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- Rysz, S, et al.
(författare)
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COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2417-
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
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- Ouellette, R., et al.
(författare)
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Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosis
- 2020
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 87:5, s. 710-724
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T1/T2 relaxometry and proton density mapping in multiple sclerosis. Methods: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosis patients and 21 age/sex-matched healthy controls, with scan–rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up. Results: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosis patients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability. Interpretation: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination.
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| 4. |
- Ineichen, BV, et al.
(författare)
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Dilated Virchow-Robin Spaces are a Marker for Arterial Disease in Multiple Sclerosis
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Virchow-Robin spaces (VRS) have been associated with neurodegeneration and neuroinflammation. However, it remains uncertain to what degree non-dilated or dilated VRS reflect specific features of neuroinflammatory pathology. Thus, we aimed at investigating the clinical relevance of VRS as imaging biomarker in multiple sclerosis (MS) and to correlate VRS to their histopathologic signature. In a cohort study comprising 205 MS patients (including a validation cohort) and 30 control subjects, we assessed the association of non-dilated and dilated VRS to clinical and magnetic resonance imaging (MRI) out-comes. Brain blocks from 6 MS patients and 3 non-MS controls were histopathologically processed to correlate VRS to their tissue substrate. The count of dilated centrum semiovale VRS was associated with increased T1 and T2 lesion volumes. There was no systematic spatial colocalization of dilated VRS with MS lesions. At tissue level, VRS mostly corresponded to arteries and were not associated with MS pathological hallmarks. Interestingly, dilated VRS in MS were associated with signs of small vessel disease. Contrary to prior beliefs, these observations suggest that VRS in MS do not associate with accumulation of immune cells. But instead, these findings indicate vascular pathology as a driver and/or consequence of neuroinflammatory pathology for this imaging feature.
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| 9. |
- Mangeat, G., et al.
(författare)
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Machine Learning and Multiparametric Brain MRI to Differentiate Hereditary Diffuse Leukodystrophy with Spheroids from Multiple Sclerosis
- 2020
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Ingår i: Journal of Neuroimaging. - : Blackwell Publishing Inc.. - 1051-2284 .- 1552-6569. ; 30:5, s. 674-682
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and multiple sclerosis (MS) are demyelinating and neurodegenerative disorders that can be hard to distinguish clinically and radiologically. HDLS is a rare disorder compared to MS, which has led to occurrent misdiagnosis of HDLS as MS. That is problematic since their prognosis and treatment differ. Both disorders are investigated by MRI, which could help to identify patients with high probability of having HDLS, which could guide targeted genetic testing to confirm the HDLS diagnosis. METHODS: Here, we present a machine learning method based on quantitative MRI that can achieve a robust classification of HDLS versus MS. Four HDLS and 14 age-matched MS patients underwent a quantitative brain MRI protocol (synthetic MRI) at 3 Tesla (T) (scan time '7 minutes). We also performed a repeatability analysis of the predicting features to assess their generalizability by scanning a healthy control with five scan-rescans at 3T and 1.5T. RESULTS: Our predicting features were measured with an average confidence interval of 1.7% (P =.01), at 3T and 2.3% (P =.01) at 1.5T. The model gave a 100% correct classification of the cross-validation data when using 5-11 predicting features. When the maximum measurement noise was inserted in the model, the true positive rate of HDLS was 97.2%, while the true positive rate of MS was 99.6%. CONCLUSIONS: This study suggests that computer-assistance in combination with quantitative MRI may be helpful in aiding the challenging differential diagnosis of HDLS versus MS.
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| 10. |
- Mickeviciute, G. -C, et al.
(författare)
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Neuroimaging phenotypes of CSF1R-related leukoencephalopathy : Systematic review, meta-analysis, and imaging recommendations
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:3, s. 269-282
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Tidskriftsartikel (refereegranskat)abstract
- Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare but fatal microgliopathy. The diagnosis is often delayed due to multifaceted symptoms that can mimic several other neurological disorders. Imaging provides diagnostic clues that help identify cases. The objective of this study was to integrate the literature on neuroimaging phenotypes of CSF1R-related leukoencephalopathy. A systematic review and meta-analysis were performed for neuroimaging findings of CSF1R-related leukoencephalopathy via PubMed, Web of Science, and Embase on 25 August 2021. The search included cases with confirmed CSF1R mutations reported under the previous terms hereditary diffuse leukoencephalopathy with spheroids, pigmentary orthochromatic leukodystrophy, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. In 78 studies providing neuroimaging data, 195 cases were identified carrying CSF1R mutations in 14 exons and five introns. Women had a statistically significant earlier age of onset (p = 0.041, 40 vs 43 years). Mean delay between symptom onset and neuroimaging was 2.3 years. Main magnetic resonance imaging (MRI) findings were frontoparietal white matter lesions, callosal thinning, and foci of restricted diffusion. The hallmark computed tomography (CT) finding was white matter calcifications. Widespread cerebral hypometabolism and hypoperfusion were reported using positron emission tomography and single-photon emission computed tomography. In conclusion, CSF1R-related leukoencephalopathy is associated with progressive white matter lesions and brain atrophy that can resemble other neurodegenerative/-inflammatory disorders. However, long-lasting diffusion restriction and parenchymal calcifications are more specific findings that can aid the differential diagnosis. Native brain CT and brain MRI (with and without a contrast agent) are recommended with proposed protocols and pictorial examples are provided.
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| 11. |
- Nowosielski, Martha, et al.
(författare)
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Radiologic progression of glioblastoma under therapy : an exploratory analysis of AVAglio
- 2018
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20:4, s. 557-566
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Tidskriftsartikel (refereegranskat)abstract
- In this exploratory analysis of AVAglio, a randomized phase III clinical study that investigated the addition of bevacizumab (Bev) to radiotherapy/temozolomide in newly diagnosed glioblastoma, we aim to radiologically characterize glioblastoma on therapy until progression and investigate whether the type of radiologic progression differs between treatment arms and is related to survival and molecular data. Five progression types (PTs) were categorized using an adapted algorithm according to MRI contrast enhancement behavior in T1- and T2-weighted images in 621 patients (Bev, n = 299; placebo, n = 322). Frequencies of PTs (designated as classic T1, cT1 relapse, T2 diffuse, T2 circumscribed, and primary nonresponder), time to progression (PFS), and overall survival (OS) were assessed within each treatment arm and compared with molecular subtypes and O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status. PT frequencies differed between the Bev and placebo arms, except for "T2 diffuse" (12.4% and 7.1%, respectively). PTs showed differences in PFS and OS; with "T2 diffuse" being associated with longest survival. Complete disappearance of contrast enhancement during treatment ("cT1 relapse") showed longer survival than only partial contrast enhancement decrease ("classic T1"). "T2 diffuse" was more commonly MGMT hypermethylated. Only weak correlations to molecular subtypes from primary tissue were detected. Progression of glioblastoma under therapy can be characterized radiologically. These radiologic phenotypes are influenced by treatment and develop differently over time with differential outcomes. Complete resolution of contrast enhancement during treatment is a favorable factor for outcome.
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