| 1. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
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| 2. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.
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| 3. |
- Bustamante, Mariana, et al.
(författare)
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Atlas-based analysis of 4D flow CMR: Automated vessel segmentation and flow quantification
- 2015
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Ingår i: Journal of Cardiovascular Magnetic Resonance. - : BIOMED CENTRAL LTD. - 1097-6647 .- 1532-429X. ; 17:87
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Tidskriftsartikel (refereegranskat)abstract
- Background: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume. However, analysis of these datasets can be demanding. The aim of this study is to develop and evaluate a fully automatic method for segmentation and analysis of 4D flow CMR data of the great thoracic vessels. Methods: The proposed method utilizes atlas-based segmentation to segment the great thoracic vessels in systole, and registration between different time frames of the cardiac cycle in order to segment these vessels over time. Additionally, net flow volumes are calculated automatically at locations of interest. The method was applied on 4D flow CMR datasets obtained from 11 healthy volunteers and 10 patients with heart failure. Evaluation of the method was performed visually, and by comparison of net flow volumes in the ascending aorta obtained automatically (using the proposed method), and semi-automatically. Further evaluation was done by comparison of net flow volumes obtained automatically at different locations in the aorta, pulmonary artery, and caval veins. Results: Visual evaluation of the generated segmentations resulted in good outcomes for all the major vessels in all but one dataset. The comparison between automatically and semi-automatically obtained net flow volumes in the ascending aorta resulted in very high correlation (r(2) = 0.926). Moreover, comparison of the net flow volumes obtained automatically in other vessel locations also produced high correlations where expected: pulmonary trunk vs. proximal ascending aorta (r(2) = 0.955), pulmonary trunk vs. pulmonary branches (r(2) = 0.808), and pulmonary trunk vs. caval veins (r(2) = 0.906). Conclusions: The proposed method allows for automatic analysis of 4D flow CMR data, including vessel segmentation, assessment of flow volumes at locations of interest, and 4D flow visualization. This constitutes an important step towards facilitating the clinical utility of 4D flow CMR.
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| 4. |
- Cibis, Merih, et al.
(författare)
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Creating Hemodynamic Atlases of Cardiac 4D Flow MRI
- 2017
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Ingår i: Journal of Magnetic Resonance Imaging. - : WILEY. - 1053-1807 .- 1522-2586. ; 46:5, s. 1389-1399
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Hemodynamic atlases can add to the pathophysiological understanding of cardiac diseases. This study proposes a method to create hemodynamic atlases using 4D Flow magnetic resonance imaging (MRI). The method is demonstrated for kinetic energy (KE) and helicity density (Hd). Materials and Methods: Thirteen healthy subjects underwent 4D Flow MRI at 3T. Phase-contrast magnetic resonance cardioangiographies (PC-MRCAs) and an average heart were created and segmented. The PC-MRCAs, KE, and Hd were nonrigidly registered to the average heart to create atlases. The method was compared with 1) rigid, 2) affine registration of the PC-MRCAs, and 3) affine registration of segmentations. The peak and mean KE and Hd before and after registration were calculated to evaluate interpolation error due to nonrigid registration. Results: The segmentations deformed using nonrigid registration overlapped (median: 92.3%) more than rigid (23.1%, P amp;lt; 0.001), and affine registration of PC-MRCAs (38.5%, P amp;lt; 0.001) and affine registration of segmentations (61.5%, P amp;lt; 0.001). The peak KE was 4.9 mJ using the proposed method and affine registration of segmentations (P50.91), 3.5 mJ using rigid registration (P amp;lt; 0.001), and 4.2 mJ using affine registration of the PC-MRCAs (P amp;lt; 0.001). The mean KE was 1.1 mJ using the proposed method, 0.8 mJ using rigid registration (P amp;lt; 0.001), 0.9 mJ using affine registration of the PC-MRCAs (P amp;lt; 0.001), and 1.0 mJ using affine registration of segmentations (P50.028). The interpolation error was 5.262.6% at mid-systole, 2.863.8% at early diastole for peak KE; 9.669.3% at mid-systole, 4.064.6% at early diastole, and 4.964.6% at late diastole for peak Hd. The mean KE and Hd were not affected by interpolation. Conclusion: Hemodynamic atlases can be obtained with minimal user interaction using nonrigid registration of 4D Flow MRI. Level of Evidence: 2 Technical Efficacy: Stage 1
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| 5. |
- Eriksson, Alexander, et al.
(författare)
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Virtual factory layouts from 3D laser scanning – A novel framework to define solid model requirements
- 2018
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Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 76, s. 36-41
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Konferensbidrag (refereegranskat)abstract
- In a world with increasing customer demands, manufacturing companies must develop and produce products more rapidly and adapt their production systems offline, to not disturb the ongoing processes. This creates a demand of using digital production development so that development can be performed in parallel with production. Virtual factory layouts (VFLs) are essential for companies in order to plan their factory layout and evaluate production scenarios. However, requirements for a VFL depends heavily on its purpose. For example, the requirements on a model for offline programming of robots are different from those on a model used to determine buffer locations. There is currently a lack of clear guidelines for how developed a VFL should be to fulfil said requirements, which contributes to unnecessary modelling time and variation in delivery quality. This paper aims to put the actual demands and requirements of a VFL in focus. By adapting a Level of Development-framework for establishment of Building Information Models (BIMs) and connecting it to the purpose of VFLs, development of a framework for detail and functionality level of VFLs is enabled. Such a purpose-oriented framework will help to define delivery packages suited for different circumstances, which will provide the modeler with knowledge of how much detail and functionality a specific model should contain. The increased clarity provided by the developed framework results in a clearer connection between expected result and actual output from a custom VFL project. Also, by connecting model properties or development to the model-purpose, the framework brings clarity and structure to a currently vague field. This provides means for a more efficient and accurate use of VFLs, which will support the rapid development of production facilities.
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| 6. |
- Eriksson, Jonatan, et al.
(författare)
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Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.
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| 7. |
- Eriksson, Jonatan, et al.
(författare)
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Merging clinical chemistry biomarker data with a COPD database - building a clinical infrastructure for proteomic studies
- 2017
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Ingår i: Proteome Science. - : Springer Science and Business Media LLC. - 1477-5956. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data from biological samples and medical evaluations plays an essential part in clinical decision making. This data is equally important in clinical studies and it is critical to have an infrastructure that ensures that its quality is preserved throughout its entire lifetime. We are running a 5-year longitudinal clinical study, KOL-Örestad, with the objective to identify new COPD (Chronic Obstructive Pulmonary Disease) biomarkers in blood. In the study, clinical data and blood samples are collected from both private and public health-care institutions and stored at our research center in databases and biobanks, respectively. The blood is analyzed by Mass Spectrometry and the results from this analysis then linked to the clinical data. Method: We built an infrastructure that allows us to efficiently collect and analyze the data. We chose to use REDCap as the EDC (Electronic Data Capture) tool for the study due to its short setup-time, ease of use, and flexibility. REDCap allows users to easily design data collection modules based on existing templates. In addition, it provides two functions that allow users to import batches of data; through a web API (Application Programming Interface) as well as by uploading CSV-files (Comma Separated Values). Results: We created a software, DART (Data Rapid Translation), that translates our biomarker data into a format that fits REDCap's CSV-templates. In addition, DART is configurable to work with many other data formats as well. We use DART to import our clinical chemistry data to the REDCap database. Conclusion: We have shown that a powerful and internationally adopted EDC tool such as REDCap can be extended so that it can be used efficiently in proteomic studies. In our study, we accomplish this by using DART to translate our clinical chemistry data to a format that fits the templates of REDCap.
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| 8. |
- Eriksson, Jonatan O., et al.
(författare)
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Clusterwise Peak Detection and Filtering Based on Spatial Distribution to Efficiently Mine Mass Spectrometry Imaging Data
- 2019
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; , s. 11888-11896
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Tidskriftsartikel (refereegranskat)abstract
- Mass spectrometry imaging (MSI) has the potential to reveal the localization of thousands of biomolecules such as metabolites and lipids in tissue sections. The increase in both mass and spatial resolution of today's instruments brings on considerable challenges in terms of data processing; accurately extracting meaningful signals from the large data sets generated by MSI without losing information that could be clinically relevant is one of the most fundamental tasks of analysis software. Ion images of the biomolecules are generated by visualizing their intensities in 2-D space using mass spectra collected across the tissue section. The intensities are often calculated by summing each compound's signal between predefined sets of borders (bins) in the m/z dimension. This approach, however, can result in mixed signals from different compounds in the same bin or splitting the signal from one compound between two adjacent bins, leading to low quality ion images. To remedy this problem, we propose a novel data processing approach. Our approach consists of a sensitive peak detection method able to discover both faint and localized signals by utilizing clusterwise kernel density estimates (KDEs) of peak distributions. We show that our method can recall more ground-truth molecules, molecule fragments, and isotopes than existing methods based on binning. Furthermore, it automatically detects previously reported molecular ions of lipids, including those close in m/z, in an experimental data set.
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| 9. |
- Eriksson, Jonatan, et al.
(författare)
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Spatial Heterogeneity of Four-Dimensional Relative Pressure Fields in the Human Left Ventricle
- 2015
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Ingår i: Magnetic Resonance in Medicine. - : WILEY-BLACKWELL. - 0740-3194 .- 1522-2594. ; 74:6, s. 1716-1725
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess the spatial heterogeneity of the four-dimensional (4D) relative pressure fields in the healthy human left ventricle (LV) and provide reference data for normal LV relative pressure. Methods: Twelve healthy subjects underwent a cardiac MRI examination where 4D flow and morphological data were acquired. The latter data were segmented and used to define the borders of the LV for computation of relative pressure fields using the pressure Poisson equation. The LV lumen was divided into 17 pie-shaped segments. Results: In the normal left ventricle, the relative pressure in the apical segments was significantly higher relative to the basal segments (P < 0.0005) along both the anteroseptal and inferolateral sides after the peaks of early (E-wave) and late (A-wave) diastolic filling. The basal anteroseptal segment showed significantly lower median pressure than the opposite basal inferolateral segment during both E-wave (P < 0.0005) and A-wave (P = 0.0024). Conclusion: Relative pressure in the left ventricle is heterogeneous. During diastole, the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences were also found in the short axis direction and may reflect important aspects of atrioventricular coupling. Additionally, this study provides reference data on LV pressure dynamics for a group of healthy subjects. (C) 2014 Wiley Periodicals, Inc.
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| 10. |
- Fredriksson, Alexandru Grigorescu, et al.
(författare)
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4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.
- 2016
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley-Blackwell. - 1053-1807 .- 1522-2586. ; 43:3, s. 558-565
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups.CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.
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