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  • 1.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lannsjö, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Extended anatomical grading in diffuse axonal injury using MRI: Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome2017In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 5, no 34, p. 341-352Article in journal (Refereed)
    Abstract [en]

    Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p  = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I—hemispheric lesions, stage II—corpus callosum lesions, stage III—brainstem lesions, and stage IV—substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).

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  • 2.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Intracranial pressure elevations in diffuse axonal injury: association with nonhemorrhagic MR lesions in central mesencephalic structures2019In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 131, no 2, p. 604-611Article in journal (Refereed)
    Abstract [en]

    Objective: Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in patients with DAI.

    Methods: Fifty-two patients with severe TBI (median age 24 years, range 9–61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression.

    Results: All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%–13%, p = 0.004) and young age (−0.2% of GMT with ICP > 20 mm Hg, 95% CI −0.07% to −0.3%, p = 0.002) were associated with increased ICP.

    Conclusions: Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.

    Abbreviations: ADC = apparent diffusion coefficient; CPP = cerebral perfusion pressure; DAI = diffuse axonal injury; DWI = diffusion-weighted imaging; EVD = external ventricular drain; GCS = Glasgow Coma Scale; GMT = good monitoring time; GOSE = Glasgow Outcome Scale–Extended; ICC = intraclass correlation coefficient; ICP = intracranial pressure; MAP = mean arterial blood pressure; NICU = neurointensive care unit; SN-T = substantia nigra and mesencephalic tegmentum; SWI = susceptibility-weighted imaging; TBI = traumatic brain injury; T2*GRE = T2*-weighted gradient echo.

  • 3.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Intracranial pressure elevations in diffuse axonal injury are associated with non-hemorrhagic MR lesions in central mesencephalic structuresIn: Article in journal (Other academic)
    Abstract [en]

    Objective: Increased intracranial pressure (ICP) in severe traumatic brain injury (TBI) patients with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in DAI patients.

    Methods: Fifty-two severe TBI patients (median 24, range 9-61 years), with ICP-monitoring and DAI on MRI, using T2*-weighted gradient echo, susceptibility-weighted and diffusion-weighted (DW) sequences, were enrolled. Proportion of good monitoring time (GMT) with ICP>20 mmHg during the first 120 hours post-injury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression. 

    Results: All patients had episodes of ICP>20 mmHg. The mean proportion of GMT with ICP>20 mmHg was 5% and 27% of the patients (14/52) had more than 5% of GMT with ICP>20 mmHg. Glasgow Coma Scale motor score at admission (P=0.04) and lesions on DW images in the substantia nigra and mesencephalic tegmentum (SN-T, P=0.001) were associated with the proportion of GMT with ICP>20 mmHg. In multivariate linear regression, lesions on DW images in SN-T (8% of GMT with ICP>20 mmHg, 95% CI 3–13%, P=0.004) and young age (-0.2% of GMT with ICP>20 mmHg, 95% CI -0.07–-0.3%, P=0.0008) were associated with increased ICP.   

    Conclusions: Increased ICP occurs in ~1/3 of severe TBI patients with DAI. Age and lesions on DW images in the central mesencephalon (SN-T) associate with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in DAI patients.

  • 4.
    Ali, Zafar
    et al.
    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. Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Zulfiqar, Shumaila
    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.
    Ullah, Farid
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Khan, Ayaz
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Abdullah, Uzma
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    Baig, Shahid
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, Faisalabad, Pakistan.
    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.
    Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features2017In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 18, no 1, article id 144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Spinocerebellar ataxias comprise a large and heterogeneous group of disorders that may present with isolated ataxia, or ataxia in combination with other neurologic or non-neurologic symptoms. Monoallelic or biallelic GRID2 mutations were recently reported in rare cases with cerebellar syndrome and variable degree of ataxia, ocular symptoms, hypotonia and developmental delay.

    CASE PRESENTATION: We report on a consanguineous family with autosomal recessive childhood onset of slowly progressive cerebellar ataxia and delayed psychomotor development in three siblings. MRI of an adult and affected family member revealed slightly widened cerebral and cerebellar sulci, suggesting generalized brain atrophy, and mild cerebellar atrophy. Using whole exome sequencing we identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in GRID2 that segregates with the disease. The missense variant is located in a conserved region encoding the extracellular serine-binding domain of the GluD2 protein and predicts a change in conformation of the protein.

    CONCLUSION: The widespread supratentorial brain abnormalities, absence of oculomotor symptoms, increased peripheral muscle tone and the novel missense mutation add to the clinical and genetic variability in GRID2 associated cerebellar syndrome. The neuroradiological findings in our family indicate a generalized neurodegenerative process to be taken into account in other families segregating complex clinical features and GRID2 mutations.

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  • 5.
    Almby, Kristina E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lundqvist, Martin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kvernby, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia2021In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 70, no 6, p. 1265-1277Article in journal (Refereed)
    Abstract [en]

    While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

  • 6.
    Almqvist Terán, Nicolas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Loayza, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ericson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Abu Hamdeh, Sami
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Svedung-Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    In Reply to the Letter to the Editor Regarding "Posterior Fossa Volume and Dimensions: Relation to Pathophysiology and Surgical Outcomes in Classical Trigeminal Neuralgia"2023In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 180, article id 268Article in journal (Other academic)
  • 7.
    Almqvist Téran, Nicolas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Loayza, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ericson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Abu Hamdeh, Sami
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Svedung Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Posterior Fossa Volume and Dimensions: Relation to Pathophysiology and Surgical Outcomes in Classic Trigeminal Neuralgia2023In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 179, p. e397-e403Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: A small posterior fossa (PF) has been hypothesized to explain the increased incidence of trigeminal neuralgia (TN) in females and could make microvascular decompression (MVD) more challenging. The aim of this study was to investigate the association between the PF volume and dimensions in relation to biological sex, type of neurovascular conflict (NVC), and outcome after MVD in classic TN.

    METHODS: In this observational study, 84 patients with TN operated on with MVD with a preoperative head computed tomography(CT) scan were included. Eighty-two adults without TN who had undergone head CT for other reasons were included as controls. PF volume and dimensions (x-axis, y-axis, and z-axis) were evaluated on the CT scans. For the patients with TN, Barrow Neurological Institute (BNI) grade was evaluated 6 months after MVD.

    RESULTS: There was no difference in PF volume or dimensions between the patients with TN and controls. Women showed a smaller volume and narrower (x-axis) PF than men, but these differences did not manifest when comparing patients with TN and controls within each sex. Patients with an NVC involving the superior cerebellar artery had a narrower (x-axis) and shorter (y-axis) PF than did patients with an NVC resulting from other arteries. PF volume or dimensions were not associated with BNI grade after MVD.

    CONCLUSIONS: PF anatomy was related to the NVC type but did not differ between patients with TN and controls and was not related to the surgical outcome after MVD.

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  • 8.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raiend, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    The Clinical Impact of Fetal Magnetic Resonance Imaging on Management of CNS Anomalies in the Second Trimester of Pregnancy2010In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, no 12, p. 20p. 1571-1581Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected CNS anomalies and to study the clinical impact of the information on pregnancy management.

    Design: Prospective study during 2004-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound.

    Setting: Uppsala University hospital.    

    Subjects: Twenty-nine pregnant women where second trimester ultrasound identified or suspected fetal CNS anomalies.

    Main outcome measures: Evaluation of the additional information gained from MRI and the consequence it had on pregnancy management.

    Results: The mean interval between ultrasound and MRI was 1.6 days (range 0 –7). In 18 fetuses (62 %)  MRI verified the ultrasound diagnosis but provided no additional information, while in 8 (28 %) MRI gave additional information without changing the management. In 3 (10 %), MRI provided additional information that changed the management of the pregnancy. Two of these women were obese.

    Conclusions: Fetal MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when ultrasound is inconclusive due to maternal obesity.

     

  • 9.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Second trimester fetal magnetic resonance imaging improves diagnosis of non-central nervous system anomalies2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 4, p. 380-389Article in journal (Refereed)
    Abstract [en]

    Objectives. To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impact of the MRI information on pregnancy management. Design. Prospective study during 2003-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound. Setting. Uppsala University hospital. Material and methods. Sixty-three women, where the second trimester ultrasound identified or raised suspicion of fetal anomalies were included. Ultrasound was compared to MRI in relation to the final diagnosis, which was based on the assessment of all available data including post-partum clinical follow-up and autopsy results. Main outcome measures. Evaluation of the additional information gained from MRI and the consequences it had on pregnancy management. Results. The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67%) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68%) fetuses MRI provided no additional information, in 17 (27%) MRI added information without changing the management and in three (5%) MRI provided additional information which changed the management. All these three cases had oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information. Conclusions. Fetal MRI of non-CNS anomalies in the second trimester seems to be a valuable adjunct to ultrasound diagnosis of non-CNS anomalies, especially in cases of oligohydramnios and diaphragmatic hernia.

  • 10.
    Andersson, Jacob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Wester, Knut
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Differences in head circumference and neuroimaging characteristics: what can they tell about the aetiologies of infant subdural haematoma?Manuscript (preprint) (Other academic)
    Abstract [en]

    Background Acute (ASDH) and chronic subdural haematoma (CSDH) in infants have been regarded as highly specific for abuse. A recent study showed different risk factors for ASDH and CSDH, indicating that CSDH in many cases was related to external hydrocephalus. 

    Purpose To investigate to what extent external hydrocephalus may explain findings and symptoms interpreted as signs of abusive head trauma. 

    Material and methods Eighty-five infants with ASDH (n=16) and CSDH (n=69) were reviewed with regard to cranio-cortical- (CCW), sino-cortical- (SCW), frontal interhemispheric-(IHW), subarachnoid space width (SSW) and head circumference (HC). In infants with unilateral SDH, the correlation between the contralateral SSW and the ipsilateral CCW and SDH width was calculated. A correlation would imply that the CSDH replaces an already existing extracerebral space.

    Results Infants with CSDH had significantly higher CCW, SCW, IHW and SSW than infants with ASDH (p < 0.05). The ipsilateral CCW (R = 0.92, p < 0.001) and SDH width (R = 0.81, p < 0.01) were correlated to the contralateral SSW. Increased HC was more prevalent in Infants with CSDH (71%) than in infants with ASDH (14%) (p < 0.01). Forty-two infants, all with CSDH, had at least one of CCW, SCW or IHW ≥ 95th percentile. Twenty infants, all with CSDH, had CCW, SCW and IHW > 5 mm and increased HC. 

    Conclusion A significant proportion of infants with CSDH may have external hydrocephalus as an underlying cause and that parts of the widened subarachnoid space in some infants is replaced by a CSDH.

  • 11.
    Andersson, Jacob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Wester, Knut
    Department of Clinical Medicine K1, University of Bergen, Bergen, Norway.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Different vulnerability profiles in acute compared to chronic subdural haematoma amongst infants with suspected abusive head traumaManuscript (preprint) (Other academic)
    Abstract [en]

    Background: In a register study based on ICD 10 coding, there was a similar vulnerability profile (male sex, preterm and small for gestational age) in infants diagnosed with non-traumatic subdural haematoma (SDH) and infants having SDH with abuse diagnosis. However, ICD-10 does not separate between acute (ASDH) and chronic subdural haematoma (CSDH). 

    Purpose: To determine the vulnerability profile in infants having CSDH and ASDH, respectively. 

    Material and methods: A descriptive review of infants with SDH/hygroma examined by the Swedish National Board of Forensic Medicine between 1994 and 2018. Included cases (n=85) were analysed with regard to possible vulnerability factors. 

    Results: Type of subdural fluid could be determined in 85 of 96 cases. Sixteen infants had ASDH and 69 CSDH. Infants with ASDH had the peak incidence during the first month of life, 56% were male, 6% were premature, 13% were twins and 44% died. In infants with CSDH, the peak incidence occurred during the third month of life, 69% were male, 34% were premature, 12% were twins and 4% died. 

    Conclusion: CSDH, but not ASDH, is associated with factors suggesting non-traumatic pathogenesis, for which reason CSDH and ASDH should be analysed separately to extend the knowledge regarding the aetiology of SDH during infancy.  

     

  • 12.
    Andersson, Jacob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Wester, Knut
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    External Hydrocephalus as a Cause of Infant Subdural Hematoma: Epidemiological and Radiological Investigations of Infants Suspected of Being Abused.2021In: Pediatric Neurology, ISSN 0887-8994, E-ISSN 1873-5150, Vol. 126, p. 26-34, article id S0887-8994(21)00212-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Acute subdural hematoma (ASDH) and chronic subdural hematoma (CSDH) in infants have been regarded as highly specific for abuse. Other causes of CSDH have not been investigated in a large population.

    PURPOSE: The purpose of this study was to investigate to what extent external hydrocephalus is present in infants with ASDH and CSDH undergoing evaluation for abuse.

    MATERIAL AND METHODS: Eighty-five infants suspected of being abused, with ASDH (n = 16) or CSDH (n = 69), were reviewed regarding age, risk factor profiles, craniocortical width (CCW), sinocortical width (SCW), frontal interhemispheric width (IHW), subarachnoid space width (SSW), and head circumference (HC). In infants with unilateral subdural hematoma (SDH), correlations between contralateral SSW and ipsilateral CCW and SDH width were investigated.

    RESULTS: Infants with CSDH had significantly lower mortality, were more often premature and male, and had significantly higher CCW, SCW, IHW, and SSW than infants with ASDH (P < 0.05). Ipsilateral CCW (R = 0.92, P < 0.001) and SDH width (R = 0.81, P < 0.01) correlated with contralateral SSW. Increased HC was more prevalent in infants with CSDH (71%) than in infants with ASDH (14%) (P < 0.01). Forty-two infants, all with CSDH, had at least one of CCW, SCW, or IHW ≥95th percentile. Twenty infants, all with CSDH, had CCW, SCW, and IHW >5 mm, in addition to increased HC.

    CONCLUSION: A substantial proportion of infants with CSDH who had been suspected of being abused had findings suggesting external hydrocephalus.

  • 13.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Asymmetric Development of the Hippocampal Region Is Common: A Fetal MR Imaging Study2012In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 33, no 3, p. 513-518Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Hippocampal development is poorly understood. This study evaluated the normal development of the hippocampal region during the fetal period by using MR imaging.

    MATERIALS AND METHODS: MR images of 63 fetuses without intracranial pathology were reviewed independently by 2 radiologists with no knowledge of the fetal GA. Three MR images were performed postmortem and 60 in vivo. The progress of hippocampal inversion was analyzed in coronal sections, and the left and right sides of the hippocampal region were compared in every case.

    RESULTS: The fetuses in the postmortem examinations were at GWs 17-18 and in the in vivo examinations, at GWs 19-36. The hippocampal sulcus was open, bi- or unilaterally, in 39 fetuses. The oldest was at GW 32. The sulcus was closed at GW 21 at the earliest, unilaterally. In 26/63 fetuses (41%), the deepening or closure of the hippocampal sulcus or hippocampal inversion was asymmetric; in 23 fetuses, the right side developed faster. A shallow collateral sulcus was found earliest at GW 17. A deep collateral sulcus was visible earliest at GW 26 unilaterally, but in all fetuses from GW 31 onward, it was seen bilaterally. The orientation of the collateral sulcus was not related to the GA.

    CONCLUSIONS: There are wide individual temporal variations in the development and the inversion process of the hippocampal sulcus as well as in the formation of the collateral sulcus. Asymmetric development is common, and in most of the asymmetric cases, the right hippocampus develops faster.

  • 14.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Development of the hippocampal region demonstrated on fetal MRI: A preliminary report2011In: NRJ Digital, ISSN 2239-7493, Vol. 1, no 12, p. 555-557Article in journal (Refereed)
    Abstract [en]

    Coronal slices of three fetal MRIs performed post mortem and 37 performed in utero, all without intracranial pathology, was assessed. Progress of the hippocampal inversion was analyzed, the left and right sides were compared and occurrence of the collateral sulcus was revealed. The fetuses in the post mortem examinations were at gestation weeks (GW) 17-18 and in the in utero examinations at GW 19-35. The symmetric development of the hippocampal sulcus was revealed in 26 subjects and asymmetric in 14. The non-ovoid hippocampal formation could be evaluated at GW 24 at earliest and an ovoid hippocampus at GW 29. The collateral sulcus could be recognized at GW 17 in post mortem and at GW 22 in in utero examinations. From GW 29 onwards it was seen in all fetuses and it was symmetric in all but one case. Evaluation of the hippocampi is difficult on fetal MRI, especially in in utero examinations. The hippocampal development is not fulfilled at GW 21 as presumed. There is a wide temporal variation in the development of the hippocampal region, and the developmental process does not progress simultaneously in the right and left side of the same individual.

  • 15.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hippocampal development demonstrated by fetal MRI. Asymmetric development is common.2011In: Insights into Imaging, Vol. 2, no Suppl 1, p. B-831-Article in journal (Refereed)
  • 16.
    Banerjee, Subhashis
    et al.
    Machine Intelligence Unit Indian Statistical Institute Kolkata, India.
    Kumar Dhara, Ashis
    National Institute of Technology, Durgapur, West Bengal, India.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Segmentation of Intracranial Aneurysm Remnant in MRA using Dual-Attention Atrous Net2021In: 25th International Conference on Pattern Recognition (ICPR), 2021, p. 9265-9272Conference paper (Refereed)
    Abstract [en]

    Due to the advancement of non-invasive medical imaging modalities like Magnetic Resonance Angiography (MRA), an increasing number of Intracranial Aneurysm (IA) cases are being reported in recent years. The IAs are typically treated by so-called endovascular coiling, where blood flow in the IA is prevented by embolization with a platinum coil. Accurate quantification of the IA Remnant (IAR), i.e. the volume with blood flow present post treatment is the utmost important factor in choosing the right treatment planning. This is typically done by manually segmenting the aneurysm remnant from the MRA volume. Since manual segmentation of volumetric images is a labour-intensive and error-prone process, development of an automatic volumetric segmentation method is required. Segmentation of small structures such as IA, that may largely vary in size, shape, and location is considered extremely difficult. Similar intensity distribution of IAs and surrounding blood vessels makes it more challenging and susceptible to false positive. In this paper we propose a novel 3D CNN architecture called Dual-Attention Atrous Net (DAtt-ANet), which can efficiently segment IAR volumes from MRA images by reconciling features at different scales using the proposed Parallel Atrous Unit (PAU) along with the use of self-attention mechanism for extracting fine-grained features and intra-class correlation. The proposed DAtt-ANet model is trained and evaluated on a clinical MRA image dataset of IAR consisting of 46 subjects. We compared the proposed DAtt-ANet with five state-of-the-art CNN models based on their segmentation performance. The proposed DAtt-ANet outperformed all other methods and was able to achieve a five-fold cross-validation DICE score of 0.73 +/- 0.06.

  • 17.
    Banerjee, Subhashis
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Toumpanakis, Dimitrios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Dhara, Ashis Kumar
    Natl Inst Technol Durgapur, Dept Elect Engn, Durgapur, India..
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Topology-Aware Learning for Volumetric Cerebrovascular Segmentation2022In: 2022 IEEE International Symposium on Biomedical Imaging (IEEE ISBI 2022), IEEE, 2022, p. 1-4Conference paper (Refereed)
    Abstract [en]

    This paper presents a topology-aware learning strategy for volumetric segmentation of intracranial cerebrovascular structures. We propose a multi-task deep CNN along with a topology-aware loss function for this purpose. Along with the main task (i.e. segmentation), we train the model to learn two related auxiliary tasks viz. learning the distance transform for the voxels on the surface of the vascular tree and learning the vessel centerline. This provides additional regularization and allows the encoder to learn higher-level intermediate representations to boost the performance of the main task. We compare the proposed method with six state-of-the-art deep learning-based 3D vessel segmentation methods, by using a public Time-Of-Flight Magnetic Resonance Angiography (TOF-MRA) dataset. Experimental results demonstrate that the proposed method has the best performance in this particular context.

  • 18.
    Banerjee, Subhashis
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division Vi3.
    Toumpanakis, Dimitrios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Dhara, Ashis
    Department of Electrical Engineering, National Institute of Technology Durgapur, India.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division Vi3.
    Deep Curriculum Learning for Follow-up MRI Registration in Glioblastoma2023In: Medical Imaging 2023: Image Processing, SPIE -Society of Photo-Optical Instrumentation Engineers , 2023, Vol. 12464, article id 124643IConference paper (Refereed)
    Abstract [en]

    This paper presents a weakly supervised deep convolutional neural network-based approach to perform voxel-level3D registration between subsequent follow-up MRI scans of the same patient. To handle the large deformation inthe surrounding brain tissues due to the tumor’s mass effect we proposed curriculum learning-based training forthe network. Weak supervision helps the network to concentrate more focus on the tumor region and resectioncavity through a saliency detection network. Qualitative and quantitative experimental results show the proposedregistration network outperformed two popular state-of-the-art methods.

  • 19.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Garavan, Hugh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The effect of premenstrual dysphoric disorder and menstrual cycle phase on brain activity during response inhibition2012In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 142, no 1-3, p. 347-350Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Premenstrual dysphoric disorder (PMDD) has generally not been associated with impulsive behavior. However, some studies suggest that women with PMDD have higher impulsivity scores than healthy controls and that brain activity during response inhibition may vary across the menstrual cycle. Therefore, our aim was to unravel potentially important cognitive aspects of PMDD by investigating brain activity during response inhibition in women with PMDD and healthy controls in relation to menstrual cycle phase.

    METHODS:

    Fourteen PMDD patients and 13 healthy controls performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging.

    RESULTS:

    Women with PMDD displayed decreased activity during both menstrual cycle phases compared to healthy controls in several task-related parietal areas. A significant group by phase interactions was found in the left insula, driven by enhanced activity among healthy controls in the follicular phase and by enhanced insula activity during the luteal phase among PMDD patients.

    LIMITATIONS:

    The limitations of the present study are the relatively limited sample size, the relatively small number of NoGo trials and the lack of a baseline contrast for the NoGo trials.

    CONCLUSIONS:

    During response inhibition women with PMDD have reduced activity in areas associated with attention and motor function which is unrelated to menstrual cycle phase. Insular cortex activity, involved in both affective and cognitive processing, was significantly activated during the luteal phase among PMDD women. These findings are relevant for the understanding of how ovarian steroids influence mood symptoms in women.

  • 20.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bäckström, Torbjörn
    Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Prefrontal activity during response inhibition decreases over time in the postpartum period2013In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 241, no 1, p. 132-138Article in journal (Refereed)
    Abstract [en]

    The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48hours of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in response inhibition performance were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted.

  • 21.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risbrough, Victoria
    Department of Psychiatry, University of California, San Diego, CA, USA.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Patients with premenstrual dysphoric disorder have increased startle modulation during anticipation in the late luteal phase period in comparison to control subjects2011In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 36, no 8, p. 1184-1192Article in journal (Refereed)
    Abstract [en]

    The acoustic startle response (ASR) is a withdrawal reflex to sudden or noxious auditory stimuli and, most importantly, an unbiased measure of emotional processing of appetitive and aversive stimuli. By exposing subjects to fearful situations, such as aversive pictures, the ASR may be enhanced, suggesting that amygdala modulates the startle circuit during threat situations. As one previous study, investigating affective modulation of the ASR in women with premenstrual dysphoric disorder (PMDD), discovered no difference during picture viewing it is possible that the mood changes observed in PMDD relate to anxious anticipation rather than to direct stimulus responding. Hence we sought to examine the effects of PMDD on picture anticipation and picture response.

    Sixteen PMDD patients and 16 controls watched slide shows containing pleasant and unpleasant pictures and positive and negative anticipation stimuli during the follicular and luteal phase of the menstrual cycle. Simultaneously, semi-randomized startle probes (105dB) were delivered and the ASR was assessed with electromyography.

    Compared with control subjects, PMDD patients displayed an enhanced startle modulation by positive and negative anticipation stimuli in the luteal phase of the menstrual cycle. This finding was mainly driven by increased modulation in the luteal phase in comparison to the follicular phase among PMDD patients but also by an increased modulation in patients compared to controls during luteal phase. This suggests that the neural circuits underlying response to emotional anticipation are more sensitive during this period and emphasize the need of examining the neural correlates of anticipatory processes in women with PMDD.

  • 22.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lower levels of prepulse inhibition in luteal phase cycling women in comparison with postmenopausal women2010In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 35, no 3, p. 422-429Article in journal (Refereed)
    Abstract [en]

    Menopause denotes the end of the reproductive period in a woman's life and is characterized by gradually declining plasma levels of ovarian hormones. Mounting evidence suggests that prepulse inhibition (PPI) is sensitive to fluctuations in estradiol and progesterone. Deficits in PPI are associated with conditions characterized by increased levels of ovarian steroids, such as the mid-luteal phase of the menstrual cycle and the third trimester of pregnancy. The aim of the current study was to further elucidate ovarian steroid-related effects on PPI by examining 43 women with regular menstrual cycles, 20 healthy postmenopausal women without hormone replacement treatment (HRT) and 21 healthy postmenopausal women with ongoing estradiol-only or estradiol and progesterone therapy (EPT). Cycling women were tested during the late luteal phase of the menstrual cycle while postmenopausal women were tested on any arbitrary day. The PPI was measured by electromyography. Cycling women exhibited lower levels of PPI than postmenopausal women (p<0.05). There were no differences in PPI between postmenopausal HRT users and non-users. However, postmenopausal women with estradiol serum concentrations in the cycling range had lower PPI than postmenopausal women with low estradiol concentrations (groupxPPI interaction, p<0.05). In conclusion, the results further suggest a role for the ovarian steroids in PPI regulation as PPI is increased in postmenopausal women in comparison to regularly menstruating women examined during the late luteal phase. Furthermore, postmenopausal women with estradiol levels in the cycling range had lower PPI than postmenopausal women with low estradiol levels.

  • 23.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Department of Clinical Sciences, Sahlgrenska Academy, Gothenburg University , Gothenburg, Sweden;Department of Obstetrics and Gynecology, Stellenbosch University , Stellenbosch, South Africa;Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Sciences, University of Bío-Bío , Chillán, Chile.
    Acurio, Jesenia
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Leon, Jose
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Gatu, Emily
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Friis, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Nelander, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lara, Evelyn
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Aguayo, Claudio
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Torres-Vergara, Pablo
    Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillán, Chile..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Escudero, Carlos
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Preeclampsia and Increased Permeability Over the Blood–Brain Barrier: A Role of Vascular Endothelial Growth Receptor 2 2021In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 34, no 1, p. 73-81Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.

    METHODS: The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert were exposed (12 h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in order to establish correlations with in vitro results.

    RESULTS: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.

    CONCLUSION: We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.

  • 24.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects2014In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 27, no 8, p. 1105-1111Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.

    METHODS:

    A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.

    RESULTS:

    Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).

    CONCLUSIONS:

    S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.

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  • 25.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynaecol, S-41650 Gothenburg, Sweden.;Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Bergman, Karl
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, S-41650 Gothenburg, Sweden..
    Langenegger, Eduard
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Moodley, Ashley
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Griffith-Richards, Stephanie
    Stellenbosch Univ, Div Radiodiag, Dept Med Imaging & Clin Oncol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hall, David
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Joubert, Lloyd
    Stellenbosch Univ, Div Cardiol, Dept Med Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Herbst, Philip
    Univ Med Ctr Groningen, Dept Obstet & Gynaecol, NL-9713 Groningen, Netherlands..
    Schell, Sonja
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    van Veen, Teelkien
    Univ Med Ctr Groningen, Dept Obstet & Gynaecol, NL-9713 Groningen, Netherlands..
    Belfort, Michael
    Baylor Coll Med, Dept Obstet & Gynaecol, Houston, TX 77004 USA..
    Tong, Stephen Y. C.
    Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3010, Australia..
    Walker, Susan
    Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3010, Australia..
    Hastie, Roxanne
    Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3010, Australia..
    Cluver, Catherine
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa.;Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia..
    PROVE-Pre-Eclampsia Obstetric Adverse Events: Establishment of a Biobank and Database for Pre-Eclampsia2021In: Cells, E-ISSN 2073-4409, Vol. 10, no 4, article id 959Article in journal (Refereed)
    Abstract [en]

    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.

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  • 26.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Torres-Vergara, Pablo
    Univ Concepcion, Fac Pharm, Pharm Dept, Concepcion, Chile ;Grp Res & Innovat Vasc Hlth GRIVAS Hlth, Chillan, Chile.
    Penny, Jeffrey
    Univ Manchester, Fac Biol Med & Hlth, Sch Hlth Sci, Div Pharm & Optometry, Manchester, Lancs, England.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nelander, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Leon, Jose
    Grp Res & Innovat Vasc Hlth GRIVAS Hlth, Chillan, Chile ; Univ Bio Bio, Fac Sci, Grp Invest Tumor Angiogenesis LFV GIANT, Vasc Physiol Lab,Dept Basic Sci, Chillan, Chile.
    Tolcher, Mary
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Roberts, James M
    Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Epidemiol & Clin & Translat Res, Pittsburgh, PA USA.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Escudero, Carlos
    Grp Res & Innovat Vasc Hlth GRIVAS Hlth, Chillan, Chile ; Univ Bio Bio, Fac Sci, Grp Invest Tumor Angiogenesis LFV GIANT, Vasc Physiol Lab,Dept Basic Sci, Chillan, Chile.
    Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort2019In: Current Hypertension Reports, ISSN 1522-6417, E-ISSN 1534-3111, Vol. 21, no 9, article id 72Article in journal (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia.

    RECENT FINDINGS: The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.

  • 27.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ribeiro, Valentina
    Teixeira, João
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikstrom, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Visualization of the Fetal Lip and Palate: Is Brain-Targeted MRI Reliable?2013In: The Cleft Palate-Craniofacial Journal, ISSN 1055-6656, E-ISSN 1545-1569, Vol. 50, no 5, p. 513-519Article in journal (Refereed)
    Abstract [en]

    Objective : 

    To evaluate the ability of brain-targeted magnetic resonance imaging (MRI) to assess the anatomy of the fetal upper lip and palate.

    Design : 

    Two independent readers made a blind retrospective review of 60 brain-targeted MRIs of fetuses from 20 to 38 gestational weeks (GW). Fifty-five MRIs were normal and five had orofacial anomalies, including one isolated cleft lip and four cleft lip and palate. Both normal and cleft MRIs had postnatal confirmation. The upper lip, primary palate, secondary palate, and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis.

    Setting :

    Collaboration between a university hospital and a large private practice MRI center.

    Results : 

    Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the primary palate, 0.86 for the secondary palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age. Normality was correctly scored in 96% to 100% of the normal lips and primary palates and in 93% to 97% of the normal secondary palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft palates. The readers identified all pathological cases.

    Conclusion :

    Brain-targeted fetal MRI in experienced hands seems to be highly accurate for the evaluation of the lip and palate in fetuses above 20 GW, regardless of gestational age. The assessment of the secondary palate may be slightly more limited than the lip or primary palate.

  • 28.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ribeiro, Valentina
    Hospital S. Antonio, Porto, Portugal.
    Teixeira, João
    Hospital S. Antonio, Porto, Portugal.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Visualisation of the fetal lip and palate: is brain-targeted MRI reliable?2011In: Neurology, ISSN 0028-3878, E-ISSN 1526-632XArticle in journal (Other academic)
    Abstract [en]

    Introduction: The purpose of the study was to evaluate the ability of brain-targeted MRI to assess the anatomy of the fetal upper lip and palate.

     

    Methods: Two independent readers made a blind retrospective review of 60 MRI of fetuses of 20 to 38 gestational weeks (GW). Fifty-five fetuses had normal post-natal follow-up.  Five fetuses had oro-facial anomalies at post-natal follow-up, including five cleft lips (two bilateral, three unilateral), four cleft primary palates (two bilateral, two unilateral) and two cleft secondary palates.

    The upper lip, primary palate, secondary palate and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis.

     

    Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the primary palate, 0.86 for the secondary palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age.

    The readers identified 100% of all pathological cases. The normality was correctly scored in 96-100% of the normal lips and primary palates and in 93-97% of the normal secondary palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft palates.

     

    Conclusion:  MRI in experienced hands seems reliable for assessment of the fetal lip and palate, even in brain-targeted examinations. Attention should therefore be paid to the lip and palate in all fetal MRI examinations, since unsuspected clefts may be revealed.

     

     

  • 29.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Teixeira, J.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    The ear in fetal MRI: What can we really see?2011In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 53, no Suppl 1, p. S23-Article in journal (Refereed)
  • 30.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Teixeira, João
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    The ear in fetal MRI: what can we really see?2011In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 53, no 12, p. 1001-1008Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The aim of this study was to investigate the ability to depict the components of the ear on brain-oriented fetal MRI studies.

    METHODS: Retrospective evaluation of the ear in MRI studies was performed post-mortem in 16 fetuses ranging from 15 to 22 gestation weeks (GW), and in 122 examinations in vivo of fetuses ranging from 20 to 38 GW. The cochlea, vestibular apparatus, middle ear, and external auditory canal were separately graded according to the components that were delineated.

    RESULTS: The components of the inner and middle ear were fully delineated in 100% of the post-mortem examinations, but the external auditory canals were only seen in only 25%. In the in vivo group, the imaging detail was much lower. Cochlear turns could be identified in 75% of the fetuses, the vestibule and the lateral semicircular canals in 72% andossicles in 70%. Before 25 GW, the ability to identify these individual parts was 50%, 30%, and 33%, respectively, and above it was 89%, 93%, and 90% . In most cases, the external auditory canals could only be seen after 29 GW.

    CONCLUSION: In fetal MRI studies in vivo, it is possible to depict the components of the ear in the majority of the fetuses, in such a manner as to exclude major malformations. However, MRI might not provide enough detail to rule out pathology of the ear before 25 GW, this being a critical age for pregnancy management in many countries.

  • 31.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Teixeira, João
    Department of Neuroradiology, H. G. S. Antonio, Porto, Portugal.
    Themudo, Raquel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Amini, Hashem
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Measurements of the normal fetal brain at gestation weeks 17 to 23: a MRI study2011In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 53, no 1, p. 43-48Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: To obtain measurements of the normal fetal brain before 24 weeks of gestation (GW), a deadline for medical decisions on fetal viability in a large number of countries. METHODS: We retrospectively reviewed 70 normal MR examinations of fetuses aged GW 17 to 23. The fronto-occipital diameter, the cerebral bi-parietal diameter, the transverse cerebellar diameter, the vermian height, and antero-posterior diameter were measured. RESULTS: The median, maximum, and minimum values for each parameter were displayed for each individual GW. CONCLUSION: The recorded data might contribute to a better assessment of fetal health by providing normal boundaries for the brain growth.

  • 32.
    Casar Borota, Olivera
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Stigare, Jerker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Boldt, Henning Bünsow
    Kristensen, Bjarne Winther
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Trouillas, Jacqueline
    Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.2017In: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 41, no 9, p. 1238-1246Article in journal (Refereed)
    Abstract [en]

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

  • 33.
    Christou, Constantina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bifurcation of the intratemporal facial nerve: A rare anatomical anomaly2018In: ACTA OTO-LARYNGOLOGICA CASE REPORTS, ISSN 2377-2484, Vol. 3, no 1, p. 15-18Article in journal (Refereed)
    Abstract [en]

    The anatomical position of the facial nerve is a critical factor in determining surgical candidacy in patients with congenital aural atresia (CAA). All patients with CAA must preoperatively be evaluated using a grading score based on information gained from a high resolution CT scan. In patients not suitable for surgical reconstruction, implantation of novel hearing implants is increasingly used for hearing rehabilitation. We, here, describe a bifurcation of the intratemporal part of the facial nerve in a 5-year old boy with CAA undergoing implantation with a bone conductive hearing device.

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  • 34.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hahn, Andreas
    Ganger, Sebastian
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Epperson, C Neill
    Lanzenberger, Rupert
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder2014In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 35, no 9, p. 4450-4458Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp, 2014. 

  • 35.
    Correia de Verdier, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Berglund, Johan
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Effect of MRI acquisition parameters on accuracy and precision of phase-contrast measurements in a small-lumen vessel phantomManuscript (preprint) (Other academic)
  • 36.
    Correia de Verdier, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Magnetic resonance imaging detected radiation-induced changes in patients with proton radiation-treated arteriovenous malformations2021In: Acta Radiologica Open, E-ISSN 2058-4601, Vol. 10, no 10, article id 205846012110508Article in journal (Refereed)
    Abstract [en]

    Background

    Treatment of intracranial arteriovenous malformations (AVMs) includes surgery, radiation therapy, endovascular occlusion, or a combination. Proton radiation therapy enables very focused radiation, minimizing dose to the surrounding brain.

    Purpose

    To evaluate the presence of radiation-induced changes on post-treatment MRI in patients with AVMs treated with proton radiation and to compare these with development of symptoms and nidus obliteration.

    Material and Methods

    Retrospective review of pre- and post-treatment digital subtraction angiography and MRI and medical records in 30 patients with AVMs treated with proton radiation. Patients were treated with two or five fractions; total radiation dose was 20–35 physical Gy. Vasogenic edema (minimal, perinidal, or severe), contrast enhancement (minimal or annular), cavitation and nidus obliteration (total, partial, or none) were assessed.

    Results

    26 of 30 patients (87%) developed MRI changes. Vasogenic edema was seen in 25 of 30 (83%), abnormal contrast enhancement in 18 of 26 (69%) and cavitation in 5 of 30 (17%). Time from treatment to appearance of MRI changes varied between 5 and 25 months (median 7, mean 10). Seven patients developed new or deteriorating symptoms that required treatment with corticosteroids; all these patients had extensive MRI changes (severe vasogenic edema and annular contrast enhancement). Not all patients with extensive MRI changes developed symptoms. We found no relation between MRI changes and nidus obliteration.

    Conclusion

    Radiation-induced MRI changes are seen in a majority of patients after proton radiation treatment of AVMs. Extensive MRI changes are associated with new or deteriorating symptoms.

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  • 37.
    Correia de Verdier, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ronne-Engström, Elisabeth
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Flow and velocity in intracranial arteries of patients with arteriovenous malformations measured with phase-contrast magnetic resonance imagingManuscript (preprint) (Other academic)
  • 38.
    Correia de Verdier, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Normal ranges and test-retest reproducibility of flow and velocity parameters in intracranial arteries measured with phase-contrast magnetic resonance imaging2016In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 58, no 5, p. 521-531Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The purpose of the present study was to investigate normal ranges and test-retest reproducibility of phase-contrast MRI (PC-MRI)-measured flow and velocity parameters in intracranial arteries.

    METHODS: Highest flow (HF), lowest flow (LF), peak systolic velocity (PSV), and end diastolic velocity (EDV) were measured at two dates in the anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries of 30 healthy volunteers using two-dimensional PC-MRI at 3 T. Least detectable difference (LDD) was calculated.

    RESULTS: In the left ACA, HF was (mean (range, LDD)) 126 ml/min (36-312, 59 %), LF 61 ml/min (0-156, 101 %), PSV 64 cm/s (32-141, 67 %), and EDV 35 cm/s (18-55, 42 %); in the right ACA, HF was 154 ml/min (42-246, 49 %), LF 77 ml/min (0-156, 131 %), PSV 75 cm/s (26-161, 82 %), and EDV 39 cm/s (7-59, 67 %). In the left MCA, HF was 235 ml/min (126-372, 35 %), LF 116 ml/min (42-186, 48 %), PSV 90 cm/s (55-183, 39 %), and EDV 46 cm/s (20-66, 28 %); in the right MCA, HF was 238 ml/min (162-342, 44 %), LF 120 ml/min (72-216, 48 %), PSV 88 cm/s (55-141, 35 %), and EDV 45 cm/s (26-67, 23 %). In the left PCA, HF was 108 ml/min (42-168, 54 %), LF 53 ml/min (18-108, 64 %), PSV 50 cm/s (24-77, 63 %), and EDV 28 cm/s (14-40, 45 %); in the right PCA, HF was 98 ml/min (30-162, 49 %), LF 49 ml/min (12-84, 55 %), PSV 47 cm/s (27-88, 59 %), and EDV 27 cm/s (16-41, 45 %).

    CONCLUSION: PC-MRI-measured flow and velocity parameters in the main intracranial arteries have large normal ranges. Reproducibility is highest in MCA.

  • 39.
    Dhara, Ashis Kumar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Arids, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Interactive segmentation of glioblastoma for post-surgical treatment follow-up2018In: Proc. 24th International Conference on Pattern Recognition, IEEE, 2018, p. 1199-1204Conference paper (Refereed)
  • 40.
    Dhara, Ashis Kumar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Ayyalasomayajula, Kalyan Ram
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Arvids, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Segmentation of Post-operative Glioblastoma in MRI by U-Net with Patient-specific Interactive Refinement2019In: Brainlesion: Glioma, Multiple Sclerosis, Stroke and Traumatic Brain Injuries / [ed] Crimi A., Bakas S., Kuijf H., Keyvan F., Reyes M & van Walsum T., Cham: Springer, 2019, p. 115-122Conference paper (Refereed)
    Abstract [en]

    Accurate volumetric change estimation of glioblastoma is very important for post-surgical treatment follow-up. In this paper, an interactive segmentation method was developed and evaluated with the aim to guide volumetric estimation of glioblastoma. U-Net based fully convolutional network is used for initial segmentation of glioblastoma from post contrast MR images. The max flow algorithm is applied on the probability map of U-Net to update the initial segmentation and the result is displayed to the user for interactive refinement. Network update is performed based on the corrected contour by considering patient specific learning to deal with large context variations among different images. The proposed method is evaluated on a clinical MR image database of 15 glioblastoma patients with longitudinal scan data. The experimental results depict an improvement of segmentation performance due to patient specific fine-tuning. The proposed method is computationally fast and efficient as compared to state-of-the-art interactive segmentation tools. This tool could be useful for post-surgical treatment follow-up with minimal user intervention.

  • 41.
    Dubol, Manon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Immenschuh, Jana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Takahashi, Kayo
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan..
    Niwa, Takashi
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan.;Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Tokyo, Japan..
    Hosoya, Takamitsu
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan.;Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Tokyo, Japan..
    Roslin, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Watanabe, Yasuyoshi
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Biegon, Anat
    SUNY Stony Brook, Dept Radiol & Neurol, Sch Med, Stony Brook, NY USA..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Comasco, Erika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology.
    Acute nicotine exposure blocks aromatase in the limbic brain of healthy women: A [11C]cetrozole PET study2023In: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 123, article id 152381Article in journal (Refereed)
    Abstract [en]

    Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain.

    Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI -based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential.

    Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d =-0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend.

    Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.

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  • 42.
    Dubol, Manon
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology.
    Stiernman, Louise
    Umeå Univ, Dept Clin Sci, S-90185 Umeå, Sweden..
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lanzenberger, Rupert
    Med Univ Vienna, Dept Psychiat & Psychotherapy, A-1090 Vienna, Austria..
    Neill Epperson, C.
    Univ Colorado, Dept Psychiat, Dept Family Med, Sch Med, Anschutz Med Campus, Aurora, CO 80045 USA..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Bixo, Marie
    Umeå Univ, Dept Clin Sci, S-90185 Umeå, Sweden..
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Differential grey matter structure in women with premenstrual dysphoric disorder: evidence from brain morphometry and data-driven classification2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 250Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is a female-specific condition classified in the Diagnostic and Statical Manual-5th edition under depressive disorders. Alterations in grey matter volume, cortical thickness and folding metrics have been associated with a number of mood disorders, though little is known regarding brain morphological alterations in PMDD. Here, women with PMDD and healthy controls underwent magnetic resonance imaging (MRI) during the luteal phase of the menstrual cycle. Differences in grey matter structure between the groups were investigated by use of voxel- and surface-based morphometry. Machine learning and multivariate pattern analysis were performed to test whether MRI data could distinguish women with PMDD from healthy controls. Compared to controls, women with PMDD had smaller grey matter volume in ventral posterior cortices and the cerebellum (Cohen's d = 0.45-0.76). Region-of-interest analyses further indicated smaller volume in the right amygdala and putamen of women with PMDD (Cohen's d = 0.34-0.55). Likewise, thinner cortex was observed in women with PMDD compared to controls, particularly in the left hemisphere (Cohen's d = 0.20-0.74). Classification analyses showed that women with PMDD can be distinguished from controls based on grey matter morphology, with an accuracy up to 74%. In line with the hypothesis of an impaired top-down inhibitory circuit involving limbic structures in PMDD, the present findings point to PMDD-specific grey matter anatomy in regions of corticolimbic networks. Furthermore, the results include widespread cortical and cerebellar regions, suggesting the involvement of distinct networks in PMDD pathophysiology.

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  • 43.
    Dubol, Manon
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lanzenberger, Rupert
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
    Epperson, C. Neill
    Department of Psychiatry, Department of Family Medicine, University of Colorado School of Medicine-Anschutz Medical Campus, Aurora, USA.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Comasco, Erika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Grey matter correlates of affective and somatic symptoms of premenstrual dysphoric disorder2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 5996Article in journal (Refereed)
    Abstract [en]

    Ovarian hormones fluctuations across the menstrual cycle are experienced by about 58% of women in their fertile age. Maladaptive brain sensitivity to these changes likely leads to the severe psychological, cognitive, and physical symptoms repeatedly experienced by women with Premenstrual Dysphoric Disorder (PMDD) during the late luteal phase of the menstrual cycle. However, the neuroanatomical correlates of these symptoms are unknown. The relationship between grey matter structure and PMDD symptom severity was delineated using structural magnetic resonance imaging during the late luteal phase of fifty-one women diagnosed with PMDD, combined with Voxel- and Surface-Based Morphometry, as well as subcortical volumetric analyses. A negative correlation was found between depression-related symptoms and grey matter volume of the bilateral amygdala. Moreover, the severity of affective and somatic PMDD symptoms correlated with cortical thickness, gyrification, sulcal depth, and complexity metrics, particularly in the prefrontal, cingulate, and parahippocampal gyri. The present findings provide the first evidence of grey matter morphological characteristics associated with PMDD symptomatology in brain regions expressing ovarian hormone receptors and of relevance to cognitive-affective functions, thus potentially having important implications for understanding how structural brain characteristics relate to PMDD symptomatology.

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  • 44.
    Edfeldt, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Abdasaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Non-echo planar diffusion-weighted MRI increases follow-up accuracy after one-step step canal wall-down obliteration surgery for cholesteatoma2013In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, no 6, p. 574-583Article in journal (Refereed)
    Abstract [en]

    Conclusion:

    Non-echo planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) increases the number of detected cholesteatoma after one-step canal-wall down (CWD) obliteration surgery for cholesteatoma compared with clinical evaluation alone.

    Objective:

    To evaluate the use of DW-MRI for detection of cholesteatoma after surgical treatment using CWD obliteration technique.

    Methods:

    Thirty-eight adult patients (41 ears) treated with identical one-step canal-wall down obliteration surgical technique were included in a prospective and blinded study. All patients were investigated with non-EPI and EPI DW-MRI 1-9 months after the clinical examination. Follow-up time after primary surgery varied between 10 and 234 months. DW-MRI were assessed by two neuroradiologists and compared with clinical results. Inter-rater agreement was calculated. Positive non-EPI DW-MRI cases underwent revision surgery within 18-159 days after imaging.

    Results:

    Out of 41 cases seven were evaluated as positive for cholesteatoma on non-EPI DW-MRI. Since one patient refused surgery six of these seven cases underwent surgical revision and all were verified. There was agreement between clinical and non-EPI findings in five of eight cases. EPI findings correlated poorly with non-EPI and clinical findings. Inter-rater agreement (Cohen´s kappa) was 0.91 for non-EPIDW-MRI (p<0.001) and -0.062 for EPI DW-MRI (p=0.43)

     

  • 45.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 555-563Article in journal (Refereed)
    Abstract [en]

    The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

  • 46.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare, Applied Science Laboratory.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evaluation of Arterial Spin Labeling MRI: Comparison with 15O-Water PET on an Integrated PET/MR Scanner2021In: Diagnostics (Basel), ISSN 2075-4418, Vol. 11, no 5, article id 821Article in journal (Refereed)
    Abstract [en]

    Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.

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  • 47.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease2020In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 41, no 3, p. 430-436Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling–derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease.

    MATERIALS AND METHODS: Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient’s 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute–based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively.

    RESULTS: A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968–0.988) and 1.8 percentage points (95% CI, 0.3–3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively.

    CONCLUSIONS: Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.

  • 48.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Svedung-Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.2023In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 14, article id 1137046Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD.

    METHODS: Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography.

    RESULTS: Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol.

    CONCLUSION: Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.

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  • 49.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Variable Temporal Cerebral Blood Flow Response to Acetazolamide in Moyamoya Patients Measured Using Arterial Spin Labeling2021In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 12, article id 615017Article in journal (Refereed)
    Abstract [en]

    Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged.

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  • 50.
    Fanni, Giovanni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kagios, Christakis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIMC—Centre d’Imagerie Médicale de Cornavin, Geneva, Switzerland.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of gastric bypass surgery on brain connectivity responses to hypoglycemia2023In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 79, no 2, p. 304-312Article in journal (Refereed)
    Abstract [en]

    Introduction

    Roux-en-Y gastric bypass (RYGB) leads to beneficial effects on glucose homeostasis, and attenuated hormonal counterregulatory responses to hypoglycemia are likely to contribute. RYGB also induces alterations in neural activity of cortical and subcortical brain regions. We aimed to characterize RYGB-induced changes in resting-state connectivity of specific brain regions of interest for energy homeostasis and behavioral control during hypoglycemia.

    Method

    Ten patients with BMI > 35 kg/m2 were investigated with brain PET/MR imaging during a hyperinsulinemic normo- and hypoglycemic clamp, before and 4 months after RYGB. Hormonal levels were assessed throughout the clamp. Resting-state (RS) fMRI scans were acquired in the glucose-lowering phase of the clamp, and they were analyzed with a seed-to-voxel approach.

    Results

    RS connectivity during initiation of hypoglycemia was significantly altered after RYGB between nucleus accumbens, thalamus, caudate, hypothalamus and their crosstalk with cortical and subcortical regions. Connectivity between the nucleus accumbens and the frontal pole was increased after RYGB, and this was associated with a reduction of ACTH (r = −0.639, p = 0.047) and cortisol (r = −0.635, p = 0.048) responses. Instead, connectivity between the caudate and the frontal pole after RYGB was reduced and this was associated with less attenuation of glucagon response during the hypoglycemic clamp (r = −0.728, p = 0.017), smaller reduction in fasting glucose (r = −0.798, p = 0.007) and less excess weight loss (r = 0.753, p = 0.012). No other significant associations were found between post-RYGB changes in ROI-to-voxel regional connectivity hormonal responses and metabolic or anthropometric outcomes.

    Conclusion

    RYGB alters brain connectivity during hypoglycemia of several neural pathways involved in reward, inhibitory control, and energy homeostasis. These changes are associated with altered hormonal responses to hypoglycemia and may be involved in the glucometabolic outcome of RYGB.

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