Total-body PET Imaging: A New Frontier for the Assessment of Metabolic Disease and Obesity.

Obesity and associated metabolic syndrome are a global public health issue. Understanding the pathophysiology of this systemic disease is of critical importance for the development of future therapeutic interventions to improve clinical outcomes. The multiorgan nature of the pathophysiology of obesity presents a unique challenge. Total-body PET imaging, either static or dynamic, provides a vital set of tools to study organ crosstalk. The visualization and quantification of tissue metabolic kinetics with total-body PET in health and disease provides essential information to better understand disease physiology and potentially develop diagnostic and therapeutic modalities.

Non-invasive methods for the assessment of brown adipose tissue in humans.

Brown adipose tissue (BAT) is a recently rediscovered tissue in people that has shown promise as a potential therapeutic target against obesity and its metabolic abnormalities. Reliable non-invasive assessment of BAT volume and activity is critical to allow its importance in metabolic control to be evaluated. Positron emission tomography/computed tomography (PET/CT) in combination with 2-deoxy-2-[18 F]fluoroglucose administration is currently the most frequently used and most established method for the detection and quantification of activated BAT in humans. However, it involves radiation exposure and can detect activated (e.g. after cold exposure), but not quiescent, BAT. Several alternative methods that overcome some of these limitations have been developed including different PET approaches, single-photon emission imaging, CT, magnetic resonance based approaches, contrast-enhanced ultrasound, near infrared spectroscopy, and temperature assessment of fat depots containing brown adipocytes. The purpose of this review is to summarize and critically evaluate the currently available methods that non-invasively probe various aspects of BAT biology in order to assess BAT volume and/or metabolism. Although several of these methods show promise for the non-invasive assessment of BAT volume and function, further research is needed to optimize them to enable an accurate, reproducible and practical means for the assessment of human BAT content and its metabolic function.

MR-based assessment of body fat distribution and characteristics.

The assessment of body fat distribution and characteristics using magnetic resonance (MR) methods has recently gained significant attention as it further extends our pathophysiological understanding of diseases including obesity, metabolic syndrome, or type 2 diabetes mellitus, and allows more detailed insights into treatment response and effects of lifestyle interventions. Therefore, the purpose of this study was to review the current literature on MR-based assessment of body fat distribution and characteristics. PubMed search was performed to identify relevant studies on the assessment of body fat distribution and characteristics using MR methods. T1-, T2-weighted MR Imaging (MRI), Magnetic Resonance Spectroscopy (MRS), and chemical shift-encoding based water-fat MRI have been successfully used for the assessment of body fat distribution and characteristics. The relationship of insulin resistance and serum lipids with abdominal adipose tissue (i.e. subcutaneous and visceral adipose tissue), liver, muscle, and bone marrow fat content have been extensively investigated and may help to understand the underlying pathophysiological mechanisms and the multifaceted obese phenotype. MR methods have also been used to monitor changes of body fat distribution and characteristics after interventions (e.g. diet or physical activity) and revealed distinct, adipose tissue-specific properties. Lastly, chemical shift-encoding based water-fat MRI can detect brown adipose tissue which is currently the focus of intense research as a potential treatment target for obesity. In conclusion, MR methods reliably allow the assessment of body fat distribution and characteristics. Irrespective of the promising findings based on these MR methods the clinical usefulness remains to be established.

Abdominal fat analyzed by DEXA scan reflects visceral body fat and improves the phenotype description and the assessment of metabolic risk in mice.

Clinical studies have demonstrated a strong relationship between visceral fat content and metabolic diseases, such as type 2 diabetes and liver steatosis. Obese mouse models are an excellent tool to study metabolic diseases; however, there are limited methods for the noninvasive measurement of fat distribution in mice. Although micromagnetic resonance imaging and microcomputed tomography are the "gold standards" in the measurement of fat distribution, more economical and accessible methods are required. Dual energy X-ray absorptiometry (DEXA) is an effective method in characterizing fat content; however, it cannot discriminate between visceral and subcutaneous fat depots. We demonstrate that an evaluation of abdominal fat content measured by DEXA through the selection of one localized abdominal area strongly correlates with visceral fat content in C57BL/6J mice. We found that DEXA is able to measure fat pad volume ex vivo with high accuracy; however, the measurement of visceral fat in vivo shows an overestimation caused by subcutaneous tissue interference. The overestimation is almost constant for a wide range of values, and thus it is possible to correct the data for a more accurate estimation of visceral fat content. We demonstrate the utility of this technique in characterizing phenotypes of several obese mouse models (ob/ob, db/db, MC4R-KO, and DIO) and evaluating the effect of treatments on visceral fat content in longitudinal studies. Additionally, we also establish abdominal obesity as a potential biomarker for metabolic abnormalities (liver fat accumulation, insulin resistance/diabetes) in mice, similar to that described in humans.

In vivo assessment of myocardial glucose uptake by positron emission tomography in adults with the PRKAG2 cardiac syndrome.

BACKGROUND: The PRKAG2 cardiac syndrome is an inherited metabolic disease of the heart characterized by excessive myocardial glycogen deposition. The biochemical alterations associated with this condition remain controversial and have not previously been studied in affected humans. METHODS AND RESULTS: Positron emission tomography (PET) imaging was used to quantitatively assess myocardial glucose uptake (MGU) in 6 adult subjects with the PRKAG2 cardiac syndrome and 6 healthy, matched control subjects using the glucose analogue (18)F-Fluoro-2-deoxyglucose (FDG). Studies were performed under a euglycemic hyperinsulinemic clamp to ensure stable blood glucose levels. Rubidium-82 perfusion scans were performed to ensure that myocardial differences in myocardial glucose uptake were not the result of significant myocardial scar. In adult patients with phenotypic expression of disease, the median myocardial glucose uptake of the left ventricle was 0.18 mumol/min/g (interquartile range, 0.14, 0.24), compared with 0.40 mumol/min/g (interquartile range, 0.30 to 0.45) in the control group (P=0.01). The median blood glucose during FDG-PET imaging was 4.72 mmol/L (interquartile range, 4.32 to 4.97) in the PRKAG2 group and 4.38 mmol/L (interquartile range, 3.90, 4.79) in the control group (P=NS). The significant decrease observed in myocardial glucose uptake in affected patients occurred in the absence of significant myocardial scar. CONCLUSIONS: The PRKAG2 cardiac syndrome is associated with a reduction of glucose uptake in adult patients affected with this genetic condition. In this pilot study, (18)F-FDG-PET imaging is a useful tool to assess alterations in myocardial glucose transport in this inherited metabolic disease and provide insight into the biochemical pathophysiology of the diseased state.

In vivo assessment of bone metabolism using the cortical striation index.

Metacarpal cortical striations were evaluated in 350 patients using fine-detail radiography with optical magnification. Compared to the control population, mean striation-indices were elevated in growing children, primary and secondary hyperparathyroidism, osteomalacia and reflex sympathetic dystrophy syndrome. This technique may provide a useful quantitative assessment of bone metabolism, allowing differentiation of normal from hypermetabolic states. Serial assessment of cortical striation may be useful in monitoring response to therapy.