Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; however, the multiple mechanisms causing insulin resistance are not yet fully understood. The aim of this study was to explore the possible contribution of intramyocellular lipid content in the pathogenesis of skeletal muscle insulin resistance. We compared insulin-resistant and insulin-sensitive subjects. To meet stringent matching criteria for other known confounders of insulin resistance, these individuals were selected from an extensively metabolically characterized group of 280 first-degree relatives of type 2 diabetic subjects. Some 13 lean insulin-resistant and 13 lean insulin-sensitive subjects were matched for sex, age, BMI, percent body fat, physical fitness, and waist-to-hip ratio. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic clamp method (for insulin-resistant subjects, glucose metabolic clearance rate [MCR] was 5.77+/-0.28 ml x kg(-1) x min(-1) [mean +/- SE]; for insulin-sensitive subjects, MCR was 10.15+/-0.7 ml x kg(-1) x min(-1); P<0.002). Proton magnetic resonance spectroscopy (MRS) was used to measure intramyocellular lipid content (IMCL) in both groups. MRS studies demonstrated that in soleus muscle, IMCL was increased by 84% (11.8+/-1.6 vs. 6.4+/-0.59 arbitrary units; P = 0.008 ), and in tibialis anterior muscle, IMCL was increased by 57% (3.26+/-0.36 vs. 2.08+/-0.3 arbitrary units; P = 0.017) in the insulin-resistant offspring, whereas the extramyocellular lipid content and total muscle lipid content were not statistically different between the two groups. These data demonstrate that in these well-matched groups of lean subjects, IMCL is increased in insulin-resistant offspring of type 2 diabetic subjects when compared with an insulin-sensitive group matched for age, BMI, body fat distribution, percent body fat, and degree of physical fitness. These results indicate that increased IMCL represents an early abnormality in the pathogenesis of insulin resistance and suggest that increased IMCL may contribute to the defective glucose uptake in skeletal muscle in insulin-resistant subjects.

Our results indicate that coronary lesion configuration might be correctly differentiated by MSCT. Since also rupture-prone soft plaques can be detected by MSCT, this noninvasive method might become an important diagnostic tool for risk stratification in the near future.

The purpose of this study was to apply a magnetic resonance (MR) imaging-compatible positron emission tomographic (PET) detector technology for simultaneous MR/PET imaging of the human brain and skull base. The PET detector ring consists of lutetium oxyorthosilicate (LSO) scintillation crystals in combination with avalanche photodiodes (APDs) mounted in a clinical 3-T MR imager with use of the birdcage transmit/receive head coil. Following phantom studies, two patients were simultaneously examined by using fluorine 18 fluorodeoxyglucose (FDG) PET and MR imaging and spectroscopy. MR/PET data enabled accurate coregistration of morphologic and multifunctional information. Simultaneous MR/PET imaging is feasible in humans, opening up new possibilities for the emerging field of molecular imaging.

Gd-BOPTA demonstrates the highest longitudinal r1 at all field strengths, which is ascribable to weak protein interaction. The R2/R1 ratio increases at higher field strength only for Gd-BOPTA, hence very short echo times are required for Gd-BOPTA to benefit from the higher longitudinal relaxivity.

An increased intramyocellular lipid (IMCL) content, as quantified by 1 H-magnetic resonance spectroscopy ( 1 H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by 1 H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 ؎ 3.4% (SOL) and 164.2 ؎ 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 ؎ 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r ‫؍‬ ؊0.98, P < 0.003) and SOL muscle (r ‫؍‬ ؊0.97, P < 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 ؎ 16.9% of baseline; P ‫؍‬ 0.005), but not in SOL muscle (to 114.4 ؎ 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 ؎ 5.6% of baseline (P ‫؍‬ 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.

OBJECTIVEBrown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass.RESEARCH DESIGN AND METHODSData from 260 subjects (98 with BAT and 162 study date–matched control subjects) who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body.RESULTSBAT activity and BAT mass were higher in female (1.59 ± 0.10 and 32 ± 5 g vs. 1.02 ± 0.10 and 18 ± 4 g, both P ≤ 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient rs = −0.38, P = 0.015 and rs = −0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P ≤ 0.09).CONCLUSIONSOur data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.

The purpose of this analysis is to explore the potential diagnostic gain provided by the viscoelastic shear properties of breast lesions for the improvement of the specificity of contrast enhanced dynamic MR mammography (