MR of Multi-Organ Involvement in the Metabolic Syndrome

The metabolic syndrome (MetS) is characterized by ectopic lipid accumulation. Magnetic resonance (MR) imaging and spectroscopy can quantify ectopic lipid accumulation. Consequences of MetS can be evaluated with MR on a whole-body level. In the liver, several techniques are used to quantify hepatic steatosis and differentiate stages of nonalcoholic fatty liver disease. Cardiac MR can quantify myocardial steatosis and associated complications. In the brain, magnetization transfer imaging and diffusion tensor imaging can detect microstructural brain damage. Various other organs can be assessed with MR. MR is a powerful tool to unravel whole-body MetS pathophysiology, monitor therapeutic efficacy, and establish prognosis.

Key points

  • State-of-the-art magnetic resonance (MR) technologies provide whole-body assessment of metabolic syndrome (MetS) pathophysiology and complications.

  • MRI and MR spectroscopy image and quantify ectopic lipid accumulation, such as pericardial/perivascular fat, visceral abdominal fat, and fatty infiltration of organs, associated with adverse outcome.

  • By using MR elastography, T1-mapping, phosphorus MR spectroscopy, and diffusion-weighted imaging, MR can assist in staging nonalcoholic fatty liver disease.

  • Using cardiac MRI, spectroscopy, and mapping techniques, key features of diabetic cardiomyopathy, such as diastolic dysfunction, left ventricular hypertrophy, myocardial steatosis and fibrosis, can be quantified.

  • Novel MR techniques, such as magnetization transfer imaging and diffusion tensor imaging, demonstrate microstructural brain damage in MetS.



About one third of the United States population of 20 years or older has metabolic syndrome (MetS) and its prevalence increases with advancing age and body mass index, stressing its tight association with the obesity epidemic.


Diagnosis of MetS requires positive identification of at least 3 out of 5 criteria displayed in Table 1 . As such, approximately 90% of type 2 diabetes mellitus (DM2) patients have MetS. Patients with MetS are heterogeneous in nature with varying risk of disease and consequently require personalized care, for example, by MR prognosis, in terms of future cardiovascular and cerebrovascular events ( Fig. 1 ).

Table 1

Diagnosis of MetS

From National Heart, Lung, and Blood Institute. Third report of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Bethesda (MD): National Heart, Lung, and Blood Institute; 2002. NIH publication number 02-5215.

MetS Criteria (NCEP-ATP III Criteria) Definition
Abdominal obesity: waist circumference Men >40 inches
Women >35 inches
Increased plasma triglyceride level >150 mg/dL
Decreased plasma HDL level Men <40 mg/dL
Women <50 mg/dL
Elevated blood pressure >130/85 mm Hg
Increased plasma fasting glucose >100 mg/dL

Three out of five criteria are necessary for the diagnosis.

Abbreviations: HDL, high-density lipoprotein; MetS, metabolic syndrome; NCEP-ATP III, National Cholesterol and Education Program – Adult Treatment Panel III.

Fig. 1

Clinical whole-body MR for risk estimation of future cardiovascular events. Images acquired in a 74-year-old man with a 21-year history of type 2 diabetes mellitus. ( A ) Cardiac MRI involving cine imaging ( top and middle ) showing hypokinesia in the anterolateral segment ( arrow ). The bottom image is a late gadolinium-enhanced image displaying subendocardial enhancement ( arrowhead ) consistent with myocardial infarction. ( B ) Cerebral arteries using time-of-flight angiography ( top ), an axial T2-weighted brain image ( middle ) and a coronal fluid-attenuated inversion-recovery image ( bottom ). These images show no overt brain abnormalities associated with the metabolic syndrome (MetS). ( C ) Contrast-enhanced MR angiograms of carotid arteries ( left ) and abdominal and lower extremity arteries ( right ) with arrowhead and arrows indicating stenosis owing to atherosclerotic disease. Using this 60-minute MR protocol, future cardiac and cerebrovascular events can be predicted in DM patients with higher accuracy compared with clinical characteristics.

( From Bamberg F, Parhofer KG, Lochner E, et al. Diabetes mellitus: long-term prognostic value of whole-body MR imaging for the occurrence of cardiac and cerebrovascular events. Radiology 2013;269(3):733, with permission.)

MRI of Multi-Organ Involvement in the Metabolic Syndrome

MetS is a systemic disease with complex pathophysiology including insulin resistance, atherogenic dyslipidemia, hypertension, ectopic lipid accumulation, low-grade inflammation, prothrombotic state, and fibrosis resulting in end-organ damage. MRI and magnetic resonance spectroscopy (MRS) can be used to quantify ectopic lipid accumulation. Importantly, as shown in Fig. 2 , functional and structural consequences of MetS can be evaluated with MR on a whole-body level. In the liver, several techniques—ranging from MRS and water fat imaging to magnetic resonance elastography (MRE) and T1 mapping—are used to quantify hepatic steatosis and differentiate between stages of nonalcoholic fatty liver disease (NAFLD). In parallel, cardiac MR can quantify myocardial steatosis and associated complications, such as diastolic dysfunction and fibrosis. In the brain, magnetization transfer imaging and diffusion tensor imaging (DTI) can detect microstructural brain damage associated with MetS. The involvement of various other organs ranging from kidney to pancreas and skeletal muscle can be assessed with MR.

Fig. 2

Overview of MR assessment of multi-organ involvement in metabolic syndrome. Key features of multi-organ involvement in the metabolic syndrome (MetS) that can be assessed with MR are shown. MRI accurately assesses the distribution of WAT showing abundance of visceral adipose tissue (VAT) and peri-organ adipose tissue. In contrast, brown adipose tissue volume is diminished in obesity, suggesting that diminished thermogenesis may be involved in the etiology of MetS. Excessive accumulation of triglycerides in the liver, that is, hepatic steatosis, may play a central role in the development of MetS. Hepatic steatosis can progress into nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Both excessive VAT and hepatic steatosis are strongly linked to insulin resistance, a key component of MetS. The cardiovascular system can be involved focally (eg, myocardial infarction) or globally (eg, diabetic cardiomyopathy). Cardiac remodeling of the cardiovascular system involves the sequelae of fatty infiltration, inflammation, fibrosis, and ultimately organ failure. Furthermore, brain involvement in MetS is increasingly being studied. In addition to macrostructural changes, such as brain atrophy and cerebral small vessel disease, microstructural changes are important features of MetS brain pathology. Various other organs, such as the kidney, pancreas, and skeletal muscle, undergo pathologic alterations in MetS patients. BAT, brown adipose tissue; WAT, white adipose tissue.

Purpose of Review

This review highlights MR techniques that assess multi-organ involvement in MetS.

Adipose tissue

White Adipose Tissue

Abdominal visceral obesity

Ectopic lipid accumulation in white adipose tissue (WAT) predominantly occurs in the visceral abdominal compartment. Visceral white adipocytes can contribute to MetS etiology by secreting excessive amounts of plasma free fatty acids, adipokines, and cytokines. MetS prevalence correlates with waist circumference, reflecting the role of abdominal obesity. However, waist circumference does not differentiate between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Given that VAT has a stronger association with MetS than SAT, differentiation between SAT and VAT is critical. Several MR techniques can be used to reliably quantify SAT and VAT. These include T1-weighted imaging, frequency-selective lipid imaging, and chemical shift-encoded water–fat imaging, all different methods that can be lumped under the umbrella of water–fat MRI ( Figs. 3 and 4 ). An appropriate sequence can be chosen on the basis of local accessibility, available scanning time, and presence of image postprocessing expertise. An overview of MR techniques for lipid quantification and their advantages/disadvantages is reviewed by Hu and Kan.

Fig. 3

Chemical shift imaging of abdominal adipose tissue and subsequent volume quantification. Transverse slice at the level of L5 vertebra acquired with an mDIXON method using 2 echoes, ( A ) 1 in-phase and ( B ) 1 out-of-phase image. From these images, ( C ) a water image and ( D ) fat image can be reconstructed. ( E ) Image post processing can be used to semiautomatically assess subcutaneous ( green ) and visceral ( red ) adipose tissue. This sequence was performed in a patient with longstanding type 2 diabetes mellitus showing relatively large amounts of visceral adipose tissue compared with subcutaneous adipose tissue.

Fig. 4

Frequency selective imaging of pericardial fat. Three-chamber view acquired with a turbo spin echo sequence with a spectral presaturation with inversion recovery (SPIR) and black blood prepulse sequence during 1 breath-hold at 3 T. This high-resolution sequence enables separate quantification of epicardial ( arrow ) and paracardial ( arrowhead ) fat volumes. Note the high paracardial fat mass in this male patient with type 2 diabetes mellitus. In addition to their different anatomic relation to coronary arteries, epicardial and paracardial fat have a different embryonic origin; epicardial fat has brown adipose tissue characteristics, whereas the paracardial fat does not. Therefore, separate quantification of epicardial and paracardial fat could reveal varying effects on end-organ damage.

Pericardial and perivascular fat

In addition to abdominal VAT, ectopic lipid accumulation around the heart (pericardial fat) and vessels (perivascular fat) is increased in MetS. Pericardial/perivascular fat is physiologically protective in terms of mechanical support and as a source of biochemical substrates, hormones, and cytokines. However, increased pericardial/perivascular lipid accumulation in MetS has been linked with low-grade systemic inflammation, adverse metabolic profile and risk of ischemic heart disease. Various electrocardiogram-gated MR sequences, including steady-state free precession short axis sequences, fat-selective imaging (see Fig. 4 ), and water–fat MRI, can be used to image pericardial fat and enable volume quantification in a reproducible manner.

Brown Adipose Tissue

In contrast to WAT, brown adipose tissue (BAT) volume and activity are diminished in obesity and may play a role in its development. BAT contributes significantly to total resting energy expenditure by dissipating glucose and free fatty acids into heat. The reference method for imaging BAT volume and activity is fluorodeoxyglucose PET-CT after mild cold exposure. The desire for a nonirradiating alternative has led to many MR techniques being evaluated to image BAT. These techniques identify BAT by its higher water fraction compared with WAT. However, MR of BAT is limited by the fact that, in humans, BAT and WAT are not entirely separated anatomically, complicating reliable BAT volume quantification. MRI of BAT activity is still in its infancy, although promising results using T2* imaging have been published recently.


Hepatic Steatosis

Ectopic lipid accumulation in the liver, that is, hepatic steatosis, is present in the majority of MetS patients and plays a central role in the pathogenesis of insulin resistance, hyperglycemia, and atherogenic dyslipidemia. The gold standard to determine hepatic steatosis is histology which requires a biopsy. However, several MR techniques can assess hepatic triglyceride (TG) content noninvasively with lower sampling error.

Currently, proton MRS ( 1 H-MRS) is the noninvasive gold standard to quantify hepatic TG content ( Fig. 5 ). 1 H-MRS has the best sensitivity for detection of small amounts of fat. A drawback of this technique is the risk of sampling error inherent to quantifying TG content in a small voxel.

Fig. 5

Proton magnetic resonance spectroscopy ( 1 H-MRS) of the liver to quantify hepatic triglyceride content. Voxel planning and examples of proton spectra acquired from the liver at 3 T. 1 H-MRS is based on the fact that different molecules have different chemical environments that translate to small differences in the strength of the magnetic field for the different metabolites. This effect is commonly known as chemical shift. In the recorded spectrum, the difference in magnetic field results in different resonance frequencies, expressed in parts per million (ppm) with respect to that of tetrametylsilane, for the various metabolites. In practice, 1 spectra without water suppression is recorded to use as an internal reference, and 1 or more with water suppression are acquired for quantification of triglycerides (TG). To be able to measure small metabolite levels, it is necessary to measure a volume much larger than the normal pixel size in MRI. Upper panel , Typical 8-mL voxel for liver 1 H-MRS. Lower panel , Acquired unsuppressed and water-suppressed spectra of an obese ( left ) and lean ( right ) volunteer. In liver spectra, TG is mainly represented by 3 different proton moieties, namely, CH 2 -CH = CH-CH 2 , (-CH 2 ) n , and -CH 3 . To quantify the fat percentage often the integrals below the (-CH 2 ) n and CH 3 peaks are summed and divided by the sum of the integrals of the water and (-CH 2 ) n and CH 3 peaks. In this example, the calculated hepatic triglyceride content was 8.26% for the obese subject and 1.24% for the lean subject.

Recently, the mDIXON technique using multiple echoes has been shown to enable liver fat quantification ( Fig. 6 ). By applying the mDIXON technique, T2* effects caused by the relatively high iron content in the liver can be compensated. The technique is becoming increasingly popular because of its advantages of small sampling error (because it is a whole-organ imaging technique) and fast data acquisition.

Fig. 6

DIXON MRI of the liver to quantify hepatic triglyceride content. The left and middle images are the reconstructed water and fat images, respectively. A 6-point DIXON sequence was used with a starting echo time of 0.74 ms and echo spacing of 1 ms. The fat fraction was calculated on a pixel-by-pixel basis by dividing the fat image by the sum of the water and fat image. For this obese subject, the calculated fat fraction was between 3% and 9%, depending on the location, illustrating the inhomogeneous nature of hepatic steatosis.

Multidimensional chemical shift imaging is a multivoxel 1 H-MRS technique that measures a grid of multiple voxels, thus reducing sampling error. The disadvantage of chemical shift imaging is that data acquisition is slow and technically challenging.

Progression of Hepatic Steatosis into Inflammation, Fibrosis, and Cirrhosis

Hepatic steatosis can progress into nonalcoholic steatohepatitis, fibrosis, and ultimately cirrhosis and hepatic failure, a disease spectrum termed NAFLD. MRE, T1 mapping, phosphorus MRS ( 31 P-MRS), and diffusion-weighted imaging (DWI) are the focus of ongoing research to differentiate between NAFLD stages, and explore potential advantages compared with histology, that is, lower sampling error and fewer complications.

MRE ( Fig. 7 ) is an emerging technique that quantitatively images shear waves in the liver produced by external mechanical waves. A few validation studies have shown MRE’s capability of differentiating between stages of NAFLD.

Fig. 7

Magnetic resonance elastography and T1 mapping: Quantitative imaging of hepatic fibrosis in nonalcoholic fatty liver disease (NAFLD). Examples of T1 mapping ( left ) and magnetic resonance elastography (MRE; right ) in healthy versus fibrotic liver tissue (as assessed by biopsy). T1 maps were acquired with a shortened modified Look Locker (shMOLLI) sequence in a single breath-hold. Increasing T1 values were correlated with increasing degrees of fibrosis. MRE is performed using mechanical waves transmitted by an acoustic pressure driver. Using automated post processing, data are translated into quantitative images displaying tissue shear stiffness in kPa. It has been shown that MRE is a useful tool to detect advanced stages of fibrosis. The dotted lines indicate the liver.

( From [ Left ] Banerjee R, Pavlides M, Tunnicliffe EM, et al. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol 2014;60(1):72, with permission; and [ right ] Kim D, Kim WR, Talwalkar JA, et al. Advanced fibrosis in nonalcoholic fatty liver disease: noninvasive assessment with MR elastography. Radiology 2013;268(2):415, with permission.)

T1 mapping is more readily available than MRE in terms of commercially available imaging sequences. This technique is based on the increased T1 relaxation time of edematous (nonalcoholic steatohepatitis) and fibrotic tissue. In NAFLD, several studies have been performed, showing a strong correlation between increasing T1 and increasing stages of fibrosis (see Fig. 7 ). In parallel with quantification of extracellular volume (ECV) expansion in cardiac imaging, ECV quantification in the liver is also feasible. However, validation studies for ECV mapping to quantify liver fibrosis have yet to be published.

31 P-MRS can quantify metabolites involved in cell membrane metabolism as well as regulators of fibrosis pathogenesis can be assessed ( Fig. 8 ). Additionally, hepatic energy metabolism can be assessed by quantifying high energy phosphates.

Fig. 8

Phosphorus magnetic resonance spectroscopy ( 31 P-MRS) of the liver to differentiate between simple steatosis, steatohepatitis, and cirrhosis. Upper panel ( A–C ), 31 P spectra, acquired at 3 T, of simple steatosis (nonalcoholic fatty liver [NAFL]), nonalcoholic steatohepatitis (NASH), and cirrhosis, respectively. This technique quantifies markers of hepatocyte membrane integrity. Corresponding liver biopsy specimens are shown in the lower panel ( D–F ). The ratio of NADPH/(PME + PDE) was significantly lower in NAFL compared with NASH and cirrhosis, whereas the ratios of PE/(PME + PDE) and GPC/(PME + PDE) were higher in cirrhosis compared with NASH and NAFL. GPC, glycerophosphocholine; GPE, glycerophosphosrylethanolamine; NADPH, nicotinamide adenine dinucleotide phosphate; NTP, nucleoside triphosphate; PC, phophoscholine; PDE, phosphodiester; PE, phosphosethanolamine; PEP, phosphoenolpyruvate; Pi, inorganic phosphate; PME, phosphomonoester; UDPG, uridine diphosphosglucose.

( From Sevastianova K, Hakkarainen A, Kotronen A, et al. Nonalcoholic fatty liver disease: detection of elevated nicotinamide adenine dinucleotide phosphate with in vivo 3-T 31P MR spectroscopy with proton decoupling. Radiology 2010;256(2):472; with permission.)

DWI is a promising technique that measures water movement in extracellular space. Unfortunately, DWI is less reliable in the presence of fat, which limits its use in NAFLD. Future studies must focus on correcting for the influence of fat in order for DWI to become suitable for NAFLD staging.


Cardiac MRI (anatomic, functional, angiography, perfusion, late gadolinium enhancement) is an important component in the assessment of a major complication of MetS, namely ischemic heart disease, which is reviewed elsewhere. This section covers MR techniques to assess nonischemic remodeling in MetS, that is, “diabetic cardiomyopathy,” which is characterized by diastolic dysfunction, hypertrophy, disrupted cardiac energy metabolism, and ECV expansion related to myocardial fibrosis.

Diastolic Dysfunction

Diastole comprises a combination of active (energy-consuming) relaxation and passive compliance. In MetS, diastolic dysfunction is an early feature and independent predictor of mortality. Diastolic dysfunction is caused by altered myocardial energetics and by diminished ventricular compliance. MR using phase contrast imaging with velocity encoding is a robust technique to quantitatively assess diastolic function ( Fig. 9 ). Although the left ventricle (LV) has been the primary focus of research, recent findings show that right ventricular diastolic dysfunction is analogous to LV diastolic dysfunction.

Jun 26, 2020 | Posted by in MAGNETIC RESONANCE IMAGING | Comments Off on MR of Multi-Organ Involvement in the Metabolic Syndrome

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