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Kullberg, Joel
Publications (10 of 100) Show all publications
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
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: 2019-06-14Bibliographically 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
Kjellberg, E., Roswall, J., Andersson, J., Bergman, S., Karlsson, A.-K., Svensson, P.-A., . . . Dahlgren, J. (2019). Metabolic Risk Factors Associated with Visceral and Subcutaneous Adipose Tissue in a Sex-Specific Manner in Seven-Year-Olds. Obesity, 27(6), 982-988
Open this publication in new window or tab >>Metabolic Risk Factors Associated with Visceral and Subcutaneous Adipose Tissue in a Sex-Specific Manner in Seven-Year-Olds
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2019 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 27, no 6, p. 982-988Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: This study aimed to investigate how visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes were associated with metabolic risk factors in 7-year-old children.

METHODS: A total of 81 children (52% girls) from a Swedish birth cohort were studied. At 6 years of age, anthropometric data, fasting insulin, glucose, cholesterol, and blood pressure were collected on 53 children with normal weight and 28 children with overweight or obesity, and insulin resistance was estimated. At 7 years of age, magnetic resonance imaging quantified VAT and SAT. Sex and regression analyses were conducted.

RESULTS: SAT was more strongly associated with metabolic risk factors than VAT. The associations between VAT and metabolic risk factors were stronger in girls (P < 0.05). When VAT was adjusted for birth weight and maternal BMI and education, it accounted for 51% of insulin variance (β = 11.72; P = 0.001) but only in girls. The key finding of this study was that adjusted SAT accounted for 63% of the fasting insulin variance in girls (β = 2.76; P < 0.001). Waist circumference was the best anthropometric marker for insulin resistance.

CONCLUSIONS: Insulin resistance was associated with abdominal adipose tissue and its associated metabolic risk factors in children as young as 7 years old.

National Category
Endocrinology and Diabetes Nutrition and Dietetics Pediatrics
Identifiers
urn:nbn:se:uu:diva-382942 (URN)10.1002/oby.22453 (DOI)000468798100018 ()31004397 (PubMedID)
Funder
Swedish Research Council, 2016-01040Swedish Research Council, 2013-2003Swedish Nutrition Foundation (SNF)
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-24Bibliographically approved
Andersson, J., Roswall, J., Kjellberg, E., Ahlström, H., Dahlgren, J. & Kullberg, J. (2019). MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume. Magnetic Resonance Imaging, 58, 135-142
Open this publication in new window or tab >>MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume
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2019 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 58, p. 135-142Article in journal (Refereed) Published
Abstract [en]

Context: Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children.

Methods: Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included. Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T-2(star)) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured.

Results: The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p < 0.01), except for VAT FF and weight, positively with sBAT T-2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p < 0.01).

Conclusions: Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2019
Keywords
Brown adipose tissue, Magnetic resonance imaging, Adiposity, Osteocalcin, Muscle volume, Quantitative MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-380416 (URN)10.1016/j.mri.2019.02.001 (DOI)000461412300018 ()30742901 (PubMedID)
Funder
Swedish Research Council, 2013-3013Swedish Research Council, 2016-01040Region Västra Götaland
Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-08-14Bibliographically approved
Lind, L., Kullberg, J., Ahlström, H., Michaëlsson, K. & Strand, R. (2019). Proof of principle study of a detailed whole-body image analysis technique, "Imiomics", regarding adipose and lean tissue distribution. Scientific Reports, 9, Article ID 7388.
Open this publication in new window or tab >>Proof of principle study of a detailed whole-body image analysis technique, "Imiomics", regarding adipose and lean tissue distribution
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7388Article in journal (Refereed) Published
Abstract [en]

This "proof-of-principle" study evaluates if the recently presented "Imiomics" technique could visualize how fat and lean tissue mass are associated with local tissue volume and fat content at high/unprecedented resolution. A whole-body quantitative water-fat MRI scan was performed in 159 men and 167 women aged 50 in the population-based POEM study. Total fat and lean mass were measured by DXA. Fat content was measured by the water-fat MRI. Fat mass and distribution measures were associated to the detailed differences in tissue volume and fat concentration throughout the body using Imiomics. Fat mass was positively correlated (r > 0.50, p < 0.05) with tissue volume in all subcutaneous areas of the body, as well as volumes of the liver, intraperitoneal fat, retroperitoneal fat and perirenal fat, but negatively to lung volume. Fat mass correlated positively with volumes of paravertebral muscles, and muscles in the ventral part of the thigh and lower limb. Fat mass was distinctly correlated with the fat content in subcutaneous adipose tissue at the trunk. Lean mass was positively related to the large skeletal muscles and the skeleton. The present study indicates the Imiomics technique to be suitable for studies of fat and lean tissue distribution, and feasible for large scale studies.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-383519 (URN)10.1038/s41598-019-43690-w (DOI)000467839800059 ()31089168 (PubMedID)
Available from: 2019-05-16 Created: 2019-05-16 Last updated: 2019-06-19Bibliographically approved
Latva-Rasku, A., Honka, M.-J., Kullberg, J., Mononen, N., Lehtimäki, T., Saltevo, J., . . . Nuutila, P. (2019). The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.. Diabetes Care, 42(5), 931-937
Open this publication in new window or tab >>The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.
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2019 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 5, p. 931-937Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS: This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA1c 6.5-10.5% (48-91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [18F]-fluorodeoxyglucose and positron emission tomography during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed.

RESULTS: After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA1c -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03).

CONCLUSIONS: In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-382943 (URN)10.2337/dc18-1569 (DOI)000465238900036 ()30885955 (PubMedID)
Funder
AstraZeneca
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-05-15Bibliographically approved
Boersma, G. J., Johansson, E., Pereira, M. J., Heurling, K., Skrtic, S., Lau, J., . . . Eriksson, J. (2018). Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study. Hormone and Metabolic Research, 50(8), 627-639
Open this publication in new window or tab >>Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study
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2018 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 50, no 8, p. 627-639Article in journal (Refereed) Published
Abstract [en]

We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=-0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

Place, publisher, year, edition, pages
Georg Thieme Verlag KG, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-356788 (URN)10.1055/a-0643-4739 (DOI)000440872200007 ()30001566 (PubMedID)
Funder
AstraZenecaEXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes AssociationSwedish Research CouncilErnfors Foundation
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-11-08Bibliographically approved
Stenlid, R., Manell, H., Halldin, M., Kullberg, J., Ahlström, H., Manukyan, L., . . . Forslund, A. (2018). High DPP-4 concentrations in adolescents are associated with low intact GLP-1. Journal of Clinical Endocrinology and Metabolism, 103(8), 2958-2966
Open this publication in new window or tab >>High DPP-4 concentrations in adolescents are associated with low intact GLP-1
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2018 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 8, p. 2958-2966Article in journal (Refereed) Published
Abstract [en]

Context: Dipeptidyl Peptidase-4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1) and increased DPP4 levels are associated with obesity and visceral adiposity in adults.

Objective: Investigating DPP-4 levels in adolescents and association with, firstly, circulating intact GLP-1 levels and glucose tolerance, secondly, BMI, and, thirdly visceral, subcutaneous and liver fat compartments.

Design: Cross-sectional study, July 2012 to April 2015.

Setting: Pediatric obesity clinic, Uppsala University Hospital.

Patients and participants: Children and adolescents with obesity (n=59) and lean controls (n=21), age 8-18.

Main outcome measures: BMI SDS, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and OGTT concentrations of glucose and visceral (VAT) and subcutaneous (SAT) adipose tissue volumes and liver fat fraction.

Results: Plasma DPP-4 decreased with age both in obese (41 ng/ml per year) and lean subjects (48 ng/ml per year). Plasma DPP-4 was higher in males both in the obesity and lean group. When adjusting for age and sex, plasma DPP-4 was negatively associated with intact GLP-1 at fasting, B=-12.3, 95% CI [-22.9, -1.8] and during OGTT, B=-12.1, 95% CI [-22.5, -1.7]. No associations were found between DPP-4 and plasma glucose measured at fasting or after a 2-hour OGTT. Plasma DPP-4 was 19% higher in the obese subjects. Among adipose tissue compartments the strongest association was with VAT, B=0.05, 95% CI [-0.02, 0.12].

Conclusions: In adolescents, high plasma DPP-4 concentrations are associated with low proportion of intact GLP-1, high BMI, young age and male sex. The observed associations are compatible with an increased metabolism of GLP-1 in childhood obesity.

Place, publisher, year, edition, pages
Endocrine Society, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-354234 (URN)10.1210/jc.2018-00194 (DOI)000442236900022 ()29850829 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 279153Swedish Diabetes Association, DIA 2016-146Ernfors Foundation, 160504Swedish Research Council, 2016-01040EXODIAB - Excellence of Diabetes Research in SwedenErik, Karin och Gösta Selanders Foundation
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2019-03-28Bibliographically approved
Kjellberg, E., Roswall, J., Andersson, J., Bergman, S., Kullberg, J. & Dahlgren, J. (2018). IGF-I at Four Months Associates to Visceral and Subcutaneous Adipose Tissue at 7 Years of Age. Hormone Research in Paediatrics, 90, 93-93
Open this publication in new window or tab >>IGF-I at Four Months Associates to Visceral and Subcutaneous Adipose Tissue at 7 Years of Age
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2018 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 90, p. 93-93Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
S. Karger, 2018
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-368675 (URN)000445204100181 ()
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2018-12-06Bibliographically approved
Guglielmo, P., Sjöholm, T., Enblad, G., Strand, R., Kullberg, J., Malberg, F. & Ahlström, H. (2018). Imiomics Using Whole-body FDG PET/MR in Staging and Treatment Response Evaluation of Non-Hodgkin Lymphoma Patients Treated With CAR-T Cells. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S37-S38
Open this publication in new window or tab >>Imiomics Using Whole-body FDG PET/MR in Staging and Treatment Response Evaluation of Non-Hodgkin Lymphoma Patients Treated With CAR-T Cells
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S37-S38Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372960 (URN)000449266200052 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-01-24Bibliographically approved
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