| 1. |
- Hammaréus, Filip, et al.
(författare)
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Wall shear stress measured with 4D flow CMR correlates with biomarkers of inflammation and collagen synthesis in mild-to-moderate ascending aortic dilation and tricuspid aortic valves
- 2024
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Ingår i: European Heart Journal Cardiovascular Imaging. - : OXFORD UNIV PRESS. - 2047-2404 .- 2047-2412.
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Tidskriftsartikel (refereegranskat)abstract
- Aims Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic haemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR), and circulating biomarkers in aortic dilation. Methods and results Forty-seven cases with aortic dilation (diameter >= 40 mm) and 50 sex-and age-matched controls (diameter < 40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D flow CMR, and biomarkers including interleukin-6, collagen type I alpha 1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared with controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between haemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, P < 0.001), and maximum oscillatory shear index and collagen type I alpha 1 chain (r = -0.575, P < 0.001 in cases). Conclusion Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between haemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.
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| 2. |
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| 3. |
- Belcastro, Luigi, et al.
(författare)
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Beneath the skin: multi-frequency SFDI to detect thin layers of skin using light scattering
- 2023
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Ingår i: PHOTONICS IN DERMATOLOGY AND PLASTIC SURGERY 2023. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510658097 - 9781510658103
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Konferensbidrag (refereegranskat)abstract
- Wound healing assessment is usually performed visually by a trained physician. This type of evaluation is very subjective and returns limited information about the wound progression. In contrast, optical imaging techniques are non-invasive ways to quantitatively measure biological parameters. Spatial frequency domain imaging (SFDI) is an optical technique that exploits sinusoidal patterns of light with multiple spatial frequencies to measure the tissue frequency-specific response, from which the absorption and scattering coefficient of the material can be derived. While SFDI is based on models of light transport that assume the tissue is homogeneous, skin is composed by several layer with very different optical properties. An underutilized property of SFDI, however, is that the spatial frequency of the patterns determines the penetration depth of photons in the tissue. By using multiple ranges of spatial frequencies, we are developing a means to obtain morphological data from different volumes of tissue. This data is used to reconstruct the optical properties in depth, allowing us to differentiate between different thin layers of tissue. In this study we have developed a 2-layer optical phantom model with realistic optical properties and dimensions, that mimics the physiology of wound healing. We have used this physical model to validate the accuracy of this approach in obtaining layer specific optical properties.
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| 4. |
- Belcastro, Luigi, et al.
(författare)
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Handheld multispectral imager for quantitative skin assessment in low resource settings
- 2020
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Ingår i: Journal of Biomedical Optics. - : SPIE - The International Society for Optics and Photonics. - 1083-3668 .- 1560-2281. ; 25:8
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Tidskriftsartikel (refereegranskat)abstract
- Significance: Spatial frequency domain imaging (SFDI) is a quantitative imaging method to measure absorption and scattering of tissue, from which several chromophore concentrations (e.g., oxy-/deoxy-/meth-hemoglobin, melanin, and carotenoids) can be calculated. Employing a method to extract additional spectral bands from RGB components (that we named cross-channels), we designed a handheld SFDI device to account for these pigments, using low-cost, consumer-grade components for its implementation and characterization.Aim: With only three broad spectral bands (red, green, blue, or RGB), consumer-grade devices are often too limited. We present a methodology to increase the number of spectral bands in SFDI devices that use RGB components without hardware modification.Approach: We developed a compact low-cost RGB spectral imager using a color CMOS camera and LED-based mini projector. The components’ spectral properties were characterized and additional cross-channel bands were calculated. An alternative characterization procedure was also developed that makes use of low-cost equipment, and its results were compared. The device performance was evaluated by measurements on tissue-simulating optical phantoms and in-vivo tissue. The measurements were compared with another quantitative spectroscopy method: spatial frequency domain spectroscopy (SFDS).Results: Out of six possible cross-channel bands, two were evaluated to be suitable for our application and were fully characterized (520 ± 20 nm; 556 ± 18 nm). The other four cross-channels presented a too low signal-to-noise ratio for this implementation. In estimating the optical properties of optical phantoms, the SFDI data have a strong linear correlation with the SFDS data (R2 = 0.987, RMSE = 0.006 for μa, R2 = 0.994, RMSE = 0.078 for μs′).Conclusions: We extracted two additional spectral bands from a commercial RGB system at no cost. There was good agreement between our device and the research-grade SFDS system. The alternative characterization procedure we have presented allowed us to measure the spectral features of the system with an accuracy comparable to standard laboratory equipment.
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| 5. |
- Belcastro, Luigi, 1992-
(författare)
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Multi-frequency SFDI : depth-resolved scattering models of wound healing
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With optical techniques, we refer to a group of methods that use of light to perform measurements on matter. Spatial frequency domain imaging (SFDI) is an optical technique that operates in the spatial frequency domain. The technique involves using sinusoidal patterns of light for illumination, to study the reflectance of the target based on the spatial frequency (ƒx) of the patterns. By analysing the frequency-specific response with the aid of light transport models, we are able to determine the intrinsic optical properties of the material, such as the absorption coefficient (μa) and reduced scattering coefficient (μ's) In biological applications, these optical properties can be correlated to physiological structures and molecules, providing a useful tool for researchers and clinicians alike in understanding the phenomena happening in biological tissue. The objective of this work is to contribute to the development of SFDI, so that the technique can be used as a diagnostic tool to study the process of wound healing in tissue. In paper I we introduce the concept of cross-channels, given by the spectral overlap of the broadband LED light sources and the RGB camera sensors used in the SFDI instrumentation. The purpose of cross-channels is to improve the limited spectral information of RGB devices, allowing to detect a larger number of biological molecules. One of the biggest limitations of SFDI is that it works on the assumption of light diffusing through a homogeneous, thick layer of material. This assumption loses validity when we want to examine biological tissue, which comprises multiple thin layers with different properties. In paper IV we have developed a new method to process SFDI data that we call multi-frequency SFDI. In this new approach, we make use of the different penetration depth of the light patterns depending on their ƒx to obtain depth-sensitive measurements. We also defined a 2-layer model of light scattering that imitates the physiology of a wound, to calculate the partial volume contributions to μ's of the single layers. The 2-layer model is based on analytical formulations of light fluence. We compared the performance of three fluence models, one of which we have derived ourselves as an improvement over an existing formulation. In paper II we were able to test our new multi-frequency SFDI method by participating in an animal study on stem-cells based regenerative therapies. We contributed by performing SFDI measurements on healing wounds, in order to provide an additional evaluation metric that complemented the clinical evaluation and cell histology performed in the study. The analysis of the SFDI data at different ƒx highlighted different processes happening on the surface compared to the deeper tissue. In paper V we further refine the technique introduced in paper IV by developing an inverse solver algorithm to isolate the thickness of the thin layer and the layer-specific μ's. The reconstructed parameters were tested both on thin silicone optical phantoms and ex-vivo burn wounds treated with stem cells.
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| 6. |
- Belcastro, Luigi, et al.
(författare)
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Multi-frequency spatial frequency domain imaging: a depth-resolved optical scattering model to isolate scattering contrast in thin layers of skin
- 2024
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Ingår i: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 29:4
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Tidskriftsartikel (refereegranskat)abstract
- Significance: Current methods for wound healing assessment rely on visual inspection, which gives qualitative information. Optical methods allow for quantitative non-invasive measurements of optical properties relevant to wound healing. Aim: Spatial frequency domain imaging (SFDI) measures the absorption and reduced scattering coefficients of tissue. Typically, SFDI assumes homogeneous tissue; however, layered structures are present in skin. We evaluate a multi-frequency approach to process SFDI data that estimates depth-specific scattering over differing penetration depths. Approach: Multi-layer phantoms were manufactured to mimic wound healing scattering contrast in depth. An SFDI device imaged these phantoms and data were processed according to our multi-frequency approach. The depth sensitive data were then compared with a two-layer scattering model based on light fluence. Results: The measured scattering from the phantoms changed with spatial frequency as our two-layer model predicted. The performance of two delta-P1 models solutions for SFDI was consistently better than the standard diffusion approximation. Conclusions: We presented an approach to process SFDI data that returns depth-resolved scattering contrast. This method allows for the implementation of layered optical models that more accurately represent physiologic parameters in thin tissue structures as in wound healing. (c) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
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| 7. |
- Bergstrand, Sara, et al.
(författare)
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Association between cardiovascular risk profile and impaired microvascular function in a Swedish middle-aged cohort (the SCAPIS study)
- 2024
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Ingår i: European Journal of Preventive Cardiology. - : OXFORD UNIV PRESS. - 2047-4873 .- 2047-4881.
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden. Methods and results The study enrolled 3809 individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 > 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76-8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS > 0 and in those with both carotid plaques and CACS > 0, compared with individuals without subclinical atherosclerotic burdens (87.5 +/- 5.6% and 86.9 +/- 6.0%, vs. 88.6 +/- 5.8%, P < 0.01). Conclusion In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments.
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| 8. |
- Callaghan, Terry V., et al.
(författare)
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Ecosystem change and stability over multiple decades in the Swedish subarctic : complex processes and multiple drivers
- 2013
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 368:1624
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Tidskriftsartikel (refereegranskat)abstract
- The subarctic environment of northernmost Sweden has changed over the past century, particularly elements of climate and cryosphere. This paper presents a unique geo-referenced record of environmental and ecosystem observations from the area since 1913. Abiotic changes have been substantial. Vegetation changes include not only increases in growth and range extension but also counterintuitive decreases, and stability: all three possible responses. Changes in species composition within the major plant communities have ranged between almost no changes to almost a 50 per cent increase in the number of species. Changes in plant species abundance also vary with particularly large increases in trees and shrubs (up to 600%). There has been an increase in abundance of aspen and large changes in other plant communities responding to wetland area increases resulting from permafrost thaw. Populations of herbivores have responded to varying management practices and climate regimes, particularly changing snow conditions. While it is difficult to generalize and scale-up the site-specific changes in ecosystems, this very site-specificity, combined with projections of change, is of immediate relevance to local stakeholders who need to adapt to new opportunities and to respond to challenges. Furthermore, the relatively small area and its unique datasets are a microcosm of the complexity of Arctic landscapes in transition that remains to be documented.
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| 9. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 10. |
- Fernlund, Eva, et al.
(författare)
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Hereditary hypertrophic cardiomyopathy in children and young adults—The value of reevaluating and expanding gene panel analyses
- 2020
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Sudden cardiac death (SCD) and early onset cardiomyopathy (CM) in the young will always lead to suspicion of an underlying genetic disorder. Incited by the rapid advances in genetic testing for disease we have revisited families, which previously tested “gene-negative” for familial predominantly pediatric CM, in hopes of finding a causative gene variant. Methods: 10 different families with non-syndromic pediatric CM or hypertrophic cardiomyopathy (HCM) with severe disease progression and/or heredity for HCM/CM related SCD with “gene-negative” results were included. The index patient underwent genetic testing with a recently updated gene panel for CM and SCD. In case of failure to detect a pathogenic variant in a relevant gene, the index patient and both parents underwent clinical (i.e., partial) exome sequencing (trio-exome) in order to catch pathogenic variants linked to the disease in genes that were not included in the CM panel. Results: The mean age at clinical presentation of the 10 index cases was 12.5 years (boys 13.4 years, n = 8; girls 9 years, n = 2) and the family history burden was 33 HCM/CM cases including 9 HCM-related SCD and one heart transplantation. In 5 (50%) families we identified a genetic variant classified as pathogenic or likely pathogenic, in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria, in MYH7 (n = 2), RBM20, ALPK3, and PGM1, respectively, and genetic variants of unknown significance (VUS) segregating with the disease in an additional 3 (30%) families, in MYBPC3, ABCC9, and FLNC, respectively. Conclusion: Our results show the importance of renewed thorough clinical assessment and the necessity to challenge previous genetic test results with more comprehensive updated gene panels or exome sequencing if the initial test failed to identify a causative gene for early onset CM or SCD in children. In pediatric cardiomyopathy cases when the gene panel still fails to detect a causative variant, a trio exome sequencing strategy might resolve some unexplained cases, especially if a multisystemic condition is clinically missed.
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