Improved geometric accuracy of whole body diffusion-weighted imaging at 1.5T and 3T using reverse polarity gradients.

Whole body diffusion-weighted imaging (WB-DWI) is increasingly used in oncological applications, but suffers from misalignments due to susceptibility-induced geometric distortion. As such, DWI and structural images acquired in the same scan session are not geometrically aligned, leading to difficulties in e.g. lesion detection and segmentation. In this work we assess the performance of the reverse polarity gradient (RPG) method for correction of WB-DWI geometric distortion. Multi-station DWI and structural magnetic resonance imaging (MRI) data of healthy controls were acquired at 1.5T (n = 20) and 3T (n = 20). DWI data was distortion corrected using the RPG method based on b = 0 s/mm2 (b0) and b = 50 s/mm2 (b50) DWI acquisitions. Mutual information  (MI) between low b-value DWI and structural data increased with distortion correction (P < 0.05), while improvements in region of interest (ROI) based similarity metrics, comparing the position of incidental findings on DWI and structural data, were location dependent. Small numerical differences between non-corrected and distortion corrected apparent diffusion coefficient (ADC) values were measured. Visually, the distortion correction improved spine alignment at station borders, but introduced registration-based artefacts mainly for the spleen and kidneys. Overall, the RPG distortion correction gave an improved geometric accuracy for WB-DWI data acquired at 1.5T and 3T. The b0- and b50-based distortion corrections had a very similar performance.

Validation of automated whole-body analysis of metabolic and morphological parameters from an integrated FDG-PET/MRI acquisition.

Automated quantification of tissue morphology and tracer uptake in PET/MR images could streamline the analysis compared to traditional manual methods. To validate a single atlas image segmentation approach for automated assessment of tissue volume, fat content (FF) and glucose uptake (GU) from whole-body [18F]FDG-PET/MR images. Twelve subjects underwent whole-body [18F]FDG-PET/MRI during hyperinsulinemic-euglycemic clamp. Automated analysis of tissue volumes, FF and GU were achieved using image registration to a single atlas image with reference segmentations of 18 volume of interests (VOIs). Manual segmentations by an experienced radiologist were used as reference. Quantification accuracy was assessed with Dice scores, group comparisons and correlations. VOI Dice scores ranged from 0.93 to 0.32. Muscles, brain, VAT and liver showed the highest scores. Pancreas, large and small intestines demonstrated lower segmentation accuracy and poor correlations. Estimated tissue volumes differed significantly in 8 cases. Tissue FFs were often slightly but significantly overestimated. Satisfactory agreements were observed in most tissue GUs. Automated tissue identification and characterization using a single atlas segmentation performs well compared to manual segmentation in most tissues and will be valuable in future studies. In certain tissues, alternative quantification methods or improvements to the current approach is needed.

A 6-month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity.

BACKGROUND: Pharmacological treatment options for adolescents with obesity are very limited. Glucagon-like-peptide-1 (GLP-1) receptor agonist could be a treatment option for adolescent obesity. OBJECTIVE: To investigate the effect of exenatide extended release on body mass index (BMI)-SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity. METHODS: Six-month, randomized, double-blinded, parallel, placebo-controlled clinical trial in patients (n = 44, 10-18 years, females n = 22) with BMI-SDS > 2.0 or age-adapted-BMI > 30 kg/m2 according to WHO were included. Patients received lifestyle intervention and were randomized to exenatide extended release 2 mg (n = 22) or placebo (n = 22) subcutaneous injections given once weekly. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention. RESULTS: Exenatide reduced (P < .05) BMI-SDS (-0.09; -0.18, 0.00), % BMI 95th percentile (-2.9%; -5.4, -0.3), weight (-3 kg; -5.8, -0.1), waist circumference (-3.2 cm; -5.8, -0.7), subcutaneous adipose tissue (-552 cm3 ; -989, -114), 2-hour-glucose during OGTT (-15.3 mg/dL; -27.5, -3.1), total cholesterol (11.6 mg/dL; -21.7, -1.5), and BMI (-0.83 kg/m2 ; -1.68, 0.01) without significant change in liver fat content (-1.36; -3.12, 0.4; P = .06) in comparison to placebo. Safety and tolerability profiles were comparable to placebo with the exception of mild adverse events being more frequent in exenatide-treated patients. CONCLUSIONS: Treatment of adolescents with severe obesity with extended-release exenatide is generally well tolerated and leads to a modest reduction in BMI metrics and improvement in glucose tolerance and cholesterol. The study indicates that the treatment provides additional beneficial effects beyond BMI reduction for the patient group.

Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver. METHODS: Ten morbidly obese women (BMI 42 ± 2.6 kg m-2 ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day-1 ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m-2 ) served as controls. RESULTS: At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. CONCLUSIONS: The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.

Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention.

BACKGROUND/OBJECTIVES: Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD). SUBJECTS/METHODS: Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included. RESULTS: Liver fat decreased after 6 months by 64% (95% confidence interval: 54-74%) in the PD group and by 43% (27-59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25-75%) in the PD group and 49% (27-71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes. CONCLUSIONS: A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.

NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.

BACKGROUND: Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation. METHODS: In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation. RESULTS: We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies. CONCLUSION: A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.

Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study.

OBJECTIVE: Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes. DESIGN: Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task. SUBJECTS: A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m(-2)) or obese (30 kg m(-2)). RESULTS: People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight. CONCLUSION: These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.

Reproducibility of hepatic triglyceride content assessment in normals using localized magnetic resonance spectroscopy.

AIM: To investigate the reproducibility of measurements of hepatic triglyceride content (HTGC) in subjects with normal HTGC using localized (1)H-magnetic resonance spectroscopy ((1)H-MRS) and a clinical 1.5T scanner. METHODS: The (1)H-MRS acquisition was performed with a common protocol using the whole-body coil and no respiratory triggering. An upper limit of normal HTGC of 5.56% was used. Duplicate measurements, including subject repositioning, were acquired from 23 subjects, 19 of whom had a normal HTGC. RESULTS: The mean coefficient of variation (CV) from the duplicate measurements was 14.8% (20.5% before exclusion of a subject who was considered to be an outlier). Mean CVs of subgroups below and above the 1% HTGC limit were 19.8 and 7.0 respectively. CONCLUSIONS: The mean CV calculated in subjects with HTGC in the normal range was found to be higher than CVs of wide range HTGC groups reported in the literature. It is concluded that the reproducibility of HTGC measurements using (1)H-MRS depends on the HTGC range. These findings are of importance in reproducibility studies and in estimations of required study group sizes.

Whole-body adipose tissue analysis: comparison of MRI, CT and dual energy X-ray absorptiometry.

The aim of this study was to validate a recently proposed MRI-based T(1)-mapping method for analysis of whole-body adipose tissue (AT) using an established CT protocol as reference and to include results from dual energy X-ray absorptiometry (DEXA). 10 subjects, drawn from the Swedish Obese Subjects Sibling-pairs study, were examined using CT, MRI and DEXA. The CT analysis was based on 28 imaged slices. T(1) maps were calculated using contiguous MRI data from two different gradient echo sequences acquired using different flip angles. CT and MRI comparison was performed slice-wise and for the whole-body region. Fat weights were compared between all three modalities. Strong correlations (r > or = 0.977, p<0.0001) were found between MRI and CT whole-body and AT volumes. MRI visceral AT volume was underestimated by 0.79 +/- 0.75 l (p = 0.005), but total AT was not significantly different from that estimated by CT (MRI - CT = -0.61+/-1.17 l; p = 0.114). DEXA underestimated fat weights by 5.23 +/- 1.71 kg (p = 0.005) compared with CT. MRI underestimated whole-body volume by 2.03 +/- 1.61 l (p = 0.005) compared with CT. Weights estimated either by CT or by DEXA were not significantly different from weights measured using scales. In conclusion, strong correlations were found between whole-body AT results from CT, MRI-based T(1) mapping and DEXA. If the differences between the results from T(1)-mapping and CT-based analysis are accepted, the T(1)-mapping method allows fully automated post-processing of whole-body MRI data, allowing longitudinal whole-body studies that are also applicable for children and adolescents.

Lipid mobilization following Roux-en-Y gastric bypass examined by magnetic resonance imaging and spectroscopy.

BACKGROUND: Recent developments of magnetic resonance imaging (MRI) and spectroscopy have made it possible to quantify lipid deposited in different tissues. To what extent an improvement of glucose tolerance shortly after Roux-en-Y gastric bypass surgery (RYGBP) is reflected in lipid levels in liver and skeletal muscle, markers of insulin resistance, has not been clarified. METHODS: Whole-body MRI and MR spectroscopy (MRS) of liver and muscle and measurements of biochemical markers of glucose and lipid metabolism were performed at baseline and 1, 6, and 12 months following surgery in seven morbidly obese women. Volumes of adipose tissue depots and liver and muscle lipids were assessed from the MRI/MRS data. RESULTS: At 1 month postoperatively, body mass index and visceral and subcutaneous adipose tissues were reduced by 9%, 26%, and 10%, respectively, whereas no reductions in intrahepatocellular or skeletal intramyocellular lipid concentrations were found. Free fatty acid and beta-hydroxybutyrate levels were elevated two- and sixfold, respectively; glucose and insulin levels were lowered, indicating increased insulin sensitivity. Further weight loss up to 1 year was associated with reductions in all investigated lipid depots investigated, with the exception of the intramyocellular compartment. CONCLUSION: RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.

Automated and reproducible segmentation of visceral and subcutaneous adipose tissue from abdominal MRI.

OBJECTIVES: (1) To develop a fully automated algorithm for segmentation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), excluding intermuscular adipose tissue (IMAT) and bone marrow (BM), from axial abdominal magnetic resonance imaging (MRI) data. (2) To evaluate the algorithm accuracy and total method reproducibility using a semi-automatically segmented reference and data from repeated measurements. BACKGROUND: MRI is a widely used in adipose tissue (AT) assessment. Manual analysis of MRI data is time consuming and biased by the operator. Automated analysis spares resources and increase reproducibility. Fully automated algorithms have been presented. However, reproducibility analysis has not been performed nor has methods for exclusion of IMAT and BM been presented. METHODS: In total, 49 data sets from 31 subjects were acquired using a clinical 1.5 T MRI scanner. Thirteen data sets were used in the derivation of the automated algorithm and 36 were used in the validation. Common image analysis tools such as thresholding, morphological operations and geometrical models were used to segment VAT and SAT. Accuracy was assessed using a semi-automatically created reference. Reproducibility was assessed from repeated measurements. RESULTS: Resulting AT volumes from the automated analysis and the reference were not found to differ significantly (2.0+/-14% and 0.84+/-2.7%, given as mean+/-s.d., for VAT and SAT, respectively). The automated analysis of the repeated measurements data significantly increased the reproducibility of the VAT measurements. One athletic subject with very small amounts of AT was considered to be an outlier. CONCLUSIONS: An automated method for segmentation of VAT and SAT and exclusion of IMAT and BM from abdominal MRI data has been reported. The accuracy and reproducibility of the method has also been demonstrated using a semi-automatically segmented reference and analysis of repeated acquisitions. The accuracy of the method is limited in lean subjects.