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  • 1151. Wester, Knut
    et al.
    Stridbeck, Ulf
    Syse, Aslak
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Re-evaluation of medical findings in alleged shaken baby syndrome and abusive head trauma in Norwegian courts fails to support abuse diagnoses2022In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 111, no 4, p. 779-792Article in journal (Refereed)
    Abstract [en]

    AIM: The criteria for diagnosing abusive head trauma (AHT) are not well defined and this condition might be diagnosed on failing premises. Our aim was to review criminal AHT cases in Norwegian courts by scrutinising the underlying medical documentation.

    METHODS: Cases were identified in the data registry for Norwegian courts from 2004 to 2015. Documentation was obtained from relevant health institutions. The medical co-authors first made independent evaluations of the documentation for each child, followed by a consensus evaluation.

    RESULTS: A total of 17 children (11 boys) were identified, all diagnosed as AHT by court appointed experts, 15 were infants (mean age 2.6 months). A high proportion (41.2%) was born to immigrant parents and 31.3% were premature. The medical findings could be explained by alternative diagnoses in 16 of the 17 children; 8 boys (7 infants - mean age 2.9 months) had clinical and radiological characteristics compatible with external hydrocephalus complicated by chronic subdural haematoma. Six children (five infants with mean age 2.1 months) had a female preponderance and findings compatible with hypoxic ischaemic insults.

    CONCLUSION: The medical condition in most children had not necessarily been caused by shaking or direct impact, as was originally concluded by the court experts.

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  • 1152. Wester, Knut
    et al.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lynøe, Niels
    Eriksson, Anders
    Unsubstantiated belief in the diagnostic accuracy of the triad of abusive head trauma may lead to incorrect diagnoses of alleged abuse cases.2022In: Acta paediatrica, ISSN 0803-5253, Vol. 111, no 4, p. 809-811Article in journal (Refereed)
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  • 1153.
    Wiemerslage, Lyle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Islam, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    van der Kamp, C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cao, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ence-Eriksson, F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Castillo, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsen, A L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Bandstein, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dahlberg, L S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Perland, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Gustavsson, V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, H
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
    Schürmann, A
    German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels2017In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 6, p. 990-994Article in journal (Refereed)
    Abstract [en]

    We investigated five methylation markers recently linked to body-mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus, and frontal gyri, some of which have been previously associated to food signaling, obesity, or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity, and genetic differences.

  • 1154.
    Wiemerslage, Lyle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Emil K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dahlberg, Linda Solstrand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ence-Eriksson, Fia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Castillo, Sandra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsen, Anna L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Bylund, Simon B. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Bandstein, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Titova, Olga E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Cape Town, Dept Psychiat, Old Groote Schuur Hosp, ZA-7925 Cape Town, South Africa..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images2016In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 43, no 9, p. 1173-1180Article in journal (Refereed)
    Abstract [en]

    Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low-or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

  • 1155.
    Wiemerslage, Lyle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A resting-state fMRI study of obese females between pre- and postprandial states before and after bariatric surgery.2017In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 45, no 3, p. 333-341Article in journal (Refereed)
    Abstract [en]

    Past studies utilizing resting-state functional MRI (rsfMRI), have shown that obese humans exhibit altered activity in brain areas related to reward compared to normal-weight controls. However, to what extent bariatric surgery-induced weight loss alters resting-state brain activity in obese humans is less well-studied. Thus, we measured the fractional amplitude of low-frequency fluctuations (fALFF) from eyes-closed, rsfMRI in obese females (n = 11, mean age = 42 years, mean BMI = 41 kg/m(2) ) in both a pre- and post-prandial state at two time points: four weeks before, and four weeks after bariatric surgery. Several brain areas showed altered resting-state activity following bariatric surgery, including the putamen, insula, cingulate, thalamus, and frontal regions. Activity augmented by surgery was also dependent on prandial state. For example, in the fasted state, activity in the middle frontal, and pre- and postcentral gyri was found to be decreased after surgery. In the sated state, activity within the insula was increased before, but not after surgery. Collectively, our results suggest that resting-state neural functions are rapidly affected following bariatric surgery and the associated weight loss and change in diet. 

  • 1156.
    Wiklund, E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Koskinen, S K
    Linder, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Åslund, P-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eklöf, Hampus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Whole body computed tomography for trauma patients in the Nordic countries 2014: survey shows significant differences and a need for common guidelines2016In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 57, no 6, p. 750-757Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Whole body computed tomography in trauma (WBCTT) is a standardized CT examination of trauma patients. It has a relatively high radiation dose. Therefore, well-defined clinical indications and imaging protocols are needed. This information regarding Nordic countries is limited.

    PURPOSE: To identify Nordic countries' WBCTT imaging protocols, radiation dose, and integration in trauma care, and to inquire about the need for common Nordic guidelines.

    MATERIAL AND METHODS: A survey with 23 multiple choice questions or free text responses was sent to 95 hospitals and 10 trauma centers in and outside the Nordic region, respectively. The questions were defined and the hospitals selected in collaboration with board members of "Nordic Forum for Trauma and Emergency Radiology" (www.nordictraumarad.com).

    RESULTS: Two Nordic hospitals declined to take part in the survey. Out of the remaining 93 Nordic hospitals, 56 completed the questionnaire. Arterial visualization is routine in major trauma centers but only in 50% of the Nordic hospitals. The CT scanner is located within 50 m of the emergency department in all non-Nordic trauma centers but only in 60% of Nordic hospitals. Radiation dose for WBCTT is in the range of 900-3600 mGy × cm. Of the 56 responding Nordic hospitals, 84% have official guidelines for WBCTT. Eighty-nine percent of the responders state there is a need for common guidelines.

    CONCLUSION: Scanning protocols, radiation doses, and routines differ significantly between hospitals and trauma centers. Guideline for WBCTT is presently defined locally in most Nordic hospitals. There is an interest in most Nordic hospitals to endorse new and common guidelines for WBCTT.

  • 1157.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Re: Placental magnetic resonance imaging T2*measurements in normal pregnancies and in those complicated by fetal growth restriction. M. Sinding, D. A. Peters, J. B. Frokjaer, O. B. Christiansen, A. Petersen, N. Uldbjerg and A. Sorensen. Ultrasound Obstet Gynecol 2016; 47: 748-754.2016In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 47, no 6, p. 673-673Article in journal (Other academic)
  • 1158.
    Wikström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Bengt, Johansson
    Örebro University Hospital, Department of Oncology.
    Lennernäs, Bo
    Örebro University Hospital, Department of Oncology.
    Magnetic Resonance Compatibility of a Transponder Aimed for Radiotherapy Positioning – A Phantom Study2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 9, p. 4993-4996Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Electromagnetic Positioning Systems (EMP) is a new position-ing technique in four-dimensional radiotherapy. Patients with implanted transponders may be referred for magnetic resonance imaging (MRI) making it important to establish the MR safety.

    Materials and Methods: Oranges were prepared with transponders and imaged on a 3T MR scanner with different sequences. Computed tomography (CT) was performed as comparison. MR artifacts were assessed. An estimation of the maximum transponder de-flection force and heating was made.

    Results: The mean measured displacement of transponders was 0.1 mm (range=0.03-0.3 mm). Artifacts were observed adjacent to transponders using all sequences. The deflection force on the transponder in the gantry was less than 38 mN. No heating was observed.

    Conclusion: The absence of any substantial movement, the weak measured deflection force and absence of observed heating speaks for the safe use of MR imaging with transponder 3T. Local artefacts makes evaluation impossible adjacent to transponders.

  • 1159.
    Wilking, H.
    et al.
    Uppsala Univ Hosp, Uppsala, Sweden.
    Ilan, Ezgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Andersson, C.
    Uppsala Univ Hosp, Uppsala, Sweden;Uppsala Univ, Uppsala, Sweden.
    Öst, A.
    Uppsala Univ Hosp, Uppsala, Sweden.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala Univ Hosp, Uppsala, Sweden.
    Fröss-Baron, Katarzyna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology. Uppsala Univ Hosp, Uppsala, Sweden.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    In-vivo stability of 177Lu-DOTATATE during peptide receptor radionuclide therapy2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Supplement 1, p. S592-S592Article in journal (Other academic)
  • 1160.
    Winberg, Hans
    et al.
    Lund Univ, Dept Clin Sci Lund, Pediat, Lund, Sweden.;Skanes Univ Lund, Dept Pediat Surg, Lund, Sweden..
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hagelsteen, Kristine
    Lund Univ, Dept Clin Sci Lund, Pediat, Lund, Sweden.;Skanes Univ Lund, Dept Pediat Surg, Lund, Sweden.;Lund Univ, Pediat, S-22185 Lund, Sweden..
    Massive Chylous Ascites in a 9-Year-Old Girl with Malrotation-A Case Report2024In: EUROPEAN JOURNAL OF PEDIATRIC SURGERY REPORTS, ISSN 2194-7619, Vol. 12, no 01, p. e1-e3Article in journal (Refereed)
    Abstract [en]

    Malrotation leading to massive chylous ascites is rare. A 9-year-old girl was investigated for slowly increasing abdominal distension under a year. She had no vomiting, weight loss, or pain, but was bothered in social situations. Medical investigations, including ultrasound and computed tomography scans, revealed massive ascites. Laparocentesis yielded milk-colored fluid, confirmed as lymph through laboratory analysis. A complete blood count, liver function and hematologic parameters, chyle cytology, bacterial cultures, and polymerase chain reaction for tuberculosis were all within normal limits.She was referred to a tertiary center for vascular anomalies. A dynamic contrast-enhanced magnetic resonance lymphangiography showed normal lymphatic anatomy without leakage or flow obstruction. A whole-body magnetic resonance imaging revealed a central mesenteric rotation.She was referred to a tertiary center for pediatric surgery, where a laparoscopic Ladd's procedure was performed using a new 5 mm pediatric sealing device, along with an appendectomy using a 5 mm stapler. To derotate the bowel, fenestrations were created in compartments containing a substantial amount of chyle and ascites, resulting in the drainage of 2.4 L of fluid. She was discharged the day after surgery and has been in good health for 1 year. We present a video illustrating the Ladd's procedure steps in this patient.

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  • 1161.
    Wu, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nordin, Elina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Behov och förutsättningar till kompetensutveckling för röntgensjuksköterskor: En intervjustudie2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Profession as radiographer is constantly developing in Sweden valid skills development. There are many different ways in order to improve the profession internationally. One can, for example, take advanced practicing to become a reporting radiographer. The advanced practicing has exclusively showed positive results. Nowadays the patients are changing in conditions rapidly that the healthcare industry needs to adapt itself. Even the international development for radiographers seems bright, the need is yet fully realized in Sweden.

    Purpose: The purpose of this study is to find out which needs and possibilities are available for Swedish radiographers to improve and develop their own professional skills.

    Method: A qualitative interview study with semi-structured questions. The participants were selected by inclusions and exclusions. The interviews were conducted by telephone or physical meetings and the interviews were recorded and analyzed using qualitative content analysis manifest.

    Results: The responses from the participants have been varied. Lack of radiographers is palpable. All participants expressed that they had opportunities and possibilities for their radiographers to receive an advanced practicing in skills development even though the supply varied. The result shows that skills development is needed in all areas. Despite this, all hospitals do not express that skill development is important for their radiology department.

    Conclusion: Advanced skills development for radiographers is an interesting topic. There are more to figure out valid skill development. There is a need to develop radiographers in order to improve individually and together as X-ray department.

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  • 1162.
    Wärnberg, Fredrik
    et al.
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Surg, Gothenburg, Sweden..
    Karakatsanis, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Abdsaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Samariterhemmet, Mammog Unit, Aleris, Uppsala, Sweden..
    Not all artifacts after magnetic guided sentinel lymph node biopsy are necessarily related to superparamagnetic iron oxide nanoparticles2020In: Breast Cancer, ISSN 1340-6868, E-ISSN 1880-4233, Vol. 27, no 4, p. 791-791Article in journal (Other academic)
  • 1163.
    Yin, Wen
    et al.
    KTH Royal Inst Technol, Dept Prot Sci, Roslagstullsbacken 21, S-11417 Stockholm, Sweden..
    Xu, Tianqi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Ding, Haozhong
    KTH Royal Inst Technol, Dept Prot Sci, Roslagstullsbacken 21, S-11417 Stockholm, Sweden..
    Zhang, Jie
    KTH Royal Inst Technol, Dept Prot Sci, Roslagstullsbacken 21, S-11417 Stockholm, Sweden..
    Bodenko, Vitalina
    Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Tretyakova, Maria S.
    Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Belousov, V. Mikhail
    Siberian State Med Univ, Minist Hlth Russian Federat, Tomsk 634050, Russia.;Natl Res Tomsk Polytech Univ, Tomsk 634050, Russia..
    Liu, Yongsheng
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Oroujeni, Maryam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab. Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Uppsala Univ, Dept Med Chem, S-75123 Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, S-75123 Uppsala, Sweden..
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Graslund, Torbjorn
    KTH Royal Inst Technol, Dept Prot Sci, Roslagstullsbacken 21, S-11417 Stockholm, Sweden..
    Vorobyeva, Anzhelika
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Comparison of HER2-targeted affibody conjugates loaded with auristatin-and maytansine-derived drugs2023In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 355, p. 515-527Article in journal (Refereed)
    Abstract [en]

    Treatment with antibody drug conjugates targeting receptors over-expressed on cancer cells is well established for clinical use in several types of cancer, however, resistance often occurs motivating the development of novel drugs. We have recently investigated a drug conjugate consisting of an affibody molecule targeting the human epidermal growth factor receptor 2 (HER2), fused to an albumin-binding domain (ABD) for half-life extension, loaded with the cytotoxic maytansine derivative DM1. In this study, we investigated the impact of the cytotoxic payload on binding properties, cytotoxicity and biodistribution by comparing DM1 with the auristatins MMAE and MMAF, as part of the drug conjugate. All constructs had specific and high affinity binding to HER2, human and mouse albumins with values in the low- to sub-nM range. ZHER2-ABD-mcMMAF demonstrated the most potent cytotoxic effect on several HER2-over-expressing cell lines. In an experimental therapy study, the MMAFbased conjugate provided complete tumor regression in 50% of BALB/c nu/nu mice bearing HER2-overexpressing SKOV3 tumors at a 2.9 mg/kg dose, while the same dose of ZHER2-ABD-mcDM1 provided only a moderate anti-tumor effect. A comparison with the non-targeting ZTaq-ABD-mcMMAF control demonstrated HER2-targeting specificity. In conclusion, a combination of potent cytotoxicity in vitro, with minimal uptake in normal organs in vivo, and efficient delivery to tumors provided a superior anti-tumor effect of ZHER2-ABDmcMMAF, while maintaining a favorable toxicity profile with no observed adverse effects.

  • 1164.
    Young, Peter
    et al.
    Univ Gothenburg, Dept Psychiat & Neurochem, Wallinsgatan 6, S-41341 Gothenburg, Sweden.;Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden..
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tolf, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Kosmidis, Savvas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Rieckmann, Anna
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden.;Max Planck Inst Social Law & Social Policy, Munich Ctr Econ Aging, Munich, Germany..
    Schoell, Michael
    Univ Gothenburg, Dept Psychiat & Neurochem, Wallinsgatan 6, S-41341 Gothenburg, Sweden.;Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden.;UCL, Queen Sq Inst Neurol, Dementia Res Ctr, London, England..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Image-derived input functions from dynamic O-15-water PET scans using penalised reconstruction2023In: EJNMMI Physics, E-ISSN 2197-7364, Vol. 10, article id 15Article in journal (Refereed)
    Abstract [en]

    Background: Quantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic O-15-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide.

    Results: IDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R-2 values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% +/- and a coefficient of variation (CoV) of 7.3%.

    Conclusion: Our results show promising results that a robust IDIF can be produced for dynamic O-15-water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with O-15-water feasible.

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  • 1165. Young, Peter
    et al.
    Heeman, Fiona
    Axelsson, Jan
    Collij, Lyduine E
    Hitzel, Anne
    Sanaat, Amirhossein
    Niñerola-Baizan, Aida
    Perissinotti, Andrés
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Frisoni, Giovanni B
    Zaidi, Habib
    Barkhof, Frederik
    Farrar, Gill
    Baker, Suzanne
    Gispert, Juan Domingo
    Garibotto, Valentina
    Rieckmann, Anna
    Schöll, Michael
    Impact of simulated reduced injected dose on the assessment of amyloid PET scans.2024In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 51, no 3, p. 734-748Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben.

    METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated.

    RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were < 1.5%. AUCs for discriminating Aβ- from Aβ + scans were high (AUC ≥ 0.94) across dose levels, and visual assessment showed intra-reader agreement of > 80% for both tracers.

    CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

  • 1166.
    Zachrisson, Karin
    et al.
    Sahlgrens Univ Hosp, Dept Radiol, Grona Straket 2, SE-41345 Gothenburg, Sweden..
    Herlitz, Hans
    Sahlgrens Univ Hosp, Dept Mol & Clin Med, Nephrol, Gothenburg, Sweden..
    Lönn, Lars
    Univ Copenhagen, Rigshosp, Dept Radiol, Copenhagen, Denmark.;Univ Copenhagen, Rigshosp, Dept Vasc Surg, Copenhagen, Denmark..
    Falkenberg, Mårten
    Sahlgrens Univ Hosp, Dept Radiol, Grona Straket 2, SE-41345 Gothenburg, Sweden..
    Eklöf, Hampus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Duplex ultrasound for identifying renal artery stenosis: direct criteria re-evaluated2017In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 58, no 2, p. 176-182Article in journal (Refereed)
    Abstract [en]

    Background: Renal artery duplex ultrasound (RADUS) is an established method for diagnosis of renal artery stenosis (RAS), but there is no consensus regarding optimal RADUS criteria. Purpose: To define optimal cutoff values for RADUS parameters when screening for RAS using intra-arterial transstenotic pressure gradient measurement (PGM) as reference. Material and Methods: The renal arteries of 58 consecutive patients evaluated for renovascular hypertension were examined by RADUS and PGM. Conclusive measurements with both methods were obtained in 76 arteries. Hemodynamically significant RAS was defined as PGM >= 15 mmHg and was found in 43 of the 76 arteries. RADUS parameters included renal artery peak systolic velocity (PSV) and the renal-aortic ratio (RAR) of flow velocities. Receiver operating characteristic curves (ROCs) and Youden's index were used to calculate optimal RADUS criteria for RAS. Results: When traditional RADUS criteria for RAS were used, with a combination of PSV >= 180 cm/s and RAR >= 3.5, the sensitivity was 62% and the specificity was 91%. When RADUS criteria were optimized for sensitivity, then RAR >= 2.6 alone resulted in a sensitivity of 89% and a specificity of 69%. Conclusion: The RAR >= 2.6 is a more sensitive criterion than traditional RADUS criteria when screening patients with clinical suspicion of RAS.

  • 1167.
    Zachrisson, Karin
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Radiol, Gothenburg, Sweden..
    Krupic, Ferid
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthoped & Anesthesiol, Gothenburg, Sweden..
    Svensson, Mikael
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Hlth Metr Unit, Gothenburg, Sweden..
    Wigelius, Ann
    Umeå Univ Hosp, Dept Radiat Sci, Diagnost Radiol, Umeå, Sweden..
    Jonsson, Andreas
    Umeå Univ Hosp, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Dimopoulou, Angeliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Stenborg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Jensen, Gert
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med Nephrol, Gothenburg, Sweden..
    Herlitz, Hans
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med Nephrol, Gothenburg, Sweden..
    Gottsäter, Anders
    Skane Univ Hosp, Vasc Ctr, Clin Vasc Dis Res, Malmö, Sweden..
    Falkenberg, Mårten
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Radiol, Gothenburg, Sweden..
    Results of renal artery revascularization in the post-ASTRAL era with 4 years mean follow-up2020In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 29, no 5, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate contemporary results of percutaneous transluminal renal angioplasty (PTRA).

    Materials and Methods: A multicentre retrospective study analysing all patients treated with PTRA for primary symptomatic renal artery stenosis (RAS) between 2010 and 2013 at four tertiary centres. Procedures during the preceding four years were counted to evaluate for change in PTRA frequency.

    Results: The number of PTRA procedures decreased by approximately 50% from 2006 to 2013. Patients treated in the post-ASTRAL period (n = 224) had a significant reduction in mean systolic pressure (168 to 146 mmHg, p < 0.01), diastolic pressure (84 to 76 mmHg, p < 0.01), number of anti-hypertensive drugs (3.54 to 3.05, p < 0.01), and anti-hypertensive treatment index (21.75 to 16.92, p < 0.01) compared to before PTRA. These improvements were maintained at one year and at the last clinical evaluation after a mean follow-up of 4.31 years. Renal function increased transiently without sustained improvement, or deterioration, during later follow-up. Thirteen patients (5.8%) eventually required dialysis, nine of these had eGFR <20 ml/min/1.73 m2 before PTRA. There was no difference in outcomes between subgroups differentiated by different indications for PTRA.

    Conclusion: The frequency of PTRA has decreased, indicating a higher threshold for invasive treatment of RAS in recent years. The reduction in blood pressures, the reduced need for anti-hypertensive medication, and stabilization of renal function over time suggest a clinical benefit for most patients who are now being treated with PTRA.

  • 1168. Zahl, Sverre Morten
    et al.
    Andersson, Jacob
    Wester, Knut
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Neuroradiological findings in children with subdural hematoma and suspected abusive head trauma2023In: Annals of the Child Neurology Society, ISSN 2831-3267, Vol. 1, no 1, p. 44-52Article in journal (Refereed)
  • 1169.
    Zakaria, Muhammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan;Centre for Human Genetics, Hazara University, Mansehra, Pakistan.
    Fatima, Ambrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Klar, Joakim
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Abdullah, Uzma
    Ali, Zafar
    Akram, Talia
    Tariq, Muhammad
    Ahmad, Habib
    Schuster, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Baig, Shahid M
    Dahl, Niklas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Primary microcephaly, primordial dwarfism, and brachydactyly in adult cases with biallelic skipping of RTTN exon 422019In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 40, no 7, p. 899-903Article in journal (Refereed)
    Abstract [en]

    Biallelic and pathogenic variants in the RTTN gene, encoding the centrosomal protein Rotatin, are associated with variable degrees of neurodevelopmental abnormalities, microcephaly, and extracranial malformations. To date, no reported case has reached their third decade. Herein, we report on a consanguineous family with three adult members, age 43, 57, and 60 years respectively, with primary microcephaly, developmental delay, primordial dwarfism, and brachydactyly segregating a homozygous splice site variant NM_173630.3:c.5648–5T>A in RTTN. The variant RTTN allele results in a nonhypomorphic skipping of exon 42 and a frameshift [(NP_775901.3:p.Ala1883Glyfs*6)]. Brain MRI of one affected individual showed markedly reduced volume of cerebral lobes and enlarged sulci but without signs of neural migration defects. Our assessment of three adult cases with a biallelic RTTN variant shows that a predicted shortened Rotatin, lacking the C‐terminal end, are associated with stationary clinical features into the seventh decade. Furthermore, our report adds brachydactyly to the phenotypic spectrum in this pleiotropic entity.

  • 1170.
    Zanchi, Davide
    et al.
    Univ Basel, Dept Psychiat UPK, Basel, Switzerland..
    Brody, Arthur
    Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.;VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA..
    Borgwardt, Stefan
    Univ Basel, Dept Psychiat UPK, Basel, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Sex Effects on Smoking Cue Perception in Non-Smokers, Smokers, and Ex-Smokers: A Pilot Study2016In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 7, article id 187Article in journal (Refereed)
    Abstract [en]

    Introduction: Recent neuroimaging research suggests sex-related brain differences in smoking addiction, In the present pilot study, we assessed gender-related differences in brain activation in response to cigarette-related video cues, investigating non-smokers, smokers, and ex-smokers. Methods: First, we compared 29 females (28.6 +/- 5.3) vs. 23 males (31.5 +/- 6.4), regardless of current smoking status to assess global gender-related effects. Second, we performed a post hoc analysis of non-smokers (9 females and 7 males). Participants performed a block-design functional magnetic resonance imaging paradigm contrasting smoking with control cue video exposures. Data analyses included task-related general linear model, voxel-based morphometry of gray matter (GM), and tract-based spatial statistics of white matter (WM). Results: First, the global effect regardless of current smoking status revealed higher activation in the bilateral superior frontal gyrus and anterior cingulate cortex (ACC) for females compared to males. Second, the analysis according to current smoking status demonstrated higher activation in female vs. male smokers vs. non-smokers in the superior frontal gyrus, anterior and posterior cingulate cortex, and precuneus, and higher activationi in female vs. male ex-smokers vs. non-smokers in the right precentral gyrus, in the right insula and ACC. No structural differences were found in GM or WM. Conclusion: The current study identifies gender-related brain functional differences in smokers and ex-smokers compared to non-smokers. The current work can be considered as a starting point for future investigations into gender differences in brain responses to cigarette-related cues

  • 1171.
    Zanchi, Davide
    et al.
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Brody, Arthur L.
    Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA.;VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA.;VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA..
    Montandon, Marie-Louise
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Kopel, Rotem
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Emmert, Kirsten
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Preti, Maria Giulia
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Van de Ville, Dimitri
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland..
    Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate2015In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 20, no 6, p. 1033-1041Article in journal (Refereed)
    Abstract [en]

    Although many smokers try to quit smoking, only about 20-25 percent will achieve abstinence despite 6months or more of gold-standard treatment. This low success rate suggests long-term changes in the brain related to smoking, which remain poorly understood. We compared ex-smokers to both active smokers and non-smokers using functional magnetic resonance imaging (fMRI) to explore persistent modifications in brain activity and network organization. This prospective and consecutive study includes 18 non-smokers (29.5 +/- 6.7years of age, 11 women), 14 smokers (10 cigarettes a day >2years of smoking, 29.3 +/- 6.0years of age, 10 women) and 14 ex-smokers (>1year of quitting 30.5 +/- 5.7years of age, 10 women). Participants underwent a block-design fMRI study contrasting smoking cue with control (neutral cue) videos. Data analyses included task-related general linear model, seed-based functional connectivity, voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking cue videos versus control videos activated the right anterior insula in ex-smokers compared with smokers, an effect correlating with cumulative nicotine intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional connectivity between right anterior insula and anterior cingulate cortex (ACC) compared with control participants, but similar to active smokers. Potentially confounding alterations in gray or white matter were excluded in VBM and TBSS analyses. In summary, ex-smokers with long-term nicotine abstinence have persistent and dose-dependent brain network changes notably in the right anterior insula and its connection to the ACC.

  • 1172.
    Zanchi, Davide
    et al.
    Univ Basel, Dept Psychiat UPK, Basel, Switzerland..
    Cunningham, Gregory
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Ladermann, Alexandre
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;La Tour Hosp, Div Orthopaed & Trauma Surg, Geneva, Switzerland..
    Ozturk, Mehmet
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Hoffmeyer, Pierre
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Affidea Carouge Radiol Diagnost Ctr, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Brain activity in the right-frontal pole and lateral occipital cortex predicts successful post-operatory outcome after surgery for anterior glenoumeral instability2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 498Article in journal (Refereed)
    Abstract [en]

    Shoulder apprehension is more complex than a pure mechanical problem of the shoulder, creating a scar at the brain level that prevents the performance of specific movements. Surgery corrects for shoulder instability at the physical level, but a re-dislocation within the first year is rather common. Predicting which patient will be likely to have re-dislocation is therefore crucial. We hypothesized that the assessment of neural activity at baseline and follow-up is the key factor to predict the postoperatory outcome. 13 patients with shoulder apprehension (30.03 +/- 7.64 years) underwent clinical and fMRI examination before and one year after surgery for shoulder dislocation contrasting apprehension cue videos and control videos. Data analyses included task-related general linear model (GLM) and correlations imaging results with clinical scores. Clinical examination showed decreased pain and increased shoulder functions for post-op vs. pre-op. Coherently, GLM results show decreased activation of the left pre-motor cortex for post-surgery vs. pre-surgery. Right-frontal pole and right-occipital cortex activity predicts good recovery of shoulder function measured by STT. Our findings demonstrate that beside physical changes, changes at the brain level also occur one year after surgery. In particular, decreased activity in pre-motor and orbito-frontal cortex is key factor for a successful post-operatory outcome.

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  • 1173. Zanchi, Davide
    et al.
    Cunningham, Gregory
    Lädermann, Alexandre
    Ozturk, Mehmet
    Hoffmeyer, Pierre
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Structural white matter and functional connectivity alterations in patients with shoulder apprehension2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 42327Article in journal (Refereed)
    Abstract [en]

    Previous functional magnetic resonance imaging (fMRI) findings indicate that shoulder apprehension is more complex than a pure mechanical problem of the shoulder, showing a direct modification in functional brain networks associated with motor inhibition and emotional regulation. The current study extends these findings by investigating further structural alterations in patients with shoulder apprehension compared to controls. 14 aged patients with shoulder apprehension (27.3 ± 2.0 years) and 10 matched healthy controls (29.6 ± 1.3 years) underwent clinical and fMRI examination including fMRI and diffusion tensor imaging (DTI). Tract-based spatial statistics procedure was used to analyze white matter (WM) alterations. Functional images were analyzed investigating resting state network connectivity. DTI results were correlated with different shoulder clinical scores and functional connectivity networks. Fractional anisotropy (FA), representing white matter integrity, is increased in the left internal capsule and partially in the thalamus in patients compared to controls. Moreover, FA correlates negatively with simple shoulder test (SST) scores (p < .05) and positively with a functional connectivity network qualitatively replicating previous results (p < .01). This study extends previous findings, showing that in addition to functional changes, structural white matter changes are also present in patients with shoulder apprehension.

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  • 1174.
    Zanchi, Davide
    et al.
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Depoorter, Antoinette
    Division of Neuropaediatrics & Developmental Medicine, University Children's Hospital, Basel, Switzerland.
    Egloff, Laura
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Centre de Diagnostic Radiologique de Carouge CDRC, Geneva, Switzerland.; Faculty of Medicine of the University of Geneva, Switzerland.; Department of Neuroradiology, University Hospital Freiburg, Germany.
    Mählmann, Laura
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Lang, Undine E
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Drewe, Jürgen
    Department of Research, St. Claraspital, Switzerland.
    Beglinger, Christoph
    Department of Research, St. Claraspital, Switzerland.
    Schmidt, André
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Borgwardt, Stefan
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review2017In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 80, p. 457-475, article id S0149-7634(17)30138-0Article in journal (Refereed)
    Abstract [en]

    The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects). Our systematic review suggests that the plasma level of ghrelin, the gut hormone promoting appetite, is positively correlated with activation in the pre-frontal cortex (PFC), amygdala and insula and negatively correlated with activation in subcortical areas such as the hypothalamus. In contrast, the plasma levels of glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely. Our study integrates previous investigations of the gut-brain matrix during food-intake and homeostatic regulation and may be of use for future meta-analyses of brain-gut interactions.

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  • 1175.
    Zanchi, Davide
    et al.
    Univ Basel, Dept Psychiat, Basel, Switzerland.;Univ Psychiat Clin, Dept Neuropsychiat, Basel, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Borgwardt, Stefan
    Univ Basel, Dept Psychiat, Basel, Switzerland..
    Rodriguez, Cristelle
    Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Carouge Radiol Diagnost Ctr, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, Dept Neuroradiol, Geneva, Switzerland..
    Hippocampal and Amygdala Gray Matter Loss in Elderly Controls with Subtle Cognitive Decline2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 50Article in journal (Refereed)
    Abstract [en]

    In contrast to the idea that hippocampal and amygdala volume loss occur in late phases of neurodegeneration, recent contributions point to the relevance of preexisting structural deficits that are associated with aging and are independent of amyloid deposition in preclinical Alzheimer disease cases. The present work explores GM hippocampal and amygdala volumes in elderly controls displaying the first signs of cognitive decline. 455 subjects (263 females), including 374 controls (228 females) and 81 middle cognitive impairment subjects (35 females), underwent two neuropsychological evaluations (baseline and 18 months follow-up) and a MRI-T1 examination (only baseline). Clinical assessment included Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale, Hospitalized Anxiety and Depression scale, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery and RI-48 Cued Recall Test (RI-48) for episodic memory. Based on their cognitive performance, we defined the controls as stable controls (sCON) and deteriorating controls (dCONs). Analyses included volumetric assessment, shape analyses and linear regressions between GM volume loss and differences in clinical scores between baseline and follow-up. Significant GM volume decrease in hippocampus bilaterally and right amygdala was found in dCON compared to sCON (p < 0.05). Lower right amygdala volumes were measured in mild cognitive impairment (MCI) compared to sCON (p < 0.05). Shape analyses revealed that atrophy was more pronounced at the superior-posterior lateral side of the hippocampus and amygdala. Significant correlations were found between GM volume of left hippocampus and the delta of MMSE and RI-48 scores in dCON and MCI groups separately. Decreased hippocampal and right amygdala volumes precede the first signs of cognitive decline in healthy elderly controls at the pre-MCI state. Left hippocampus volume may also predict short-term changes of overall cognition in these vulnerable cases.

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  • 1176.
    Zanchi, Davide
    et al.
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Meyer-Gerspach, Anne Christin
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland..
    Suenderhauf, Claudia
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Janach, Katharina
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland..
    le Roux, Carel W.
    Univ Coll Dublin, Conway Inst, Diabet Complicat Res Ctr, Dublin, Ireland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Affidea CDRC Ctr Diagnost Radiolog Carouge, Carouge, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Drewe, Jurgen
    St Clara Hosp, Dept Res, Basel, Switzerland..
    Beglinger, Christoph
    St Clara Hosp, Dept Res, Basel, Switzerland..
    Wlnerhanssen, Bettina K.
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland.;St Clara Hosp, Dept Res, Basel, Switzerland..
    Borgwardt, Stefan
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Differential effects of L-tryptophan and L-leucine administration on brain resting state functional networks and plasma hormone levels2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 35727Article in journal (Refereed)
    Abstract [en]

    Depending on their protein content, single meals can rapidly influence the uptake of amino acids into the brain and thereby modify brain functions. The current study investigates the effects of two different amino acids on the human gut-brain system, using a multimodal approach, integrating physiological and neuroimaging data. In a randomized, placebo-controlled trial, L-tryptophan, L-leucine, glucose and water were administered directly into the gut of 20 healthy subjects. Functional MRI (fMRI) in a resting state paradigm (RS), combined with the assessment of insulin and glucose blood concentration, was performed before and after treatment. Independent component analysis with dual regression technique was applied to RS-fMRI data. Results were corrected for multiple comparisons. In comparison to glucose and water, L-tryptophan consistently modifies the connectivity of the cingulate cortex in the default mode network, of the insula in the saliency network and of the sensory cortex in the somatosensory network. L-leucine has lesser effects on these functional networks. L-tryptophan and L-leucine also modified plasma insulin concentration. Finally, significant correlations were found between brain modifications after L-tryptophan administration and insulin plasma levels. This study shows that acute L-tryptophan and L-leucine intake directly influence the brain networks underpinning the food-reward system and appetite regulation.

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  • 1177. Zanchi, Davide
    et al.
    Montandon, Marie-Louise
    Sinanaj, Indrit
    Rodriguez, Cristelle
    Depoorter, Antoinette
    Herrmann, Francois R
    Borgwardt, Stefan
    Giannakopoulos, Panteleimon
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Carouge Radiologic Diagnostic Center, Geneva, Switzerland.
    Decreased Fronto-Parietal and Increased Default Mode Network Activation is Associated with Subtle Cognitive Deficits in Elderly Controls2017In: NeuroSignals (Print), ISSN 1424-862X, E-ISSN 1424-8638, Vol. 25, no 1, p. 127-138Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cognitive functions progressively deteriorate during aging and neurodegenerative diseases. The present study aims at investigating differences in working memory performance as well as functional brain changes during the earliest stages of cognitive decline in health elderly individuals.

    METHODS: 62 elderly individuals (41 females), including 41 controls (35 females) and 21 middle cognitive impairment subjects (6 females), underwent neuropsychological assessment at baseline and an fMRI examination in a N-back paradigm contrasting 2-back vs. 0-back condition. Upon a 18 months follow-up, we identified stable controls (sCON) with preserved cognition and deteriorating controls (dCON) with -1SD decrease of performances in at least two neuropsychological tests. Data analyses included accuracy and reaction time (RT) for the 2-back condition and general linear model (GLM) for the fMRI sequence.

    RESULTS: At the behavioral level, sCON and dCON performed better than MCI in terms of accuracy and reaction time. At the brain level, functional differences in regions of the fronto-parietal network (FPN) and of the Default Mode Network (DFM) were observed. Significantly lower neural activations in the bilateral inferior and middle frontal gyri were found in MCI versus both dCON / sCON and for dCON versus sCON. Significantly increased activations in the anterior cingulate cortex and posterior cingulate cortex and bilateral insula were found in MCI versus both dCON / sCON and in dCON versus sCON.

    CONCLUSION: The present study suggests that brain functional changes in FPN and DMN anticipate differences in cognitive performance in healthy elderly individuals with subsequent subtle cognitive decline.

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  • 1178.
    Zanchi, Davide
    et al.
    Univ Basel Hosp, Dept Psychiat, Basel, Switzerland.
    Viallon, Magalie
    Univ Jean Monnet St Etienne, Univ Lyon, INSA Lyon, CNRS,UMR 5220,INSERM,U1206,CREATIS, St Etienne, France.; CHU St Etienne, Dept Radiol, St Etienne, France.
    Le Goff, Caroline
    Univ Liege, Dept Clin Chem, Liege, Belgium.
    Millet, Grégoire P
    Univ Lausanne, Inst Sports Sci, Lausanne, Switzerland.
    Giardini, Guido
    Department of Neurology and Stroke Unit, Mountain Medicine and Neurology Center Valle d'Aosta Regional Hospital, Aosta, Italy.
    Croisille, Pierre
    Univ Jean Monnet St Etienne, Univ Lyon, INSA Lyon, CNRS,UMR 5220,INSERM,U1206,CREATIS, St Etienne, France.; CHU St Etienne, Dept Radiol, St Etienne, France.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.; Univ Geneva, Fac Med, Geneva, Switzerland.; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes2017In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 7, article id 664Article in journal (Refereed)
    Abstract [en]

    Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters.

    Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points.

    Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations.

    Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport.

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  • 1179.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Roodakker, Kenney Roy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Berntsson, Shala Ghaderi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Linköping Univ, Ctr Med Image Sci & Visualizat, Linköping, Sweden.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Danish Epilepsy Ctr, Dianalund, Denmark.
    Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data2016In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 125, no 5, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    Background: Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed.

    Methods: Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices.

    Results: Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H–positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences.

    Conclusions: The authors present a new method for the coregistration of histological and radiological characteristics of en bloc–removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.

  • 1180.
    Zetterström, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jakobson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lörelius, L-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Assessment of lung water content by roentgen videodensitometry1984In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 12, p. 457-460Article in journal (Refereed)
  • 1181.
    Zhang, Han
    et al.
    Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC USA.;Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC USA..
    Chen, Xiaobo
    Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC USA.;Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC USA..
    Shi, Feng
    Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC USA.;Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC USA..
    Li, Gang
    Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC USA.;Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC USA..
    Kim, Minjeong
    Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC USA.;Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC USA..
    Giannakopoulos, Panteleimon
    Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Shen, Dinggang
    Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC USA.;Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC USA.;Korea Univ, Dept Brain & Cognit Engn, Seoul, South Korea..
    Topographical Information-Based High-Order Functional Connectivity and Its Application in Abnormality Detection for Mild Cognitive Impairment2016In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 54, no 3, p. 1095-1112Article in journal (Refereed)
    Abstract [en]

    Temporal synchronization-based functional connectivity (FC) has long been used by the neuroscience community. However, topographical FC information may provide additional information to characterize the advanced relationship between two brain regions. Accordingly, we proposed a novel method, namely high-order functional connectivity (HOFC), to capture this second-level relationship using inter-regional resemblance of the FC topographical profiles. Specifically, HOFC first calculates an FC profile for each brain region, notably between the given brain region and other brain regions. Based on these FC profiles, a second layer of correlations is computed between all pairs of brain regions (i.e., correlation's correlation). On this basis, we generated an HOFC network, where "high-order" network properties were computed. We found that HOFC was discordant with the traditional FC in several links, indicating additional information being revealed by the new metrics. We applied HOFC to identify biomarkers for early detection of Alzheimer's disease by comparing 77 mild cognitive impairment patients with 89 healthy individuals (control group). Sensitivity in detection of group difference was consistently improved by similar to 25% using HOFC compared to using FC. An HOFC network analysis also provided complementary information to an FC network analysis. For example, HOFC between olfactory and orbitofrontal cortices was found significantly reduced in patients, besides extensive alterations in HOFC network properties. In conclusion, our results showed promise in using HOFC to comprehensively map the human brain connectome.

  • 1182.
    Zhang, Han
    et al.
    Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, USA.
    Giannakopoulos, Panteleimon
    Geneva Univ Hosp, Div Psychiat, Geneva, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge, Carouge, Switzerland; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany; Univ Geneva, Fac Med, Geneva, Switzerland.
    Lee, Seong-Whan
    Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea.
    Qiu, Shijun
    Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
    Shen, Dinggang
    Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, USA; Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea.
    Inter-Network High-Order Functional Connectivity (IN-HOFC) and its Alteration in Patients with Mild Cognitive Impairment2019In: Neuroinformatics, ISSN 1539-2791, E-ISSN 1559-0089, Vol. 17, no 4, p. 547-561Article in journal (Refereed)
    Abstract [en]

    Little is known about the high-order interactions among brain regions measured by the similarity of higher-order features (other than the raw blood-oxygen-level-dependent signals) which can characterize higher-level brain functional connectivity (FC). Previously, we proposed FC topographical profile-based high-order FC (HOFC) and found that this metric could provide supplementary information to traditional FC for early Alzheimer's disease (AD) detection. However, whether such findings apply to network-level brain functional integration is unknown. In this paper, we propose an extended HOFC method, termed inter-network high-order FC (IN-HOFC), as a useful complement to the traditional inter-network FC methods, for characterizing more complex organizations among the large-scale brain networks. In the IN-HOFC, both network definition and inter-network FC are defined in a high-order manner. To test whether IN-HOFC is more sensitive to cognition decline due to brain diseases than traditional inter-network FC, 77 mild cognitive impairments (MCIs) and 89 controls are compared among the conventional methods and our IN-HOFC. The result shows that IN-HOFCs among three temporal lobe-related high-order networks are dampened in MCIs. The impairment of IN-HOFC is especially found between the anterior and posterior medial temporal lobe and could be a potential MCI biomarker at the network level. The competing network-level low-order FC methods, however, either revealing less or failing to detect any group difference. This work demonstrates the biological meaning and potential diagnostic value of the IN-HOFC in clinical neuroscience studies.

  • 1183.
    Zhang, Yuhang
    et al.
    Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA..
    Kashani, Rojano
    Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA..
    Cao, Yue
    Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA..
    Lawrence, Theodore S.
    Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA..
    Johansson, Adam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Balter, James M.
    Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA..
    A hierarchical model of abdominal configuration changes extracted from golden angle radial magnetic resonance imaging2021In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 66, no 4, article id 045018Article in journal (Refereed)
    Abstract [en]

    Abdominal organs are subject to a variety of physiological forces that superimpose their effects to influence local motion and configuration. These forces not only include breathing, but can also arise from cyclic antral contractions and a range of slow configuration changes. To elucidate each individual motion pattern as well as their combined effects, a hierarchical motion model was built for characterization of these 3 motion modes (characterized as deformation maps between states) using golden angle radial MR signals. Breathing motions are characterized first. Antral contraction states are then reconstructed after breathing motion-induced deformation are corrected; slow configuration change states are further extracted from breathing motion-corrected image reconstructions. The hierarchical model is established based on these multimodal states, which can be either individually shown or combined to demonstrate any arbitrary composited motion patterns. The model was evaluated using 20 MR scans acquired from 9 subjects. Poor reproducibility of breathing motions both within as well as between scan sessions was observed, with an average intra-subject difference of 1.6 cycles min(-1) for average breathing frequencies of 12.0 cycles min(-1). Antral contraction frequency distributions were more stable than breathing, but also presented poor reproducibility between scans with an average difference of 0.3 cycles min(-1) for average frequencies of 3.2 cycles min(-1). The magnitudes of motions beyond breathing were found to be significant, with 14.4 and 33.8 mm maximal motions measured from antral contraction and slow configuration changes, respectively. Hierarchical motion models have potential in multiple applications in radiotherapy, including improving the accuracy of dose delivery estimation, providing guidance for margin creation, and supporting advanced decisions and strategies for immobilization, treatment monitoring and gating.

  • 1184.
    Zheng, Fenglian
    et al.
    Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China..
    Li, Yuxin
    Fudan Univ, Huashan Hosp, Dept Radiol, Shanghai, Peoples R China..
    Zhuo, Zhizheng
    Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China..
    Duan, Yunyun
    Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China..
    Cao, Guanmei
    Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China..
    Tian, Decai
    Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China..
    Zhang, Xinghu
    Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China..
    Li, Kuncheng
    Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing, Peoples R China..
    Zhou, Fuqing
    Nanchang Univ, Affiliated Hosp 1, Dept Radiol, Nanchang, Jiangxi, Peoples R China.;Jiangxi Prov Med Imaging Res Inst, Neuroimaging Lab, Nanchang, Jiangxi, Peoples R China..
    Huang, Muhua
    Nanchang Univ, Affiliated Hosp 1, Dept Radiol, Nanchang, Jiangxi, Peoples R China.;Jiangxi Prov Med Imaging Res Inst, Neuroimaging Lab, Nanchang, Jiangxi, Peoples R China..
    Li, Haiqing
    Fudan Univ, Huashan Hosp, Dept Radiol, Shanghai, Peoples R China..
    Li, Yongmei
    Chongqing Med Univ, Affiliated Hosp 1, Dept Radiol, Chongqing, Peoples R China..
    Zeng, Chun
    Chongqing Med Univ, Affiliated Hosp 1, Dept Radiol, Chongqing, Peoples R China..
    Zhang, Ningnannan
    Tianjin Med Univ, Dept Radiol, Gen Hosp, Tianjin, Peoples R China.;Tianjin Med Univ, Tianjin Key Lab Funct Imaging, Gen Hosp, Tianjin, Peoples R China..
    Sun, Jie
    Tianjin Med Univ, Dept Radiol, Gen Hosp, Tianjin, Peoples R China.;Tianjin Med Univ, Tianjin Key Lab Funct Imaging, Gen Hosp, Tianjin, Peoples R China..
    Yu, Chunshui
    Tianjin Med Univ, Dept Radiol, Gen Hosp, Tianjin, Peoples R China.;Tianjin Med Univ, Tianjin Key Lab Funct Imaging, Gen Hosp, Tianjin, Peoples R China..
    Han, Xuemei
    Jilin Univ, Dept Neurol, China Japan Union Hosp, Changchun, Peoples R China..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China.;Ctr Imagerie Med Cornavin, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Barkhof, Frederik
    Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands.;UCL, Queen Sq Inst Neurol, London, England.;UCL, Ctr Med Image Comp, London, England..
    Liu, Yaou
    Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China..
    Structural and functional hippocampal alterations in Multiple sclerosis and neuromyelitis optica spectrum disorder2022In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, no 5, p. 707-717, article id 13524585211032800Article in journal (Refereed)
    Abstract [en]

    Background: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Objective: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. Methods: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. Results: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC (p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS (p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS (R = -0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). Conclusions: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.

  • 1185.
    Zollikofer, Christoph L.
    et al.
    Kantonsspital Baden AG, Dept Radiol, CH-5404 Baden, Switzerland.
    Allison, David J.
    Imperial Coll Univ London, London, England.
    Erikson, Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    The History and Birth of CIRSE: An Exercise in Unification2020In: Journal of Vascular and Interventional Radiology, ISSN 1051-0443, E-ISSN 1535-7732, Vol. 31, no 10, p. 1717-1719Article in journal (Other academic)
  • 1186.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ, Dept Immunol Genet & Pathol Oncol, Uppsala, Sweden.
    Sports and Tumors2020In: Seminars in Musculoskeletal Radiology, ISSN 1089-7860, E-ISSN 1098-898X, Vol. 24, no 03, p. 201-201Article in journal (Other academic)
  • 1187.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Krenning, Eric
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bodei, Lisa
    Kidd, Mark
    Tesselaar, Margot
    Ambrosini, Valentina
    Baum, Richard P
    Kulke, Matthew
    Pavel, Marianne
    Cwikla, Jaroslaw
    Drozdov, Ignat
    Falconi, Massimo
    Fazio, Nicola
    Frilling, Andrea
    Jensen, Robert
    Koopmans, Klaus
    Korse, Tiny
    Kwekkeboom, Dik
    Maecke, Helmut
    Paganelli, Giovanni
    Salazar, Ramon
    Severi, Stefano
    Strosberg, Jonathan
    Prasad, Vikas
    Scarpa, Aldo
    Grossman, Ashley
    Walenkamp, Annemeik
    Cives, Mauro
    Virgolini, Irene
    Kjaer, Andreas
    Modlin, Irvin M
    A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management2016In: Endocrine Connections, E-ISSN 2049-3614, Vol. 5, no 5, p. 174-187Article in journal (Refereed)
    Abstract [en]

    The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

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  • 1188.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Imaging of Neuroendocrine Tumors2016In: Imaging in Endocrine Disorders / [ed] M Buchfelder, F Guaraldi, E Ghigo, F Guaraldi, A Benso, Basel: S. Karger, 2016, p. 142-151Chapter in book (Refereed)
  • 1189.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Imaging of Neuroendocrine Tumors2016In: Imaging in Endocrine Disorders / [ed] Buchfelder M., Guaraldi F., Basel: Karger , 2016, Vol. 45, p. 142-151Chapter in book (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with a very variable clinical expression and progression. They present unique properties that are important to consider for radiological and nuclear imaging, such as APUD-characteristics (amine precursor uptake and dearboxylation), as well as the expression of somatostatin receptors. The most common localizations are the lungs, gastrointestinal tract and pancreas. The only curative treatment is surgery, but more than 50% present metastatic disease at the time of diagnosis. The systemic treatment includes chemotherapy and targeted agents, as well as peptide receptor radiotherapy. The diagnosis and follow-up of these tumors necessitate a large number of different imaging methods, such as CT, MRI, US, SRS and PET. Ultrasonography offers the possibility to take guided biopsies from different lesions. Somatostatin receptor scintigraphy was developed in the 1990s and nowadays presents the standard of care for NETs in most countries. The procedure offers a total body examination and a better staging of the disease. However, it has been replaced in most centers by PET/CT with 68Ga-DOTA-somatostatin analogues with a superior spatial resolution and faster imaging (one-stop procedure). Another tracer used for PET/CT is 18FDG, particularly for high-grade tumors. Other more specific tracers are 18F-L-DOPA, 11C-L-DOPA and 11C-5-hydroxytryptophan, which have demonstrated excellent imaging results. The new targeted agents present a challenge in the evaluation procedure of treatment and, therefore, new imaging techniques and an improvement of currently available techniques are mandatory.

  • 1190.
    Öhman Fuchs, Peder
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Calitz, Carlemi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Pavlovic, Natasa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Binet, Francois
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Solbak, Sara Marie Øie
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Danielson, U. Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kreuger, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Heindryckx, Femke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala Univ, Dept Med Cell Biol, POB 571, SE-75123 Uppsala, Sweden..
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fibrin fragment E potentiates TGF-beta-induced myofibroblast activation and recruitment2020In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 72, article id 109661Article in journal (Refereed)
    Abstract [en]

    Fibrin is an essential constituent of the coagulation cascade, and the formation of hemostatic fibrin clots is central to wound healing. Fibrin clots are over time degraded into fibrin degradation products as the injured tissue is replaced by granulation tissue. Our goal was to study the role of the fibrin degradation product fragment E (FnE) in fibroblast activation and migration. We present evidence that FnE is a chemoattractant for fibroblasts and that FnE can potentiate TGF-beta-induced myofibroblast formation. FnE forms a stable complex with alpha(v)beta(3) integrin, and the integrin beta(3) subunit is required both for FnE-induced fibroblast migration and for potentiation of TGF-beta-induced myofibroblast formation. Finally, subcutaneous infusion of FnE in mice results in a fibrotic response in the hypodermis. These results support a model where FnE released from clots in wounded tissue promote wound healing and fibrosis by both recruitment and activation of fibroblasts. Fibrin fragment E could thus represent a therapeutic target for treatment of pathological fibrosis.

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