of 121.30 +/- 7.0 cm2 (P < 0.01). Thus, the mantle area increased a further 20% when the bowel was fully distended, reflecting different physiologic distention patterns for air and fluid. A jejunal single-pass perfusion study was performed in a further seven volunteers. In each experiment furosemide was perfused during 200 min, and in the treatment period (100-200 min), fexofenadine was added to the perfusion solution. The mean (+/-SD) P (eff) for furosemide was 0.17 +/- 0.07 and 0.12 +/- 0.09 x 10-4 cm/s in the control and treatment period, respectively. This study showed that the calculation of human in vivo permeability is based on physiological values, which are important for the wide application of these in vivo permeability data in physiologically based pharmacokinetic modeling.

  • 242.
    Källman, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Halsius, Erik
    Folkesson, Mikael
    Larsson, Ylva
    Stenstrom, Mats
    Bath, Magnus
    Automated detection of changes in patient exposure in digital projection radiography using exposure index from DICOM header metadata2011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 6, p. 960-965Article in journal (Refereed)
    Abstract [en]

    Purpose. Automated collection of image data from DICOM headers enables monitoring of patient dose and image quality parameters. Manual monitoring is time consuming, owing to the large number of exposure scenarios, thus automated methods for monitoring needs to be investigated. The aim of the present work was to develop and optimise such a method. Material and methods. Exposure index values from digital systems in projection radiography were collected over a period of five years, representing data from 1.2 million projection images. The exposure index values were converted to detector dose and an automated method for detection of sustained level shifts in the resulting detector dose time series was applied using the statistical analysis tool R. The method combined handling of outliers, filtering and estimation of variation in combination with two different statistical rank tests for level shift detection. A set of 304 time series representing central body parts was selected and the level shift detection method was optimised using level shifts identified by ocular evaluation as the gold standard. Results. Two hundred and eighty-one level changes were identified that were deemed in need of further investigation. The majority of these changes were abrupt. The sensitivity and specificity of the optimised and automated detection method concerning the ocular evaluation were 0.870 and 0.997, respectively, for detected abrupt changes. Conclusions. An automated analysis of exposure index values, with the purpose of detecting changes in exposure, can be performed using the R software in combination with a DICOM header metadata repository containing the exposure index values from the images. The routine described has good sensitivity and acceptable specificity for a wide range of central body part projections and can be optimised for more specialised purposes.

  • 243.
    Ladjevardi, Sam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Auer, Gert
    Castro, Juan
    Ericsson, Christer
    Zetterberg, Anders
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Wiksell, Hans
    Jorulf, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Prostate biopsy sampling causes hematogenous dissemination of epithelial cellular material2014In: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, p. 707529-Article in journal (Refereed)
    Abstract [en]

    The extent of epithelial cellular material (ECM) occurring in venous blood samples after diagnostic core needle biopsy (CNB) was studied in 23 patients with CNB diagnosed prostate cancer without provable metastases and 15 patients without cancer. The data show a significant increase of ECM in the peripheral blood sampled 20 seconds or 30 minutes after the last of 10 CNB procedures compared to the number of ECM detectable in the blood samples taken before the performance of CNB. The data indicate that diagnostic CNB of prostate cancer causes an extensive tissue trauma with a potential risk of cancer cell dissemination.

  • 244.
    Ladjevardi, Sam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Jorulf, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    A Comparison of Different Imaging Techniques for Localisation of Cancers in the Prostate2014In: Open Prostate Cancer Journal, ISSN 1876-8229, Vol. 7, p. 1-6Article in journal (Refereed)
    Abstract [en]

    The diagnostic accuracy of standard transrectal ultrasound-guided (TRUL) biopsy is limited due to the finite number of cores that can be obtained. It has been shown that the technique is not sufficiently reliable in defining the location and extent of prostatic cancer. The main aim of this study was to investigate the effectiveness of magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) imaging techniques in pinpointing potential tumour lesions prior to prostate biopsy.

    Material and methods

    The study cohort consisted of 45 men with a raised prostate specific-antigen (PSA) level and/or suspected prostate cancer (PCa) at digital rectal examinations (DRE). Of the 45 patients, 23 had PCa detected with core needle biopsy (CNB). All had 11C acetate PET/CT imaging. Ten of those 23 patients underwent radical prostatectomy (RP), of those ten patients, eight patients had MR spectroscopic imaging (MRSI) with 3 T and six had diffusion weighted imaging (DWI) with apparent diffusion coefficient calculation (MRI DWI ADC). CNB, PET/CT, 2D MRSI and ADC map results were compared with postoperative specimen histopathology.

    Results

    The sensitivity of CNB, PET/CT, MRSI and DWI ADC were 0.53, 0.55, 0.79 and 0.95, whereas the specificity of was 0.88, 0.87, 0.46 and 0.73, respectively.

    Conclusion

    MRI improves the PCa detection by defining the areas of interest for targeted CNB of the prostate and can reduce the number of biopsies required

  • 245.
    Lannsjö, Marianne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bustamante, Mariana
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    von Seth, Charlotta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Borg, Jörgen
    Brain pathology after mild traumatic brain injury: An exploratory study by repeated magnetic resonance examination2013In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 45, no 8, p. 721-728Article in journal (Refereed)
    Abstract [en]

    Objective:

    To explore brain pathology after mild traumatic brain injury by repeated magnetic resonance examination.

    Design:

    A prospective follow-up study.

    Subjects:

    Nineteen patients with mild traumatic brain injury presenting with Glasgow Coma Scale (GCS) 14-15.

    Methods:

    The patients were examined on day 2 or 3 and 3-7 months after the injury. The magnetic resonance protocol comprised conventional T1- and T2-weighted sequences including fluid attenuated inversion recovery (FLAIR), two susceptibility-weighted sequences to reveal haemorrhages, and diffusion-weighted sequences. Computer-aided volume comparison was performed. Clinical outcome was assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Glasgow Outcome Scale Extended (GOSE).

    Results:

    At follow-up, 7 patients (37%) reported ≥  3 symptoms in RPQ, 5 reported some anxiety and 1 reported mild depression. Fifteen patients reported upper level of good recovery and 4 patients lower level of good recovery (GOSE 8 and 7, respectively). Magnetic resonance pathology was found in 1 patient at the first examination, but 4 patients (21%) showed volume loss at the second examination, at which 3 of them reported < 3 symptoms and 1 ≥ 3 symptoms, all exhibiting GOSE scores of 8.

    Conclusion:

    Loss of brain volume, demonstrated by computer-aided magnetic resonance imaging volumetry, may be a feasible marker of brain pathology after mild traumatic brain injury.

  • 246. Latifi, Ali
    et al.
    Labruto, Fausto
    Kaiser, Sylvie
    Ullberg, Ulla
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Torkzad, Michael R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Does enteral contrast increase the accuracy of appendicitis diagnosis?2011In: Radiologic Technology, ISSN 0033-8397, E-ISSN 1943-5657, Vol. 82, no 4, p. 294-299Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several approaches traditionally have helped opacify the bowel when computed tomography (CT) is used to diagnose appendicitis. With the development of multidetector row CT (MDCT), the need for enteral contrast agents is less obvious. Purpose The objective of this study was to evaluate retrospectively the accuracy of MDCT demonstration of appendicitis using enteral contrast agents.

    METHODS: We reviewed radiologic reports of all 246 adult patients with suspected appendicitis who underwent 16-slice MDCT during 2005-2006 at our department. The use of enteral contrast agents and the route of administration were documented by one investigator. A radiologist evaluated whether the responses in the reports were consistent with diagnosis of appendicitis. The accuracy of the radiologic reports was assessed using the results of surgery, histopathology and 3 to 21 months of follow-up.

    RESULTS: Of patients studied, 14.6% received no enteral contrast agent, 8.5% received both oral contrast and rectal contrast (enema), 46.7% received oral contrast and 30.1% received rectal contrast enemas. The accuracies for the CT diagnosis of appendicitis with different combinations of agents ranged from 95% to 100%, with no significant difference among groups.

    CONCLUSION: Our study shows that the accuracy for diagnosis of appendicitis by abdominal 16-slice MDCT is high regardless of enteral contrast use. Therefore, further use of enteral contrast agents for CT diagnosis of appendicitis in adults cannot be recommended.

  • 247.
    Lennmyr, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ericsson, A.
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased brain injury and vascular leakage after pretreatment with p38-inhibitor SB203580 in transient ischemia2003In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 108, no 5, p. 339-45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days. RESULTS: The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially. CONCLUSION: Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.

  • 248.
    Lennmyr, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ericsson, A.
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Akterin, S.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Src family kinase-inhibitor PP2 reduces focal ischemic brain injury2004In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, no 3, p. 175-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the neuroprotective potential of the Src family kinase (SFK) inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo(3,4-d)pyrimidine (PP2) in transient focal cerebral ischemia in the rat. MATERIAL AND METHODS: Sprague-Dawley rats were exposed to transient (90 min) middle cerebral artery occlusion (MCAO) and evaluated after 1 day of survival. PP2 (1.5 mg/kg i.p.) or vehicle was given 30 min after MCAO. The lesions were examined with magnetic resonance imaging (MRI), tri-phenyl tetrazolium chloride (TTC) staining and the functional outcome was determined using neurological scoring according to Bederson et al. RESULTS: PP2-treated rats showed approximately 50% reduction of infarct size on T2-weighted MRI and in TTC staining compared with controls (P < 0.05). Moreover, the neurological score was better in the PP2 group than controls (P < 0.05). CONCLUSION: PP2 is a potential neuroprotective agent in cerebral ischemia-reperfusion. The interference of PP2 with SFKs and/or other pathways remains to be elucidated.

  • 249. Letocha, H
    et al.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Westlin, J E
    Fasth, K J
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Positron emission tomography with L-methyl-11C-methionine in the monitoring of therapy response in muscle-invasive transitional cell carcinoma of the urinary bladder1994In: British Journal of Urology, ISSN 0007-1331, E-ISSN 1365-2176, Vol. 74, no 6, p. 767-774Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate whether positron emission tomography (PET) with L-methyl-11C-methionine as a tracer could be used for diagnostic purposes and for evaluation of therapy in patients with varying stages of urinary bladder cancer treated with chemotherapy.

    PATIENTS AND METHODS:

    PET was employed in 44 separate examinations involving 29 patients (24 men and five women with a median age of 68 years [mean 66, range 47-78]) with localized or metastatic transitional cell carcinoma of the urinary bladder. In four patients PET examinations were performed prior to the commencement of chemotherapy, and after one course and after three courses.

    RESULTS:

    The diagnostic accuracy of PET was poor. The technique did not monitor the therapeutic effect of neoadjuvant chemotherapy, producing results that correlated with therapy outcome. PET identified those patients who responded less successfully to therapy.

    CONCLUSION:

    PET with L-methyl-11C-methionine demonstrates alterations in tumour metabolism long before visible changes appear on computed tomography or magnetic resonance imaging. Further work is required to develop more specific tracers.

  • 250.
    Lilienberg, Elsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Ebeling-Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Axén, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lennernas, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Investigation of Hepatobiliary Disposition of Doxorubicin Following Intrahepatic Delivery of Different Dosage Forms2014In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 11, no 1, p. 131-144Article in journal (Refereed)
    Abstract [en]

    Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI–TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28–53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15–22)% and 4.2 (3.2–5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580–660) and 5000 (3900–5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.

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