Resistance training decreased abdominal adiposity in postmenopausal women.

OBJECTIVE: To investigate if abdominal adipose tissue volumes and ratios change after a 15-week structured resistance training intervention in postmenopausal women with vasomotor symptoms (VMS). STUDY DESIGN: Sixty-five postmenopausal women with VMS and low physical activity were randomized to either three days/week supervised resistance training or unchanged physical activity for 15 weeks. Women underwent clinical anthropometric measurements and magnetic resonance imaging (MRI) at baseline and after 15 weeks. MRI was done using a Philips Ingenia 3.0 T MR scanner (Philips, Best, The Netherlands). The per protocol principle was used in the analysis of data. MAIN OUTCOME MEASUREMENTS: The absolute change from baseline to week 15 in visceral adipose tissue (VAT) volume and the relative ratio (VAT ratio) between VAT and total abdominal adipose tissue (TAAT), i.e. the sum of abdominal subcutaneous adipose tissue (ASAT) and VAT. RESULTS: There were no significant differences between the groups in characteristics, anthropometry or MRI measures at baseline. Women who were compliant with the intervention (i.e. participated in at least two of the three scheduled training sessions per week) had significantly different reduction over time in ASAT (p = 0.006), VAT (p = 0.002), TAAT (p = 0.003) and fat ratio (p < 0.001) compared with women in the control group. CONCLUSIONS: Implementation of a 15-week resistance training regimen in midlife may help women to counteract the abdominal fat redistribution associated with the menopausal transition. CLINICAL TRIALS: gov registered ID: NCT01987778.

Fatty infiltrate and neck muscle volume in individuals with chronic whiplash associated disorders compared to healthy controls - a cross sectional case-control study.

BACKGROUND: The underlying pathophysiological mechanisms of chronic Whiplash Associated Disorders (WAD) are not fully understood. More knowledge of morphology is needed to better understand the disorder, improve diagnostics and treatments. The aim was to investigate dorsal neck muscle volume (MV) and muscle fat infiltration (MFI) in relation to self-reported neck disability among 30 participants with chronic WAD grade II-III compared to 30 matched healthy controls. METHODS: MV and MFI at spinal segments C4 through C7 in both sexes with mild- to moderate chronic WAD (n = 20), severe chronic WAD (n = 10), and age- and sex matched healthy controls (n = 30) was compared. Muscles: trapezius, splenius, semispinalis capitis and semispinalis cervicis were segmented by a blinded assessor and analyzed. RESULTS: Higher MFI was found in right trapezius (p = 0.007, Cohen's d = 0.9) among participants with severe chronic WAD compared to healthy controls. No other significant difference was found for MFI (p = 0.22-0.95) or MV (p = 0.20-0.76). CONCLUSIONS: There are quantifiable changes in muscle composition of right trapezius on the side of dominant pain and/or symptoms, among participants with severe chronic WAD. No other statistically significant differences were shown for MFI or MV. These findings add knowledge of the association between MFI, muscle size and self-reported neck disability in chronic WAD. TRIAL REGISTRATION: NA. This is a cross-sectional case-control embedded in a cohort study.

Assessment of anterior thigh muscle size and fat infiltration using single-slice CT imaging versus automated MRI analysis in adults.

OBJECTIVES: We examined the longitudinal and cross-sectional relationship between automated MRI-analysis and single-slice axial CT imaging for determining muscle size and muscle fat infiltration (MFI) of the anterior thigh. METHODS: Twenty-two patients completing sex-hormone treatment expected to result in muscle hypertrophy (n = 12) and atrophy (n = 10) underwent MRI scans using 2-point Dixon fat/water-separated sequences and CT scans using a system operating at 120 kV and a fixed flux of 100 mA. At baseline and 12 months after, automated volumetric MRI analysis of the anterior thigh was performed bilaterally, and fat-free muscle volume and MFI were computed. In addition, cross-sectional area (CSA) and radiological attenuation (RA) (as a marker of fat infiltration) were calculated from single slice axial CT-images using threshold-assisted planimetry. Linear regression models were used to convert units. RESULTS: There was a strong correlation between MRI-derived fat-free muscle volume and CT-derived CSA (R = 0.91), and between MRI-derived MFI and CT-derived RA (R = -0.81). The 95% limits of agreement were ±0.32 L for muscle volume and ±1.3% units for %MFI. The longitudinal change in muscle size and MFI was comparable across imaging modalities. CONCLUSIONS: Both automated MRI and single-slice CT-imaging can be used to reliably quantify anterior thigh muscle size and MFI. ADVANCES IN KNOWLEDGE: This is the first study examining the intermodal agreement between automated MRI analysis and CT-image assessment of muscle size and MFI in the anterior thigh muscles. Our results support that both CT- and MRI-derived measures of muscle size and MFI can be used in clinical settings.

Cardiometabolic Health Outcomes Associated With Discordant Visceral and Liver Fat Phenotypes: Insights From the Dallas Heart Study and UK Biobank.

OBJECTIVE: To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts. PATIENTS AND METHODS: Participants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable-adjusted regression and were replicated in the independent UK Biobank. RESULTS: The Dallas Heart Study included 2064 participants (mean ± SD age, 44±9 years; 54% female; 47% black). High VAT-high LF and high VAT-low LF were associated with prevalent atherosclerosis, whereas low VAT-high LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VAT-high LF and high VAT-low LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VAT-high LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N=22,354; April 2014-May 2020), only high VAT-low LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9]). CONCLUSION: Although VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual.

The effect on precision and T1 bias comparing two flip angles when estimating muscle fat infiltration using fat-referenced chemical shift-encoded imaging.

Investigation of the effect on accuracy and precision of different parameter settings is important for quantitative MRI. The purpose of this study was to investigate T1 bias and precision for muscle fat infiltration (MFI) measurements using fat-referenced chemical shift MFI measurements at flip angles of 5° and 10°. The fat-referenced measurements were compared with fat fractions, which is a more commonly used measure of MFI. This retrospective study was performed on data from a clinical intervention study including 40 postmenopausal women. Test and retest images were acquired with a 3-T scanner using four-point 3D spoiled gradient multiecho acquisition. Postprocessing included T2* correction and fat-referenced calibration, where the fat signal was calibrated using adipose tissue as reference. The mean MFI was calculated in six different muscle regions using both the fat-referenced fat signal and the fat fraction, defined as the fat signal divided by the sum of the fat and water signals. Both methods used the same fat and water images as input. The variance of the difference between mean MFI from test and retest was used as the measure of precision. The signal-to-noise ratio (SNR) characteristics were analyzed by measuring the full width at half maximum (FWHM) of the fat signal distribution. There was no difference in the mean MFI at different flip angles for the fat-referenced technique (p = 0.66), while the measured fat fractions were 3.3 percentage points larger for 10° compared with 5° (p < 0.001). No significant difference in the precision was found in any of the muscles analyzed. However, the FWHM of the fat signal distribution was significantly (p = 0.01) lower at 10°. This strenghtens the hypothesis that fat-referenced MFI is insensitive to flip angle-induced T1 bias in CSE-MRI, enabling usage of a higher and more SNR-effective flip angle. The lower FWHM in fat-referenced MFI at 10° indicates that high flip angle acquisition is advantageous even although no significant differences in precision were observed comparing 5° and 10°.

Reproducibility and repeatability of MRI-based body composition analysis.

PURPOSE: There is an absence of reproducibility studies on MRI-based body composition analysis in current literature. Therefore, the aim of this study was to investigate the between-scanner reproducibility and the repeatability of a method for MRI-based body composition analysis. METHODS: Eighteen healthy volunteers of varying body mass index and adiposity were each scanned twice on five different 1.5T and 3T scanners from three different vendors. Two-point Dixon neck-to knee images and two additional liver scans were acquired with similar protocols. Visceral adipose tissue (VAT) volume, abdominal subcutaneous adipose tissue (ASAT) volume, thigh muscle volume, and muscle fat infiltration (MFI) in the thigh muscle were measured. Liver proton density fat fraction (PDFF) was assessed using two different methods, the scanner vendor's 6-point method and an in-house 2-point method. Within-scanner test-retest repeatability and between-scanner reproducibility were calculated using analysis of variance. RESULTS: Repeatability coefficients were 13 centiliters (cl) (VAT), 24 cl (ASAT), 17 cl (total thigh muscle volume), 0.53% (MFI), and 1.27-1.37% for liver PDFF. Reproducibility coefficients were 24 cl (VAT), 42 cl (ASAT), 31 cl (total thigh muscle volume), 1.44% (MFI), and 2.37-2.40% for liver PDFF. CONCLUSION: For all measures except MFI, the within-scanner repeatability explained much of the overall reproducibility. The two methods for measuring liver fat had similar reproducibility. This study showed that the investigated method eliminates effects due to scanner differences. The results can be used for power calculations in clinical studies or to better understand the scanner-induced variability in clinical applications.

The relation between local and distal muscle fat infiltration in chronic whiplash using magnetic resonance imaging.

The objective of this study was to investigate the relationship between fat infiltration in the cervical multifidi and fat infiltration measured in the lower extremities to move further into understanding the complex signs and symptoms arising from a whiplash trauma. Thirty-one individuals with chronic whiplash associated disorders, stratified into a mild/moderate group and a severe group, together with 31 age- and gender matched controls were enrolled in this study. Magnetic resonance imaging was used to acquire a 3D volume of the neck and of the whole-body. Cervical multifidi was used to represent muscles local to the whiplash trauma and all muscles below the hip joint, the lower extremities, were representing widespread muscles distal to the site of the trauma. The fat infiltration was determined by fat fraction in the segmented images. There was a linear correlation between local and distal muscle fat infiltration (p<0.001, r2 = 0.28). The correlation remained significant when adjusting for age and WAD group (p = 0.009) as well as when correcting for age, WAD group and BMI (p = 0.002). There was a correlation between local and distal muscle fat infiltration within the severe WAD group (p = 0.0016, r2 = 0.69) and in the healthy group (p = 0.022, r2 = 0.17) but not in the mild/moderate group (p = 0.29, r2 = 0.06). No significant differences (p = 0.11) in the lower extremities' MFI between the different groups were found. The absence of differences between the groups in terms of lower extremities' muscle fat infiltration indicates that, in this particular population, the whiplash trauma has a local effect on muscle fat infiltration rather than a generalized.

Sub-phenotyping Metabolic Disorders Using Body Composition: An Individualized, Nonparametric Approach Utilizing Large Data Sets.

OBJECTIVE: This study performed individual-centric, data-driven calculations of propensity for coronary heart disease (CHD) and type 2 diabetes (T2D), utilizing magnetic resonance imaging-acquired body composition measurements, for sub-phenotyping of obesity and nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 10,019 participants from the UK Biobank imaging substudy were included and analyzed for visceral and abdominal subcutaneous adipose tissue, muscle fat infiltration, and liver fat. An adaption of the k-nearest neighbors algorithm was applied to the imaging variable space to calculate individualized CHD and T2D propensity and explore metabolic sub-phenotyping within obesity and NAFLD. RESULTS: The ranges of CHD and T2D propensity for the whole cohort were 1.3% to 58.0% and 0.6% to 42.0%, respectively. The diagnostic performance, area under the receiver operating characteristic curve (95% CI), using disease propensities for CHD and T2D detection was 0.75 (0.73-0.77) and 0.79 (0.77-0.81). Exploring individualized disease propensity, CHD phenotypes, T2D phenotypes, comorbid phenotypes, and metabolically healthy phenotypes were found within obesity and NAFLD. CONCLUSIONS: The adaptive k-nearest neighbors algorithm allowed an individual-centric assessment of each individual's metabolic phenotype moving beyond discrete categorizations of body composition. Within obesity and NAFLD, this may help in identifying which comorbidities a patient may develop and consequently enable optimization of treatment.

Pathophysiology behind prolonged whiplash associated disorders: study protocol for an experimental study.

BACKGROUND: There is insufficient knowledge of pathophysiological parameters to understand the mechanism behind prolonged whiplash associated disorders (WAD), and it is not known whether or not changes can be restored by rehabilitation. The aims of the projects are to investigate imaging and molecular biomarkers, cervical kinaesthesia, postural sway and the association with pain, disability and other outcomes in individuals with longstanding WAD, before and after a neck-specific exercise intervention. Another aim is to compare individuals with WAD with healthy controls. METHODS: Participants are a sub-group (n = 30) of individuals recruited from an ongoing randomized controlled study (RCT). Measurements in this experimental prospective study will be carried out at baseline (before intervention) and at a three month follow-up (end of physiotherapy intervention), and will include muscle structure and inflammation using magnetic resonance imaging (MRI), brain structure and function related to pain using functional MRI (fMRI), muscle function using ultrasonography, biomarkers using samples of blood and saliva, cervical kinaesthesia using the "butterfly test" and static balance test using an iPhone app. Association with other measures (self-reported and clinical measures) obtained in the RCT (e.g. background data, pain, disability, satisfaction with care, work ability, quality of life) may be investigated. Healthy volunteers matched for age and gender will be recruited as controls (n = 30). DISCUSSION: The study results may contribute to the development of improved diagnostics and improved rehabilitation methods for WAD. TRIAL REGISTRATION: Clinicaltrial.gov Protocol ID: NCT03664934, initial release 09/11/2018.

Unexpected Fat Distribution in Adolescents With Narcolepsy.

Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease.

Correction: A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate.

[This corrects the article DOI: 10.1371/journal.pone.0147149.].

MRI adipose tissue and muscle composition analysis-a review of automation techniques.

MRI is becoming more frequently used in studies involving measurements of adipose tissue and volume and composition of skeletal muscles. The large amount of data generated by MRI calls for automated analysis methods. This review article presents a summary of automated and semi-automated techniques published between 2013 and 2017. Technical aspects and clinical applications for MRI-based adipose tissue and muscle composition analysis are discussed based on recently published studies. The conclusion is that very few clinical studies have used highly automated analysis methods, despite the rapidly increasing use of MRI for body composition analysis. Possible reasons for this are that the availability of highly automated methods has been limited for non-imaging experts, and also that there is a limited number of studies investigating the reproducibility of automated methods for MRI-based body composition analysis.

Body Composition Profiling in the UK Biobank Imaging Study.

OBJECTIVE: This study aimed to investigate the value of imaging-based multivariable body composition profiling by describing its association with coronary heart disease (CHD), type 2 diabetes (T2D), and metabolic health on individual and population levels. METHODS: The first 6,021 participants scanned by UK Biobank were included. Body composition profiles (BCPs) were calculated, including abdominal subcutaneous adipose tissue, visceral adipose tissue (VAT), thigh muscle volume, liver fat, and muscle fat infiltration (MFI), determined using magnetic resonance imaging. Associations between BCP and metabolic status were investigated using matching procedures and multivariable statistical modeling. RESULTS: Matched control analysis showed that higher VAT and MFI were associated with CHD and T2D (P < 0.001). Higher liver fat was associated with T2D (P < 0.001) and lower liver fat with CHD (P < 0.05), matching on VAT. Multivariable modeling showed that lower VAT and MFI were associated with metabolic health (P < 0.001), and liver fat was nonsignificant. Associations remained significant adjusting for sex, age, BMI, alcohol, smoking, and physical activity. CONCLUSIONS: Body composition profiling enabled an intuitive visualization of body composition and showed the complexity of associations between fat distribution and metabolic status, stressing the importance of a multivariable approach. Different diseases were linked to different BCPs, which could not be described by a single fat compartment alone.

Advanced body composition assessment: from body mass index to body composition profiling.

This paper gives a brief overview of common non-invasive techniques for body composition analysis and a more in-depth review of a body composition assessment method based on fat-referenced quantitative MRI. Earlier published studies of this method are summarized, and a previously unpublished validation study, based on 4753 subjects from the UK Biobank imaging cohort, comparing the quantitative MRI method with dual-energy X-ray absorptiometry (DXA) is presented. For whole-body measurements of adipose tissue (AT) or fat and lean tissue (LT), DXA and quantitative MRIs show excellent agreement with linear correlation of 0.99 and 0.97, and coefficient of variation (CV) of 4.5 and 4.6 per cent for fat (computed from AT) and LT, respectively, but the agreement was found significantly lower for visceral adipose tissue, with a CV of >20 per cent. The additional ability of MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat, in combination with rapid scanning protocols and efficient image analysis tools, makes quantitative MRI a powerful tool for advanced body composition assessment.

Precision of MRI-based body composition measurements of postmenopausal women.

OBJECTIVES: To determine precision of magnetic resonance imaging (MRI) based fat and muscle quantification in a group of postmenopausal women. Furthermore, to extend the method to individual muscles relevant to upper-body exercise. MATERIALS AND METHODS: This was a sub-study to a randomized control trial investigating effects of resistance training to decrease hot flushes in postmenopausal women. Thirty-six women were included, mean age 56 ± 6 years. Each subject was scanned twice with a 3.0T MR-scanner using a whole-body Dixon protocol. Water and fat images were calculated using a 6-peak lipid model including R2*-correction. Body composition analyses were performed to measure visceral and subcutaneous fat volumes, lean volumes and muscle fat infiltration (MFI) of the muscle groups' thigh muscles, lower leg muscles, and abdominal muscles, as well as the three individual muscles pectoralis, latissimus, and rhomboideus. Analysis was performed using a multi-atlas, calibrated water-fat separated quantification method. Liver-fat was measured as average proton density fat-fraction (PDFF) of three regions-of-interest. Precision was determined with Bland-Altman analysis, repeatability, and coefficient of variation. RESULTS: All of the 36 included women were successfully scanned and analysed. The coefficient of variation was 1.1% to 1.5% for abdominal fat compartments (visceral and subcutaneous), 0.8% to 1.9% for volumes of muscle groups (thigh, lower leg, and abdomen), and 2.3% to 7.0% for individual muscle volumes (pectoralis, latissimus, and rhomboideus). Limits of agreement for MFI was within ± 2.06% for muscle groups and within ± 5.13% for individual muscles. The limits of agreement for liver PDFF was within ± 1.9%. CONCLUSION: Whole-body Dixon MRI could characterize a range of different fat and muscle compartments with high precision, including individual muscles, in the study-group of postmenopausal women. The inclusion of individual muscles, calculated from the same scan, enables analysis for specific intervention programs and studies.

Quantifying Abdominal Adipose Tissue and Thigh Muscle Volume and Hepatic Proton Density Fat Fraction: Repeatability and Accuracy of an MR Imaging-based, Semiautomated Analysis Method.

Purpose To determine the repeatability and accuracy of a commercially available magnetic resonance (MR) imaging-based, semiautomated method to quantify abdominal adipose tissue and thigh muscle volume and hepatic proton density fat fraction (PDFF). Materials and Methods This prospective study was institutional review board- approved and HIPAA compliant. All subjects provided written informed consent. Inclusion criteria were age of 18 years or older and willingness to participate. The exclusion criterion was contraindication to MR imaging. Three-dimensional T1-weighted dual-echo body-coil images were acquired three times. Source images were reconstructed to generate water and calibrated fat images. Abdominal adipose tissue and thigh muscle were segmented, and their volumes were estimated by using a semiautomated method and, as a reference standard, a manual method. Hepatic PDFF was estimated by using a confounder-corrected chemical shift-encoded MR imaging method with hybrid complex-magnitude reconstruction and, as a reference standard, MR spectroscopy. Tissue volume and hepatic PDFF intra- and interexamination repeatability were assessed by using intraclass correlation and coefficient of variation analysis. Tissue volume and hepatic PDFF accuracy were assessed by means of linear regression with the respective reference standards. Results Adipose and thigh muscle tissue volumes of 20 subjects (18 women; age range, 25-76 years; body mass index range, 19.3-43.9 kg/m2) were estimated by using the semiautomated method. Intra- and interexamination intraclass correlation coefficients were 0.996-0.998 and coefficients of variation were 1.5%-3.6%. For hepatic MR imaging PDFF, intra- and interexamination intraclass correlation coefficients were greater than or equal to 0.994 and coefficients of variation were less than or equal to 7.3%. In the regression analyses of manual versus semiautomated volume and spectroscopy versus MR imaging, PDFF slopes and intercepts were close to the identity line, and correlations of determination at multivariate analysis (R2) ranged from 0.744 to 0.994. Conclusion This MR imaging-based, semiautomated method provides high repeatability and accuracy for estimating abdominal adipose tissue and thigh muscle volumes and hepatic PDFF. © RSNA, 2017.

Robust water fat separated dual-echo MRI by phase-sensitive reconstruction.

PURPOSE: The purpose of this work was to develop and evaluate a robust water-fat separation method for T1-weighted symmetric two-point Dixon data. THEORY AND METHODS: A method for water-fat separation by phase unwrapping of the opposite-phase images by phase-sensitive reconstruction (PSR) is introduced. PSR consists of three steps; (1), identification of clusters of tissue voxels; (2), unwrapping of the phase in each cluster by solving Poisson's equation; and (3), finding the correct sign of each unwrapped opposite-phase cluster, so that the water-fat images are assigned the correct identities. Robustness was evaluated by counting the number of water-fat swap artifacts in a total of 733 image volumes. The method was also compared to commercial software. RESULTS: In the water-fat separated image volumes, the PSR method failed to unwrap the phase of one cluster and misclassified 10. One swap was observed in areas affected by motion and was constricted to the affected area. Twenty swaps were observed surrounding susceptibility artifacts, none of which spread outside the artifact affected regions. The PSR method had fewer swaps when compared to commercial software. CONCLUSION: The PSR method can robustly produce water-fat separated whole-body images based on symmetric two-echo spoiled gradient echo images, under both ideal conditions and in the presence of common artifacts. Magn Reson Med 78:1208-1216, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo.

Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment. Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1ß was decreased in dense breasts. No differences were found in levels of IL-1ß, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue. Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies.

INTRODUCTION: Quantitative and accurate measurements of fat and muscle in the body are important for prevention and diagnosis of diseases related to obesity and muscle degeneration. Manually segmenting muscle and fat compartments in MR body-images is laborious and time-consuming, hindering implementation in large cohorts. In the present study, the feasibility and success-rate of a Dixon-based MR scan followed by an intensity-normalised, non-rigid, multi-atlas based segmentation was investigated in a cohort of 3,000 subjects. MATERIALS AND METHODS: 3,000 participants in the in-depth phenotyping arm of the UK Biobank imaging study underwent a comprehensive MR examination. All subjects were scanned using a 1.5 T MR-scanner with the dual-echo Dixon Vibe protocol, covering neck to knees. Subjects were scanned with six slabs in supine position, without localizer. Automated body composition analysis was performed using the AMRA Profiler™ system, to segment and quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT) and thigh muscles. Technical quality assurance was performed and a standard set of acceptance/rejection criteria was established. Descriptive statistics were calculated for all volume measurements and quality assurance metrics. RESULTS: Of the 3,000 subjects, 2,995 (99.83%) were analysable for body fat, 2,828 (94.27%) were analysable when body fat and one thigh was included, and 2,775 (92.50%) were fully analysable for body fat and both thigh muscles. Reasons for not being able to analyse datasets were mainly due to missing slabs in the acquisition, or patient positioned so that large parts of the volume was outside of the field-of-view. DISCUSSION AND CONCLUSIONS: In conclusion, this study showed that the rapid UK Biobank MR-protocol was well tolerated by most subjects and sufficiently robust to achieve very high success-rate for body composition analysis. This research has been conducted using the UK Biobank Resource.

Test-retest reliability of rapid whole body and compartmental fat volume quantification on a widebore 3T MR system in normal-weight, overweight, and obese subjects.

PURPOSE: To measure the test-retest reliability of rapid (<15 min) whole body and visceral fat volume quantification in normal and obese subjects on a widebore 3T MR system and compare it with conventional manual segmentation. MATERIALS AND METHODS: Thirty participants (body mass index [BMI] 20.1-48.6 kg/m2 ) underwent two whole-body magnetic resonance imaging (MRI) examinations on a widebore 3T machine using a 2-point Dixon technique. Phase sensitive reconstruction and intensity inhomogeneity correction produced quantitative datasets of total adipose tissue (TAT), abdominal subcutaneous adipose tissue (ASAT), and visceral adipose tissue (VAT). The quantification was performed automatically using nonrigid atlas-based segmentation and compared with manual segmentation (SliceOmatic). RESULTS: The mean TAT was 31.74 L with a coefficient of variation (CV) of 0.79% and a coefficient of repeatability (CR) of 0.49 L. The ASAT was 7.92 L with a CV of 2.98% and a CR of 0.46 L. There was no significant difference in the semiautomated and manually segmented VAT (P = 0.73) but there were differences in the reliability of the two techniques. The mean semiautomated VAT was 2.56 L, CV 1.8%, and CR 0.09 L compared to the mean manually segmented VAT of 3.12 L, where the CV was 6.3% and the CR was 0.39 L. CONCLUSION: Rapid semiautomated whole body and compartmental fat volume quantification can be derived from a widebore 3T system, for a range of body sizes including obese patients, with "almost perfect" test-retest reliability. J. Magn. Reson. Imaging 2016;44:1464-1473.