| 1. |
- Gram, Magnus, et al.
(författare)
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Extracellular hemoglobin - mediator of inflammation and cell death in the choroid plexus following preterm intraventricular hemorrhage
- 2014
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intraventricular hemorrhage (IVH) with post-hemorrhagic ventricular dilatation (PHVD) is a major cause of neurodevelopmental impairment and mortality in preterm infants. The mechanisms leading to PHVD and brain damage remain largely unknown. The choroid plexus and the ependyma, which constitute an essential part of the blood-brain barrier (BBB), are the first structures to encounter the damaging effects of extravasated blood. The breakdown of the BBB is a critical upstream event leading to brain damage following IVH. In this study we investigated the impact of hemorrhage and hemoglobin (Hb) metabolites on the choroid plexus epithelium. Methods: Using a preterm rabbit pup model of IVH, the structural and functional integrity, cellular, inflammatory and oxidative response of the choroid plexus, at 24 and 72 hours following IVH + PHVD, were investigated. In order to further characterize cellular and molecular mechanisms, primary human choroid plexus epithelial cells were exposed to cerebrospinal fluid (CSF) from preterm infants with IVH as well as to Hb-metabolites. Finally, the blocking effects of the Hb-scavenger haptoglobin (Hp) were investigated both in vivo and in vitro. Results: Following IVH + PHVD, an up-regulation of mRNA for the receptor-related genes TLR-4, IL1R1, FAS, the transcription factor NF-kappa beta and for the pro-inflammatory and chemotactic effector molecules, IL-1 beta, TNF alpha, MCP-1, IL-8, and IL-6 was observed in the choroid plexus at 24 and 72 hours. This was associated with structural disintegration, caspase activation and cell death in the choroid plexus epithelium. In vitro characterization of choroid plexus epithelial cells, following exposure to hemorrhagic CSF and to the Hb-metabolites metHb and heme, displayed apoptotic and necrotic cell death and an up-regulation of receptor-related and inflammatory effector molecules similar to that observed in vivo following IVH + PHVD. Intraventricular injection of the Hb-scavenger Hp in vivo and co-incubation with Hp in vitro reversed or reduced the cellular activation, inflammatory response, structural damage and cell death. Conclusion: Hb-metabolites are important causal initiators of cell death following IVH and removal or scavenging of Hb-metabolites may present an efficient means to reduce the damage to the immature brain following IVH.
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| 2. |
- Gram, Magnus, et al.
(författare)
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Hemoglobin induces inflammation after preterm intraventricular hemorrhage by methemoglobin formation.
- 2013
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 10:Aug.,6
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral intraventricular hemorrhage (IVH) is a major cause of severe neurodevelopmental impairment in preterm infants. To date, no therapy is available that prevents infants from developing serious neurological disability following IVH. Thus, to develop treatment strategies for IVH, it is essential to characterize the initial sequence of molecular events that leads to brain damage. In this study, we investigated extracellular hemoglobin (Hb) as a causal initiator of inflammation in preterm IVH.
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| 3. |
- Romantsik, Olga, et al.
(författare)
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The heme and radical scavenger α1-microglobulin (A1M) confers early protection of the immature brain following preterm intraventricular hemorrhage
- 2019
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with cerebro-cerebellar damage in very preterm infants, leading to neurodevelopmental impairment. Penetration, from the intraventricular space, of extravasated red blood cells and extracellular hemoglobin (Hb), to the periventricular parenchyma and the cerebellum has been shown to be causal in the development of brain injury following GM-IVH. Furthermore, the damage has been described to be associated with the cytotoxic nature of extracellular Hb-metabolites. To date, there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. Mechanisms previously described to cause brain damage following GM-IVH, i.e., oxidative stress and Hb-metabolite toxicity, suggest that the free radical and heme scavenger α1-microglobulin (A1M) may constitute a potential neuroprotective intervention. Methods: Using a preterm rabbit pup model of IVH, where IVH was induced shortly after birth in pups delivered by cesarean section at E29 (3 days prior to term), we investigated the brain distribution of recombinant A1M (rA1M) following intracerebroventricular (i.c.v.) administration at 24 h post-IVH induction. Further, short-term functional protection of i.c.v.-administered human A1M (hA1M) following IVH in the preterm rabbit pup model was evaluated. Results: Following i.c.v. administration, rA1M was distributed in periventricular white matter regions, throughout the fore- and midbrain and extending to the cerebellum. The regional distribution of rA1M was accompanied by a high co-existence of positive staining for extracellular Hb. Administration of i.c.v.-injected hA1M was associated with decreased structural tissue and mitochondrial damage and with reduced mRNA expression for proinflammatory and inflammatory signaling-related genes induced by IVH in periventricular brain tissue. Conclusions: The results of this study indicate that rA1M/hA1M is a potential candidate for neuroprotective treatment following preterm IVH.
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| 4. |
- Sveinsdottir, Snjolaug, et al.
(författare)
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Altered Expression of Aquaporin 1 and 5 in the Choroid Plexus following Preterm Intraventricular Hemorrhage.
- 2014
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Ingår i: Developmental Neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 36:6, s. 542-551
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Tidskriftsartikel (refereegranskat)abstract
- Intraventricular hemorrhage (IVH) with posthemorrhagic ventricular dilatation (PHVD) is a common cause of hydrocephalus in infants. Dysregulation of cerebrospinal fluid (CSF) production by the choroid plexus may contribute to the development of PHVD. The aquaporins (AQPs), transmural water transporting proteins, are believed to contribute to CSF production. The aim of the study was to characterize the expression and localization of AQP1, 4 and 5 in the choroid plexus following preterm IVH. Using a preterm rabbit pup model, the mRNA expression, protein level and localization of AQP1, 4 and 5 were investigated in the choroid plexus at 24 and 72 h following IVH with PHVD. Further, AQP1, 4 and 5 expression were characterized in primary human plexus epithelial cells exposed to CSF from preterm human infants with IVH and to hemoglobin metabolites. IVH with PHVD in the immature brain caused a downregulation of AQP1 mRNA, the key AQP in CSF production, but an upregulation of AQP1 protein level with apical epithelial cell localization. Notably, AQP5 was expressed in the choroid plexus with upregulated mRNA expression and protein levels during PHVD with apical epithelial cell localization. Analysis of human choroid plexus epithelial cells in vitro, following exposure to posthemorrhagic CSF and to hemin, displayed results concordant with those observed in vivo, i.e. downregulation of AQP1 mRNA and upregulation of AQP5 mRNA expression. AQP4 was neither detectable in vivo nor in vitro. The changes observed in AQP1 and AQP5 expression in the choroid plexus suggest an adaptive response following IVH with possible functional implications for the development of PHVD. © 2014 S. Karger AG, Basel.
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| 5. |
- Ahlgren, Åsa Rydén, et al.
(författare)
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Response of the carotid artery longitudinal motion to submaximal physical activity in healthy humans-Marked changes already at low workload
- 2023
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- The longitudinal motion of the arterial wall, that is, the displacement of the arterial wall along the artery, parallel to blood flow, is still largely unexplored. The magnitude and nature of putative changes in longitudinal motion of the arterial wall in response to physical activity in humans remain unknown. The aim of this study was therefore to study the longitudinal motion of the carotid artery wall during physical activity in healthy humans. Using in-house developed non-invasive ultrasonic methods, the longitudinal motion of the intima-media complex and the diameter changes of the right common carotid artery (CCA) in 40 healthy volunteers (20 volunteers aged 22-35 years; 20 volunteers aged 55-68 years) were assessed at rest and during submaximal supine bicycle exercise. In a subset of the subjects (n = 18) also intramural shear strain were analyzed. The longitudinal motion of the intima-media complex underwent marked changes in response to physical activity, already at low workload; with most evident a marked increase of the first antegrade displacement (p < 0.001) in early systole. Likewise, the corresponding shear strain also increased significantly (p = 0.004). The increase in longitudinal motion showed significant correlation to increase in blood pressure, but not to blood flow velocity or wall shear stress. In conclusion, physical activity markedly influences the longitudinal motion of the carotid artery wall in healthy humans already at low load. A possible "cushioning" function as well as possible implications for the function of the vasa vasorum, endothelium, and smooth muscle cells and extracellular matrix of the media, are discussed.
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| 6. |
- Albinsson, John, et al.
(författare)
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A combination of parabolic and grid slope interpolation for 2D tissue displacement estimations
- 2017
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Ingår i: Medical & Biological Engineering & Computing. - : Springer Science and Business Media LLC. - 0140-0118 .- 1741-0444. ; 55:8, s. 1327-1338
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Tidskriftsartikel (refereegranskat)abstract
- Parabolic sub-sample interpolation for 2D block-matching motion estimation is computationally efficient. However, it is well known that the parabolic interpolation gives a biased motion estimate for displacements greater than |y.2| samples (y = 0, 1, …). Grid slope sub-sample interpolation is less biased, but it shows large variability for displacements close to y.0. We therefore propose to combine these sub-sample methods into one method (GS15PI) using a threshold to determine when to use which method. The proposed method was evaluated on simulated, phantom, and in vivo ultrasound cine loops and was compared to three sub-sample interpolation methods. On average, GS15PI reduced the absolute sub-sample estimation errors in the simulated and phantom cine loops by 14, 8, and 24% compared to sub-sample interpolation of the image, parabolic sub-sample interpolation, and grid slope sub-sample interpolation, respectively. The limited in vivo evaluation of estimations of the longitudinal movement of the common carotid artery using parabolic and grid slope sub-sample interpolation and GS15PI resulted in coefficient of variation (CV) values of 6.9, 7.5, and 6.8%, respectively. The proposed method is computationally efficient and has low bias and variance. The method is another step toward a fast and reliable method for clinical investigations of longitudinal movement of the arterial wall.
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| 7. |
- Albinsson, John, et al.
(författare)
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Combined use of Iteration, Quadratic Interpolation and an Extra Kernel for high-resolution 2D particle tracking : a first evaluation
- 2010
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Ingår i: 2010 ieee international ultrasonics symposium. - New York : IEEE Press. - 9781457703829 ; , s. 2000-2003
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Konferensbidrag (refereegranskat)abstract
- A novel 2D particle tracking method, that uses 1) iteration, 2) fast quadratic sub-pixel estimation (with only 28 multiplications per movement), and 3) a previous kernel, has been evaluated and compared with a full-search block-matching method. The comparison with high-frequency ultrasound data (40 MHz) was conducted in silico and on phantoms, which comprised lateral, diagonal, and ellipsoidal movement patterns with speeds of 0–15 mm/s. The mean tracking error was reduced by 68% in silico and 71% for the phantom measurements. When only sub-pixel estimation was used, the decrease in the tracking error was 61% in silico and 57% for the phantom measurements. As well as decreasing the tracking error, the new method only used 70% of the computational time needed by the full-search block-matching method. With a fast method having good tracking ability for high-frequency ultrasound data, we now have a tool to better investigate tissue movements and its dynamic functionality.
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| 8. |
- Albinsson, John, et al.
(författare)
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Improved tracking performance of lagrangian block-matching methodologies using block expansion in the time domain : In silico, phantom and invivo evaluations
- 2014
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier. - 0301-5629 .- 1879-291X. ; 40:10, s. 2508-2520
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate tracking performance when an extra reference block is added to a basic block-matching method, where the two reference blocks originate from two consecutive ultrasound frames. The use of an extra reference block was evaluated for two putative benefits: (i) an increase in tracking performance while maintaining the size of the reference blocks, evaluated using in silico and phantom cine loops; (ii) a reduction in the size of the reference blocks while maintaining the tracking performance, evaluated using in vivo cine loops of the common carotid artery where the longitudinal movement of the wall was estimated. The results indicated that tracking accuracy improved (mean - 48%, p<0.005 [in silico]; mean - 43%, p<0.01 [phantom]), and there was a reduction in size of the reference blocks while maintaining tracking performance (mean - 19%, p<0.01 [in vivo]). This novel method will facilitate further exploration of the longitudinal movement of the arterial wall. (C) 2014 World Federation for Ultrasound in Medicine & Biology.
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| 9. |
- Albinsson, John, et al.
(författare)
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Iterative 2D tissue motion tracking in ultrafast ultrasound imaging
- 2018
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Ingår i: Applied Sciences (Switzerland). - : MDPI AG. - 2076-3417. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- In order to study longitudinal movement and intramural shearing of the arterial wall with a Lagrangian viewpoint using ultrafast ultrasound imaging, a new tracking scheme is required. We propose the use of an iterative tracking scheme based on temporary down-sampling of the frame-rate, anteroposterior tracking, and unbiased block-matching using two kernels per position estimate. The tracking scheme was evaluated on phantom B-mode cine loops and considered both velocity and displacement for a range of down-sampling factors (k = 1-128) at the start of the iterations. The cine loops had a frame rate of 1300-1500 Hz and were beamformed using delay-and-sum. The evaluation on phantom showed that both the mean estimation errors and the standard deviations decreased with an increasing initial down-sampling factor, while they increased with an increased velocity or larger pitch. A limited in vivo study shows that the major pattern of movement corresponds well with state-of-the-art low frame rate motion estimates, indicating that the proposed tracking scheme could enable the study of longitudinal movement of the intima-media complex using ultrafast ultrasound imaging, and is one step towards estimating the propagation velocity of the longitudinal movement of the arterial wall.
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| 10. |
- Albinsson, John, et al.
(författare)
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Tracking Performance of Several Combinations of Common Evaluation Metrics and Sub-pixel Methods
- 2015
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Ingår i: 16th Nordic-Baltic Conference on Biomedical Engineering. - Cham : Springer International Publishing. - 1680-0737. ; 48, s. 13-16, s. 13-16
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Konferensbidrag (refereegranskat)abstract
- Motion estimation in a series of consecutive images is used in a variety of areas, e.g. video compression and investigation of tissue characteristics and organ function in medical images. Several methods exist both for estimating motions on a pixel level, e.g. block-matching in which two blocks in consecutive images are compared by an evaluation metric, and on a sub-pixel level. In this paper, we have evaluated the tracking performance of all combinations between three evaluation metrics and eight sub-pixel estimation methods. The tracking performance of a sub-pixel method varies depending on the evaluation metric used. This indicates that a reported tracking performance for a sub-pixel estimation method can be significantly different when combined with another evaluation metric. Also there is a large variation in the time needed for the motion estimations depending primarily on the sub-pixel method used but also on the evaluation metric.
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