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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
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
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
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-393367 (URN)10.1038/s41598-019-42613-z (DOI)
Available from: 2019-04-16 Created: 2019-09-20 Last updated: 2019-09-20Bibliographically 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
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
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., Michaëlsson, K., Söderberg, S., Larsson, A., Johansson, L., Kullberg, J., . . . Sundström, J. (2019). On the association between body fat and left ventricular mass. Journal of Hypertension, 37(8), 1699-1704
Open this publication in new window or tab >>On the association between body fat and left ventricular mass
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2019 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, no 8, p. 1699-1704Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: As intervention studies have shown a reduction in body weight to be paralleled with a reduction in left ventricular mass (LVM), we quantified a hypothesized causal relationship between fat mass and LVM, and how much of these effects that was mediated by blood pressure (BP), diabetes and adipokines. Also visceral and subcutaneous adipose tissue (VAT and SAT) were explored in the same fashion.

METHODS: In the Prospective Study of the Vasculature in Uppsala Seniors study (n = 1016, 50% women, all aged 70 years), LVM was measured by echocardiography (indexed for lean mass, LVMI), fat and lean mass by dual-energy X-ray. VAT and SAT were measured by abdominal MRI (in n = 275).

RESULTS: In a structural equation model adjusting for sex, the total effect of fat mass on LVMI was large (standardized coefficient 0.280, P = 3.2 × 10, 95% confidence interval 0.210-0.349). Out of the total effect of fat mass on LVMI, 29.0% was mediated by BP and glucose (P = 2.4 × 10). The BP pathway was most important, mediating 24.4% of the total effect of fat mass on LVMI (P = 4.6 × 10), while the glucose pathway accounted for 4.6% (P = 0.033). The association of VAT with LVMI (0.202, P = 2.4 × 10) was slightly weaker than that of SAT with LVMI (0.283, P = 1.0 × 10). Of several measured adipokines, leptin was a significant mediator of the effect of fat mass on LVMI (P = 3.0 × 10).

CONCLUSION: One-third of the hypothesized association between body fat and LVMI was mediated by BP and glucose in this population-based cohort. Leptin was also an important mediator. Visceral adipose tissue was not more closely related to LVMI than subcutaneous abdominal fat.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-382932 (URN)10.1097/HJH.0000000000002095 (DOI)000480767600020 ()31058795 (PubMedID)
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-10-01Bibliographically 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
Lind, L., Strand, R., Michaëlsson, K., Kullberg, J. & Ahlström, H. (2019). Relationship between endothelium-dependent vasodilation and fat distribution using the new "imiomics" image analysis technique. NMCD. Nutrition Metabolism and Cardiovascular Diseases, 29(10), 1077-1086
Open this publication in new window or tab >>Relationship between endothelium-dependent vasodilation and fat distribution using the new "imiomics" image analysis technique
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2019 (English)In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 29, no 10, p. 1077-1086Article in journal (Refereed) Published
Abstract [en]

Background and aims: We investigated how vasoreactivity in the brachial artery and the forearm resistance vessels were related to fat distribution and tissue volume, using both traditional imaging analysis and a new technique, called “Imiomics”, whereby vasoreactivity was related to each of the >2M 3D image elements included in the whole-body magnetic resonance imaging (MRI).

Methods and results: In 326 subjects in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (all aged 50 years), endothelium-dependent vasodilation was measured by acetylcholine infusion in the brachial artery (EDV) and flow-mediated vasodilation (FMD). Fat distribution was evaluated by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). EDV, but not FMD, was significantly related to total fat mass, liver fat, subcutaneous (SAT) and visceral (VAT) adipose tissue in a negative fashion in women, but not in men. Using Imiomics, an inverse relationship was seen between EDV and a local tissue volume of SAT in both the upper part of the body, as well as the gluteo-femoral part and the medial parts of the legs in women. Also the size of the liver, heart and VAT was inversely related to EDV. In men, less pronounced relationships were seen. FMD was also significantly related to local tissue volume of upper-body SAT and liver fat in women, but less so in men.

Conclusion: EDV, and to a lesser degree also FMD, were related to liver fat, SAT and VAT in women, but less so in men. Imiomics both confirmed findings from traditional methods and resulted in new, more detailed results.

Keywords
Magnetic resonance imaging, Whole body imaging, Image analysis, Atherosclerosis, Endothelial dysfunction, Obesity
National Category
Medical Image Processing Radiology, Nuclear Medicine and Medical Imaging
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-392832 (URN)10.1016/j.numecd.2019.06.017 (DOI)000484832100011 ()31377180 (PubMedID)
Funder
Swedish Research Council, 2016-01040Swedish Heart Lung Foundation, 20170492
Available from: 2019-06-24 Created: 2019-09-10 Last updated: 2019-10-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8205-7569

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