Thobias Romu

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.

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.

MRI-Visual Order–Disorder Micellar Nanostructures for Smart Cancer Theranostics

The development of MRI-visual order-disorder structures for cancer nanomedicine explores a pH-triggered mechanism for theragnosis of tumor hallmark functions. Superparamagnetic iron oxide nanoparticles (SPIONs) stabilized with amphiphilic poly(styrene)-b-poly(acrylic acid)-doxorubicin with folic acid (FA) surfacing are employed as a multi-functional approach to specifically target, diagnose, and deliver drugs via a single nanoscopic platform for cancer therapy. The functional aspects of the micellar nanocomposite is investigated in vitro using human breast SkBr3 and colon cancer HCT116 cell lines for the delivery, release, localization, and anticancer activity of the drug. For the first time, concentration-dependent T2 -weighted MRI contrast for a monolayer of clustered cancer cells is shown. The pH tunable order-disorder transition of the core-shell structure induces the relative changes in MRI contrast. The outcomes elucidate the potential of this material for smart cancer theranostics by delivering non-invasive real-time diagnosis, targeted therapy, and monitoring the course and response of the action before, during, and after the treatment regimen.

MANA - Multi scale adaptive normalized averaging

It is possible to correct intensity inhomogeneity in fat-water Magnetic Resonance Imaging (MRI) by estimating a bias field based on the observed intensities of voxels classified as the pure adipose tissue [1]. The same procedure can also be used to quantify fat volume and its distribution [2] which opens up for new medical applications. The bias field estimation method has to be robust since pure fat voxels are irregularly located and the density varies greatly within and between image volumes. This paper introduces Multi scale Adaptive Normalized Average (MANA) that solves this problem by basing the estimate on a scale space of weighted averages. By using the local certainty of the data MANA preserves details where the local data certainty is high and provides realistic values in sparse areas.

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

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.

Fat Quantification in Skeletal Muscle Using Multigradient-Echo Imaging: Comparison of Fat and Water References

To investigate the precision, accuracy, and repeatability of water/fat imaging‐based fat quantification in muscle tissue using a large flip angle (FA) and a fat reference for the calculation of the proton density fat fraction (FF). Comparison is made to a small FA water reference approach.

A randomized trial of cold-exposure on energy expenditure and supraclavicular brown adipose tissue volume in humans.

OBJECTIVE To study if repeated cold-exposure increases metabolic rate and/or brown adipose tissue (BAT) volume in humans when compared with avoiding to freeze. DESIGN Randomized, open, parallel-group trial. METHODS Healthy non-selected participants were randomized to achieve cold-exposure 1hour/day, or to avoid any sense of feeling cold, for 6weeks. Metabolic rate (MR) was measured by indirect calorimetry before and after acute cold-exposure with cold vests and ingestion of cold water. The BAT volumes in the supraclavicular region were measured with magnetic resonance imaging (MRI). RESULTS Twenty-eight participants were recruited, 12 were allocated to controls and 16 to cold-exposure. Two participants in the cold group dropped out and one was excluded. Both the non-stimulated and the cold-stimulated MR were lowered within the group randomized to avoid cold (MR at room temperature from 1841±199 kCal/24h to 1795±213 kCal/24h, p=0.047 cold-activated MR from 1900±150 kCal/24h to 1793±215 kCal/24h, p=0.028). There was a trend towards increased MR at room temperature following the intervention in the cold-group (p=0.052). The difference between MR changes by the interventions between groups was statistically significant (p=0.008 at room temperature, p=0.032 after cold-activation). In an on-treatment analysis after exclusion of two participants that reported ≥8days without cold-exposure, supraclavicular BAT volume had increased in the cold-exposure group (from 0.0175±0.015l to 0.0216±0.014l, p=0.049). CONCLUSIONS We found evidence for plasticity in metabolic rate by avoiding to freeze compared with cold-exposure in a randomized setting in non-selected humans.