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| 2. |
- Engblom, Henrik, et al.
(författare)
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A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance : Experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data
- 2016
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Ingår i: Journal of Cardiovascular Magnetic Resonance. - : Springer Science and Business Media LLC. - 1097-6647 .- 1532-429X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data. Methods: The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images). Results: Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49). Conclusions: The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images. Clinical trial registration: CHILL-MI: NCT01379261. MITOCARE: NCT01374321.
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| 3. |
- Engblom, Henrik, et al.
(författare)
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Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index, Infarct Size, or Biochemical Markers as Endpoint.
- 2016
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:3, s. 002708-002708
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac magnetic resonance (CMR) can quantify myocardial infarct (MI) size and myocardium at risk (MaR), enabling assessment of myocardial salvage index (MSI). We assessed how MSI impacts the number of patients needed to reach statistical power in relation to MI size alone and levels of biochemical markers in clinical cardioprotection trials and how scan day affect sample size.
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| 4. |
- Khuyagbaatar, J., et al.
(författare)
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New Short-Lived Isotope 221U and the Mass Surface Near N=126
- 2015
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Ingår i: Physical Review Letters. - 1079-7114. ; 115:24
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Tidskriftsartikel (refereegranskat)abstract
- Two short-lived isotopes 221U and 222U were produced as evaporation residues in the fusion reaction 50Ti+176Yb at the gas-filled recoil separator TASCA. An α decay with an energy of Eα=9.31(5) MeV and half-life T1/2=4.7(7) μs was attributed to 222U. The new isotope 221U was identified in α-decay chains starting with Eα=9.71(5) MeV and T1/2=0.66(14) μs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.
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| 5. |
- Niazi, Yasmeen, et al.
(författare)
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Genetic variation associated with chromosomal aberration frequency : A genome-wide association study
- 2018
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280.
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10−5 in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. 2018 Wiley Periodicals, Inc.
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| 6. |
- Nordlund, David, et al.
(författare)
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Extent of myocardium at risk for left anterior descending artery, right coronary artery, and left circumflex artery occlusion depicted by contrast-enhanced steady state free precession and T2-weighted short tau inversion recovery magnetic resonance imaging
- 2016
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Ingår i: Circulation Cardiovascular Imaging. - 1941-9651. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Background - Contrast-enhanced steady state free precession (CE-SSFP) and T2-weighted short tau inversion recovery (T2-STIR) have been clinically validated to estimate myocardium at risk (MaR) by cardiovascular magnetic resonance while using myocardial perfusion single-photon emission computed tomography as reference standard. Myocardial perfusion single-photon emission computed tomography has been used to describe the coronary perfusion territories during myocardial ischemia. Compared with myocardial perfusion single-photon emission computed tomography, cardiovascular magnetic resonance offers superior image quality and practical advantages. Therefore, the aim was to describe the main coronary perfusion territories using CE-SSFP and T2-STIR cardiovascular magnetic resonance data in patients after acute ST-segment-elevation myocardial infarction. Methods and Results - CE-SSFP and T2-STIR data from 2 recent multicenter trials, CHILL-MI and MITOCARE (n=215), were used to assess MaR. Angiography was used to determine culprit vessel. Of 215 patients, 39% had left anterior descending artery occlusion, 49% had right coronary artery occlusion, and 12% had left circumflex artery occlusion. Mean extent of MaR using CE-SSFP was 44±10% for left anterior descending artery, 31±7% for right coronary artery, and 30±9% for left circumflex artery. Using T2-STIR, MaR was 44±9% for left anterior descending artery, 30±8% for right coronary artery, and 30±12% for left circumflex artery. MaR was visualized in polar plots, and expected overlap was found between right coronary artery and left circumflex artery. Detailed regional data are presented for use in software algorithms as a priori information on the extent of MaR. Conclusions - For the first time, cardiovascular magnetic resonance has been used to show the main coronary perfusion territories using CE-SSFP and T2-STIR. The good agreement between CE-SSFP and T2-STIR from this study and myocardial perfusion single-photon emission computed tomography from previous studies indicates that these 3 methods depict MaR accurately in individual patients and at a group level. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01379261 and NCT01374321.
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| 7. |
- Nordlund, David, et al.
(författare)
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Multi-vendor, multicentre comparison of contrast-enhanced SSFP and T2-STIR CMR for determining myocardium at risk in ST-elevation myocardial infarction
- 2016
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Ingår i: European Heart Journal-Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 17:7, s. 744-753
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2-short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2-STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi-vendor settings.METHODS AND RESULTS: A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1-8 days. These patients participated in the MITOCARE or CHILL-MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 ± 6%, P = 0.96, r(2) = 0.71, P < 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44).CONCLUSION: In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials.
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| 8. |
- Orrem, Hilde L., et al.
(författare)
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Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction
- 2018
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 268, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- Background: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1 alpha and IL-1 beta are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. Methods: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n=65). Results: IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. Conclusion: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI. (C 18 Elsevier B.V. All rights reserved.
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| 10. |
- Thomsen, Hauke, et al.
(författare)
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Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)
- 2017
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441. ; 99:1, s. 70-79
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM).METHODS: We conducted the first genomewide association study (GWAS) on MGUS on 243 German cases with a replication on 294 Czech cases. Identified loci were further analyzed in 1508 German MM patients. New MM loci recently reported in a meta-analysis were also tested in the MGUS GWAS.RESULTS: In GWAS, we identified 10 loci contributing to development of MGUS at P-value threshold of 10-5 . The Czech cohort gave support for two associations (6q26, rs6933936; 7p21.3 rs10251201). In GWAS, rs974120 (8p23.2) reached genomewide significance (P=2.94×10-9 ), with a nominal significance in MM. The locus of rs974120 shows marks of transcriptional activity in leukemia according to ENCODE data. rs10251201 (7p21.3), rs9318227 (13q22.1), and rs10405859 (19q13.32) were associated with markers related to leukemogenesis and immune and inflammatory responses. Two newly identified candidate loci for MM, rs1948915 (8q24.21) and rs8058578 (16p11.2), were nominally associated with MGUS.CONCLUSIONS: These data allow a cautious first proposal for a germ line architecture of MGUS with links to leukemia and autoimmune conditions, the latter agreeing with a family study showing clustering of MGUS with autoimmune diseases.
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