Background and Aim: The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron emission tomography (PET). The aim of this study was to use proton magnetic resonance spectroscopy (¹H MRS) to investigate whether the temperature and the fat fraction (FF) of BAT and white adipose tissue (WAT) are associated with BAT metabolic activity determined by deoxy-2-¹⁸F-fluoro-d-glucose (¹⁸F-FDG)-PET. Materials and Methods: Ten healthy subjects (four women, six men; 25 to 45 years of age) were studied using PET–magnetic resonance imaging during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT ¹H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on eight subjects. Results: The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid-burning capacity of BAT associated with whole-body insulin sensitivity. During cold exposure, the FF of BAT was lower than at room temperature, and cold-induced FF of BAT associated inversely with high-density lipoprotein and directly with low-density lipoprotein cholesterol. Conclusion: Both ¹H MRS–derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid-burning capacity of BAT and whole-body insulin sensitivity emphasizes the role of BAT in glucose handling. Furthermore, the relation of FF to high-density lipoprotein and low-density lipoprotein cholesterol suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.

Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors. These effects may be mediated partly via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents. To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography radioligand [¹⁸F]FMPEP-d₂ and measured BAT activation in parallel with the glucose analog [¹⁸F]fluorodeoxyglucose. Activation by cold exposure markedly increased CB1R density and glucose uptake in the BAT of lean men. Similarly, β3-receptor agonism increased CB1R density in the BAT of rats. In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes. Our results highlight that CB1Rs are significant for human BAT activity, and the CB1Rs provide a novel therapeutic target for BAT activation in humans.

Noninvasive imaging methods of internal body temperature are in high demand in both clinical medicine and physiological research. Thermography and thermometry can be used to assess tissue temperature during thermal therapies: ablative and hyperthermia treatments to ensure adequate temperature rise in target tissues but also to avoid collateral damage by heating healthy tissues. In research use, measurement of internal body temperature enables us the production of thermal maps on muscles, internal organs, and other tissues of interest. The most used methods for noninvasive imaging of internal body temperature are based on different parameters acquired with magnetic resonance imaging, ultrasound, computed tomography, microwave radiometry, photoacoustic imaging, and near-infrared spectroscopy. In the current review, we examine the aforementioned imaging methods, their use in estimating internal body temperature in vivo with their advantages and disadvantages, and the physical phenomena the thermography or thermometry modalities are based on.

Background: Folate receptor-β (FR-β) is a cell surface receptor that is significantly upregulated on activated macrophages during inflammation and provides a potential target for folate-based therapeutic and diagnostic agents. FR-β expression in central nervous system inflammation remains relatively unexplored. Therefore, we used focally induced acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) to study patterns of FR-β expression and evaluated its potential as an in vivo imaging target.Methods: Focal EAE was induced in rats using heat-killed Bacillus Calmette-Guérin followed by activation with complete Freund’s adjuvant supplemented withMycobacterium tuberculosis. The rats were assessed with magnetic resonance imaging and positron emission tomography/computed tomography (PET/CT) at acute (14 days) and chronic (90 days) phases of inflammation. The animals were finally sacrificed for ex vivo autoradiography of their brains. PET studies were performed using FR-β-targeting aluminum [¹⁸F]fluoride-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate ([¹⁸F]AlF-NOTA-folate,¹⁸F-FOL) and 18 kDa translocator protein (TSPO)-targetingN-acetyl-N-(2-[¹¹C]methoxybenzyl)-2-phenoxy-5-pyridinamine (¹¹C-PBR28). Post-mortem immunohistochemistry was performed using anti-FR-β, anti-cluster of differentiation 68 (anti-CD68), anti-inducible nitric oxide synthase (anti-iNOS), and anti-mannose receptor C-type 1 (anti-MRC-1) antibodies. The specificity of¹⁸F-FOL binding was verified using in vitro brain sections with folate glucosamine used as a blocking agent.Results: Immunohistochemical evaluation of focal EAE lesions demonstrated anti-FR-β positive cells at the lesion border in both acute and chronic phases of inflammation. We found that anti-FR-β correlated with anti-CD68 and anti-MRC-1 immunohistochemistry; for MRC-1, the correlation was most prominent in the chronic phase of inflammation. Both¹⁸F-FOL and¹¹C-PBR28 radiotracers bound to the EAE lesions. Autoradiography studies verified that this binding took place in areas of anti-FR-β positivity. A blocking assay using folate glucosamine further verified the tracer’s specificity. In the chronic phase of EAE, the lesion-to-background ratio of¹⁸F-FOL was significantly higher than that of¹¹C-PBR28 (P = 0.016).Conclusion: Our EAE results imply that FR-β may be a useful target for in vivo imaging of multiple sclerosis-related immunopathology. FR-β-targeted PET imaging with¹⁸F-FOL may facilitate the monitoring of lesion development and complement the information obtained from TSPO imaging by bringing more specificity to the PET imaging armamentarium for neuroinflammation.

Bone marrow insulin sensitivity may be an important factor for bone health in addition to bone mineral density especially in insulin resistant conditions. First we aimed to study if prenatal maternal obesity plays a role in determining bone marrow insulin sensitivity in elderly female offspring. Secondly we studied if a four-month individualized resistance training intervention increases bone marrow insulin sensitivity in elderly female offspring and whether this possible positive outcome is regulated by the offspring’s mother’s obesity status. 37 frail elderly females (mean age 71.9 ± 3.1 years) of which 20 were offspring of lean/normal-weight mothers (OLM, maternal BMI ≤ 26.3 kg/m²) and 17 were offspring of obese/overweight mothers (OOM, maternal BMI ≥ 28.1 kg/m²) were studied before and after a four-month individualized resistance training intervention. Nine age- and sex-matched non-frail controls (maternal BMI ≤ 26.3 kg/m²) were studied at baseline. Femoral bone marrow (FBM) and vertebral bone marrow (VBM) insulin sensitivity were measured using [¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography with computer tomography under hyperinsulinemic euglycemic clamp. We found that bone marrow insulin sensitivity was not related to maternal obesity status but FBM insulin sensitivity correlated with whole body insulin sensitivity (R = 0.487, p = 0.001). A four-month resistance training intervention increased FBM insulin sensitivity by 47% (p = 0.006) only in OOM, while VBM insulin sensitivity remained unchanged regardless of the maternal obesity status. In conclusion, FBM and VBM glucose metabolism reacts differently to a four-month resistance training intervention in elderly women according to their maternal obesity status. ClinicalTrials.gov NCT01931540