Can the use of blood-based biomarkers in addition to anthropometric indices substantially improve the prediction of visceral fat volume as measured by magnetic resonance imaging?

PURPOSE: To investigate whether blood-based biomarkers can improve the prediction of visceral fat volume as measured by magnetic resonance imaging (MRI) and thus be used as proxies of visceral adiposity in large-scale epidemiological studies. METHODS: Whole-body MRI was performed to determine overall and regional body compartments in 542 participants aged 48-80 years (52% men) of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. Anthropometric measures were taken, and clinical chemistry profiles including 15 routine biomarkers were obtained. Furthermore, nine novel biomarkers of visceral fat were assayed in a discovery sample of 100 participants. Multivariable regression models were calculated to assess associations between anthropometric variables, biomarkers, and visceral fat volume. RESULTS: The proportion of variance in visceral fat volume explained by anthropometric measures was 65.2% in women and 60.8% in men. By using blood-based biomarkers in addition to anthropometric indices, the variance in visceral fat volume explained could be increased by 4.8% in women and 4.0% in men. After backward selection, HbA1c, triglycerides, and adiponectin remained in the final multivariable regression model in women, while in men hsCRP, leukocytes, AST (GOT), GGT, LDL, and adiponectin remained in the final model. CONCLUSIONS: In the present study, blood-based biomarkers moderately improved the prediction of visceral fat volume. This finding suggests that the underestimation of true associations between visceral fat and disease outcomes in epidemiological studies remains critical, even when using comprehensive sets of anthropometric and biomarker variables as proxies of visceral adiposity.

Weight Loss and Changes in Adipose Tissue and Skeletal Muscle Volume after Laparoscopic Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: a Prospective Study with 12-Month Follow-Up.

BACKGROUND: This study aimed to evaluate changes in body tissue composition with obesity surgery regarding visceral fat, subcutaneous fat, and skeletal muscle. DESIGN: Prospective non-randomized single-center cohort study METHODS: Whole-body magnetic resonance imaging (MRI) measured volumes of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle (SM) in 31 patients with laparoscopic sleeve gastrectomy (LSG, 20) or Roux-en-Y gastric bypass (RYGB, 11) preoperatively, at three- and 12-months follow-up. RESULTS: Body mass index (BMI) went down from 45.2 ± 6.5 preoperatively to 37.2 ± 5.6 (p < 0.001) at three months and 32.2 ± 5.3 kg/m2 (p < 0.001) at 12 months. SAT went down from 55.0 ± 14.0 L (liter) to 42.2 ± 13.3 L (p < 0.001) at three months and 31.7 ± 10.5 L (p < 0.001) at 12 months (- 42.3%). VAT went down from 6.5 ± 2.3 to 4.5 ± 1.7 (p < 0.001) at three months and 3.1 ± 1.7 L (p < 0.001) at 12 months (- 52.3%). SM went down from 22.7 ± 4.8 to 20.4 ± 3.6 (p = 0.008) at three months and remained 20.2 ± 4.6 L at 12 months (p = 0.17 relative three-month; p = 0.04 relative preop, - 11.1%). Relative loss was higher for VAT than that for SAT (52.3 ± 18.2% vs. 42.3 ± 13.8%; p = 0.03). At 12 months, there was no difference between LSG and RYGB for relative changes in BMI or body tissue composition. CONCLUSION: Postoperatively, there was higher net loss of SAT but higher relative loss of VAT with weight loss. SM was lost only during the first three months. MRI provides accurate evaluation of surgeries' effect on individual patients' tissue composition. This can benefit risk assessment for related cardiovascular and metabolic health but cost-related factors will likely reserve the used methods for research.

Quantification of Liver, Subcutaneous, and Visceral Adipose Tissues by MRI Before and After Bariatric Surgery.

BACKGROUND: Morbid obesity is a worldwide epidemic and is increasingly treated by bariatric surgery. Fatty liver is a common finding; almost half of all patients with non-alcoholic steatohepatitis develop steatohepatitis. Bariatric surgery improves steatohepatitis documented by liver biopsy and single voxel magnetic resonance imaging (MRI) techniques. OBJECTIVE: To investigate changes before and after bariatric surgery using whole organ MRI quantification of liver, visceral, and subcutaneous fat. SETTING: University of Basel Hospital and St. Clara Research Ltd, Basel, Switzerland. METHODS: Sixteen morbidly obese patients were evaluated by abdominal MRI-scanning before and 3, 6, 12, and 24 months after bariatric surgery to measure percentage liver fat (%-LF), total liver volume (TLV) and visceral and subcutaneous adipose tissues (VAT and SAT). Fasting plasma samples were taken for measurement of glucose, insulin, blood lipids, and liver biomarkers. In a control group of 12 healthy lean volunteers, the liver biomarker was also measured. RESULTS: The reproducibility of fat quantification by use of MRI was excellent. LF decreased significantly faster than VAT and SAT (%-LF vs. VAT p < 0.001 and %-LF vs. SAT p < 0.001). At certain time points, %-LF, VAT, and SAT were associated with changes in blood lipids and insulin. CONCLUSIONS: MRI quantification offers excellently reproducible results in measurement of liver fat and visceral and subcutaneous adipose tissues. Liver fat decreased significantly faster than visceral or subcutaneous adipose tissue. Decrease in %-LF and VAT is associated with decrease in total cholesterol, LDL, and plasma insulin.

Similar Weight Loss Induces Greater Improvements in Insulin Sensitivity and Liver Function among Individuals with NAFLD Compared to Individuals without NAFLD.

BACKGROUND: Preliminary evidence suggests that weight loss among obese has differential metabolic effects depending on the presence of non-alcoholic fatty liver disease (NAFLD). We assessed whether NAFLD predisposes to differential changes in liver fat content, liver function, and metabolic parameters upon diet-induced weight loss in a 50-week intervention trial. METHODS: 143 overweight and obese non-smokers underwent a 12-week dietary intervention and a 38-week follow-up. Diet-induced changes in anthropometric measures, circulating biomarkers, and magnetic resonance (MR)-derived liver fat content and adipose tissue volumes were evaluated by mixed linear models stratifying by NAFLD at baseline. RESULTS: The prevalence of NAFLD at baseline was 52%. Diet-induced weight loss after 12 (NAFLD: 4.8 ± 0.5%, No NAFLD: 5.1 ± 0.5%) and 50 weeks (NAFLD: 3.5 ± 0.7%, No NAFLD: 3.5 ± 0.9%) was similar in both groups, while the decrease in liver fat was significantly greater in the NAFLD group (week 12: 32.9 ± 9.5% vs. 6.3 ± 4.0%; week 50: 23.3 ± 4.4% vs. 5.0 ± 4.2%). Decreases in biomarkers of liver dysfunction (GGT, ALT, AST) and HOMA IR were also significantly greater in the NAFLD group. Other metabolic parameters showed no significant differences. CONCLUSION: Our data suggest that individuals with NAFLD show greater improvements of liver function and insulin sensitivity after moderate diet-induced weight loss than individuals without NAFLD.

Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial.

Background: Although preliminary evidence suggests that intermittent calorie restriction (ICR) exerts stronger effects on metabolic parameters, which may link obesity and major chronic diseases, compared with continuous calorie restriction (CCR), there is a lack of well-powered intervention studies. Objective: We conducted a randomized controlled trial to test whether ICR, operationalized as the "5:2 diet," has stronger effects on adipose tissue gene expression, anthropometric and body composition measures, and circulating metabolic biomarkers than CCR and a control regimen. Design: One hundred and fifty overweight and obese nonsmokers [body mass index (kg/m2) ≥25 to <40, 50% women], aged 35-65 y, were randomly assigned to an ICR group (5 d without energy restriction and 2 d with 75% energy deficit, net weekly energy deficit ∼20%), a CCR group (daily energy deficit ∼20%), or a control group (no advice to restrict energy) and participated in a 12-wk intervention phase, a 12-wk maintenance phase, and a 26-wk follow-up phase. Results: Loge relative weight change over the intervention phase was -7.1% ± 0.7% (mean ± SEM) with ICR, -5.2% ± 0.6% with CCR, and -3.3% ± 0.6% with the control regimen (Poverall < 0.001, PICR vs. CCR = 0.053). Despite slightly greater weight loss with ICR than with CCR, there were no significant differences between the groups in the expression of 82 preselected genes in adipose tissue implicated in pathways linking obesity to chronic diseases. At the final follow-up assessment (week 50), weight loss was -5.2% ± 1.2% with ICR, -4.9% ± 1.1% with CCR, and -1.7% ± 0.8% with the control regimen (Poverall = 0.01, PICR vs. CCR = 0.89). These effects were paralleled by proportional changes in visceral and subcutaneous adipose tissue volumes. There were no significant differences between ICR and CCR regarding various circulating metabolic biomarkers. Conclusion: Our results on the effects of the "5:2 diet" indicate that ICR may be equivalent but not superior to CCR for weight reduction and prevention of metabolic diseases. This trial was registered at clinicaltrials.gov as NCT02449148.

Intra-operative adjustment of standard planes in C-arm CT image data.

PURPOSE: With the help of an intra-operative mobile C-arm CT, medical interventions can be verified and corrected, avoiding the need for a post-operative CT and a second intervention. An exact adjustment of standard plane positions is necessary for the best possible assessment of the anatomical regions of interest but the mobility of the C-arm causes the need for a time-consuming manual adjustment. In this article, we present an automatic plane adjustment at the example of calcaneal fractures. METHODS: We developed two feature detection methods (2D and pseudo-3D) based on SURF key points and also transferred the SURF approach to 3D. Combined with an atlas-based registration, our algorithm adjusts the standard planes of the calcaneal C-arm images automatically. The robustness of the algorithms is evaluated using a clinical data set. Additionally, we tested the algorithm's performance for two registration approaches, two resolutions of C-arm images and two methods for metal artifact reduction. RESULTS: For the feature extraction, the novel 3D-SURF approach performs best. As expected, a higher resolution ([Formula: see text] voxel) leads also to more robust feature points and is therefore slightly better than the [Formula: see text] voxel images (standard setting of device). Our comparison of two different artifact reduction methods and the complete removal of metal in the images shows that our approach is highly robust against artifacts and the number and position of metal implants. CONCLUSIONS: By introducing our fast algorithmic processing pipeline, we developed the first steps for a fully automatic assistance system for the assessment of C-arm CT images.

The effects of intermittent calorie restriction on metabolic health: Rationale and study design of the HELENA Trial.

Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction (CCR), even at equal net calorie intake. Despite promising results from first trials, it remains largely unknown whether ICR-induced metabolic alterations reported from experimental studies can also be observed in humans, and whether ICR diets are practicable and effective in real life situations. Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet on five days and very low energy intake on two days per week) on metabolic parameters and body composition over one year. We will assess the effectiveness of ICR compared to CCR and a control diet over a 12-week intervention, 12-week maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking adults (50 per group, 50% women). Our primary endpoint is the difference between ICR and CCR with respect to fold-changes in expression levels of 82 candidate genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the intervention phase. The candidate genes represent pathways, which may link obesity-related metabolic alterations with the risk for major chronic diseases. In secondary and exploratory analyses, changes in metabolic, hormonal, inflammatory and metagenomic parameters measured in different biospecimens (SATb, blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging-based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study is the first randomized trial over one year testing the effects of ICR on metabolism, body composition and psychosocial factors in humans.

Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT).

OBJECTIVES: To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification. METHODS: Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10th-90th percentile in 5th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles. RESULTS: In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5%/year (interquartile: 0%/y; +11%/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Δ) in OE and Δ 40th percentile (r=0.69; p<0.001) as compared to Δ 80th percentile (r=0.58; p<0.001); closer correlation was found between Δ ground-glass extent and Δ 40th percentile (r=0.66, p<0.001) as compared to Δ 80th percentile (r=0.47, p=0.002), while the Δ reticulations correlated better with the Δ 80th percentile (r=0.56, p<0.001) in comparison to Δ 40th percentile (r=0.43, p=0.003). CONCLUSIONS: There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Δ 40th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern; furthermore Δ 80th percentile might reveal the course of reticular opacities.

Intraoperative detection and localization of cylindrical implants in cone-beam CT image data.

PURPOSE: Orthopedic fractures are often fixed using metal implants. The correct positioning of cylindrical implants such as surgical screws, rods and guide wires is highly important. Intraoperative 3D imaging is often used to ensure proper implant placement. However, 3D image interaction is time-consuming and requires experience. We developed an automatic method that simplifies and accelerates location assessment of cylindrical implants in 3D images. METHODS: Our approach is composed of three major steps. At first, cylindrical characteristics are detected by analyzing image gradients in small image regions. Next, these characteristics are grouped in a cluster analysis. The clusters represent cylindrical implants and are used to initialize a cylinder-to-image registration. Finally, the two end points are optimized regarding image contrast along the cylinder axis. RESULTS: A total of 67 images containing 420 cylindrical implants were used for testing. Different anatomical regions (calcaneus, spine) and various image sources (two mobile devices, three reconstruction methods) were investigated. Depending on the evaluation set, the detection performance was between 91.7 and 96.1% true- positive rate with a false-positive rate between 2.0 and 3.2%. The end point distance errors ranged from [Formula: see text] to [Formula: see text] mm and the orientation errors from [Formula: see text] to [Formula: see text] degrees. The average computation time was less than 5 seconds. CONCLUSIONS: An automatic method was developed and tested that obviates the need for 3D image interaction during intraoperative assessment of cylindrical orthopedic implants. The required time for working with the viewing software of cone-beam CT device is drastically reduced and leads to a shorter time under anesthesia for the patient.