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Evidence for two types of brown adipose tissue in humans
Medicinsk genetik, Göteborgs universitet.
Medicinsk genetik, Göteborgs universitet.
Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
Medicinsk genetik, Göteborgs universitet.
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2013 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 19, no 5, p. 631-634Article in journal (Refereed) Published
Abstract [en]

The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was commonly believed to be the equivalent of the interscapular thermogenic organ of small mammals. This view was recently disputed on the basis of the demonstration that this depot consists of beige (also called brite) brown adipocytes, a newly identified type of brown adipocyte that is distinct from the classical brown adipocytes that make up the interscapular thermogenic organs of other mammals. A combination of high-resolution imaging techniques and histological and biochemical analyses showed evidence for an anatomically distinguishable interscapular BAT (iBAT) depot in human infants that consists of classical brown adipocytes, a cell type that has so far not been shown to exist in humans. On the basis of these findings, we conclude that infants, similarly to rodents, have the bona fide iBAT thermogenic organ consisting of classical brown adipocytes that is essential for the survival of small mammals in a cold environment.

Place, publisher, year, edition, pages
Nature Publishing Group, 2013. Vol. 19, no 5, p. 631-634
Keywords [en]
BAT, MRI
National Category
Medical Genetics Cell and Molecular Biology Medical Image Processing Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-91307DOI: 10.1038/nm.3017ISI: 000318583000037OAI: oai:DiVA.org:liu-91307DiVA, id: diva2:617032
Funder
Knut and Alice Wallenberg Foundation, 2011.0059Available from: 2013-04-21 Created: 2013-04-21 Last updated: 2018-02-22Bibliographically approved
In thesis
1. Fat-Referenced MRI: Quanitaive MRI for Tissue Characterizaion and Volume Measurement
Open this publication in new window or tab >>Fat-Referenced MRI: Quanitaive MRI for Tissue Characterizaion and Volume Measurement
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The amount and distribution of adipose and lean tissues has been shown to be predictive of mortality and morbidity in metabolic disease. Traditionally these risks are assessed by anthropometric measurements based on weight, length, girths or the body mass index (BMI). These measurements are predictive of risks on a population level, where a too low or a too high BMI indicates an increased risk of both mortality and morbidity. However, today a large part of the world’s population belongs to a group with an elevated risk according to BMI, many of which will live long and healthy lives. Thus, better instruments are needed to properly direct health-care resources to those who need it the most.

Medical imaging method can go beyond anthropometrics. Tomographic modalities, such as magnetic resonance imaging (MRI), can measure how we have stored fat in and around organs. These measurements can eventually lead to better individual risk predictions. For instance, a tendency to store fat as visceral adipose tissue (VAT) is associated with an increased risk of diabetes type 2, cardio-vascular disease, liver disease and certain types of cancer. Furthermore, liver fat is associated with liver disease, diabetes type 2. Brown adipose tissue (BAT), is another emerging component of body-composition analysis. While the normal white adipose tissue stores fat, BAT burns energy to produce heat. This unique property makes BAT highly interesting, from a metabolic point of view.

Magnetic resonance imaging can both accurately and safely measure internal adipose tissue compartments, and the fat infiltration of organs. Which is why MRI is often considered the reference method for non-invasive body-composition analysis. The two major challenges of MRI based body-composition analysis are, the between-scanner reproducibility and a cost-effective analysis of the images. This thesis presents a complete implementation of fat-referenced MRI, a technique that produces quantitative images that can increase both inter-scanner and automation of the image analysis.

With MRI, it is possible to construct images where water and fat are separated into paired images. In these images, it easy to depict adipose tissue and lean tissue structures. This thesis takes water-fat MRI one step further, by introducing a quantitative framework called fat-referenced MRI. By calibrating the image using the subjects' own adipose tissue (paper II), the otherwise non-quantitative fat images are made quantitative. In these fat-referenced images it is possible to directly measure the amount of adipose tissue in different compartments. This quantitative property makes image analysis easy and accurate, as lean and adipose tissues can be separated on a sub-voxel level. Fat-referenced MRI further allows the quantification and characterization of BAT.

This thesis work starts by formulating a method to produce water-fat images (paper I) based on two gradient recall images, i.e.\ 2-point Dixon images (2PD). It furthers shows that fat-referenced 2PD images can be corrected for T2*, making the 2PD body-composition measurements comparable with confounder-corrected Dixon measurements (paper III}).

Both the water-fat separation method and fat image calibration are applied to BAT imaging. The methodology is first evaluated in an animal model, where it is shown that it can detect both BAT browning and volume increase following cold acclimatization (paper IV). It is then applied to postmortem imaging, were it is used to locate interscapular BAT in human infants (paper V). Subsequent analysis of biopsies, taken based on the MRI images, showed that the interscapular BAT was of a type not previously believed to exist in humans. In the last study, fat-referenced MRI is applied to BAT imaging of adults. As BAT structures are difficult to locate in many adults, the methodology was also extended with a multi-atlas segmentation methods (paper VI).

In summary, this thesis shows that fat-referenced MRI is a quantitative method that can be used for body-composition analysis. It also shows that fat-referenced MRI can produce quantitative high-resolution images, a necessity for many BAT applications.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 85
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1910
Keywords
MRI, water-fat separation, quantitative MRI
National Category
Medical Image Processing
Identifiers
urn:nbn:se:liu:diva-145316 (URN)10.3384/diss.diva-145316 (DOI)9789176853511 (ISBN)
Public defence
2018-03-21, Grantisalen, Campus US, Linköping, 09:15 (English)
Opponent
Supervisors
Note

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Available from: 2018-02-27 Created: 2018-02-22 Last updated: 2018-02-28Bibliographically approved

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