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Sjöholm, T., Ekström, S., Strand, R., Ahlström, H., Lind, L., Malmberg, F. & Kullberg, J. (2019). A whole-body FDG PET/MR atlas for multiparametric voxel-based analysis. Scientific Reports, 9, Article ID 6158.
Open this publication in new window or tab >>A whole-body FDG PET/MR atlas for multiparametric voxel-based analysis
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 6158Article in journal (Refereed) Published
Abstract [en]

Quantitative multiparametric imaging is a potential key application for Positron Emission Tomography/Magnetic Resonance (PET/MR) hybrid imaging. To enable objective and automatic voxel-based multiparametric analysis in whole-body applications, the purpose of this study was to develop a multimodality whole-body atlas of functional 18F-fluorodeoxyglucose (FDG) PET and anatomical fat-water MR data of adults. Image registration was used to transform PET/MR images of healthy control subjects into male and female reference spaces, producing a fat-water MR, local tissue volume and FDG PET whole-body normal atlas consisting of 12 male (66.6 +/- 6.3 years) and 15 female (69.5 +/- 3.6 years) subjects. Manual segmentations of tissues and organs in the male and female reference spaces confirmed that the atlas contained adequate physiological and anatomical values. The atlas was applied in two anomaly detection tasks as proof of concept. The first task automatically detected anomalies in two subjects with suspected malignant disease using FDG data. The second task successfully detected abnormal liver fat infiltration in one subject using fat fraction data.

National Category
Medical Image Processing
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-382934 (URN)10.1038/s41598-019-42613-z (DOI)000464652400029 ()30992502 (PubMedID)
Available from: 2019-04-16 Created: 2019-05-07 Last updated: 2020-02-05Bibliographically approved
Marchesi, S., Ortiz-Nieto, F., Ahlgren, K. M., Roneus, A., Feinstein, R., Lipcsey, M., . . . Hedenstierna, G. (2019). Abdominal organ perfusion and inflammation in experimental sepsis: a magnetic resonance imaging study. American Journal of Physiology - Gastrointestinal and Liver Physiology, 316(1), G187-G196
Open this publication in new window or tab >>Abdominal organ perfusion and inflammation in experimental sepsis: a magnetic resonance imaging study
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2019 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 316, no 1, p. G187-G196Article in journal (Refereed) Published
Abstract [en]

Diffusion-weighted magnetic resonance imaging (DW-MRI) uses water as contrast and enables the study of perfusion in many organs simultaneously in situ. We used DW-MRI in a sepsis model, comparing abdominal organs perfusion with global hemodynamic measurements and inflammation. Sixteen anesthetized piglets were randomized into 3 groups: HighMAP (mean arterial pressure, MAP > 65 mmHg), LowMAP (MAP between 50 and 60 mmHg) and Healthy Controls (HC). Sepsis was obtained with endotoxin and the desired MAP maintained with noradrenaline. After 6 hours DW-MRI was performed. Acute inflammation was assessed with IL-6 and TNFα in abdominal organs, ascites, and blood and by histology of intestine (duodenum). Perfusion of abdominal organs was reduced in the LowMAP group compared to the HighMAP group and HC. Liver perfusion was still reduced by 25% in the HighMAP group compared with HC. Intestinal perfusion did not differ significantly between the study groups. Cytokines concentration were generally higher in the LowMAP group but did not correlate with global hemodynamics. However, cytokines correlated with regional perfusion and, for liver and intestine, also with intra-abdominal pressure. Histopathology of intestine worsened with decreasing perfusion. In conclusion, although a low MAP (≤60 mmHg) indicated impeded abdominal perfusion in experimental sepsis, it did not predict inflammation, nor did other global measures of circulation. Decreased abdominal perfusion predicted partially inflammation but intestine, occupying most of the abdomen, and liver, were also affected by intra-abdominal pressure.

Keywords
Abdominal organs, inflammation, magnetic resonance, perfusion, sepsis
National Category
Surgery Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-364356 (URN)10.1152/ajpgi.00151.2018 (DOI)000455670700012 ()30335473 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research Council
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2019-02-05Bibliographically approved
Pilia, M., Kullberg, J., Ahlström, H., Malmberg, F., Ekström, S. & Strand, R. (2019). Average volume reference space for large scale registration of whole-body magnetic resonance images. PLoS ONE, 14(10), Article ID e0222700.
Open this publication in new window or tab >>Average volume reference space for large scale registration of whole-body magnetic resonance images
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 10, article id e0222700Article in journal (Refereed) Published
National Category
Medical Image Processing
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-397325 (URN)10.1371/journal.pone.0222700 (DOI)
Funder
Swedish Research Council, 2016–01040Swedish Heart Lung Foundation, HLF 20170492
Available from: 2019-10-01 Created: 2019-11-19 Last updated: 2019-11-20Bibliographically approved
Lundström, E., Ljungberg, J., Andersson, J., Manell, H., Strand, R., Forslund, A., . . . Kullberg, J. (2019). Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents. Pediatric Obesity, 14(9), Article ID e12531.
Open this publication in new window or tab >>Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents
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2019 (English)In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 14, no 9, article id e12531Article in journal (Refereed) Published
Abstract [en]

Background

Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored.

Objectives

To investigate possible associations between magnetic resonance imaging (MRI) estimates of BAT and glucose metabolism, whilst considering sex, age, and adiposity, in adolescents with normal and overweight/obese phenotypes.

Methods

In 143 subjects (10‐20 years), MRI estimates of BAT were assessed as cervical‐supraclavicular adipose tissue (sBAT) fat fraction (FF) and T*2 from water‐fat MRI. FF and T*2 of neighbouring subcutaneous adipose tissue (SAT) were also assessed. Adiposity was estimated with a standardized body mass index, the waist‐to‐height ratio, and abdominal visceral and subcutaneous adipose tissue volumes. Glucose metabolism was represented by the 2h plasma glucose concentration, the Matsuda index, the homeostatic model assessment of insulin resistance, and the oral disposition index; obtained from oral glucose tolerance tests.

Results

sBAT FF and T*2 correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not T*2, correlated with 2h glucose and Matsuda index, also after adjustment for sex, age, and adiposity. The association with 2h glucose persisted after additional adjustment for SAT FF.

Conclusions

The association between sBAT FF and 2h glucose, observed independently of sex, age, adiposity, and SAT FF, indicates a role for BAT in glucose metabolism, which potentially could influence the risk of developing diabetes. The lacking association with sBAT T*2 might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the T*2 quantification.

Keywords
adolescent, brown adipose tissue, glucose metabolism, magnetic resonance imaging
National Category
Pediatrics Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-380052 (URN)10.1111/ijpo.12531 (DOI)000482155600007 ()31290284 (PubMedID)
Funder
Swedish Heart Lung Foundation, 2170492Swedish Research Council, 2016-01040EU, FP7, Seventh Framework Programme, 279153
Available from: 2019-07-09 Created: 2019-03-22 Last updated: 2019-10-23Bibliographically approved
Johansson, H.-E., Edholm, D., Kullberg, J., Rosqvist, F., Rudling, M., Straniero, S., . . . Risérus, U. (2019). Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements. Nutrition & Diabetes, 9(1), Article ID 34.
Open this publication in new window or tab >>Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements
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2019 (English)In: Nutrition & Diabetes, ISSN 2044-4052, E-ISSN 2044-4052, Vol. 9, no 1, article id 34Article in journal (Refereed) Published
Abstract [en]

Energy restriction reduces liver fat, improves hepatic insulin resistance and lipid metabolism. However, temporal data in which these metabolic improvements occur and their interplay is incomplete. By performing repeated MRI scans and blood analysis at day 0, 3, 7, 14 and 28 the temporal changes in liver fat and related metabolic factors were assessed at five times during a low-calorie diet (LCD, 800-1100 kcal/day) in ten obese non-diabetic women (BMI 41.7 ± 2.6 kg/m2) whereof 6 had NAFLD. Mean weight loss was 7.4 ± 1.2 kg (0.7 kg/day) and liver fat decreased by 51 ± 16%, resulting in only three subjects having NAFLD at day 28. Marked alteration of insulin, NEFA, ALT and 3-hydroxybuturate was evident 3 days after commencing LCD, whereas liver fat showed a moderate but a linear reduction across the 28 days. Other circulating-liver fat markers (e.g. triglycerides, adiponectin, stearoyl-CoA desaturase-1 index, fibroblast growth factor 21) demonstrated modest and variable changes. Marked elevations of NEFA, 3-hydroxybuturate and ALT concentrations occurred until day 14, likely reflecting increased tissue lipolysis, fat oxidation and upregulated hepatic fatty acid oxidation. In summary, these results suggest linear reduction in liver fat, time-specific changes in metabolic markers and insulin resistance in response to energy restriction.

National Category
Endocrinology and Diabetes Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-397554 (URN)10.1038/s41387-019-0100-2 (DOI)000497994200004 ()31685793 (PubMedID)
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2019-12-18Bibliographically approved
Andersson, J., Lundström, E., Engström, M., Lubberink, M., Ahlström, H. & Kullberg, J. (2019). Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI. Scientific Reports, 9, Article ID 12358.
Open this publication in new window or tab >>Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12358Article in journal (Refereed) Published
Abstract [en]

Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.

Keywords
brown adipose tissue, 18F-FDG positron emission tomography, infrared thermography, magnetic resonance imagingm PET/MRI, water–fat signal separation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-390410 (URN)10.1038/s41598-019-48879-7 (DOI)000482564800014 ()31451711 (PubMedID)
Funder
Swedish Research Council, 2016-01040Swedish Heart Lung Foundation, 2170492EXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-10-18Bibliographically approved
Schiza, A., Irenaeus, S., Ortiz-Nieto, F., Loskog, A. S., Tötterman, T., Sundin, A., . . . Ahlström, H. (2019). Evaluation of Diffusion-Weighted MRI and FDG-PET/CT to Assess Response to AdCD40L treatment in Metastatic Melanoma Patients. Scientific Reports, 9, Article ID 18069.
Open this publication in new window or tab >>Evaluation of Diffusion-Weighted MRI and FDG-PET/CT to Assess Response to AdCD40L treatment in Metastatic Melanoma Patients
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 18069Article in journal (Refereed) Published
Abstract [en]

The purpose was to evaluate the potential of diffusion-weighted-magnetic resonance imaging (DW-MRI) and F-18-fludeoxy-glucose-positron emission tomography integrated with CT (FDG-PET/CT) for prediction of overall survival (OS) following AdCD40L-immunotherapy in patients with metastatic malignant melanoma (MMM). Twenty-four patients with refractory MMM were treated with immunostimulatory AdCD40L gene therapy in a phase I/IIa study. Pre-therapeutic DW-MRI and FDG-PET/CT were performed and then repeated at 5 and 9 weeks post-treatment. Evaluation was conducted according to RECIST 1.1 and EORTC criteria. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), maximum standardized uptake value (SUVmax) were measured in the injected lesions. Fold changes (F) in ADC (F ADC), D (FD), SUVmax (FSUVmax) were statistically assessed. F D >= 1 and F ADC >= 1 were associated with better OS in scans at week 5 and 9 respectively. F SUVmax was not correlated to OS. F ADC >= 1 in both post-treatment scans and F D >= 1 at week 5 were related to a significant decrease of size of the injected lesions. These results suggest that in patients with MMM treated with AdCD401, functional parameters of DW-MRI are better early predictors of OS than the established metabolic and morphologic criteria for FDG-PET/CT and MRI, respectively.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-400411 (URN)10.1038/s41598-019-54438-x (DOI)000500557500001 ()31792256 (PubMedID)
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved
Linder, G., Korsavidou Hult, N., Bjerner, T., Ahlström, H. & Hedberg, J. (2019). F-18-FDG-PET/MRI in preoperative staging of oesophageal and gastroesophageal junctional cancer. Clinical Radiology, 74(9), 718-725
Open this publication in new window or tab >>F-18-FDG-PET/MRI in preoperative staging of oesophageal and gastroesophageal junctional cancer
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2019 (English)In: Clinical Radiology, ISSN 0009-9260, E-ISSN 1365-229X, Vol. 74, no 9, p. 718-725Article in journal (Refereed) Published
Abstract [en]

AIM: To evaluate integrated 2-[F-18]-fluoro-2-deoxy-D-glucose (F-18-FDG) positron-emission tomography (PET)/magnetic resonance imaging (MRI), in comparison with the standard technique, integrated F-18-FDG-PET/computed tomography (CT), in preoperative staging of oesophageal or gastroesophageal junctional cancer.

MATERIALS AND METHODS: In the preoperative staging of 16 patients with oesophageal or gastroesophageal junctional cancer, F-18-FDG-PET/MRI was performed immediately following the clinically indicated F-18-FDG-PET/CT. MRI-sequences included T1-weighted fat-water separation (Dixon's technique), T2-weighted, diffusion-weighted imaging (DWI), and gadolinium contrast-enhanced T1-weighted three-dimensional (3D) imaging. PET was performed with F-18-FDG. Two separate teams of radiologists conducted structured blinded readings of F-18-FDG-PET/MRI or F-18-FDG-PET/CT, which were then compared regarding tumour measurements and characteristics as well as assessment of inter-rater agreement (Cohen's kappa) for the clinical tumour, nodal and metastatic (TNM) stage.

RESULTS: There were no medical complications. Comparison of tumour measurements revealed high correlations without significant differences between modalities. The maximum standardised uptake value (SUVmax) values of the primary tumour with F-18-FDG-PET/MRI had excellent correlation to those of F-18-FDG-PET/CT (0.912, Spearman's rho). Inter-rater agreement between the techniques regarding T-stage was only fair (Cohen's kappa, 0.333), arguably owing to relative over-classification of the T-stage using F-18-FDG-PET/CT. Agreements in the assessment of N- and M-stage were substantial (Cohen's kappa, 0.849 and 0.871 respectively).

CONCLUSION: Preoperative staging with F-18-FDG-PET/MRI is safe and promising with the potential to enhance tissue resolution in the area of interest. F-18-FDG-PET/MRI and F-18-FDG-PET/CT correlated well for most of the measured values and discrepancies were seen mainly in the assessment of the T-stage. These results facilitate further studies investigating the role of F-18-FDG-PET/MRI in, e.g., predicting or determining the response to neoadjuvant therapy. 

Place, publisher, year, edition, pages
W B SAUNDERS CO LTD, 2019
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-392125 (URN)10.1016/j.crad.2019.05.016 (DOI)000477841300010 ()31221468 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-09-03 Created: 2019-09-03 Last updated: 2019-09-03Bibliographically approved
Langner, T., Hedström, A., Mörwald, K., Weghuber, D., Forslund, A., Bergsten, P., . . . Kullberg, J. (2019). Fully convolutional networks for automated segmentation of abdominal adipose tissue depots in multicenter water–fat MRI. Magnetic Resonance in Medicine, 81(4), 2736-2745
Open this publication in new window or tab >>Fully convolutional networks for automated segmentation of abdominal adipose tissue depots in multicenter water–fat MRI
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2019 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 81, no 4, p. 2736-2745Article in journal (Refereed) Published
Abstract [en]

Purpose: An approach for the automated segmentation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in multicenter water–fat MRI scans of the abdomen was investigated, using 2 different neural network architectures.

Methods: The 2 fully convolutional network architectures U‐Net and V‐Net were trained, evaluated, and compared using the water–fat MRI data. Data of the study Tellus with 90 scans from a single center was used for a 10‐fold cross‐validation in which the most successful configuration for both networks was determined. These configurations were then tested on 20 scans of the multicenter study beta‐cell function in JUvenile Diabetes and Obesity (BetaJudo), which involved a different study population and scanning device.

Results: The U‐Net outperformed the used implementation of the V‐Net in both cross‐validation and testing. In cross‐validation, the U‐Net reached average dice scores of 0.988 (VAT) and 0.992 (SAT). The average of the absolute quantification errors amount to 0.67% (VAT) and 0.39% (SAT). On the multicenter test data, the U‐Net performs only slightly worse, with average dice scores of 0.970 (VAT) and 0.987 (SAT) and quantification errors of 2.80% (VAT) and 1.65% (SAT).

Conclusion: The segmentations generated by the U‐Net allow for reliable quantification and could therefore be viable for high‐quality automated measurements of VAT and SAT in large‐scale studies with minimal need for human intervention. The high performance on the multicenter test data furthermore shows the robustness of this approach for data of different patient demographics and imaging centers, as long as a consistent imaging protocol is used.

Keywords
abdominal, adipose tissue, deep learning, fully convolutional networks, segmentation, water-fat MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-364355 (URN)10.1002/mrm.27550 (DOI)000462092100044 ()30311704 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 279153
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2019-04-17Bibliographically approved
Manell, H., Kristinsson, H., Kullberg, J., Ubhayasekera, S. J., Mörwald, K., Staaf, J., . . . Bergsten, P. (2019). Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance. Pediatric Diabetes, 20(7), 880-891
Open this publication in new window or tab >>Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance
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2019 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, no 7, p. 880-891Article in journal (Refereed) Published
Abstract [en]

Objective: To delineate mechanisms for fasting hyperglucagonemia in childhood obesity bystudying the associations between fasting plasma glucagon concentrations and plasmalipid parameters and fat compartments.

Methods: Cross-sectional study of children and adolescents with obesity (n=147) and leancontrols (n=43). Differences in free fatty acids (FFA), triglycerides, insulin and fatcompartments (quantified by magnetic resonance imaging) across quartiles of fastingplasma glucagon concentration were analysed. Differences in OGTT glucagonresponse was tested in high vs low FFAs, triglycerides and insulin. Human islets ofLangerhans were cultured at 5.5 mmol/l glucose and in the absence or presence of aFFA mixture with total FFA concentration of 0.5 mmol/l and glucagon secretionquantified.

Results: In children with obesity, the quartile with the highest fasting glucagon had higherinsulin (201±174 vs 83±39 pmol/l, p<0.01), FFAs (383±52 vs 338±109 μmol/l,p=0.02), triglycerides (1.5±0.9 vs 1.0±0.7 mmol/l, p<0.01), visceral adipose tissuevolume (1.9±0.8 vs 1.2±0.3 dm3, p<0.001) and a higher prevalence of impairedglucose tolerance (41% vs 8%, p=0.01) than the lowest quartile. During OGTT,children with obesity and high insulin had a worse suppression of glucagon during thefirst 10 minutes after glucose intake. Glucagon secretion was 2.6-fold higher in isletstreated with FFAs than in those not treated with FFAs.4

Conclusion: Hyperglucagonemia in childhood obesity is associated with hyperinsulinemia, highplasma FFAs, high plasma triglycerides, visceral adiposity and impaired glucosetolerance. The glucagonotropic effect of FFAs on isolated human islets provides apotential mechanism linking high fasting plasma FFAs and glucagon levels.

Keywords
Childhood obesity, glucagon, free fatty acids, insulin, visceral adiposity, impaired glucose tolerance, type 2 diabetes
National Category
Pediatrics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-380313 (URN)10.1111/pedi.12890 (DOI)000476081000001 ()31271247 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 279153EXODIAB - Excellence of Diabetes Research in SwedenErnfors FoundationErik, Karin och Gösta Selanders FoundationSwedish Research Council, 2015-4870Swedish Diabetes Association
Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-12-06Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8701-969x

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