Artificial intelligence-aided CT segmentation for body composition analysis: a validation study

Background: Body composition is associated with survival outcome in oncological patients, but it is not routinely calculated. Manual segmentation of subcutaneous adipose tissue (SAT) and muscle is time-consuming and therefore limited to a single CT slice. Our goal was to develop an artificial-intelligence (AI)-based method for automated quantification of three-dimensional SAT and muscle volumes from CT images. Methods: Ethical approvals from Gothenburg and Lund Universities were obtained. Convolutional neural networks were trained to segment SAT and muscle using manual segmentations on CT images from a training group of 50 patients. The method was applied to a separate test group of 74 cancer patients, who had two CT studies each with a median interval between the studies of 3 days. Manual segmentations in a single CT slice were used for comparison. The accuracy was measured as overlap between the automated and manual segmentations. Results: The accuracy of the AI method was 0.96 for SAT and 0.94 for muscle. The average differences in volumes were significantly lower than the corresponding differences in areas in a single CT slice: 1.8% versus 5.0% (p < 0.001) for SAT and 1.9% versus 3.9% (p < 0.001) for muscle. The 95% confidence intervals for predicted volumes in an individual subject from the corresponding single CT slice areas were in the order of \ub1 20%. Conclusions: The AI-based tool for quantification of SAT and muscle volumes showed high accuracy and reproducibility and provided a body composition analysis that is more relevant than manual analysis of a single CT slice

AATCT-IDS: A Benchmark Abdominal Adipose Tissue CT Image Dataset for Image Denoising, Semantic Segmentation, and Radiomics Evaluation

Methods: In this study, a benchmark \emph{Abdominal Adipose Tissue CT Image Dataset} (AATTCT-IDS) containing 300 subjects is prepared and published. AATTCT-IDS publics 13,732 raw CT slices, and the researchers individually annotate the subcutaneous and visceral adipose tissue regions of 3,213 of those slices that have the same slice distance to validate denoising methods, train semantic segmentation models, and study radiomics. For different tasks, this paper compares and analyzes the performance of various methods on AATTCT-IDS by combining the visualization results and evaluation data. Thus, verify the research potential of this data set in the above three types of tasks. Results: In the comparative study of image denoising, algorithms using a smoothing strategy suppress mixed noise at the expense of image details and obtain better evaluation data. Methods such as BM3D preserve the original image structure better, although the evaluation data are slightly lower. The results show significant differences among them. In the comparative study of semantic segmentation of abdominal adipose tissue, the segmentation results of adipose tissue by each model show different structural characteristics. Among them, BiSeNet obtains segmentation results only slightly inferior to U-Net with the shortest training time and effectively separates small and isolated adipose tissue. In addition, the radiomics study based on AATTCT-IDS reveals three adipose distributions in the subject population. Conclusion: AATTCT-IDS contains the ground truth of adipose tissue regions in abdominal CT slices. This open-source dataset can attract researchers to explore the multi-dimensional characteristics of abdominal adipose tissue and thus help physicians and patients in clinical practice. AATCT-IDS is freely published for non-commercial purpose at: \url{https://figshare.com/articles/dataset/AATTCT-IDS/23807256}.Comment: 17 pages, 7 figure

Nonalcoholic Fatty Liver Disease in Obesity and Type 2 Diabetes - Studies using 1H MRS and PET

Siirretty Doriast

Berry polyphenol absorption and the effect of northern berries on metabolism, ectopic fat accumulation, and associated diseases

The prevalence of obesity and type 2 diabetes has increased at an alarming rate in developed countries. It seems in the light of current knowledge that metabolic syndrome may not develop at all without NAFLD, and NAFLD is estimated to be as common as metabolic syndrome in western population (23 % occurrence). Fat in the liver is called ectopic fat, which is triacylglycerols within the cells of non-adipose tissue. Serum alanine aminotransferase (ALT) values correlate positively with liver fat proportions, and increased activity of ALT predicts type 2 diabetes independently from obesity. Berries, high in natural bioactive compounds, have indicated the potential to reduce the risk of obesity-related diseases. Ectopic fat induces common endocrine excretion of adipose tissue resulting in the overproduction of inflammatory markers, which further induce insulin resistance by multiple mechanisms. Insulin resistance inducing hyperinsulinemia and lipolysis in adipocytes increases the concentration of free fatty acids and consequently causes further fat accumulation in hepatocytes. Polyphenolic fractions of berries have been shown to reverse inflammatory reaction cascades in in vitro and animal studies, and moreover to decrease ectopic fat accumulation. The aim of this thesis was to explore the role of northern berries in obesity-related diseases. The absorption and metabolism of selected berry polyphenols, flavonol glycosides and anthocyanins, was investigated in humans, and metabolites of the studied compounds were identified in plasma and urine samples (I, II). Further, the effects of berries on the risk factors of metabolic syndrome were studied in clinical intervention trials (III, IV), and the different fractions of sea buckthorn berry were tested for their ability to reduce postprandial glycemia and insulinemia after high-glucose meal in a postprandial study with humans (V). The marked impact of mixed berries on plasma ALT values (III), as well as indications of the positive effects of sea buckthorn, its fractions and bilberry on omental adiposity and adhesion molecules (IV) were observed. In study V, sea buckthorn and its polyphenol fractions had a promising effect on potprandial metabolism after high-glucose meal. In the literature review, the possible mechanisms behind the observed effects have been discussed with a special emphasis on ectopic fat accumulation. The literature review indicated that especially tannins and flavonoids have shown potential in suppressing diverse reaction cascades related to systemic inflammation, ectopic fat accumulation and insulin resistance development.Siirretty Doriast

A Drosophila model to study the redox regulation of FOXO in vivo

Insulin/insulin-like growth factor signaling (IIS) is a key evolutionarily-conserved pathway associated with growth, metabolism and ageing from flies to humans. Forkhead box O (FOXO) transcription factors are the principal downstream effectors of the IIS pathway. FOXO is implicated in the regulation of many biological processes, such as energy metabolism, oxidative stress resistance and healthy ageing. FOXO proteins are known to be strongly post-translationally modified, however the contribution of redox regulation to the modulation of FOXO function is still underappreciated. Using Drosophila as a powerful in vivo model system, my goal is to dissect the redox regulation of the single fly orthologue, dFOXO, in the context of metabolic health, stress responses and survival. Redox signalling operates through reversible changes to cysteine residues on target proteins. Using differential labelling of cysteine residues, I have developed a mobility shift approach to assess the redox state dFOXO, and confirmed the presence of solvent-exposed cysteines implicated in redox signalling. I have optimised the redox proteomic analysis of dFOXO to uncover the redox state of all its nine cysteine residues. To gain mechanistic insight into FOXO redox regulation in vivo, I have generated a series of novel transgenic knock-in fly lines. These dFOXO redox-mutants each contain a single cysteine residue in an otherwise cysteine-less background. The methods developed and optimised in this study are applied to explore the redox regulation of dFOXO at the level of the cysteine residue, the protein and the whole fly. Studying the redox control of dFOXO in vivo will be important to understand how its key role in the regulation of metabolism, stress resistance and healthy lifespan is orchestrated.Open Acces

Production of a Soybean Meal with High-Protein and Low Anti-Nutritional Factors for Fish Feed

Aquaculture is one of the fastest growing areas of the food production system. According to the FAO, its rise is expected to continue through the year 2030 in order to maintain per-capita consumption levels required for the increasing population. Fishmeal--obtained from wild-harvested fish--has been the source of protein for fish feed. However, data indicates that these fish harvests are in decline, which could restrain that growth. The possibility of a shortage of fishmeal prompted the industry to look into possible alternatives. Soybean meal appears as a promising substitute since it is an affordable high quality source of protein. However, the presence of anti-nutritional factors--trypsin inhibitors, lectins, glycinin, β-conglycinin, saponins, phytates, and oligosaccharides--can negatively affect the growth and the general health of fish, limiting its inclusion as fish food. Several studies have been done in order to reduce these anti-nutritional factors. However, there is no method that eliminates all of them while preserving the protein content of the soybean meal. The aim of this work was to obtain a protein-rich soybean meal with low anti-nutritional factors and a greater protein digestibility to be used for fish food. To accomplish this, the deactivation kinetics (D and Z-values) of glycinin and β-conglycinin at different temperatures were studied using Differential Scanning Calorimetry (DSC). The reduction in the content of phytate was evaluated by pre-treatment of soybean meal with phytase. And lastly, Central Composite Rotatable Design (CCRD) was employed to determine the best combination of factors (temperature, time, pH, and ethanol concentration) that maximizes the extraction of soluble sugars, saponins, and phytate while increasing protein content and digestibility. Results indicated that the inclusion of phytase under different conditions reduced the phytate content. The CCRD determined that a pH of 4.5 at 59oC, 35% ethanol concentration for 65 minutes are the optimal conditions for the highest extraction of soluble anti-nutritional factors, which increased the content of total protein and digestibility of the soybean meal. However, according to the kinetics studies, the deactivation of glycinin--the more resistant of the two proteins--at this temperature is not complete

Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics

VASCULAR CHANGES IN TYPE 2 DIABETES MELLITUS: APPLICATION TO RESTENOSIS AFTER STENTING

Stents used to decrease cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) are prone to increased rates of restenosis. The mechanisms are incompletely elucidated, but low wall shear stress (WSS) and altered intracellular signaling likely contribute. We tested the hypothesis that neointimal hyperplasia (NH) after bare-metal stenting is due to vascular remodeling (enhanced formation of advanced glycation end-products (AGEs), increased downstream vascular resistance (DVR), and decreased WSS), and that decreasing AGEs with ALT-711 (Alagebrium) mitigates this response. Stents were implanted into the abdominal aorta of Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. After 21 days, the stented region was sectioned for NH quantification or casted and imaged for regional estimation of WSS and local intrastrut WSS by computational fluid dynamics. The thoracic and abdominal aorta, carotid, iliac, femoral and arterioles in cremaster muscle were harvested to detect AGEs related collagen cross-linking, and protein expression including transforming growth factor beta (TGFβ) and receptor for AGE (RAGE). A trend toward elevated DVR was observed, whereas blood flow (BF) and intrastrut TAWSS were significantly decreased in ZD compared to ZL and ZO rats (eg. TAWSS: 14.5 ± 1.9 vs 30.6 ± 1.6 and 25.4 ± 2.2 dyn/cm2, respectively; mean±SEM P\u3c0.05). Intrastrut NH was increased in ZO but not ZD rats. ALT-711 reduced DVR in ZD rats (15.6±2.5x105 to 8.39±0.6x105 dyn∙s/cm5), while decreasing NH (ZL: 7.7±1.0 to 4.3±0.9%; ZO: 12.0±1.5 to 4.9±0.8%; ZD: 9.4±0.7 to 3.7±0.4%) and causing similar regional TAWSS results in all groups. AGEs related collagen cross-linking was elevated in the arterioles of ZD rats, but alleviated by ALT-711. No consistent differences in RAGE or TGFβ expression were observed in treated versus untreated rats. Remodeling of the distal vasculature appears to play an important role in modulating WSS in T2DM, but WSS alone does not predict NH response as observed under normoglycemia. ALT-711 led to similar values for AGEs related arteriolar collagen cross-linking, BF through the stent, and regional WSS, while decreasing NH in all rats. Although TGFβ and RAGE expression did not appear to be modified by ALT-711, other intracellular signaling pathways remain to be explored