Olof Dahlqvist Leinhard

Evidence for two types of brown adipose tissue in humans

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.

Automatic and quantitative assessment of regional muscle volume by multi-atlas segmentation using whole-body water–fat MRI

To develop and demonstrate a rapid whole‐body magnetic resonance imaging (MRI) method for automatic quantification of total and regional skeletal muscle volume.

Quantitative abdominal fat estimation using MRI

This paper introduces a new method for automatic quantification of subcutaneous, visceral and non-visceral internal fat from MR-images acquired using the two point Dixon technique in the abdominal region. The method includes (1) a three dimensional phase unwrapping to provide water and fat images, (2) an image intensity inhomogeneity correction, and (3) a morphon based registration and segmentation of the tissue. This is followed by an integration of the corrected fat images within the different fat compartments that avoids the partial volume effects associated with traditional fat segmentation methods. The method was tested on 18 subjects before and after a period of fast-food hyper-alimentation showing high stability and performance in all analysis steps.

Men develop more intraabdominal obesity and signs of the metabolic syndrome after hyperalimentation than women

We prospectively studied the effects of fast food-based hyperalimentation on insulin sensitivity and components of the metabolic syndrome and analyzed this with respect to sex. Twelve nonobese men and 6 nonobese women (26 +/- 6.6 years old), and an age-matched control group were recruited. Subjects in the intervention group aimed for 5% to 15% weight increase by doubling their regular caloric intake based on at least 2 fast food meals a day while also adopting a sedentary lifestyle for 4 weeks (<5000 steps a day). Weight of subjects in the intervention group increased from 67.6 +/- 9.1 to 74.0 +/- 11 kg (P < .001), with no sex difference with regard to this or with respect to changes of total abdominal fat volumes or waist circumferences. Fasting insulin (men: before, 3.8 +/- 1.7 microU/mL; after, 7.4 +/- 3.1 microU/mL; P = .004; women: before, 4.9 +/- 2.3 microU/mL; after, 5.9 +/- 2.8 microU/mL; P = .17), systolic blood pressure (men: before, 117 +/- 13 mm Hg; after, 127 +/- 9.1 mm Hg; P = .002; women: before, 102 +/- 5.1 mm Hg; after, 98 +/- 5.4 mm Hg; P = .39), serum low-density lipoprotein cholesterol, and apolipoprotein B increased only in the men of the intervention group. The sex differences in the metabolic responses to the intervention were linked to a considerable difference in the fat accumulation pattern; 41.4% +/- 9.2% of the increase of the fat volume in the abdominal region was accumulated intraabdominally in men and 22.7 +/- 6.5% in women (P < .0001). This study thus showed that women are protected, compared with men, against developing intraabdominal obesity when adopting a standardized obesity-provoking lifestyle. Our findings suggest that it is not different lifestyles and/or behaviors that underlie the fact that men have a higher cardiovascular risk at the same level of percentage of body fat than women.

Brown adipose tissue in humans : detection and functional analysis using PET (Positron Emission Tomography), MRI (Magnetic Resonance Imaging), and DECT (Dual Energy Computed Tomography)

If the beneficial effects of brown adipose tissue (BAT) on whole body metabolism, as observed in nonhuman experimental models, are to be translated to humans, tools that accurately measure how BAT influences human metabolism will be required. This chapter discusses such techniques, how they can be used, what they can measure and also some of their limitations. The focus is on detection and functional analysis of human BAT and how this can be facilitated by applying advanced imaging technology such as positron emission tomography, magnetic resonance imaging, and dual energy computed tomography.

Increased Concentrations of Glutamate and Glutamine in Normal Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans

In Multiple Sclerosis (MS) the relationship between disease process in normal-appearing white matter (NAWM) and the development of white matter lesions is not well understood. In this study we used single voxel proton ‘Quantitative Magnetic Resonance Spectroscopy’ (qMRS) to characterize the NAWM and thalamus both in atypical ‘Clinically Definite MS’ (CDMS) patients, MRIneg (N = 15) with very few lesions (two or fewer lesions), and in typical CDMS patients, MRIpos (N = 20) with lesions, in comparison with healthy control subjects (N = 20). In addition, the metabolite concentrations were also correlated with extent of brain atrophy measured using Brain Parenchymal Fraction (BPF) and severity of the disease measured using ‘Multiple Sclerosis Severity Score’ (MSSS). Elevated concentrations of glutamate and glutamine (Glx) were observed in both MS groups (MRIneg 8.12 mM, p<0.001 and MRIpos 7.96 mM p<0.001) compared to controls, 6.76 mM. Linear regressions of Glx and total creatine (tCr) with MSSS were 0.16±0.06 mM/MSSS (p = 0.02) for Glx and 0.06±0.03 mM/MSSS (p = 0.04) for tCr, respectively. Moreover, linear regressions of tCr and myo-Inositol (mIns) with BPF were −6.22±1.63 mM/BPF (p<0.001) for tCr and −7.71±2.43 mM/BPF (p = 0.003) for mIns. Furthermore, the MRIpos patients had lower N-acetylaspartate and N-acetylaspartate-glutamate (tNA) and elevated mIns concentrations in NAWM compared to both controls (tNA: p = 0.04 mIns p<0.001) and MRIneg (tNA: p = 0.03 , mIns: p = 0.002). The results suggest that Glx may be an important marker for pathology in non-lesional white matter in MS. Moreover, Glx is related to the severity of MS independent of number of lesions in the patient. In contrast, increased glial density indicated by increased mIns and decreased neuronal density indicated by the decreased tNA, were only observed in NAWM of typical CDMS patients with white matter lesions.

Normal Appearing and Diffusely Abnormal White Matter in Patients with Multiple Sclerosis Assessed with Quantitative MR

Introduction: Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. Because of this, changes in both ‘normal appearing white matter’ (NAWM) and ‘diffusely abnormal white matter’ (DAWM) have been of interest in recent years. MR techniques, including quantitative magnetic resonance imaging (qMRI) and quantitative magnetic resonance spectroscopy (qMRS), have been developed in order to detect and quantify such changes. In this study, qMRI and qMRS were used to investigate NAWM and DAWM in typical MS patients and in MS patients with low number of WM lesions. Patient data were compared to ‘normal white matter’ (NWM) in healthy controls. Methods: QMRI and qMRS measurements were performed on a 1.5 T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Twenty of the patients fulfilled the ‘Barkhof-Tintoré criteria’ for MS, (‘MRIpos’), whereas 15 showed radiologically atypical findings with few WM lesions (‘MRIneg’). QMRI properties were determined in ROIs of NAWM, DAWM and lesions in the MS groups and of NWM in controls. Descriptive statistical analysis and comparisons were performed. Correlations were calculated between qMRI measurements and (1) clinical parameters and (2) WM metabolite concentrations. Regression analyses were performed with brain parenchyma fraction and MSSS. Results: NAWM in the MRIneg group was significantly different from NAWM in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group correlated negatively with EDSS and MSSS. DAWM was significantly different from NWM, but similar in the MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. R2 of DAWM was associated with BPF. Conclusions: Changes in NAWM and DAWM are independent pathological entities in the disease. The correlation between qMRI and clinical status may shed new light on the clinicoradiological paradox.

Effects of moderate red wine consumption on liver fat and blood lipids: a prospective randomized study

Abstract Background: There have been no human prospective randomized studies of the amount of alcohol that can induce hepatic steatosis. Methods: Thirty-two healthy women and twelve healthy men (34 ± 9 years of age) were randomized to consume 150 ml of red wine/day for women (16 g ethanol/day) or double that amount for men (33 g ethanol/day), or to alcohol abstention for 90 days. Participants underwent proton-nuclear magnetic-resonance spectroscopy for measurement of hepatic triglyceride content (HTGC). Blood samples for assessment of cardiovascular risk were drawn before and after the intervention. Results: After exclusion of three subjects with steatosis at baseline a trend towards increased HTGC was apparent for red wine (before median: 1.1%, range 0.2–3.9%, after median: 1.1%, range 0.5–5.2 %, P = 0.059) a difference that was statistically significant compared with abstainers (p = 0.02). However, no subject developed hepatic steatosis. Low–density lipoprotein (LDL)-cholesterol was lowered by red wine (–0.3 mmol/l, SE –0.1, 95% CI –0.6 to –0.04). Conclusions: Moderate consumption of red wine during three months increased HTGC in subjects without steatosis at baseline. However, since not a single participant developed steatosis we suggest that the threshold of alcohol consumption to define nonalcoholic fatty liver disease should not be lower than the amount in our study. Trial registration: ClinicalTrials.gov identifier: NCT00954434.

Consistent intensity inhomogeneity correction in water–fat MRI

To quantitatively and qualitatively evaluate the water‐signal performance of the consistent intensity inhomogeneity correction (CIIC) method to correct for intensity inhomogeneities

Validation of a fast method for quantification of intra-abdominal and subcutaneous adipose tissue for large-scale human studies.

Central obesity is the hallmark of a number of non‐inheritable disorders. The advent of imaging techniques such as MRI has allowed for a fast and accurate assessment of body fat content and distribution. However, image analysis continues to be one of the major obstacles to the use of MRI in large‐scale studies. In this study we assess the validity of the recently proposed fat–muscle quantitation system (AMRATM Profiler) for the quantification of intra‐abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (ASAT) from abdominal MR images. Abdominal MR images were acquired from 23 volunteers with a broad range of BMIs and analysed using sliceOmatic, the current gold‐standard, and the AMRATM Profiler based on a non‐rigid image registration of a library of segmented atlases. The results show that there was a highly significant correlation between the fat volumes generated by the two analysis methods, (Pearson correlation r = 0.97, p < 0.001), with the AMRATM Profiler analysis being significantly faster (~3 min) than the conventional sliceOmatic approach (~40 min). There was also excellent agreement between the methods for the quantification of IAAT (AMRA 4.73 ± 1.99 versus sliceOmatic 4.73 ± 1.75 l, p = 0.97). For the AMRATM Profiler analysis, the intra‐observer coefficient of variation was 1.6% for IAAT and 1.1% for ASAT, the inter‐observer coefficient of variation was 1.4% for IAAT and 1.2% for ASAT, the intra‐observer correlation was 0.998 for IAAT and 0.999 for ASAT, and the inter‐observer correlation was 0.999 for both IAAT and ASAT. These results indicate that precise and accurate measures of body fat content and distribution can be obtained in a fast and reliable form by the AMRATM Profiler, opening up the possibility of large‐scale human phenotypic studies. Copyright