Distribution of adipose tissue: Quantification and relationship with hepatic steatosis and vascular profiles of type 2 diabetic patients with metabolic syndrome

AimAs the distribution of fat is increasingly related to cardiovascular events, we examined whether or not abdominal-fat quantification using magnetic resonance imaging (MRI) software is reliable, and whether or not it is related to clinical markers of fat distribution as well as to metabolic and vascular status. Methods We recorded the anthropometric measurements of 34 obese type 2 diabetic patients with metabolic syndrome. The patients were enrolled to evaluate their abdominal (visceral and subcutaneous) adipose tissue by single-slice L3–L4 MRI. Manual and automated analyses were compared. The relationships between anthropometric measurements, biological markers and intima-media thickness of the common carotid artery were also assessed. Results We validated the automated software to quantify abdominal-fat deposition with MRI compared with manual measurements (r2 = 0.95). The waist-to-hip-circumference ratio (WHR) was the only clinical parameter that correlated with the proportion and quantity of visceral and subcutaneous abdominal-adipose tissue evaluated by MRI (r = 0.60). In addition, fat repartition as evaluated by WHR was related to hepatic steatosis parameters (ferritin and ALAT) and to intima-media thickness, whereas simple waist circumference was not a determinant in these obese patients. We also showed that the adiponectin-to-leptin ratio was related to adipose tissue distribution. Conclusion Distribution of abdominal fat, as evaluated by MRI, can be reflected by clinical determination of the WHR. Differences in regional accumulations of abdominal fat may be specifically related to variations in the risks of steatosis and vascular rigidity among obese type 2 diabetic patients

Precise and simple quantitation of liver steatosis by MRI in an animal model and in patients with NAFLD

International audienc

Fuzzy algorithms: Application to adipose tissue quantification on MR images

Abstract Metabolic syndrome, which is related to abdominal obesity, is a fast growing disease in our western countries. Its presence greatly increases the risk of developing cardiovascular diseases. The accumulation of visceral adipose tissue plays a key role in the development of the metabolic syndrome. The increase of waist circumference is one of the five criteria of the metabolic syndrome diagnosis. But this increase can be due to visceral or subcutaneous adipose tissues. And these adipose tissues do not play the same rule in metabolic syndrome. The purpose of this study was to develop software for automatic and reliable quantification of visceral and subcutaneous adipose tissues, to detect patient with high risk to develop metabolic syndrome and to follow the evolution of adipose tissue repartition after treatment. A gradient echo magnetic resonance (MR) technique is used, with a TE such that fat and water are opposed in phase. The developed process is based on two fuzzy algorithms. First, we fuzzy generalized clustering algorithms allow to merge pixels according to their intensities. Then, fuzzy connectedness algorithm allows to merge pixels according to cost function related to distance, gradient distance and intensities. A validation is performed with a comparison between expert results made by manual drawing and purpose-made software results. Our software provides an automatic and reliable method to segment visceral and subcutaneous adipose tissue and additionally avoids in some case the problem of inhomogeneity of signal intensity

Non-invasive diagnosis of liver lesions by blood tests in NAFLD

Background and Aims: Non invasive tests are not well developedin NAFLD. This could be partly due to the pathological description of certain lesions that is hampered by semi-quantitative scorings. Our aim was to develop an accurate non-invasive measurement of main liver lesions in NAFLD by blood tests based on a thorough pathological and morphometric analysis. Methods: Steatosis, NASH and fibrosis were graded according to CRN-NASH (Kleiner, Hepatology 2005) and Metavir systems in 226 patients with NAFLD. A fully automated, in-house software measured the fractal dimension (reflecting architecture) and the area (reflecting amount) of steatosis or fibrosis on liver specimens. Independent predictors were selected by logistic or multiple regression repeated in 1000 random bootstrap samples. When models were determined, a second bootstrap resampling was performed to measure optimism bias (Steyerberg et al. 2001)

Distribution of abdominal adipose tissue as a predictor of hepatic steatosis assessed by MRI

AIM: To evaluate the relationship between the distribution of visceral and subcutaneous adipose tissue and hepatic steatosis assessed using magnetic resonance imaging (MRI). MATERIALS AND METHODS: One T1-weighted, in-/out-of-phase, single-section sequence at the L3/L4 level and one multi-echo gradient MRI (MGRE) sequence were performed on 65 patients [19 females and 46 males; age 57+/-9.5 years; body mass index (BMI) 31+/-5.1kg/m(2)]. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) surfaces, and hepatic steatosis were automatically calculated using in-house software. Weight, height, BMI, waist circumference, hip circumference, and waist:hip ratio were recorded. The probability of having a steatosis greater than 10% on MRI was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The anthropometric parameter best correlated to hepatic steatosis was the waist-to-hip ratio (r=0.301). VAT and proportion of VAT were correlated to liver fat content (r=0.307 and r=0.249, respectively). No significant correlations were found for BMI, hip circumference, and SAT. The area under the receiver operating characteristics (AUROCs) for the relationship between liver steatosis and BMI, waist circumference, waist:hip ratio, VAT surface, and proportion of VAT, were respectively 0.52, 0.63, 0.71, 0.73 and 0.75. CONCLUSION: Adipose tissue distribution is more relevant than total fat mass when assessing the possibility of liver steatosis in overweight patients

Noninvasive liver steatosis quantification using MRI techniques combined with blood markers:

Aims: To evaluate the accuracy of different techniques of MRI steatosis quantification, based on histological grading and quantification of liver steatosis.Patients and methods: Twenty-three patients (21 with nonalcoholic fatty liver disease and two controls) were included. Steatosis was evaluated in liver specimens using histological grading (five grades) and steatosis area (% of liver surface) was computed using an inhouse automated image analysis. The following five MRI quantification techniques were performed: two-point Dixon, three-point Dixon, DUAL, spin echo method and a new technique called multi-echo gradient-echo (MFGRE). Interobserver (two observers) and intersite (three different liver sites) agreements were evaluated for the two best-performing methods. Results: Steatosis area was correlated with steatosis grade: Rs (Spearman coefficient)=0.82, P value of less than 0.001. The steatosis area was significantly different between S0–S2 and S3–S4 grades: 4.2±2.4 versus 16.4±8.9% (P<0.001). Correlations between the MRI techniques and steatosis area (or grading) were: MFGRE, Rs=0.72 (0.78); spin echo method, Rs=0.72 (0.76); DUAL, Rs=0.71 (0.76); two-point Dixon, Rs=0.71 (0.75); three-point Dixon, Rs=0.67 (0.77). Interobserver (Ric=0.99) and intersite (Ric=0.97) agreements were excellent for the liver steatosis measurement by MFGRE. The noninvasive diagnosis of the steatosis area was improved by adding blood markers like ALT and triglycerides to MFGRE (aR2: 0.805). Conclusion: MRI, and in particular the MFGRE method, provides accurate and automatic quantification for the noninvasive evaluation of liver steatosis, either as a single measurement or in combination with blood variables

MRI measurement of liver fat content predicts the metabolic syndrome

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk

Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus

Maitotoxins (MTXs) are among the most potent toxins known. These toxins are produced by epi-benthic dinoflagellates of the genera Gambierdiscus and Fukuyoa and may play a role in causing the symptoms associated with Ciguatera Fish Poisoning. A recent survey revealed that, of the species tested, the newly described species from the Canary Islands, G. excentricus, is one of the most maitotoxic. The goal of the present study was to characterize MTX-related compounds produced by this species. Initially, lysates of cells from two Canary Island G. excentricus strains VGO791 and VGO792 were partially purified by (i) liquid-liquid partitioning between dichloromethane and aqueous methanol followed by (ii) size-exclusion chromatography. Fractions from chromatographic separation were screened for MTX toxicity using both the neuroblastoma neuro-2a (N2a) cytotoxicity and Ca2+ flux functional assays. Fractions containing MTX activity were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to pinpoint potential MTX analogs. Subsequent non-targeted HRMS analysis permitted the identification of a novel MTX analog, maitotoxin-4 (MTX4, accurate mono-isotopic mass of 3292.4860 Da, as free acid form) in the most toxic fractions. HRMS/MS spectra of MTX4 as well as of MTX are presented. In addition, crude methanolic extracts of five other strains of G. excentricus and 37 other strains representing one Fukuyoa species and ten species, one ribotype and one undetermined strain/species of Gambierdiscus were screened for the presence of MTXs using low resolution tandem mass spectrometry (LRMS/MS). This targeted analysis indicated the original maitotoxin (MTX) was only present in one strain (G. australes S080911_1). Putative maitotoxin-2 (p-MTX2) and maitotoxin-3 (p-MTX3) were identified in several other species, but confirmation was not possible because of the lack of reference material. Maitotoxin-4 was detected in all seven strains of G. excentricus examined, independently of their origin (Brazil, Canary Islands and Caribbean), and not detected in any other species. MTX4 may therefore serve as a biomarker for the highly toxic G. excentricus in the Atlantic area

Quantum Dot Targeting with Lipoic Acid Ligase and HaloTag for Single-Molecule Imaging on Living Cells

We present a methodology for targeting quantum dots to specific proteins on living cells in two steps. In the first step, Escherichia coli lipoic acid ligase (LplA) site-specifically attaches 10-bromodecanoic acid onto a 13 amino acid recognition sequence that is genetically fused to a protein of interest. In the second step, quantum dots derivatized with HaloTag, a modified haloalkane dehalogenase, react with the ligated bromodecanoic acid to form a covalent adduct. We found this targeting method to be specific, fast, and fully orthogonal to a previously reported and analogous quantum dot targeting method using E. coli biotin ligase and streptavidin. We used these two methods in combination for two-color quantum dot visualization of different proteins expressed on the same cell or on neighboring cells. Both methods were also used to track single molecules of neurexin, a synaptic adhesion protein, to measure its lateral diffusion in the presence of neuroligin, its trans-synaptic adhesion partner.National Institutes of Health (U.S.) (R01 GM072670)Camille & Henry Dreyfus FoundationMassachusetts Institute of Technology. Computational and Systems Biology Program. MIT-Merck Postdoctoral Fellowshi