Short-term effects of obesity surgery versus low-energy diet on body composition and tissue-specific glucose uptake: a randomised clinical study using whole-body integrated 18F-FDG-PET/MRI.

AIMS/HYPOTHESIS: Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes. METHODS: In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic-euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change. RESULTS: One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: -7.7±1.4 kg and -7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (-26.3% [95% CI -49.5, -3.0], p=0.009) and non-significantly following LCD (-20.9% [95% CI -58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected. CONCLUSIONS/INTERPRETATION: The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT02988011 FUNDING: This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union's Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants.

Metabolic profiling of galectin-1 and galectin-3: a cross-sectional, multi-omics, association study.

OBJECTIVES: Experimental studies indicate a role for galectin-1 and galectin-3 in metabolic disease, but clinical evidence from larger populations is limited. METHODS: We measured circulating levels of galectin-1 and galectin-3 in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study, participants (n = 502, all aged 50 years) and characterized the individual association profiles with metabolic markers, including clinical measures, metabolomics, adipose tissue distribution (Imiomics) and proteomics. RESULTS: Galectin-1 and galectin-3 were associated with fatty acids, lipoproteins and triglycerides including lipid measurements in the metabolomics analysis adjusted for body mass index (BMI). Galectin-1 was associated with several measurements of adiposity, insulin secretion and insulin sensitivity, while galectin-3 was associated with triglyceride-glucose index (TyG) and fasting insulin levels. Both galectins were associated with inflammatory pathways and fatty acid binding protein (FABP)4 and -5-regulated triglyceride metabolic pathways. Galectin-1 was also associated with several proteins related to adipose tissue differentiation. CONCLUSIONS: The association profiles for galectin-1 and galectin-3 indicate overlapping metabolic effects in humans, while the distinctly different associations seen with fat mass, fat distribution, and adipose tissue differentiation markers may suggest a functional role of galectin-1 in obesity.

Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Voxel-wise body composition analysis using image registration of a three-slice CT imaging protocol: methodology and proof-of-concept studies.

BACKGROUND: Computed tomography (CT) is an imaging modality commonly used for studies of internal body structures and very useful for detailed studies of body composition. The aim of this study was to develop and evaluate a fully automatic image registration framework for inter-subject CT slice registration. The aim was also to use the results, in a set of proof-of-concept studies, for voxel-wise statistical body composition analysis (Imiomics) of correlations between imaging and non-imaging data. METHODS: The current study utilized three single-slice CT images of the liver, abdomen, and thigh from two large cohort studies, SCAPIS and IGT. The image registration method developed and evaluated used both CT images together with image-derived tissue and organ segmentation masks. To evaluate the performance of the registration method, a set of baseline 3-single-slice CT images (from 2780 subjects including 8285 slices) from the SCAPIS and IGT cohorts were registered. Vector magnitude and intensity magnitude error indicating inverse consistency were used for evaluation. Image registration results were further used for voxel-wise analysis of associations between the CT images (as represented by tissue volume from Hounsfield unit and Jacobian determinant) and various explicit measurements of various tissues, fat depots, and organs collected in both cohort studies. RESULTS: Our findings demonstrated that the key organs and anatomical structures were registered appropriately. The evaluation parameters of inverse consistency, such as vector magnitude and intensity magnitude error, were on average less than 3 mm and 50 Hounsfield units. The registration followed by Imiomics analysis enabled the examination of associations between various explicit measurements (liver, spleen, abdominal muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), thigh SAT, intermuscular adipose tissue (IMAT), and thigh muscle) and the voxel-wise image information. CONCLUSION: The developed and evaluated framework allows accurate image registrations of the collected three single-slice CT images and enables detailed voxel-wise studies of associations between body composition and associated diseases and risk factors.

Automatic segmentation of large-scale CT image datasets for detailed body composition analysis.

BACKGROUND: Body composition (BC) is an important factor in determining the risk of type 2-diabetes and cardiovascular disease. Computed tomography (CT) is a useful imaging technique for studying BC, however manual segmentation of CT images is time-consuming and subjective. The purpose of this study is to develop and evaluate fully automated segmentation techniques applicable to a 3-slice CT imaging protocol, consisting of single slices at the level of the liver, abdomen, and thigh, allowing detailed analysis of numerous tissues and organs. METHODS: The study used more than 4000 CT subjects acquired from the large-scale SCAPIS and IGT cohort to train and evaluate four convolutional neural network based architectures: ResUNET, UNET++, Ghost-UNET, and the proposed Ghost-UNET++. The segmentation techniques were developed and evaluated for automated segmentation of the liver, spleen, skeletal muscle, bone marrow, cortical bone, and various adipose tissue depots, including visceral (VAT), intraperitoneal (IPAT), retroperitoneal (RPAT), subcutaneous (SAT), deep (DSAT), and superficial SAT (SSAT), as well as intermuscular adipose tissue (IMAT). The models were trained and validated for each target using tenfold cross-validation and test sets. RESULTS: The Dice scores on cross validation in SCAPIS were: ResUNET 0.964 (0.909-0.996), UNET++ 0.981 (0.927-0.996), Ghost-UNET 0.961 (0.904-0.991), and Ghost-UNET++ 0.968 (0.910-0.994). All four models showed relatively strong results, however UNET++ had the best performance overall. Ghost-UNET++ performed competitively compared to UNET++ and showed a more computationally efficient approach. CONCLUSION: Fully automated segmentation techniques can be successfully applied to a 3-slice CT imaging protocol to analyze multiple tissues and organs related to BC. The overall best performance was achieved by UNET++, against which Ghost-UNET++ showed competitive results based on a more computationally efficient approach. The use of fully automated segmentation methods can reduce analysis time and provide objective results in large-scale studies of BC.

International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology.

PREAMBLE: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Spatial mapping of tumor heterogeneity in whole-body PET-CT: a feasibility study.

BACKGROUND: Tumor heterogeneity is recognized as a predictor of treatment response and patient outcome. Quantification of tumor heterogeneity across all scales may therefore provide critical insight that ultimately improves cancer management. METHODS: An image registration-based framework for the study of tumor heterogeneity in whole-body images was evaluated on a dataset of 490 FDG-PET-CT images of lung cancer, lymphoma, and melanoma patients. Voxel-, lesion- and subject-level features were extracted from the subjects' segmented lesion masks and mapped to female and male template spaces for voxel-wise analysis. Resulting lesion feature maps of the three subsets of cancer patients were studied visually and quantitatively. Lesion volumes and lesion distances in subject spaces were compared with resulting properties in template space. The strength of the association between subject and template space for these properties was evaluated with Pearson's correlation coefficient. RESULTS: Spatial heterogeneity in terms of lesion frequency distribution in the body, metabolic activity, and lesion volume was seen between the three subsets of cancer patients. Lesion feature maps showed anatomical locations with low versus high mean feature value among lesions sampled in space and also highlighted sites with high variation between lesions in each cancer subset. Spatial properties of the lesion masks in subject space correlated strongly with the same properties measured in template space (lesion volume, R = 0.986, p < 0.001; total metabolic volume, R = 0.988, p < 0.001; maximum within-patient lesion distance, R = 0.997, p < 0.001). Lesion volume and total metabolic volume increased on average from subject to template space (lesion volume, 3.1 ± 52 ml; total metabolic volume, 53.9 ± 229 ml). Pair-wise lesion distance decreased on average by 0.1 ± 1.6 cm and maximum within-patient lesion distance increased on average by 0.5 ± 2.1 cm from subject to template space. CONCLUSIONS: Spatial tumor heterogeneity between subsets of interest in cancer cohorts can successfully be explored in whole-body PET-CT images within the proposed framework. Whole-body studies are, however, especially prone to suffer from regional variation in lesion frequency, and thus statistical power, due to the non-uniform distribution of lesions across a large field of view.

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

BACKGROUND: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. METHODS: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. RESULTS: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. CONCLUSIONS: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

Evaluation of the Value of Waist Circumference and Metabolomics in the Estimation of Visceral Adipose Tissue.

Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008-2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm2 and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006-2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000-2007). Performance was comparable to the development setting in PIVUS (R2 = 0.63, RMSE = 42.4 cm2, calibration slope = 0.94) but lower in MESA (R2 = 0.44, RMSE = 60.7 cm2, calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements.

The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL. PURPOSE: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability. STUDY TYPE: Prospective. SUBJECTS: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability. FIELD STRENGTH/SEQUENCE: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence). ASSESSMENT: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2-4) and no or mild fibrosis (F0-1), based on the histopathological results, were identified. STATISTICAL TESTS: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05. RESULTS: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2-4 and F0-1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2-4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively. DATA CONCLUSION: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Serum levels of perfluoroalkyl substances (PFAS) and body composition - A cross-sectional study in a middle-aged population.

BACKGROUND: It has been suggested that per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors with a potential to influence fat mass. OBJECTIVE: The primary hypothesis tested was that we would find positive relationships for PFAS vs measures of adiposity. METHODS: In 321 subjects all aged 50 years in the POEM study, five PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA)) were measured in serum together with a Dual-energy X-ray absorptiometry (DXA) scan for determination of fat and lean mass. Whole-body magnetic resonance imaging scan was performed and the body was divided into >1 million voxels. Voxel-wise statistical analysis was carried out by a novel method denoted Imiomics. RESULTS: PFOS and PFHxS, did not show any consistent associations with body composition. However, PFOA, and especially PFNA and PFDA, levels were inversely related to most traditional measures reflecting the amount of fat in women, but not in men. In the Imiomics analysis of tissue volume, PFDA and PFNA levels were inversely related to the volume of subcutaneous fat, mainly in the arm, trunk and hip regions in women, while no such clear relationship was seen in men. Also, the visceral fat content of the liver, the pericardium, and the gluteus muscle were inversely related to PFDA and PFNA in women. DISCUSSION: Contrary to our hypothesis, some PFAS showed inverse relationships vs measurements of adiposity. CONCLUSION: PFOS and PFHxS levels in plasma did not show any consistent associations with body composition, but PFOA, and especially PFNA and PFDA were inversely related to multiple measures reflecting the amount of fat, but in women only.

Association between alanine aminotransferase as surrogate of fatty liver disease and physical activity and sedentary time in adolescents with obesity.

To compare patterns of sedentary (SED) time (more sedentary, SED + vs less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA + vs less active, MVPA-), and combinations of behaviors (SED-/MVPA + , SED-/MVPA-, SED + /MVPA + , SED + /MVPA-) regarding nonalcoholic fatty liver diseases (NAFLD) markers. This cross-sectional study included 134 subjects (13.4 ± 2.2 years, body mass index (BMI) 98.9 ± 0.7 percentile, 48.5% females) who underwent 24-h/7-day accelerometry, anthropometric, and biochemical markers (alanine aminotransferase (ALT) as first criterion, and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), AST/ALT ratio as secondary criteria). A subgroup of 39 patients underwent magnetic resonance imaging-liver fat content (MRI-LFC). Hepatic health was better in SED- (lower ALT, GGT, and MRI-LFC (p < 0.05), higher AST/ALT (p < 0.01)) vs SED + and in MVPA + (lower ALT (p < 0.05), higher AST/ALT (p < 0.01)) vs MVPA- groups after adjustment for age, gender, and Tanner stages. SED-/MVPA + group had the best hepatic health. SED-/MVPA- group had lower ALT and GGT and higher AST/ALT (p < 0.05) in comparison with SED + /MVPA + group independently of BMI. SED time was positively associated with biochemical (high ALT, low AST/ALT ratio) and imaging (high MRI-LFC) markers independently of MVPA. MVPA time was associated with biochemical markers (low ALT, high AST/ALT) but these associations were no longer significant after adjustment for SED time. CONCLUSION: Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible. WHAT IS KNOWN: • MVPA and SED times are associated with cardiometabolic risks in youths with obesity. • The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population. WHAT IS NEW: • Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. • While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health.

In vitro CT visualization of the biopsy location by filling the core biopsy needle with contrast media.

BACKGROUND: When performing computed tomography (CT)-guided biopsy procedures with non-disposable, automatic biopsy instruments, the actual course of the biopsy needle is not registered. PURPOSE: To evaluate the ability to visualize the sampling location after CT-guided biopsy in vitro using a novel method, where the space between the inner needle and the outer cannula in a core biopsy needle is filled with contrast media; and to compare the grade of visibility for two different concentrations of contrast media. MATERIAL AND METHODS: Core needle biopsies were performed in a tissue phantom using biopsy needles primed with two different iodine contrast media concentrations (140 mg I/mL and 400 mg I/mL). Commercially available needle-filling contraptions with sealing membranes were used to fill the needles. Each biopsy was imaged with CT, and the visibility was evaluated twice by three senior radiologists in a randomized order. RESULTS: The presence of traces was confirmed after biopsy, almost without exception for both concentrations. The visibility was sufficient to determine the biopsy location in all observations with the 400 mg I/mL filling, and in 7/10 observations with the 140 mg I/mL filling. The grade of visibility of the trace and the proportion of the biopsy needle course outlined were higher with the 400 mg I/mL filling. CONCLUSION: With CT-guided biopsy in vitro, the sampling location can be visualized using a novel method of priming the biopsy needle with iodine contrast media, specifically highly concentrated contrast media.

Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET.

BACKGROUND: We assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference with a fully integrated PET-MR scanner. METHODS: 15 patients underwent simultaneous DCE MRI and 15O-water PET scans at rest and adenosine-stress on an integrated PET-MR scanner. Correlation and agreement between MRI- and PET-based global and regional MBF values were assessed using correlation and Bland-Altman analysis. RESULTS: Three subjects were excluded due to technical problems. Global mean (± SD) MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for PET (P = 0.66 and P = 0.81). The correlations between global and regional MRI- and PET-based MBF values were strong (r = 0.86 and r = 0.75). The biases were negligible for both global and regional MBF comparisons (0.01 and 0.00 mL/min/g for both), but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values. CONCLUSION: The correlation between simultaneous MBF measurements with DCE MRI and 15O-water PET measured in an integrated PET-MRI was strong but the agreement was only moderate indicating that MRI-based quantitative MBF measurements is not ready for clinical introduction.

Cardiovascular-related proteins and the abdominal visceral to subcutaneous adipose tissue ratio.

BACKGROUND AND AIMS: An increased amount of visceral adipose tissues has been related to atherosclerosis and future cardiovascular events. The present study aims to investigate how the abdominal fat distribution links to plasma levels of cardiovascular-related proteins. METHOD AND RESULTS: In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 326, all aged 50 years), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue volumes were quantified by MRI. Eighty-six cardiovascular-related proteins were measured by the proximity extension assay (PEA). Similar investigations were carried out in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 400, all aged 75 years). In the discovery dataset (POEM), 10 proteins were related to the VAT/SAT-ratio using false discovery rate <.05. Of those, Cathepsin D (CTSD), Interleukin-1 receptor antagonist protein (IL-1RA) and Growth hormone (GH) (inversely) were related to the VAT/SAT-ratio in the validation in PIVUS following adjustment for sex, BMI, smoking, education level and exercise habits (p < 0.05). In a secondary analysis, a meta-analysis of the two samples suggested that 15 proteins could be linked to the VAT/SAT-ratio following adjustment as above and Bonferroni-correction of the p-value. CONCLUSION: Three cardiovascular-related proteins, cathepsin D, IL-1RA and growth hormone, were being associated with the distribution of abdominal adipose tissue using a discovery/validation approach. A meta-analysis of the two samples suggested that also a number of other cardiovascular-related proteins could be associated with an unfavorable abdominal fat distribution.

Voxel-wise Study of Cohort Associations in Whole-Body MRI: Application in Metabolic Syndrome and Its Components.

Background The metabolic syndrome is related to obesity and ectopic fat distribution. Purpose To investigate whether an image analysis approach that uses image registration for whole-body voxel-wise analysis could provide additional information about the relationship between metabolic syndrome and body composition compared with traditional image analysis. Materials and Methods Whole-body quantitative water-fat MRI was performed in a population-based prospective study on obesity, energy, and metabolism between October 2010 and November 2016. Fat mass was measured with dual-energy x-ray absorptiometry (DXA). Whole-body voxel-wise analysis of tissue volume and fat content was applied in more than 2 million voxels from the whole-body examinations by automated interindividual deformable image registration of the water and fat MRI data. Metabolic syndrome was diagnosed by the harmonized National Cholesterol Education Program criteria. Two-tailed t tests were used and P values less than .05 were considered to indicate statistical significance. Results This study evaluated 167 women and 159 men (mean age, 50 years) by using voxel-wise analysis. Metabolic syndrome (13.5%; 44 of 326) was related to traditional measurements of fat distribution, such as total fat mass at DXA, visceral and subcutaneous adipose tissue, and liver and pancreatic fat at MRI. Voxel-wise analysis found metabolic syndrome related to liver, heart, and perirenal fat volume; fat content in subcutaneous fat in the hip region in both sexes; fatty infiltration of leg muscles in men, especially in gluteus maximus; and pericardial and aortic perivascular fat mainly in women. Sex differences in associations with subcutaneous adipose tissue were identified. In women, metabolic syndrome diagnosis was linked to regional differences in associations to adipose tissue volumes in upper versus lower body, and dorsal versus ventral abdominal depots. In men similar gradients were only seen in individual components. Conclusion In addition to showing the relationships between metabolic syndrome and body composition in a detailed and intuitive fashion in the whole body, the voxel-wise analysis provided additional information compared with traditional image analysis. © RSNA, 2020 Online supplemental material is available for this article.

Prognostic impact of abdominal lymph node involvement in diffuse large B-cell lymphoma.

OBJECTIVE: The prognostic value of site of nodal involvement in diffuse large B-cell lymphomas (DLBCL) is mainly unknown. We aimed to determine the prognostic significance of nodal abdominal involvement in relation to tumour cell markers and clinical characteristics of 249 DLBCL patients in a retrospective single-centre study. METHODS: Contrast-enhanced computed tomography (CT) of the abdomen and thorax revealed pathologically enlarged abdominal lymph nodes in 156 patients, while in 93 patients there were no pathologically enlarged lymph nodes in the abdomen. In 81 cases, the diagnosis of DLBCL was verified by histopathological biopsy obtained from abdominal lymph node. RESULTS: Patients with abdominal nodal disease had inferior lymphoma-specific survival (P = .04) and presented with higher age-adjusted IPI (P < .001), lactate dehydrogenase (P < .001) and more often advanced stage (P < .001), bulky disease (P < .001), B symptoms (P < .001), and double expression of MYC and BCL2 (P = .02) compared to patients without nodal abdominal involvement, but less often extranodal involvement (P < .02). The worst outcome was observed in those where the abdominal nodal involvement was verified by histopathological biopsy. CONCLUSION: Diffuse large B-cell lymphomas patients with abdominal nodal disease had inferior outcome and more aggressive behaviour, reflected both in clinical and biological characteristics.

Feasibility of Assessing Inflammation in Asymptomatic Abdominal Aortic Aneurysms With Integrated 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to evaluate the feasibility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with contrast enhanced magnetic resonance imaging (MRI) to identify inflammation in asymptomatic abdominal aortic aneurysms (AAA). METHODS: FDG PET/MRI was performed on 15 patients with asymptomatic infrarenal AAAs >45 mm diameter. Prevalence of FDG uptake and MRI findings of inflammatory changes (oedema, wall thickening, and late gadolinium enhancement [LGE]) in the aortic wall were investigated at three levels: suprarenal aorta; non-aneurysmal aortic neck; and AAA. RESULTS: The median diameter of the AAAs was 54 mm (range 47-65 mm) and the median expansion rate in the last 12 months was 3 mm (range 1-13 mm). The standard uptake value (SUV) of FDG in the aneurysmal wall (SUVmax 2.5) was higher than the blood pool (SUVmax 1.0; p < .001). The maximum target to background ratio was higher in the suprarenal aorta (mean ± SD; 3.1 ± 0.6) and aortic neck (2.7 ± 0.5) than in the aneurysmal aorta (2.5 ± 0.5; p < .001). Thirty-six FDG hotspots were observed in the aneurysmal wall of 13 patients. Wall thickening and LGE were identified in eight patients. The number of FDG hotspots correlated with recent AAA growth (r = 0.62, p = .01). The recent aneurysm expansion rate was higher in aneurysms with LGE than in those without (7 mm vs. 2 mm; p = .03). MRI inflammatory changes were observed in nine of 36 hot spots (25%) and in three of 13 patients with focal FDG uptake. CONCLUSION: Fully integrated FDG PET/MRI can be used to study inflammation in asymptomatic AAAs. Heterogenous uptake of FDG in the aneurysmal wall indicates increased glucose metabolism, suggesting an ongoing inflammation. However, these FDG hotspots rarely correspond to MRI findings of inflammation, raising the question of which type of cellular activity is present in these areas. The presence of LGE and FDG hotspots both correlated to recent aneurysm growth, and their usefulness as clinical markers of aneurysm growth warrant additional investigation.

Filling of Fine and Core Biopsy Needles With the Contrast Agent Sulfur Hexafluoride: Ex Vivo and in vitro Evaluation of Ultrasound Needle Visibility.

OBJECTIVES: To investigate whether the ex vivo and in vitro ultrasound visibility of fine needles (FNs) and core biopsy needles (CNBs) can be improved by filling them with an ultrasound contrast agent. METHODS: After needle filling with the contrast agent sulfur hexafluoride, punctures with FNs and CBNs were recorded in the B-mode and contrast-specific imaging mode (10 observations in each of the 4 groups). Recordings were made in both butchered bovine liver (experiment I) and a water bath (experiment II). Air and normal saline were used as controls (total n = 120 for each experiment). In experiment I, 4 ultrasound specialists subjectively assessed the relative needle visibility in the recordings by using an arbitrary scale (integers 0-10). In experiment II, the contrast-to-noise ratio was calculated for both the entire needle course and the needle tip area. RESULTS: In experiment I, subjective visibility was increased compared with both controls only for CBNs in the contrast-specific imaging mode (P < .01). In experiment II, the contrast-to-noise ratio for both the entire needle course and the needle tip area increased compared with both controls for both FNs and CBNs in the contrast-specific imaging mode (P < .05). CONCLUSIONS: Ultrasound contrast agent needle filling is a promising new method to increase the visibility of CBNs in the contrast-specific imaging mode. This finding needs to be confirmed in vivo before its clinical value can be assessed.

Abdominal organ perfusion and inflammation in experimental sepsis: a magnetic resonance imaging study.

Diffusion-weighted magnetic resonance imaging (DW-MRI) uses water as contrast and enables the study of perfusion in many organs simultaneously in situ. We used DW-MRI in a hypodynamic sepsis model, comparing abdominal organ perfusion with global hemodynamic measurements and inflammation. Sixteen anesthetized piglets were randomized into 3 groups: 2 intervention (sepsis) groups: HighMAP (mean arterial pressure, MAP > 65 mmHg) and LowMAP (MAP between 50 and 60 mmHg), and a Healthy Control group (HC). Sepsis was obtained with endotoxin and the desired MAP maintained with norepinephrine. After 6 h, DW-MRI was performed. Acute inflammation was assessed with IL-6 and TNFα in abdominal organs, ascites, and blood and by histology of intestine (duodenum). Perfusion of abdominal organs was reduced in the LowMAP group compared with the HighMAP group and HC. Liver perfusion was still reduced by 25% in the HighMAP group compared with HC. Intestinal perfusion did not differ significantly between the intervention groups. Cytokine concentrations were generally higher in the LowMAP group but did not correlate with global hemodynamics. However, cytokines correlated with regional perfusion and, for liver and intestine, also with intra-abdominal pressure. Histopathology of intestine worsened with decreasing perfusion. In conclusion, although a low MAP (≤60 mmHg) indicated impeded abdominal perfusion in experimental sepsis, it did not predict inflammation, nor did other global measures of circulation. Decreased abdominal perfusion partially predicted inflammation but intestine, occupying most of the abdomen, and liver were also affected by intra-abdominal pressure. NEW & NOTEWORTHY The study increases the knowledge of abdominal perfusion during sepsis. We used diffusion weighted imaging to assess perfusion simultaneously and noninvasively in different abdominal organs. The technique has not been used in a sepsis model before. Cytokine concentrations were measured in different abdominal organs and vascular beds and related to regional perfusion. Decreased abdominal perfusion, but not global measures of circulation, predicted inflammation. Intestine, occupying most of the abdomen, and liver were also affected by intra-abdominal pressure.