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Kihlberg, Johan, Medicine doktorORCID iD iconorcid.org/0000-0003-3124-8044
Publications (10 of 32) Show all publications
Kihlberg, J. (2017). Magnetic Resonance Imaging of Myocardial Deformation and Scarring in Coronary Artery Disease.. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Magnetic Resonance Imaging of Myocardial Deformation and Scarring in Coronary Artery Disease.
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Although improved treatments have reduced the rates of acute complications from myocardial infarction, sequelae such as heart failure and sudden death threaten the future wellbeing of those patients. Secondary prevention after myocardial infarction is related to cardiovascular risk factors and the effect of the infarct on left ventricular function. Cardiovascular magnetic resonance imaging (CMR) is necessary to determine the size of the infarct scar and can with great precision determine left ventricular volumes, left ventricular ejection fraction, and deformation (strain and torsion). The purpose of this thesis was to improve on CMR methods to facilitate image acquisition and post processing in patients with high risk of coronary artery disease (CAD).

In Paper 1, a three-dimensional phase-sensitive inversion-recovery (3D PSIR) sequence was modified to measure T1 during a single breath hold. The measured T1 values were used to extrapolate a map of T1 relaxation, which avoided the time-consuming manual determination of the inversion time. The data collection consisted of phantom experiments, Monte Carlo simulations of the effect of various heart rates, and clinical investigation of 18 patients with myocardial infarction. Scar images created with the modified sequence were compared to those created with the standard sequence. The 3D PSIR sequence was able to measure T1 relaxation with a high accuracy up to 800 ms, which is in the suitable range for scar imaging. Simulated arrhythmias showed that the method was robust and able to tolerate some variation in heart rate. The modified sequence provides measurements of inversion time that can be used to facilitate standard scar imaging or to reconstruct synthetic scar images. Images of infarct scar obtained with the 3D PSIR sequence bore striking similarity to images obtained with the standard sequence.

In Paper 2, 125 patients with high risk of CAD were investigated using the displacement encoding with stimulated echoes (DENSE) sequence. Image segments with infarct scar area >50% (transmurality) could be identified with a sensitivity of 95% and a specificity of 80% based on circumferential strain calculated from the DENSE measurements. The DENSE sequence was also applied in other directions, but its sensitivity and specificity to detect scar was lower than when used for circumferential strain.

In Paper 3, 90 patients with high risk of CAD were examined by DENSE, tagging with harmonic phase (HARP) imaging and cine imaging with feature tracking (FT), to detect cardiac abnormalities as manifested in end-systolic circumferential strain. Circumferential strain calculated with DENSE had higher sensitivity and specificity than the competing methods to detect infarction with transmurality >50%. Global circumferential strain measured by DENSE correlated better with global parameters such as left ventricular ejection fraction, myocardial wall mass, left ventricular end-diastolic and end-systolic volume; than strain measured by FT or HARP.

In Paper 4, myocardial torsion was investigated using DENSE, HARP, and FT in 48 patients with high risk of CAD. Torsion measured by each of the three methods was correlated with other global measures such as left ventricular ejection fraction, left ventricular mass, and left ventricular end-diastolic and end-systolic volumes. The torsion measurements obtained with DENSE had a stronger relationship with left ventricular ejection fraction, left ventricular mass, and volumes than those obtained with HARP or FT.

DENSE was superior to the other methods for strain and torsion measurement and can be used to describe myocardial deformation quantitatively and objectively.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. p. 61
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1595
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-143028 (URN)10.3384/diss.diva-143028 (DOI)9789176854310 (ISBN)
Public defence
2017-12-07, Berzeliussalen, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2017-11-15Bibliographically approved
Andersson, C., Kihlberg, J., Ebbers, T., Lindström, L., Carlhäll, C. & Engvall, J. (2016). Phase-contrast MRI volume flow - a comparison of breath held and navigator based acquisitions. BMC Medical Imaging, 16(26)
Open this publication in new window or tab >>Phase-contrast MRI volume flow - a comparison of breath held and navigator based acquisitions
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2016 (English)In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 16, no 26Article in journal (Refereed) Published
Abstract [en]

Background: Magnetic Resonance Imaging (MRI) 2D phase-contrast flow measurement has been regarded as the gold standard in blood flow measurements and can be performed with free breathing or breath held techniques. We hypothesized that the accuracy of flow measurements obtained with segmented phase-contrast during breath holding, and in particular higher number of k-space segments, would be non-inferior compared to navigator phase-contrast. Volumes obtained from anatomic segmentation of cine MRI and Doppler echocardiography were used for additional reference. Methods: Forty patients, five women and 35 men, mean age 65 years (range 53-80), were randomly selected and consented to the study. All underwent EKG-gated cardiac MRI including breath hold cine, navigator based free-breathing phase-contrast MRI and breath hold phase-contrast MRI using k-space segmentation factors 3 and 5, as well as transthoracic echocardiography within 2 days. Results: In navigator based free-breathing phase-contrast flow, mean stroke volume and cardiac output were 79.7 +/- 17.1 ml and 5071 +/- 1192 ml/min, respectively. The duration of the acquisition was 50 +/- 6 s. With k-space segmentation factor 3, the corresponding values were 77.7 ml +/- 17.5 ml and 4979 +/- 1211 ml/min (p = 0.15 vs navigator). The duration of the breath hold was 17 +/- 2 s. K-space segmentation factor 5 gave mean stroke volume 77.9 +/- 16.4 ml, cardiac output 5142 +/- 1197 ml/min (p = 0.33 vs navigator), and breath hold time 11 +/- 1 s. Anatomical segmentation of cine gave mean stroke volume and cardiac output 91.2 +/- 20.8 ml and 5963 +/- 1452 ml/min, respectively. Echocardiography was reliable in 20 of the 40 patients. The mean diameter of the left ventricular outflow tract was 20.7 +/- 1.5 mm, stroke volume 78.3 ml +/- 15.2 ml and cardiac output 5164 +/- 1249 ml/min. Conclusions: In forty consecutive patients with coronary heart disease, breath holding and segmented k-space sampling techniques for phase-contrast flow produced stroke volumes and cardiac outputs similar to those obtained with free-breathing navigator based phase-contrast MRI, using less time. The values obtained agreed fairly well with Doppler echocardiography while there was a larger difference when compared with anatomical volume determinations using SSFP (steady state free precession) cine MRI.

Place, publisher, year, edition, pages
BioMed Central, 2016
Keywords
Phase-contrast flow; Magnetic resonance imaging; Segmentation; 2D Doppler echocardiography
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127432 (URN)10.1186/s12880-016-0128-x (DOI)000372901200001 ()27021353 (PubMedID)
Note

Funding Agencies|Swedish Heart and Lung Foundation [20120449, 20140398]; Region of Ostergotland [281281]; European Union FP 7 [223615]; Medical Research Council of Southeast Sweden [88731, 157921]

Available from: 2016-05-01 Created: 2016-04-26 Last updated: 2018-03-20Bibliographically approved
Kihlberg, J., Haraldsson, H., Sigfridsson, A., Ebbers, T. & Engvall, J. (2015). Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments. Journal of Cardiovascular Magnetic Resonance, 17, Article ID 50.
Open this publication in new window or tab >>Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments
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2015 (English)In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, article id 50Article in journal (Refereed) Published
Abstract [en]

Background

We hypothesised that myocardial deformation determined with magnetic resonance imaging (MRI) will detect myocardial scar.

Methods

Displacement Encoding with Stimulated Echoes (DENSE) was used to calculate left ventricular strain in 125 patients (29 women and 96 men) with suspected coronary artery disease. The patients also underwent cine imaging and late gadolinium enhancement. 57 patients had a scar area >1 % in at least one segment, 23 were considered free from coronary artery disease (control group) and 45 had pathological findings but no scar (mixed group). Peak strain was calculated in eight combinations: radial and circumferential strain in transmural, subendocardial and epicardial layers derived from short axis acquisition, and transmural longitudinal and radial strain derived from long axis acquisitions. In addition, the difference between strain in affected segments and reference segments, “differential strain”, from the control group was analysed.

Results

In receiver-operator-characteristic analysis for the detection of 50 % transmurality, circumferential strain performed best with area-under-curve (AUC) of 0.94. Using a cut-off value of -17 %, sensitivity was 95 % at a specificity of 80 %. AUC did not further improve with differential strain. There were significant differences between the control group and global strain circumferential direction (-17 % versus -12 %) and in the longitudinal direction (-13 % versus -10 %). Interobserver and scan-rescan reproducibility was high with an intraclass correlation coefficient (ICC) >0.93.

Conclusions

DENSE-derived circumferential strain may be used for the detection of myocardial segments with >50 % scar area. The repeatability of strain is satisfactory. DENSE-derived global strain agrees with other global measures of left ventricular ejection fraction.

Place, publisher, year, edition, pages
BioMed Central, 2015
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-119846 (URN)10.1186/s12968-015-0155-8 (DOI)000356652000001 ()26104510 (PubMedID)
Available from: 2015-06-26 Created: 2015-06-26 Last updated: 2017-12-04
Forsgren, M., Norén, B., Kihlberg, J., Dahlqvist Leinhard, O., Kechagias, S. & Lundberg, P. (2015). Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences. European Journal of Radiology Open, 2, 66-70
Open this publication in new window or tab >>Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences
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2015 (English)In: European Journal of Radiology Open, E-ISSN 2352-0477, Vol. 2, p. 66-70Article in journal (Refereed) Published
Abstract [en]

Purpose

Continuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable.

Materials and methods

Seven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist.

Results

Stiffness correlated well with the elasticity, R2 = 0.96 (P < 0.001; slope = 1.08, intercept = 0.61 kPa), as well as with ‘Gabs,ElasticR2 = 0.96 (P < 0.001; slope = 0.95, intercept = 0.28 kPa).

Conclusion

This pilot study shows that different MRE methods can produce comparable measurements of the viscoelastic properties of the liver. The existence of such comparable measurements is important, both from a clinical as well as a research perspective, since it allows for equipment-independent monitoring of disease progression.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Liver; Rheology; Elastography; Fibrosis; MRE; MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-119848 (URN)10.1016/j.ejro.2015.04.001 (DOI)
Available from: 2015-06-26 Created: 2015-06-26 Last updated: 2019-06-14Bibliographically approved
Forsgren, M., Norén, B., Kihlberg, J., Dahlqvist Leinhard, O., Kechagias, S. & Lundberg, P. (2014). Comparing 2D and 3D Magnetic Resonance Elastography Techniques in a Clinical Setting: Initial Experiences. In: : . Paper presented at ISMRM 2014, International Society for Magnetic Resonance in Medicine, 10-16 May 2014, Milan, Italy.
Open this publication in new window or tab >>Comparing 2D and 3D Magnetic Resonance Elastography Techniques in a Clinical Setting: Initial Experiences
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2014 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Purpose: It has been shown that liver fibrosis, and even cirrhosis, may be reversible in humans. For this reason there is a great need for the imminent introduction of non-invasive and clinically useful methods in order to monitor fibrosis in patients [1, 2]. A body of evidence points to the fact that MRE is a highly useful candidate towards this end [3]. However, before using such techniques more widely, it is important to verify that comparable physical measures are provided by alternative and clinically relevant MRE approaches. The aim of this pilot study was to compare 2D and 3D MRE, also known as MR Rheology, using a commercially available 2D system, with an acoustic transducer, and 3D MRE research system, with an electromagnetic transducer, with respect to liver stiffness and elasticity in patients with diffuse or suspected diffuse liver disease. Materials and Methods: Seven patients, referred to our hospital for evaluation of elevated serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) levels but without signs of cirrhosis on physical examination, were recruited from a previous study [4], and examined in the course of one day. Fibrosis staging from prior biopsy were gained from [4], see Table 1. The 3D MRE method included an active electromagnetic transducer generating waves at 56 Hz, and a 1.5 T Philips Achieva MR-scanner, with a phased array body coil (Sense TorsoXL, all 16 coil elements), GRE sequence parameters include; FOV = 320x256 mm2, matrix = 80x38, slice thickness = 4 mm, # slices = 9, FA = 15°, TR = 112 ms, TE = 9.21 ms, SENSE = 2. The 2D MRE method included a passive acoustic transducer generating waves at 60 Hz, and a 1.5 T GE 450W MR-scanner, with a phased array body coil (HD8 Torso, all 8 coil elements), GRE sequence parameters include; FOV = 440x440 mm2, matrix = 256x64, slice thickness = 10 mm, # slices = 4, FA = 30°, TR = 50 ms, TE = 21.7 ms, ASSET = 2. The transducers were on both systems placed on the anterior chest wall to the right of xiphoid process (patient in a supine position), the time between each MRE acquisition was dependent on how long it took to transfer the patient between the two MR systems in the hospital (<10 min) A region of interest (ROI) was placed in an appropriate single 10 mm slice acquired using the GE MR-scanner. A corresponding ROI for the Philips system, covering the same anatomical region, was placed over three slices (4 mm thickness each). This yielded a total cranio-caudal coverage of the ROIs equal to 10 mm (on the GE data) and 12 mm (on the Philips data). The mean and standard deviations of the stiffness (GE), elasticity (Philips) and Gabs,Elastic (Philips) were calculated. Gabs,Elastic is the absolute value of the shear modulus, which in principle is equivalent to the viscoelastic property, shear stiffness. In the 3D method the shear waves were obtained by applying the curl operator and using the Voigt rheological model to obtain shear elasticity maps [5, 6]. In the 2D method the GE system provided the stiffness maps. Statistics was performed using Mathematica 9. ROI drawing and quantification of the data from the GE system was performed using Sectra PACS IDS7, and ROI drawing and quantification of the data from the Philips system was performed using a custom software package implemented in ROOT, generously provided by R. Sinkus (Kings College, London, UK). Results: The measured values are presented in Table 1. Both elasticity and Gabs,Elastic correlates well with the stiffness measurement carried out in the GE system (Fig. 1), as was shown by the elasticity and stiffness correlation R2 = 0.96 (P < 0.001) slope = 1.08 (P < 0.001), intercept = 0.61 kPa (P = 0.08), Gabs,Elastic and stiffness correlation R2 = 0.96 (P < 0.001), slope = 0.95 (P< 0.001) intercept = 0.28 kPa (P = 0.43)

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-109079 (URN)
Conference
ISMRM 2014, International Society for Magnetic Resonance in Medicine, 10-16 May 2014, Milan, Italy
Available from: 2014-08-05 Created: 2014-08-05 Last updated: 2019-06-14
Kihlberg, J., Haraldsson, H., Ebbers, T. & Engvall, J. (2013). Practical Application of DENSE in Ischemic Heart Disease.. In: : . Paper presented at SCMR.
Open this publication in new window or tab >>Practical Application of DENSE in Ischemic Heart Disease.
2013 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-113516 (URN)
Conference
SCMR
Available from: 2015-01-20 Created: 2015-01-20 Last updated: 2015-03-13
Norén, B., Forsgren, M. F., Dahlqvist Leinhard, O., Dahlström, N., Kihlberg, J., Romu, T., . . . Lundberg, P. (2013). Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA. European Radiology, 23(1), 174-181
Open this publication in new window or tab >>Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
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2013 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 23, no 1, p. 174-181Article in journal (Refereed) Published
Abstract [en]

Objectives

To apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.

Methods

A total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.

Results

Area under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.

Conclusions

Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

Place, publisher, year, edition, pages
Springer, 2013
Keywords
Quantification, Gd-EOB-DTPA, Dynamic contrast-enhanced MRI, Pharmacokinetics, Liver
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-87242 (URN)10.1007/s00330-012-2583-2 (DOI)000312324500022 ()
Projects
NILB
Note

Funding Agencies|Swedish Research Council|VR/M 2007-2884|Medical Research Council of South-east Sweden|FORSS 12621|Linkoping University, Linkoping University Hospital Research Foundations||County Council of Ostergotland||

Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2019-06-14
Björck, H. M., Renner, J., Maleki, S., Nilsson, S. F. .., Kihlberg, J., Folkersen, L., . . . Länne, T. (2012). Characterization of Shear-Sensitive Genes in the NormalRat Aorta Identifies Hand2 as a Major Flow-ResponsiveTranscription Factor. PLoS ONE, 7(12)
Open this publication in new window or tab >>Characterization of Shear-Sensitive Genes in the NormalRat Aorta Identifies Hand2 as a Major Flow-ResponsiveTranscription Factor
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12Article in journal (Refereed) Published
Abstract [en]

Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to determine wall shear stress (WSS) in the rat aorta and study flow-dependent vessel wall biology under physiological conditions.

Methods and Results: Animal-specific aortic WSS magnitude and vector direction were estimated using computational fluid dynamic simulation based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis revealed a strong differential expression between the flow regions, particularly associated with transcriptional regulation. In particular, several genes related to Ca2+-signalling, inflammation, proliferation and oxidative stress were among the most highly differentially expressed.

Conclusions: Microarray analysis validated the CFD-defined WSS regions in the rat aorta, and several novel flow-dependent genes were identified. The importance of these genes in relation to atherosusceptibility needs further investigation.

Keywords
Aorta, wall shear stress, magnetic resonance imaging, computational fluid dynamics, gene expression
National Category
Physiology Fluid Mechanics and Acoustics
Identifiers
urn:nbn:se:liu:diva-73954 (URN)10.1371/journal.pone.0052227 (DOI)000312794500119 ()
Available from: 2012-01-17 Created: 2012-01-17 Last updated: 2018-01-12
Dahlström, N., Dahlqvist Leinhard, O., Kihlberg, J., Quick, P., Forsgren, M., Lundberg, P. & Persson, A. (2012). Dual-Energy CT Detects Standard-Dose Gd-EOB-DTPA in the Hepatobiliary and Renal Systems of Patients Having Undergone Liver MRI. In: : . Paper presented at RSNA 2012, November 25-30, 2012, Chicago, USA.
Open this publication in new window or tab >>Dual-Energy CT Detects Standard-Dose Gd-EOB-DTPA in the Hepatobiliary and Renal Systems of Patients Having Undergone Liver MRI
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2012 (English)Conference paper, Oral presentation with published abstract (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90382 (URN)
Conference
RSNA 2012, November 25-30, 2012, Chicago, USA
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2019-06-14
Kihlberg, J., Haraldsson, H., Ebbers, T. & Engvall, J. (2012). Myocardial deformation (“Strain”) measured by DENSE reliably detects myocardial scar.. In: : . Paper presented at SCMR.
Open this publication in new window or tab >>Myocardial deformation (“Strain”) measured by DENSE reliably detects myocardial scar.
2012 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-113517 (URN)
Conference
SCMR
Available from: 2015-01-20 Created: 2015-01-20 Last updated: 2015-01-20
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3124-8044

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