| 11. |
- Andersson, Karin, 1972, et al.
(author)
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Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis.
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:51
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is an inflammatory joint disease with a neurological component including depression, cognitive deficits, and pain, which substantially affect patients' quality of daily life. Insulin-like growth factor 1 receptor (IGF1R) signaling is one of the factors in RA pathogenesis as well as a known regulator of adult neurogenesis. The purpose of this study was to investigate the association between IGF1R signaling and the neurological symptoms in RA. In experimental RA, we demonstrated that arthritis induced enrichment of IBA1+ microglia in the hippocampus. This coincided with inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) and up-regulation of IGF1R in the pyramidal cell layer of the cornus ammoni and in the dentate gyrus, reproducing the molecular features of the IGF1/insulin resistance. The aberrant IGF1R signaling was associated with reduced hippocampal neurogenesis, smaller hippocampus, and increased immobility of RA mice. Inhibition of IGF1R in experimental RA led to a reduction of IRS1 inhibition and partial improvement of neurogenesis. Evaluation of physical functioning and brain imaging in RA patients revealed that enhanced functional disability is linked with smaller hippocampus volume and aberrant IGF1R/IRS1 signaling. These results point to abnormal IGF1R signaling in the brain as a mediator of neurological sequelae in RA and provide support for the potentially reversible nature of hippocampal changes.
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| 12. |
- Bergquist, Magnus, 1960-, et al.
(author)
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Trust and stakeholder perspectives on the implementation of AI tools in clinical radiology
- 2024
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In: European Radiology. - Heidelberg : Springer. - 0938-7994 .- 1432-1084. ; 34:1, s. 338-347
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Journal article (peer-reviewed)abstract
- Objectives: To define requirements that condition trust in artificial intelligence (AI) as clinical decision support in radiology from the perspective of various stakeholders and to explore ways to fulfil these requirements.Methods: Semi-structured interviews were conducted with twenty-five respondents—nineteen directly involved in the development, implementation, or use of AI applications in radiology and six working with AI in other areas of healthcare. We designed the questions to explore three themes: development and use of AI, professional decision-making, and management and organizational procedures connected to AI. The transcribed interviews were analysed in an iterative coding process from open coding to theoretically informed thematic coding.Results: We identified four aspects of trust that relate to reliability, transparency, quality verification, and inter-organizational compatibility. These aspects fall under the categories of substantial and procedural requirements.Conclusions: Development of appropriate levels of trust in AI in healthcare is complex and encompasses multiple dimensions of requirements. Various stakeholders will have to be involved in developing AI solutions for healthcare and radiology to fulfil these requirements. Clinical relevance statement: For AI to achieve advances in radiology, it must be given the opportunity to support, rather than replace, human expertise. Support requires trust. Identification of aspects and conditions for trust allows developing AI implementation strategies that facilitate advancing the field.Key Points:• Dimensions of procedural and substantial demands that need to be fulfilled to foster appropriate levels of trust in AI in healthcare are conditioned on aspects related to reliability, transparency, quality verification, and inter-organizational compatibility. • Creating the conditions for trust to emerge requires the involvement of various stakeholders, who will have to compensate the problem’s inherent complexity by finding and promoting well-defined solutions. © 2023, The Author(s).
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| 13. |
- Faillenot, Isabelle, et al.
(author)
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Macroanatomy and 3D probabilistic atlas of the human insula.
- 2017
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In: NeuroImage. - : Elsevier BV. - 1095-9572 .- 1053-8119. ; 150, s. 88-98
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Journal article (peer-reviewed)abstract
- The human insula is implicated in numerous functions. More and more neuroimaging studies focus on this region, however no atlas offers a complete subdivision of the insula in a reference space. The aims of this study were to define a protocol to subdivide insula, to create probability maps in the MNI152 stereotaxic space, and to provide normative reference volume measurements for these subdivisions. Six regions were manually delineated bilaterally on 3D T1 MR images of 30 healthy subjects: the three short gyri, the anterior inferior cortex, and the two long gyri. The volume of the insular grey matter was 7.7 ± 0.9cm(3) in native space and 9.9 ± 0.6cm(3) in MNI152 space. These volumes expressed as a percentage of the ipsilateral grey matter volume were minimally larger in women (2.7±0.2%) than in men (2.6±0.2%). After spatial normalization, a stereotactic probabilistic atlas of each subregion was produced, as well as a maximum-probability atlas taking into account surrounding structures. Automatically labelling insular subregions via a multi-atlas propagation and label fusion strategy (MAPER) in a leave-one-out experiment showed high spatial overlaps of such automatically defined insular subregions with the manually derived ones (mean Jaccard index 0.65, corresponding to a mean Dice index of 0.79), with an average mean volume error of 2.6%. Probabilistic and maximum probability atlases and the original delineations are available on the web under free academic licences.
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| 14. |
- Gryska, Emilia, 1992, et al.
(author)
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Automatic brain lesion segmentation on standard magnetic resonance images: a scoping review.
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:1
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Journal article (peer-reviewed)abstract
- Medical image analysis practices face challenges that can potentially be addressed with algorithm-based segmentation tools. In this study, we map the field of automatic MR brain lesion segmentation to understand the clinical applicability of prevalent methods and study designs, as well as challenges and limitations in the field.Scoping review.Three databases (PubMed, IEEE Xplore and Scopus) were searched with tailored queries. Studies were included based on predefined criteria. Emerging themes during consecutive title, abstract, methods and whole-text screening were identified. The full-text analysis focused on materials, preprocessing, performance evaluation and comparison.Out of 2990 unique articles identified through the search, 441 articles met the eligibility criteria, with an estimated growth rate of 10% per year. We present a general overview and trends in the field with regard to publication sources, segmentation principles used and types of lesions. Algorithms are predominantly evaluated by measuring the agreement of segmentation results with a trusted reference. Few articles describe measures of clinical validity.The observed reporting practices leave room for improvement with a view to studying replication, method comparison and clinical applicability. To promote this improvement, we propose a list of recommendations for future studies in the field.
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| 15. |
- Gryska, Emilia, 1992, et al.
(author)
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Automatic brain lesion segmentation on standard MRIs of the human head: a scoping review protocol.
- 2019
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In: BMJ open. - : BMJ. - 2044-6055. ; 9:2
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Journal article (peer-reviewed)abstract
- Automatic brain lesion segmentation from medical images has great potential to support clinical decision making. Although numerous methods have been proposed, significant challenges must be addressed before they will become established in clinical and research practice. We aim to elucidate the state of the art, to provide a synopsis of competing approaches and identify contrasts between them.We present the background and study design of a scoping review for automatic brain lesion segmentation methods for conventional MRI according to the framework proposed by Arksey and O'Malley. We aim to identify common image processing steps as well as mathematical and computational theories implemented in these methods. We will aggregate the evidence on the efficacy and identify limitations of the approaches. Methods to be investigated work with standard MRI sequences from human patients examined for brain lesions, and are validated with quantitative measures against a trusted reference. PubMed, IEEE Xplore and Scopus will be searched using search phrases that will ensure an inclusive and unbiased overview. For matching records, titles and abstracts will be screened to ensure eligibility. Studies will be excluded if a full paper is not available or is not written in English, if non-standard MR sequences are used, if there is no quantitative validation, or if the method is not automatic. In the data charting phase, we will extract information about authors, publication details and study cohort. We expect to find information about preprocessing, segmentation and validation procedures. We will develop an analytical framework to collate, summarise and synthesise the data.Ethical approval for this study is not required since the information will be extracted from published studies. We will submit the review report to a peer-reviewed scientific journal and explore other venues for presenting the work.
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| 16. |
- Gryska, Emilia, 1992, et al.
(author)
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Deep learning for automatic brain tumour segmentation on MRI: evaluation of recommended reporting criteria via a reproduction and replication study.
- 2022
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In: BMJ open. - : BMJ. - 2044-6055. ; 12:7
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Journal article (peer-reviewed)abstract
- To determine the reproducibility and replicability of studies that develop and validate segmentation methods for brain tumours on MRI and that follow established reproducibility criteria; and to evaluate whether the reporting guidelines are sufficient.Two eligible validation studies of distinct deep learning (DL) methods were identified. We implemented the methods using published information and retraced the reported validation steps. We evaluated to what extent the description of the methods enabled reproduction of the results. We further attempted to replicate reported findings on a clinical set of images acquired at our institute consisting of high-grade and low-grade glioma (HGG, LGG), and meningioma (MNG) cases.We successfully reproduced one of the two tumour segmentation methods. Insufficient description of the preprocessing pipeline and our inability to replicate the pipeline resulted in failure to reproduce the second method. The replication of the first method showed promising results in terms of Dice similarity coefficient (DSC) and sensitivity (Sen) on HGG cases (DSC=0.77, Sen=0.88) and LGG cases (DSC=0.73, Sen=0.83), however, poorer performance was observed for MNG cases (DSC=0.61, Sen=0.71). Preprocessing errors were identified that contributed to low quantitative scores in some cases.Established reproducibility criteria do not sufficiently emphasise description of the preprocessing pipeline. Discrepancies in preprocessing as a result of insufficient reporting are likely to influence segmentation outcomes and hinder clinical utilisation. A detailed description of the whole processing chain, including preprocessing, is thus necessary to obtain stronger evidence of the generalisability of DL-based brain tumour segmentation methods and to facilitate translation of the methods into clinical practice.
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| 17. |
- Hellström, William, et al.
(author)
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Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants
- 2023
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 93:3, s. 666-674
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Journal article (peer-reviewed)abstract
- Background Growth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term. Material/methods Infants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)-1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age. Results In total, 49 infants (median [range] GA 25.4 [22.9-27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, beta = 0.90), white matter (p = 0.007, beta = 0.33), cortical gray matter (p = 0.002, beta = 0.43), deep gray matter (p = 0.008, beta = 0.05), and cerebellar (p = 0.006, beta = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors. Conclusions Endogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants. Impact High serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants. IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood. Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).
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| 18. |
- Holmberg, Mats, 1958, et al.
(author)
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A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease
- 2022
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:4, s. 1040-1052
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Journal article (peer-reviewed)abstract
- Context: Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels. Objective: This work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes. Methods: Sixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4±4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests. Results: Patients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3′-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes. Conclusion: Dynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.
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| 19. |
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| 20. |
- Holmberg, Mats, 1958, et al.
(author)
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Structural brain changes in hyperthyroid Graves' disease: protocol for an ongoing longitudinal, case-controlled study in Göteborg, Sweden-the CogThy project.
- 2019
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In: BMJ open. - : BMJ. - 2044-6055. ; 9:11
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Journal article (peer-reviewed)abstract
- Cognitive impairment and reduced well-being are common manifestations of Graves' disease (GD). These symptoms are not only prevalent during the active phase of the disease but also often prevail for a long time after hyperthyroidism is considered cured. The pathogenic mechanisms involved in these brain-derived symptoms are currently unknown. The overall aim of the CogThy study is to identify the mechanism behind cognitive impairment to be able to recognise GD patients at risk.The study is a longitudinal, single-centre, case-controlled study conducted in Göteborg, Sweden on premenopausal women with newly diagnosed GD. The subjects are examined: at referral, at inclusion and then every 3.25 months until 15 months. Examinations include: laboratory measurements; eye evaluation; neuropsychiatric and neuropsychological testing; structural MRI of the whole brain, orbits and medial temporal lobe structures; functional near-infrared spectroscopy of the cerebral prefrontal cortex and self-assessed quality of life questionnaires. The primary outcome measure is the change in medial temporal lobe structure volume. Secondary outcome measures include neuropsychological, neuropsychiatric, hormonal and autoantibody variables. The study opened for inclusion in September 2012 and close for inclusion in October 2019. It will provide novel information on the effect of GD on medial temporal lobe structures and cerebral cortex functionality as well as whether these changes are associated with cognitive and affective impairment, hormonal levels and/or autoantibody levels. It should lead to a broader understanding of the underlying pathogenesis and future treatment perspectives.The study has been reviewed and approved by the Regional Ethical Review Board in Göteborg, Sweden. The results will be actively disseminated through peer-reviewed journals, national and international conference presentations and among patient organisations after an appropriate embargo time.44321 at the public project database for research and development in Västra Götaland County, Sweden (https://www.researchweb.org/is/vgr/project/44321).
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