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      Semi-automated segmentation and quantification of adipose tissue in calf and thigh by MRI: a preliminary study in patients with monogenic metabolic syndrome

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          Abstract

          Background

          With the growing prevalence of obesity and metabolic syndrome, reliable quantitative imaging methods for adipose tissue are required. Monogenic forms of the metabolic syndrome include Dunnigan-variety familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3), which are characterized by the loss of subcutaneous fat in the extremities. Through magnetic resonance imaging (MRI) of FPLD patients, we have developed a method of quantifying the core FPLD anthropometric phenotype, namely adipose tissue in the mid-calf and mid-thigh regions.

          Methods

          Four female subjects, including an FPLD2 subject ( LMNA R482Q), an FPLD3 subject ( PPARG F388L), and two control subjects were selected for MRI and analysis. MRI scans of subjects were performed on a 1.5T GE MR Medical system, with 17 transaxial slices comprising a 51 mm section obtained in both the mid-calf and mid-thigh regions. Using ImageJ 1.34 n software, analysis of raw MR images involved the creation of a connectedness map of the subcutaneous adipose tissue contours within the lower limb segment from a user-defined seed point. Quantification of the adipose tissue was then obtained after thresholding the connected map and counting the voxels (volumetric pixels) present within the specified region.

          Results

          MR images revealed significant differences in the amounts of subcutaneous adipose tissue in lower limb segments of FPLD3 and FPLD2 subjects: respectively, mid-calf, 15.5% and 0%, and mid-thigh, 25.0% and 13.3%. In comparison, old and young healthy controls had values, respectively, of mid-calf, 32.5% and 26.2%, and mid-thigh, 52.2% and 36.1%. The FPLD2 patient had significantly reduced subcutaneous adipose tissue compared to FPLD3 patient.

          Conclusion

          Thus, semi-automated quantification of adipose tissue of the lower extremity can detect differences between individuals of various lipodystrophy genotypes and represents a potentially useful tool for extended quantitative phenotypic analysis of other genetic metabolic disorders.

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          Most cited references13

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          Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity.

          Obesity is related to the risk for developing non-insulin-dependent diabetes mellitus (NIDDM), hypertension, and cardiovascular disease. Visceral adipose tissue (VAT) has been proposed to mediate these relationships. Abdominal subcutaneous adipose tissue (SAT) is divided into 2 layers by a fascia, the fascia superficialis. Little is known about the radiologic anatomy or metabolic correlates of these depots. The objective of this study was to relate the amounts of VAT, SAT, deep subcutaneous abdominal adipose tissue (DSAT), and superficial subcutaneous abdominal adipose tissue (SSAT) to gender and the metabolic complications of obesity after adjusting for total body fat and to discuss the implications of these findings on the measurement of adipose tissue mass and adipose tissue function. The design was a cross-sectional database study set in a nutrition research center. Subjects included 199 volunteers participating in nutrition research protocols who also had computed tomography (CT) and dual energy x-ray absorptiometry (DEXA) measurement of body fat. The amount of DSAT was sexually dimorphic, with women having 51% of the subcutaneous abdominal fat in the deep layer versus 66% for men (P <.05). Abdominal fat compartments were compared with metabolic variables before and after adjusting for body fat measured by DEXA using 2 separate methods. The unadjusted correlation coefficients between the body fat measures, R(2), were largest for fasting insulin and triglyceride and smaller for high-density lipoprotein (HDL) cholesterol and blood pressure. A large portion of the variance of fasting insulin levels in both men and women was explained by total body fat. In both men and women, the addition of VAT and subcutaneous abdominal adipose tissue depots only slightly increased the R(2). In men, when body fat compartments were considered independently, DSAT explained a greater portion of the variance (R(2) =.528) in fasting insulin than VAT (R(2) =.374) or non-VAT, non-DSAT subcutaneous adipose tissue (R(2) =.375). These data suggest that total body fat is a major contributor to the metabolic sequelae of obesity, with specific fat depots, VAT, and DSAT also making significant contributions. Copyright 2001 by W.B. Saunders Company
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            Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus.

            Insulin resistance is a principal feature of type 2 diabetes and precedes the clinical development of the disease by 10 to 20 years. Insulin resistance is caused by the decreased ability of peripheral target tissues (especially muscle) to respond properly to normal circulating concentrations of insulin. Defects in muscle glycogen synthesis play a significant role in insulin resistance, and 3 potentially rate-controlling steps in muscle glucose metabolism have been implicated in its pathogenesis: glycogen synthase, hexokinase, and GLUT4 (the major insulin-stimulated glucose transporter). Results from recent studies using nuclear magnetic resonance (NMR) spectroscopy implicate intracellular defects in glucose transport as the rate-controlling step for insulin-mediated glucose uptake in muscle. These alterations in glucose transport activity are likely the result of dysregulation of intramyocellular fatty acid metabolism, whereby fatty acids cause insulin resistance by activation of a serine kinase cascade, leading to decreased insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and decreased IRS-1-associated phosphatidylinositol 3-kinase activity, a required step in insulin-stimulated glucose transport into muscle. The thiazolidinedione class of antidiabetic agents directly targets insulin resistance in skeletal muscle by improving glucose transport activity and insulin-stimulated muscle glycogen synthesis. Although the precise mechanism of action is not known, recent NMR studies support the hypothesis that these agents improve insulin action in skeletal muscle and liver by promoting a redistribution of fat out of these tissues and into peripheral adipocytes.
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              In vivo determination of intra-myocellular lipids in human muscle by means of localized 1H-MR-spectroscopy.

              Intra-myocellular lipids (IMCL) are stored in droplets in the cytoplasm of muscle cells and are an energy storage form readily accessed during long-term exercise. 1H-MR spectroscopy methods are presented for noninvasive determination of IMCL in human muscle. This is based on (a) the separation of two resonances in the lipid-CH2-region, with the one assigned to IMCL being independent of muscle orientation relative to the magnetic field and (b) the fact that IMCL resonances scale along with signal amplitudes of metabolites in the muscle cell (e.g., creatine) when voxel size is increased, while lipid signals of bulk fat show a disproportionate growth. Inter-individual and intra-individual reproducibility studies indicate that the error of the method is about 6% and that IMCL levels differ significantly between identical muscles in different subjects, as well as intra-individually when measured at 1 week intervals. IMCL determinations in a single subject before and after strenuous exercise indicate that lipid stores recover with a t1/2 of about 1 day.
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                Author and article information

                Journal
                BMC Med Imaging
                BMC Medical Imaging
                BioMed Central (London )
                1471-2342
                2006
                31 August 2006
                : 6
                : 11
                Affiliations
                [1 ]Vascular Biology Research Group, Robarts Research Institute, London, Ontario, Canada
                [2 ]Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada
                [3 ]Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
                Article
                1471-2342-6-11
                10.1186/1471-2342-6-11
                1564131
                16945131
                e262e006-a3d1-4cda-a4e2-31086d087a9d
                Copyright © 2006 Al-Attar et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 June 2006
                : 31 August 2006
                Categories
                Research Article

                Radiology & Imaging
                Radiology & Imaging

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