Many efforts have been made to standardize the interpretation of 18 f-fDG pet/ct in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of 18 F-FDG PET/CT considering the extent and intensity of bone 18 F-FDG uptake: Intensity of Bone Involvement (IBI). Whole body 18 F-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with 18 F-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement -PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00-1.35). Visual analysis categorized PET exams into three groups (negative/ mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients' hemoglobin values and IBI (r = −0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting.Lytic bone lesions are reported in approximately 80% of myeloma multiple (MM) patients 1,2 . Early and precise evaluation of bone involvement is crucial for staging and correct disease management.Hybrid image of positron emission tomography with 18 F-fluordeoxyglucose and computed tomography ( 18 F-FDG PET/CT) is one of the main methods for the evaluation of MM patients. It allows whole-body images, intra and extramedullary lesion detection, distinction between active lesions and scar or necrotic tissue and has been more sensitive than MRI in treatment assessment 3-5 .Many efforts have been attempted to standardize the interpretation of 18 F-FDG PET/CT in MM, using qualitative visual analysis or quantitative metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) 6-9 . However, none of these methods have been extensively used in clinical practice or research projects, probably because of the complexity of the visual quantification 6,7 or due to the lack of standardization of MTV and TLG calculations 8-10 . Also, MTV and TLG only consider areas visually defined as lesions and ignore diffuse uptake of the bone marrow.

Leucine can stimulate protein synthesis in skeletal muscle, and recent studies have shown an increase in leucine-related mitochondrial biogenesis and oxidative phosphorylation capacity in muscle cells. However, leucine-related effects in tumour tissues are still poorly understood. Thus, we described the effects of leucine in both in vivo and in vitro models of a Walker-256 tumour. Tumour-bearing Wistar rats were randomly distributed into a control group (W; normoprotein diet) and leucine group (LW; leucine-rich diet [normoprotein + 3% leucine]). After 20 days of tumour evolution, the animals underwent 18-fludeoxyglucose positron emission computed tomography (18F-FDG PET-CT) imaging, and after euthanasia, fresh tumour biopsy samples were taken for oxygen consumption rate measurements (Oroboros Oxygraph), electron microscopy analysis and RNA and protein extraction. Our main results from the LW group showed no tumour size change, lower tumour glucose (18F-FDG) uptake, and reduced metastatic sites. Furthermore, leucine stimulated a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, higher mRNA and protein expression of oxidative phosphorylation components, and enhanced mitochondrial density/area even though the leucine-treated tumour had a higher number of apoptotic nuclei with increased oxidative stress. In summary, a leucine-rich diet directed Walker-256 tumour metabolism to a less glycolytic phenotype profile in which these metabolic alterations were associated with a decrease in tumour aggressiveness and reduction in the number of metastatic sites in rats fed a diet supplemented with this branched-chain amino acid.

BackgroundInflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue.MethodsThe relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice.FindingsIL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression.InterpretationIL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function.FundSao Paulo Research Foundation grant 2013/07607-8.

Purpose Quantifications in nuclear medicine are occasionally limited by the lack of standardization for defining volumes of interest (VOIs) on functional images. In the present article, we propose the use of computed tomography (CT)–based skeletal segmentation to determine anatomically the VOI in order to calculate quantitative parameters of fluorine 18 fluorodeoxyglucose (18F-FDG) PET/CT images from patients with multiple myeloma. Methods We evaluated 101 whole-body 18F-FDG PET/CTs of 58 patients with multiple myeloma. An initial subjective visual analysis of the PET images was used to classify the bone involvement as negative/mild, moderate, or marked. Then, a fully automated CT–based segmentation of the skeleton was performed on PET images. The maximum, mean, and SD of the standardized uptake values (SUVmax, SUVmean, and SDSUV) were calculated for bone tissue and compared with the visual analysis. Results Forty-five (44.5%), 32 (31.7%), and 24 (23.8%) PET images were, respectively, classified as negative/mild, moderate, or marked bone involvement. All quantitative parameters were significantly related to the visual assessment of bone involvement. This association was stronger for the SUVmean [odds ratio (OR): 10.52 (95% confidence interval (CI), 5.68–19.48); P < 0.0001] and for the SDSUV [OR: 5.58 (95% CI, 3.31–9.42); P < 0.001) than for the SUVmax [OR: 1.01 (95% CI, 1.003–1.022); P = 0.003]. Conclusion CT–based skeletal segmentation allows for automated and therefore reproducible calculation of PET quantitative parameters of bone involvement in patients with multiple myeloma. Using this method, the SUVmean and its respective SD correlated better with the visual analysis of 18F-FDG PET images than SUVmax. Its value in staging and evaluating therapy response needs to be evaluated.