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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Curr Opin Clin Nutr Metab Care. Author manuscript; available in PMC 2007 June 19.
Published in final edited form as:
PMCID: PMC1894644

Pediatric obesity phenotyping by magnetic resonance methods


Purpose of review

Accurate measurement of adiposity in obese children is required for characterizing the condition’s phenotype, severity, and treatment effects in vivo. Non-invasive and safe, magnetic resonance imaging and spectroscopy provide an important new approach for characterizing key aspects of pediatric obesity. This review focuses on recent advances in non-invasive magnetic resonance imaging and spectroscopy for quantifying total body and regional adiposity, mapping adipose tissue distribution, and evaluating selected metabolic disturbances in children. The aim is to provide an investigator-focused overview of magnetic resonance methods for use in the study of pediatric body composition and metabolism.

Recent findings

Whole body axial images can be rapidly acquired on most clinical magnetic resonance imaging scanners. The images can then be semi-automatically segmented into subcutaneous, visceral, and intramuscular adipose tissue. Specific pediatric studies of errors related to slice gap and number are available. The acquisition of scans in healthy and premature infants is now feasible with recent technological advances. Spectroscopic, Dixon, and other approaches can be used to quantify the lipid content of liver, skeletal muscle, and other organs. Protocol selection is based on factors such as subject age and cost. Particular attention should be directed towards identification of landmarks in growth studies. Recent advances promise to reduce the requirement of subjects to remain motionless for relatively long periods.


Magnetic resonance imaging and spectroscopy are safe, practical, and widely available methods for phenotyping adiposity in children that open new opportunities for metabolism and nutritional research.

Keywords: body composition, genetics, magnetic resonance spectroscopy, nutritional assessment


Although the increasing prevalence of excess adiposity in children was first reported almost two decades ago [1], childhood obesity continues to increase at an alarming rate [24]. Obesity in childhood is not only related to health risks [5] such as the metabolic syndrome [6] and insulin resistance [7], but also often progresses to adult obesity [8,9] associated with morbidity and mortality [10,11]. Accurate measurement of adiposity in phenotyping children is central to contemporary genetic and clinical research.

Many adiposity phenotyping methods are currently available that range from simple to complex and that provide estimates of total and regional body composition [12]. Refining phenotypes, improving their resolution in detecting small between-individual differences, is a high research priority.

The currently accepted adiposity phenotyping reference methods are magnetic resonance imaging (MRI) and computed tomography (CT). Both methods provide high-resolution images that are usually then quantified as specific component areas or volumes. MRI is increasing in use, particularly in children, because of radiation exposure associated with CT. MRI has been used in studying physiological conditions such as adiposity [13], growth and development [14,15], and pathological conditions such as lipodystrophy [16] and muscular dystrophy [17].

While in adults MRI had been extensively used for body composition studies, adaptation is needed when it is applied in children. In this review we will examine aspects of pediatric image acquisition and segmentation along with other key methodology concerns. The purpose of this review is to demonstrate the novel applications of advanced MRI adiposity phenotyping approaches in children.


MRI can be used to measure total body and regional tissue and organ volumes. The mass of each tissue or organ is then calculated as the product of volume and corresponding density (i.e. adipose tissue 0.92 kg/l, skeletal muscle 1.04 kg/l) [18]. Adipose tissue can be further divided into subcutaneous, visceral, and intramuscular adipose tissue [19]. Organ volumes that are usually quantified by MRI include liver, kidney, spleen, and brain [20]. Cardiac MRI can be used to separately study heart mass and function. The mass of these metabolically active organs accurately predicts resting energy expenditure in adults [20], but the energy cost of growth requires additional model development for estimation of resting energy expenditure in children [21].

Usually whole body magnetic resonance T1-weighted images are acquired as axial images with 5–10 mm thickness and 40 mm or less between-slice intervals. Due to both the long analysis time and the incurred high cost, contiguous whole body MRI is rarely recommended for use, except in infants [22,23], who require much fewer slices. The subject is usually positioned either prone or supine with their arms stretched above their head. Due to the limited magnet bore length, the upper and lower body are scanned separately in adults with repositioning using the L4–L5 intervertebral disc as the point of origin. In young children this repositioning may not be necessary. Some technician training will facilitate acquisition of the whole body protocol, which is different from most clinical diagnostic scans. It is also very important to keep the body within the field of view, especially when scanning obese subjects.

Once acquired, MRI and CT scans must be analyzed by the process referred to as image segmentation. There are various segmentation programs available, both commercial and developed in-house. The segmentation procedure for MRI is partially automated, although expert analyst input is still required.

Generally, the segmentation tools can be divided into three groups: manual delineation; low-level segmentation such as thresholding and region growing; and model-based segmentation methods [24]. Specific technical considerations are required for analyzing each tissue and organ. For example, analyzing small adipose tissue depots requires consideration of the regional threshold, particularly when inhomogeneity of the magnetic field is present. On the other hand, organ analysis is carried out by manual tracing in most cases and knowledge of anatomy is required.

Segmentation of a ‘whole-body’ into subcutaneous, visceral, and intramuscular adipose tissue, skeletal muscle, and ‘residual’ usually requires about 4–8 h with a slice gap of 5 cm (i.e. 40 slices) and three to five working days for contiguous MRI scans (i.e. 200 slices), depending on the number of acquired slices and the expertise of the analyst. MRI segmentation solely for adipose tissue requires less time than for segmenting a scan for all compartments. The analyst’s training includes use of segmentation software and knowledge of cross-sectional anatomy. Moreover, it is important for the analyst to recognize some commonly observed artifacts that could influence the differentiation of tissues. These include motion artifacts caused by breathing or bowel peristaltic movements, blood flow artifacts, and other sources of image distortion. Some scanners also have magnetic field inhomogeneity. Although artifacts can be reduced or eliminated by setting specific scan parameters and breath holding, analysts should be trained to recognize the presence of image artifacts.

Most image analysis software now offers three-dimensional reconstruction based on image segmentation data (Fig. 1). Three-dimensional reconstructions are very useful for demonstration purposes. Investigators can visually sense not only the size and distribution of tissue compartments, but also longitudinal changes in tissue/organ size and distribution.

Figure 1
Magnetic resonance scan and three-dimensional reconstruction of the different tissue compartments of a healthy 16-year-old girl

Quality control

Like all measurement procedures, quality control is an important aspect of image analysis. Reproducibility, such as intra-analyst variation, should be routinely evaluated. As large studies may require analysis by more than one technician over a relatively long time, it is essential to evaluate inter-analyst variation and to explore for any time drift. In adults, the intra-class correlation coefficient among trained analysts is reported – skeletal muscle 0.99 (0.89, 1.0); subcutaneous adipose tissue 0.99 (0.81, 1.0); visceral adipose tissue 0.95 (0.58, 0.99) [25] – and these values indicate a high degree of absolute agreement across image readers. The variation in repeated measurements is larger for intramuscular adipose tissue [26,27] and use of high resolution MRI in the future may improve segmentation of this compartment [28]. Adipose tissue within small anatomic areas has a large measurement error [29] and tissue compartments are much smaller in children than in adults. Reproducibility data should be acquired in future pediatric studies to provide more reliable power calculations and assessment of pediatric data accuracy.

As noted earlier, whole body MRI scans are always acquired by slices with a gap of variable magnitude. The volume between two adjacent slices is then estimated by geometric models [30]. There are differences between the measured and the true volumes but the difference is usually within 5% when the slice gap is below 40 mm [30]. Errors caused by slice gap in subcutaneous adipose tissue and skeletal muscle are similar in children and adults [31,32]. Slice gaps cause larger errors in visceral adipose tissue volume estimates in children than in adults, but these errors can be compensated by studying large numbers of subjects [32]. While Chen et al. [32] included children of ages 5–17 years in their studies, future studies need to examine measurement errors in groups with a narrower age range.

In addition to volume quantification of tissue compartments by whole-body imaging protocols, tissue compartments, especially visceral and abdominal subcutaneous adipose tissue, are often reported as the area of a single slice. Because of the cost of whole body scans and concerns over radiation exposure with CT studies, single-slice MRI scans have often been used even though they are less accurate than whole body scans for component estimation [33●,34●]. It is important to recognize that single-slice studies only provide an area when reporting tissue compartments, in contrast to the volumes reported in multiple slice and whole body MRI studies. The single-slice CT and MRI studies are usually performed at the L4–L5 level. In both adults [33●] and children [35], however, a slice in the abdomen higher than the L4–L5 level has been shown to represent visceral adipose tissue better than that at the L4–L5 level.

Magnetic resonance imaging of infants

The nutritional status during infancy and in utero have been linked to obesity and health risks in later life [36,37]. MRI is a well-suited method for evaluating infants as no radiation exposure is present. As infants are usually below 70 cm in length, they are scanned by contiguous MRI scan protocols instead of discrete slices and the required scan time is usually less than 10 min [22,23]. On the other hand, as the tissue structures in infants are small, higher resolution is required than in adults for adequate accuracy. This is usually achieved by using receive coils in addition to the built-in scanner body coil used in adult studies.

Although there are no known risks of MRI, monitoring of infants and some protective procedures are essential. To avoid artifacts caused by motion, infants are ideally scanned sleeping after being fed. A pulse oximeter is often attached to the fingers or toes of infants and the MRI technician can then monitor blood oxygen saturation from the workstation. A fluctuation in oxygen saturation levels occurs when the infant cries. Infants should also be protected from the scanner noise by using infant-specific earplugs. As most MRI scanner rooms tend to have a low temperature because of the liquid helium or liquid nitrogen in the superconducting magnet, it is important to keep the infant warm with blankets. In fact, until recently, premature infants could not be scanned due to the low room temperature of the MRI suite. Recent development of the MRI compatible incubator, however, opens the potential for studying the nutritional status of premature infants [38].

Magnetic resonance spectroscopy

Intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) have been increasingly measured in children by non-invasive proton (or 1-hydrogen) magnetic resonance spectroscopy (MRS) [39]. Both lipid compartments are closely related to insulin resistance [4042] and the sensitivity and repeatability of these approaches were established in recent patient studies [4345]. The utility and practicality of MRS are further advanced by the availability of three tesla clinical magnetic resonance scanners and other whole-body high-field magnetic resonance scanners in hospitals and research centers. These spectroscopic methods require more advanced pre-scan adjustments, such as selection of anatomic location, shimming of local magnetic field, and suppression of water signals. The quality of the obtained MRS data depends on the rigor of these pre-scan adjustments, which require investigator expertise and time. The IMCL or IHL is quantified from corresponding spectral peaks through a numerical fitting/integration procedure and results are typically expressed as a ratio to creatine or water content. Currently, there are two main types of MRS approaches, single voxel spectroscopy (SVS) and chemical shift imaging (CSI).

Single voxel spectroscopy

A single magnetic resonance spectrum is obtained with SVS from a localized volume of interest in liver parenchyma or muscle tissue. Two variations of the technique are generally implemented on magnetic resonance scanners. One method is ‘point resolved spectroscopy’ (PRESS), and the other is ‘stimulated echo acquisition mode’ (STEAM). A number of metabolites in the resulting muscle spectrum, such as creatine, extramyocelluar lipid (EMCL) from infiltrated adipose tissue, and IMCL, exhibit well-defined spectral peaks at 3.0, 1.5, and 1.3 ppm, respectively [44]. As noted, the spectral separation of EMCL and IMCL peaks is small and the reliability of IMCL quantification depends on the sharpness of spectral line width, which reflects the shimming quality achieved prior to acquisition. Generally, to avoid contamination of lipid signals from infiltrated adipose tissue in muscle, especially in extremely obese and diabetic subjects, it is highly desirable to capture data from a small volume of muscle (i.e. 1–3 cm3) [40,46]. The small volume leads to a reduced MRS signal and a large number of signal averages are therefore typically necessary to reach a reasonable signal to noise ratio. Fortunately, children usually do not have much adipose tissue infiltration in their muscles. On the other hand, muscle size in children is much smaller than that of adults and some MRI scanners may not be able to scan a small voxel within a single muscle of young children.

Signals of hepatic lipid in children can be detected and quantified similarly as in adults. The thin abdominal wall in children also favors the use of a surface coil in the exam, which can be placed in proximity to the liver. Because the surface coil significantly improves the signal to noise ratio (SNR) of the resulting magnetic resonance spectrum, a single scan acquisition without data averaging is often sufficient. If multiple acquisitions are needed to improve SNR, respiratory gating of data acquisition is recommended.

Chemical shift imaging

CSI, a spectroscopic imaging method that may be available on some MRI scanners, can be performed in one, two, or three spatial dimensions, and collects spectroscopic data from a relatively large volume in a spatially resolved manner. The small-yielded nominal size of multi-voxel MRS (i.e. 0.125 cm3) potentially solves the problem of scanning the small muscles in young children. With its large volume of coverage and high spatial resolution compared to SVS, CSI provides more information such as the lipid content of different muscles [47]. Through a given spatial encoding scheme, CSI yields a set of spectra that are spatially resolved over the intended volume. To resolve spectra spatially in practice, encoding magnetic resonance signals in multiple dimensions is required using gradient pulses with linear increments in a large number of steps, such as 16, 24, and so forth. This is why a CSI scan is typically slower than SVS methods (i.e. 15–20 min versus 3–6 min). CSI, however, provides multiple, spatially-resolved spectra that often justifies the effort in practice. Also, CSI will likely become faster in the near future with newly developed acquisition techniques that combine the CSI approach with the volume selection methods used with SVS.

Dixon methods

The Dixon method, which was initially developed and demonstrated more than a decade ago [48], can provide quantitative information on regional tissue fat content. This method has greater potential use in research than pure image ‘segmentation’ methods that quantify only tissue volumes. The fat content of a region of interest within an organ or of the entire organ can be obtained with processing of Dixon image data sets. The Dixon method is not only useful for separating muscle from fat tissues, but is also applicable for evaluating liver and even pancreas fat content [49●]. Although not quantifying fat solely within β cells, the quantification of pancreas fat by the Dixon method is unique, as spectroscopy methods usually cannot be applied for the pancreas that is located deep in the abdomen. The Dixon approach generally collects anatomical images with water and fat signals encoded differently in two or three imaging acquisitions [50]. Exploiting chemical shift differences between water and fat magnetic resonance signals, a Dixon method selects several gradient echo times (TEs) to allow the evolution of magnetic resonance signals according to their chemical shifts. Water and fat-only images are calculated from these resulting Dixon images. The drawback of the Dixon method is that it requires longer scanning times, post processing, and the method is not currently available on all clinical MRI scanners.

Cardiac magnetic resonance imaging

Cardiac MRI is now being used along with adipose tissue measurements in pediatrics, as cardiovascular disease is a major consequence of obesity. Cine MRI is a clinically available technique that can assess the physiology and function of the heart. Accurate assessment of ventricular mass, stoke volume, and ejection fraction is a major strength of cine MRI. Tagging of cardiac tissue and blood, a unique feature of MRI compared with other cardiac measurement technologies, enables the evaluation of regional wall motion and velocity mapping of blood flow [51]. Early detection of changes in cardiovascular function, such as aortic elasticity, is of research interest in children. In young children that cannot hold their breath, cardiac synchronization and respiratory gating are both necessary [52]. State-of-the-art MRI equipment now permits many magnetic resonance acquisitions to be completed in just a few seconds [52] and some ultra-fast imaging methods in combination with sensitivity encoding (SENSE) are necessary [53].

Potential pediatric magnetic resonance imaging problems and solutions

Compared with adults, it is usually difficult for children to stay immobile within the MRI system and to follow instructions. The problem of restlessness can at least be partially solved by having children play beforehand in a simulated MRI scanner. Video games for educating children in following specific instructions have also been developed and proven successful in teaching them the study process and how to cooperate. Nevertheless, there remains difficulty in scanning children between the ages of 6 months and 4 years. Most children in this age group are unable to remain still and to understand instructions. Sedation, for ethical reasons, is usually not used on children participating for research purposes.

Recent advances in MRI technology provide a potential solution to the problem of restlessness and motion during the scan. The Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction (PROPELLER) data acquisition has proven successful in reducing artifacts caused by movement in only one direction at a time [54]. This technique reduces movement artifacts in pediatric brain scans [55], although there remains a need to develop techniques that can compensate artifacts induced by muscle movement or breathing that cause organs and soft tissues to move simultaneously in different directions. Recently, 1.5 T MRI scanners with bore diameters up of to 70 cm have been developed [56]. Wide bore scanners provide the option for the child’s mother to lie with the subject during the scan.

A special coil design might be needed for adequate resolution of scans in children. While head coils have been used in scanning the whole body of infants, these coils are not long enough to cover the whole body of most children. To our knowledge there is no single coil designed to scan the whole body of toddlers. Although pediatric coils have been built for scanning the spine together with the head of children, these coils are not long enough to cover the whole body and cannot generate images with adequate signals of the anterior side of the body.

Protocol selection

There are several factors that influence the selection of an MRI protocol for a specific study. Cost and benefit is a key consideration as image segmentation or postprocessing is expensive for most investigators outside of specialized center. For example, scanning a subject with a rare, weight-related genetic disease should include both total body adipose tissue and adipose tissue distribution. This will require 40 to 50 separate images in a typical adult scanned with a 4 cm slice gap. Similarly, evaluating the effects of a new weight control drug may require detection of small total body and regional adipose tissue changes that are best captured in longitudinal whole body scans of a small number of experimental participants. On the other hand, for large-scale studies with adequate power and restricted budgets or for children that cannot remain immobile long enough inside the MRI scanner, single slice MRI or a few MRI slices are the appropriate protocol choice.

Another consideration is subject age and maturity. For infants and young children, whole body contiguous MRI scans should be considered as the total body length is relatively small. The scan can therefore be completed quickly and the analysis time is reasonable due to the small overall slice number. On the other hand, well-developed adolescents can be scanned by protocols similar to that of adults. A smaller slice gap than used in adults can be applied in pre-pubertal children without having much impact on the total body compartment estimates.

Protocol consideration is important when scanning growing children over time in longitudinal studies. Adipose tissue distribution can change dramatically, especially during puberty, and thus multi-slice whole body MRI scans would avoid missing fat loss at one site and gain in another. Another problem in children is landmark identification with elongation of bones during growth. In comparison, anatomic sites remain relatively stable in adults over long time periods. For example, when evaluating calf IMCL in adults, the imaging location is marked by the site distance from the knee. This distance changes in children as they grow. Thus, measurement from multiple bony landmarks and calculation of the relative distance will provide a more reproducible means of site identification in longitudinal pediatric studies. Measuring variation within a muscle will also help to evaluate the effects of positioning on IMCL variation. If IMCL variation within a muscle is negligible, the exact anatomical location is therefore likely unimportant.


MRI scanners are widely available and the acquired data in pediatric studies safely provide unique nutritional and metabolic information not obtainable by other methods. A misconception is that scanning times are long, complex and require substantial interruption of usual clinical patient flow. Once acquired, however, the present post-processing and segmentation procedures are more limited. Educational and consulting resources are available at specialized centers, thus facilitating MRI and MRS as powerful pediatric research tools. Moreover, advances in MRI technology, including rapid imaging sequences with more channels for data acquisition along with advanced coil designs and motion artifact corrections, will improve magnetic resonance capabilities for use in infants and young children.


chemical shift imaging
computed tomography
intramyocellular lipid
magnetic resonance imaging
single voxel spectroscopy


Sponsorship: Supported by National Institutes of Health grant DK-PO1-42618.


Papers of particular interest, published within the annual period of review have been highlighted as

● of special interest

●● of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 651).

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