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Magnetic Resonance Imaging of Human Brown Adipose Tissue: Methodological Development and Application
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Brown adipose tissue (BAT) is a thermogenic organ with the main human depot located in the cervical-supraclavicular (sBAT) region. BAT is proposed as a potential therapeutic target for obesity and diabetes. This thesis aims to contribute to the development of magnetic resonance imaging (MRI)-based methods and to the application of these in studies of human BAT. Water-fat MRI enables separation of water and fat, the dominant contributors to the MR signal, and the quantification of fat fraction (FF) and effective transverse relaxation rate (R2*). FF and R2* are often used in studies of human BAT, e.g. for characterizing the tissue and distinguishing it from white adipose tissue. A Cooling-reheating protocol was introduced for studying changes in sBAT, related to lipid content and perfusion. sBAT FF decreased after cold exposure. The sustained low FF after reheating suggested lipid consumption as the primary cause. This conclusion was based on the assumption of a normalized perfusion after reheating. An automated method for segmentation of sBAT was developed. The method compared well with a semi-automated reference method with respect to segmentation overlap and estimated mean sBAT FF and R2*. A modified version of the automated method was applied to a large-scale study where an association between sBAT FF and glucose tolerance indicated a role for BAT in glucose metabolism, potentially linked to the risk of developing diabetes.  A Cooling-reheating protocol was evaluated with positron emission tomography measurements of perfusion and cold-stimulated BAT activity. Inverse correlations between sBAT FF and BAT activity suggested sBAT FF to predict cold-induced BAT activity. After reheating, the cold-induced increase in perfusion normalized and the cold-induced decrease in FF partially normalized. This suggested potential decreases in FF after reheating to mainly be due to lipid consumption and decreases in FF after cold exposure to possibly be influenced by perfusion.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 83
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1572
Keywords [en]
Brown adipose tissue, Magnetic resonance imaging, Positron emission tomography, Image segmentation, Glucose metabolism
National Category
Medical and Health Sciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-381766ISBN: 978-91-513-0651-3 (print)OAI: oai:DiVA.org:uu-381766DiVA, id: diva2:1305172
Public defence
2019-06-07, Rosénsalen, Entrance 95/96, Akademiska sjukhuset, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2019-05-17 Created: 2019-04-15 Last updated: 2019-06-18
List of papers
1. Magnetic resonance imaging cooling–reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue
Open this publication in new window or tab >>Magnetic resonance imaging cooling–reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0126705Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.

MATERIALS AND METHODS: Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).

RESULTS: sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).

CONCLUSIONS: The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-254074 (URN)10.1371/journal.pone.0126705 (DOI)000353713100132 ()25928226 (PubMedID)
Available from: 2015-04-30 Created: 2015-06-04 Last updated: 2019-04-15Bibliographically approved
2. Automated segmentation of human cervical-supraclavicular adipose tissue in magnetic resonance images
Open this publication in new window or tab >>Automated segmentation of human cervical-supraclavicular adipose tissue in magnetic resonance images
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3064Article in journal (Refereed) Published
Abstract [en]

Human brown adipose tissue (BAT), with a major site in the cervical-supraclavicular depot, is a promising anti-obesity target. This work presents an automated method for segmenting cervical-supraclavicular adipose tissue for enabling time-efficient and objective measurements in large cohort research studies of BAT. Fat fraction (FF) and R2* maps were reconstructed from water-fat magnetic resonance imaging (MRI) of 25 subjects. A multi-atlas approach, based on atlases from nine subjects, was chosen as automated segmentation strategy. A semi-automated reference method was used to validate the automated method in the remaining subjects. Automated segmentations were obtained from a pipeline of preprocessing, affine registration, elastic registration and postprocessing. The automated method was validated with respect to segmentation overlap (Dice similarity coefficient, Dice) and estimations of FF, R2* and segmented volume. Bias in measurement results was also evaluated. Segmentation overlaps of Dice = 0.93 +/- 0.03 (mean +/- standard deviation) and correlation coefficients of r > 0.99 (P < 0.0001) in FF, R2* and volume estimates, between the methods, were observed. Dice and BMI were positively correlated (r = 0.54, P = 0.03) but no other significant bias was obtained (P >= 0.07). The automated method compared well with the reference method and can therefore be suitable for time-efficient and objective measurements in large cohort research studies of BAT.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-323968 (URN)10.1038/s41598-017-01586-7 (DOI)000402865000003 ()28596551 (PubMedID)
Funder
Swedish Research CouncilEU, FP7, Seventh Framework Programme, 279153
Available from: 2017-06-08 Created: 2017-06-12 Last updated: 2019-04-15Bibliographically approved
3. Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents
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
4. PET/MRI of glucose uptake, lipid content and perfusion in human brown adipose tissue
Open this publication in new window or tab >>PET/MRI of glucose uptake, lipid content and perfusion in human brown adipose tissue
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-381764 (URN)
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-29

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