Deep learning-based BMI inference from structural brain MRI reflects brain alterations following lifestyle intervention.

Obesity is associated with negative effects on the brain. We exploit Artificial Intelligence (AI) tools to explore whether differences in clinical measurements following lifestyle interventions in overweight population could be reflected in brain morphology. In the DIRECT-PLUS clinical trial, participants with criterion for metabolic syndrome underwent an 18-month lifestyle intervention. Structural brain MRIs were acquired before and after the intervention. We utilized an ensemble learning framework to predict Body-Mass Index (BMI) scores, which correspond to adiposity-related clinical measurements from brain MRIs. We revealed that patient-specific reduction in BMI predictions was associated with actual weight loss and was significantly higher in active diet groups compared to a control group. Moreover, explainable AI (XAI) maps highlighted brain regions contributing to BMI predictions that were distinct from regions associated with age prediction. Our DIRECT-PLUS analysis results imply that predicted BMI and its reduction are unique neural biomarkers for obesity-related brain modifications and weight loss.

Associations between adiposity and white matter hyperintensities: Cross-sectional and longitudinal analyses of 34,653 participants.

OBJECTIVES: White matter hyperintensities (WMH) increase the risk of stroke and cognitive impairment. This study aims to determine the cross-sectional and longitudinal associations between adiposity and WMH. METHODS: Participants were enrolled from the UK Biobank cohort. Associations of concurrent, past, and changes in overall and central adiposity with WMH were investigated by linear and nonlinear regression models. The association of longitudinal adiposity and WMH volume changes was determined by a linear mixed model. Mediation analysis investigated the potential mediating effect of blood pressure. RESULTS: In 34,653 participants with available adiposity measures and imaging data, the concurrent obese group had a 25.3% (ß [95% CI] = 0.253 [0.222-0.284]) higher WMH volume than the ideal weight group. Increment in all adiposity measures was associated with a higher WMH volume. Among them, waist circumference demonstrated the strongest effect (ß [95% CI] = 0.113 [0.101-0.125]). Past adiposity also demonstrated similar effects. Among the subset of 2664 participants with available WMH follow-up data, adiposity measures were predictive of WMH change. Regarding changes of adiposity, compared with ideal weight stable group, those who turned from ideal weight to overweight/obese had a 8.1% higher WMH volume (ß [95% CI] = 0.081 [0.039-0.123]), while participants who turned from overweight/obese to ideal weight demonstrated no significant WMH volume change. Blood pressure partly meditates the associations between adiposity and WMH. CONCLUSIONS: Both concurrent and past adiposity were associated with a higher WMH volume. The detrimental effects of adiposity on WMH occurred throughout midlife and in the elderly and may still exist after changes in obesity status.

Metabolic interactions between organs in overweight and obesity using total-body positron emission tomography.

BACKGROUND AND OBJECTIVES: Overweight and obesity is a complex condition resulting from unbalanced energy homeostasis among various organs. However, systemic abnormalities in overweight and obese people are seldom explored in vivo by metabolic imaging techniques. The aim of this study was to determine metabolic abnormities throughout the body in overweight and obese adults using total-body positron emission tomography (PET) glucose uptake imaging. METHODS: Thirty normal weight subjects [body mass index (BMI) < 25 kg/m2, 55.47 ± 13.94 years, 16 men and 14 women], and 26 overweight and obese subjects [BMI ≥ 25 kg/m2, 52.38 ± 9.52 years, 21 men and 5 women] received whole-body 18F-fluorodeoxyglucose PET imaging using the uEXPLORER. Whole-body standardized uptake value normalized by lean body mass (SUL) images were calculated. Metabolic networks were constructed based on the whole-body SUL images using covariance network approach. Both group-level and individual-level network differences between normal weight and overweight/obese subjects were evaluated. Correlation analysis was conducted between network properties and BMI for the overweight/obese subjects. RESULTS: Compared with normal weight subjects, overweight/obese subjects exhibited altered network connectivity strength in four network nodes, namely the pancreas (p = 0.033), spleen (p = 0.021), visceral adipose tissue (VAT) (p = 1.12 × 10-5) and bone (p = 0.021). Network deviations of overweight/obese subjects from the normal weight were positively correlated with BMI (r = 0.718, p = 3.64 × 10-5). In addition, overweight/obese subjects experienced altered connections between organs, and some of the altered connections, including pancreas-right lung and VAT-bilateral lung connections were significantly correlated with BMI. CONCLUSION: Overweight/obese individuals exhibit metabolic alterations in organ level, and altered metabolic interactions at the systemic level. The proposed approach using total-body PET imaging can reveal individual metabolic variability and metabolic deviations between organs, which would open up a new path for understanding metabolic alterations in overweight and obesity.

Automated abdominal adipose tissue segmentation and volume quantification on longitudinal MRI using 3D convolutional neural networks with multi-contrast inputs.

OBJECTIVE: Increased subcutaneous and visceral adipose tissue (SAT/VAT) volume is associated with risk for cardiometabolic diseases. This work aimed to develop and evaluate automated abdominal SAT/VAT segmentation on longitudinal MRI in adults with overweight/obesity using attention-based competitive dense (ACD) 3D U-Net and 3D nnU-Net with full field-of-view volumetric multi-contrast inputs. MATERIALS AND METHODS: 920 adults with overweight/obesity were scanned twice at multiple 3 T MRI scanners and institutions. The first scan was divided into training/validation/testing sets (n = 646/92/182). The second scan from the subjects in the testing set was used to evaluate the generalizability for longitudinal analysis. Segmentation performance was assessed by measuring Dice scores (DICE-SAT, DICE-VAT), false negatives (FN), and false positives (FP). Volume agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: ACD 3D U-Net achieved rapid (< 4.8 s/subject) segmentation with high DICE-SAT (median ≥ 0.994) and DICE-VAT (median ≥ 0.976), small FN (median ≤ 0.7%), and FP (median ≤ 1.1%). 3D nnU-Net yielded rapid (< 2.5 s/subject) segmentation with similar DICE-SAT (median ≥ 0.992), DICE-VAT (median ≥ 0.979), FN (median ≤ 1.1%) and FP (median ≤ 1.2%). Both models yielded excellent agreement in SAT/VAT volume versus reference measurements (ICC > 0.997) in longitudinal analysis. DISCUSSION: ACD 3D U-Net and 3D nnU-Net can be automated tools to quantify abdominal SAT/VAT volume rapidly, accurately, and longitudinally in adults with overweight/obesity.

Comparative study of abdominal CT enhancement in overweight and obese patients based on different scanning modes combined with different contrast medium concentrations.

PURPOSE: To compare image quality, iodine intake, and radiation dose in overweight and obese patients undergoing abdominal computed tomography (CT) enhancement using different scanning modes and contrast medium. METHODS: Ninety overweight and obese patients (25 kg/m2≤body mass index (BMI)< 30 kg/m2 and BMI≥30 kg/m2) who underwent abdominal CT-enhanced examinations were randomized into three groups (A, B, and C) of 30 each and scanned using gemstone spectral imaging (GSI) +320 mgI/ml, 100 kVp + 370 mgI/ml, and 120 kVp + 370 mgI/ml, respectively. Reconstruct monochromatic energy images of group A at 50-70 keV (5 keV interval). The iodine intake and radiation dose of each group were recorded and calculated. The CT values, contrast-to-noise ratios (CNRs), and subjective scores of each subgroup image in group A versus images in groups B and C were by using one-way analysis of variance or Kruskal-Wallis H test, and the optimal keV of group A was selected. RESULTS: The dual-phase CT values and CNRs of each part in group A were higher than or similar to those in groups B and C at 50-60 keV, and similar to or lower than those in groups B and C at 65 keV and 70 keV. The subjective scores of the dual-phase images in group A were lower than those of groups B and C at 50 keV and 55 keV, whereas no significant difference was seen at 60-70 keV. Compared to groups B and C, the iodine intake in group A decreased by 12.5% and 13.3%, respectively. The effective doses in groups A and B were 24.7% and 25.8% lower than those in group C, respectively. CONCLUSION: GSI +320 mgI/ml for abdominal CT-enhanced in overweight patients satisfies image quality while reducing iodine intake and radiation dose, and the optimal keV was 60 keV.

[State of the hepatobiliary system on the data of ultrasonic examination in children and adolescents with overweight and obesity].

Currently, a stable increase in the incidence of overweight and obesity is noted, this fact leads to an elevation in comorbidity with them. The relevance of the study is due to the involvement of the hepatobiliary system in the development of metabolic dysfunction and the formation of non-alcoholic fatty liver disease in the future. The aim of the research was to study the effect of overweight and obesity in children and adolescents on the state of the hepatobiliary system on the basis of ultrasound examination. Material and methods. A single-center retrospective comparative study was conducted. The main group consisted of 112 children and adolescents with Z-score body mass index (BMI) above +1SD, the comparison group consisted of 264 persons with a BMI from -2 to +1SD aged 5-17 years. An analysis of the results of anthropometric, including the assessment of BMI, ultrasound and biochemical studies was carried out. Results. The Z-score of BMI corresponding to overweight was recorded in 54 (13.8%) examined persons, and obesity - in 58 (14.8%) patients. In children of the main group, an increase in the size of the liver was recorded 3.6 fold more often, diffuse changes in the liver were revealed 32.4 fold more often, an increase in the volume of the gallbladder - 2.1 fold, signs of excessive aerocolia - 3.3 fold more often (p<0.001). In children with overweight and obesity, the level of triglycerides (p=0.003), low-density lipoprotein cholesterol (p=0.035), glucose (p=0.012), C-reactive protein (p=0.011), malon dyalldehyde (p=0.012), the activity of alaninaminotransferase (p<0.001) and alkaline phosphatase (p=0.001) were statistically significant, with a significantly lower level of high-density lipoprotein cholesterol (p<0.001). Statistically significant logistic models of the probability of an increase in the linear dimensions of the liver, diffuse changes, an increase in the volume of the gallbladder, the presence of excessive aerocolia signs from the Z-score BMI value were obtained. The Nigelkirk determination coefficient was 0.34, 0.17, 0.11 and 0.10 c.u. respectively. Conclusion. The contribution of overweight and obesity to the increase in the linear dimensions of the liver and the volume of the gallbladder, the formation of diffuse changes and excessive aerocolia according to the ultrasound examination was 10-34%.

The influence of insulin on anticipation and consummatory reward to food intake: A functional imaging study on healthy normal weight and overweight subjects employing intranasal insulin delivery.

Aberrant responses within homeostatic, hedonic and cognitive systems contribute to poor appetite control in those with an overweight phenotype. The hedonic system incorporates limbic and meso-limbic regions involved in learning and reward processing, as well as cortical regions involved in motivation, decision making and gustatory processing. Equally important within this complex, multifaceted framework are the cognitive systems involved in inhibitory control and valuation of food choices. Regions within these systems display insulin receptors and pharmacologically increasing central insulin concentrations using intranasal administration (IN-INS) has been shown to significantly reduce appealing food cue responsiveness and also food intake. In this work we describe a placebo-controlled crossover pharmacological functional magnetic resonance imaging (fMRI) study that looks at how IN-INS (160 IU) affects anticipatory and consummatory responses to sweet stimuli and importantly how these responses differ between healthy normal weight and overweight male individuals. This work shows that age matched normal weight and overweight (not obese) individuals respond similarly to both the anticipation and receipt of sweet stimuli under placebo conditions. However, increased central insulin concentrations produce marked differences between groups when anticipating sweet stimuli within the prefrontal cortex and midbrain as well as observed differences in the amygdala during consummatory responses.

Impact of BMI on Left Atrial Strain and Abnormal Atrioventricular Interaction in Patients With Type 2 Diabetes Mellitus: A Cardiac Magnetic Resonance Feature Tracking Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity often coexist and together contribute to left atrial (LA) functional abnormalities. However, little is known about the impact of body mass index (BMI) on LA strains measured using cardiac magnetic resonance feature tracking (MR-FT). PURPOSE: To investigate the additive effect of BMI on LA functional remodeling using MR-FT as well as to explore abnormal atrioventricular interaction in T2DM patients. STUDY TYPE: Retrospective. POPULATION: One hundred and fifty-nine T2DM patients (53, 34, and 72 normal-weight, overweight, and obese individuals) and 105 non-diabetic controls (46, 32, and 27 normal-weight, overweight, and obese individuals). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession. ASSESSMENT: LA reservoir strain (εs ), conduit strain (εe ), and active strain (εa ) and their corresponding strain rates (SRs, SRe, SRa) were measured together with left ventricular (LV) radial, circumferential, and longitudinal peak strain, peak systolic strain rate, and peak diastolic strain rate. STATISTICAL TESTS: Student's t-test or Mann-Whitney U test, one-way ANOVA, univariate and multivariate linear regression. A P value <0.05 was considered statistically significant. RESULTS: Compared to controls in the same BMI category, T2DM patients had significantly decreased reservoir and conduit function, while pump function was not significantly different (εa and SRa: P = 0.757 and 0.583 for normal-weight, P = 0.171 and 0.426 for overweight, P = 0.067 and 0.330 for obese). LA strains were significantly correlated with BMI (r = -0.346 for εs , -0.345 for εe ) in T2DM patients. Multivariable linear regression analysis indicated that BMI was independently associated with LA εs and εe , LV global longitudinal strain was independently associated with LA εs and εa , and LV circumferential peak diastolic strain rate was independently associated with LA εe . DATA CONCLUSION: These findings suggest that the coexistence of increased body weight and T2DM patients can exacerbate the impairment of LA strains and indicate abnormal atrioventricular interactions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Effusion detected by ultrasonography and overweight may predict the risk of knee osteoarthritis in females with early knee osteoarthritis: a retrospective analysis of Iwaki cohort data.

BACKGROUND: Knee osteoarthritis (OA) has enormous medical and socioeconomic burdens, which early diagnosis and intervention can reduce. We investigated the influence of knee effusion on the progression of knee OA in patients with early knee OA. METHODS: A total of 404 participants without radiographic knee OA were assessed from a 3-year longitudinal analysis. Participants were classified into non-OA and early knee OA groups. The effusion area (mm2) was quantified using ultrasonography. Receiver operating characteristic and logistic regression analyses were performed. RESULTS: At the 3-year follow-up, 114 of 349 knees (32%) had progressed from non-OA and 32 of 55 knees (58%) had progressed from early knee OA to radiographic knee OA. Logistic regression analysis showed that female sex (odds ratio [OR] 3.36, 95% confidence interval [CIs] 2.98-5.42), early knee OA (OR 2.02, 95% CI 1.08-3.75), body mass index (OR 1.11, 95% CI 1.02-1.19), and effusion area (OR 1.01, 95% CI 1.01-1.02) were significantly correlated with knee OA progression. Women who were overweight (body mass index ≥ 25 kg/m2) with more severe effusion had a higher risk of OA progression (area under the curve = 0.691, OR = 6.00) compared to those not overweight (area under the curve = 0.568, OR = 1.91). CONCLUSION: Knee effusion may be an indicator of the progression of early-stage knee OA.

The impact of body mass index on patient radiation dose in general radiography.

The aim of the present study was to determine the influence of the body mass index (BMI) on the dose area product (DAP) and effective dose (ED) in overweight and obese patients. We also wanted to determine the typical dose values as well as suggest adjustments to clinical practice for overweight and obese patients. In this study we considered 597 patients referred for imaging of the chest in posteroanterior and lateral projection, the lumbar spine in anteroposterior (AP) and lateral projection, the pelvis, the knee in AP and lateral projection, and the shoulder in AP projection. For each examination, the image field size, tube voltage, mAs product, source-to-image receptor distance and values of DAP were collected. Based on their BMI, the patients were divided into three groups (normal weight, overweight and obese). At the end, PCXMC 2.0 software was used to calculate the ED. The study showed a statistically significant DAP and ED increase in overweight and obese patients by 28.9% up to 275.4% in the case of DAP and an increase in ED from 11.0% to 241.9% in all mentioned examinations except knee and shoulder imaging. Typical DAP values ranged from 2.2 to 54.8µGym2for normal-weight patients, from 2.2 to 87.6µGym2for overweight patients, and from 2.2 to 172.5µGym2for obese patients. Spearman's correlation coefficient revealed very weak to very strong correlations when comparing BMI and DAP, as well as when comparing BMI and ED. A strong and very strong correlation was found in the case of examinations of the torso (except for the comparison of BMI and ED in the case of lateral lumbar spine projection).

Comparing feasibility of different tube voltages and different concentrations of contrast medium in coronary CT angiography of overweight patients.

OBJECTIVES: To compare image quality, radiation dose, and iodine intake of coronary computed tomography angiography (CCTA) acquired by wide-detector using different tube voltages and different concentrations of contrast medium (CM) for overweight patients. MATERIALS AND METHODS: A total of 150 overweight patients (body mass index≥25 kg/m2) who underwent CCTA are enrolled and divided into three groups according to scan protocols namely, group A (120 kVp, 370 mgI/ml CM); group B (100 kVp, 350 mgI/ml CM); and group C (80 kVp, 320 mgI/ml CM). The CT values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and figure-of-merit (FOM) of all images are calculated. Images are subjectively assessed using a 5-point scale. In addition, the CT dose index volume (CTDIvol) and dose length product (DLP) of each patient are recorded. The effective radiation dose (ED) is also calculated. Above data are then statistically analyzed. RESULTS: The mean CT values, SNR, CNR, and subjective image quality of group A are significantly lower than those of groups B and C (P < 0.001), but there is no significant difference between groups B and C (P > 0.05). FOMs show a significantly increase trend from group A to C (P < 0.001). The ED values and total iodine intake in groups B and C are 30.34% and 68.53% and 10.22% and 16.85% lower than those in group A, respectively (P < 0.001). CONCLUSION: The lower tube voltage and lower concentration of CM based on wide-detector allows for significant reduction in iodine load and radiation dose in CCTA for overweight patients comparing to routine scan protocols. It also enhances signal intensity of CCTA and maintains image quality.

Associations between ghrelin and leptin and neural food cue reactivity in a fasted and sated state.

Food cue exposure can trigger eating. Food cue reactivity (FCR) is a conditioned response to food cues and includes physiological responses and activation of reward-related brain areas. FCR can be affected by hunger and weight status. The appetite-regulating hormones ghrelin and leptin play a pivotal role in homeostatic as well as hedonic eating. We examined the association between ghrelin and leptin levels and neural FCR in the fasted and sated state and the association between meal-induced changes in ghrelin and neural FCR, and in how far these associations are related to BMI and HOMA-IR. Data from 109 participants from three European centers (age 50±18 y, BMI 27±5 kg/m2) who performed a food viewing task during fMRI after an overnight fast and after a standardized meal were analyzed. Blood samples were drawn prior to the viewing task in which high-caloric, low-caloric and non-food images were shown. Fasting ghrelin was positively associated with neural FCR in the inferior and superior occipital gyrus in the fasted state. This was partly attributable to BMI and HOMA-IR. These brain regions are involved in visual attention, suggesting that individuals with higher fasting ghrelin have heightened attention to food cues. Leptin was positively associated with high calorie FCR in the medial prefrontal cortex (PFC) in the fasted state and to neural FCR in the left supramarginal gyrus in the fasted versus sated state, when correcting for BMI and HOMA-IR, respectively. This PFC region is involved in assessing anticipated reward value, suggesting that for individuals with higher leptin levels high-caloric foods are more salient than low-caloric foods, but foods in general are not more salient than non-foods. There were no associations between ghrelin and leptin and neural FCR in the sated state, nor between meal-induced changes in ghrelin and neural FCR. In conclusion, we show modest associations between ghrelin and leptin and neural FCR in a relatively large sample of European adults with a broad age and BMI range. Our findings indicate that people with higher leptin levels for their weight status and people with higher ghrelin levels may be more attracted to high caloric foods when hungry. The results of the present study form a foundation for future studies to test whether food intake and (changes in) weight status can be predicted by the association between (mainly fasting) ghrelin and leptin levels and neural FCR.

Influence of maternal body mass index on interobserver variability of fetal ultrasound biometry and amniotic-fluid assessment in late pregnancy.

OBJECTIVE: To determine the interobserver reproducibility of fetal ultrasound biometric and amniotic-fluid measurements in the third trimester of pregnancy, according to maternal body mass index (BMI) category. METHODS: This was a prospective cohort study of women with a singleton gestation beyond 34 weeks, recruited into four groups according to BMI category: normal (18.0-24.9 kg/m2 ), overweight (25.0-29.9 kg/m2) , obese (30.0-39.9 kg/m2 ) and morbidly obese (≥ 40 kg/m2 ). Multiple pregnancies, women with diabetes and pregnancies with a fetal growth, structural or genetic abnormality were excluded. In each woman, fetal biometric (biparietal diameter (BPD), head circumference, abdominal circumference (AC), femur length (FL) and estimated fetal weight) and amniotic-fluid (amniotic-fluid index (AFI) and maximum vertical pocket (MVP)) measurements were obtained by two experienced sonographers or physicians, blinded to gestational age and each other's measurements. Differences in measurements between observers were expressed as gestational age-specific Z-scores. The interobserver intraclass correlation coefficient (ICC) and Cronbach's reliability coefficient (CRC) were calculated. Bland-Altman analysis was used to assess the degree of reproducibility. RESULTS: In total, 110 women were enrolled prospectively (including 1320 measurements obtained by 17 sonographers or physicians). Twenty (18.2%) women had normal BMI, 30 (27.3%) women were overweight, 30 (27.3%) women were obese and 30 (27.3%) women were morbidly obese. Except for AFI (ICC, 0.65; CRC, 0.78) and MVP (ICC, 0.49; CRC, 0.66), all parameters had a very high level of interobserver reproducibility (ICC, 0.72-0.87; CRC, 0.84-0.93). When assessing reproducibility according to BMI category, BPD measurements had a very high level of reproducibility (ICC ≥ 0.85; CRC > 0.90) in all groups. The reproducibility of AC and FL measurements increased with increasing BMI, while the reproducibility of MVP measurements decreased. Among the biometric parameters, the difference between the BMI categories in measurement-difference Z-score was significant only for FL. Interobserver differences for biometric measurements fell within the 95% limits of agreement. CONCLUSION: Obesity does not seem to impact negatively on the reproducibility of ultrasound measurements of fetal biometric parameters when undertaken by experienced sonographers or physicians who commonly assess overweight, obese and morbidly obese women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Obese and overweight individuals have greater knee synovial inflammation and associated structural and cartilage compositional degeneration: data from the osteoarthritis initiative.

OBJECTIVE: This work aims to study (i) the relationship between body mass index (BMI) and knee synovial inflammation using non-contrast-enhanced MRI and (ii) the association of synovial inflammation versus degenerative abnormalities and pain. MATERIALS AND METHODS: Subjects with risk for and mild to moderate radiographic osteoarthritis were selected from the Osteoarthritis Initiative. Subjects were grouped into three BMI categories with 87 subjects per group: normal weight (BMI, 20-24.9 kg/m2), overweight (BMI, 25-29.9 kg/m2), and obese (BMI, ≥ 30 kg/m2), frequency matched for age, sex, race, Kellgren-Lawrence grade, and history of knee surgery and injury. Semi-quantitative synovial inflammation imaging biomarkers were obtained including effusion-synovitis, size and intensity of infrapatellar fat pad signal abnormality, and synovial proliferation score. Cartilage composition was measured using T2 relaxation time and structural abnormalities using the whole-organ magnetic resonance imaging score (WORMS). The Western Ontario and McMasters (WOMAC) Osteoarthritis Index was used for pain assessment. Intra- and inter-reader reproducibility was assessed by kappa values. RESULTS: Overweight and obese groups had higher prevalence and severity of all synovial inflammatory markers (p ≤ 0.03). Positive associations were found between synovial inflammation imaging biomarkers and average T2 values, WORMS maximum scores and total WOMAC pain scores (p < 0.05). Intra- and inter-reader kappa values for imaging biomarkers were high (0.76-1.00 and 0.60-0.94, respectively). CONCLUSION: Being overweight or obese was significantly associated with a greater prevalence and severity of synovial inflammation imaging biomarkers. Substantial reproducibility and high correlation with knee structural, cartilage compositional degeneration, and WOMAC pain scores validate the synovial inflammation biomarkers used in this study.

Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals.

BACKGROUND: The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women. METHODS AND RESULTS: Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04). CONCLUSIONS: In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.

Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects.

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.

Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence.

Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examines: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm2). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (ß = 0.321 and ß = 0.302, respectively; both P < 0.05), and in turn, cortical thickness was associated with higher intelligence (ß = 0.198, P < 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p > 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% & 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.

Early life factors, gray matter brain volume and academic performance in overweight/obese children: The ActiveBrains project.

Early life factors may influence brain and academic outcomes later in life, especially during childhood. Here we investigate the associations of early life factors (i.e., birth weight, birth length, and breastfeeding) with gray matter volume, adjusted for body mass index and cardiorespiratory fitness, and ii) we test whether early-life factor-related differences in gray matter volume are associated with academic performance in overweight/obese children. 96 children with overweight/obesity aged 8-11 years participated. Birth weight, birth length and gestational age were collected from birth records, and breastfeeding practices were asked to parents. T1-weighted images were acquired with a 3.0 T Magnetom Tim Trio system. Academic performance was assessed with the Bateria III Woodcock-Muñoz Tests of Achievement. Whole-brain voxel-wise multiple regressions were used to test the associations of each early life factor with gray matter volume. Higher birth weight and birth length were associated with greater gray matter volume in 9 brain regions including the middle frontal gyrus, rectal gyrus, thalamus, putamen, middle temporal gyrus, lingual gyrus, middle occipital gyrus, calcarine cortex and cerebellum bilaterally (ß ranging from 0.361 to 0.539, t ranging from 3.46 to 5.62 and cluster size from 82 to 4478 voxels; p < 0.001); and greater duration of any breastfeeding was associated with greater gray matter volume in 3 regions including the bilateral inferior frontal gyrus and rolandic operculum (ß ranging from 0.359 to 0.408, t ranging from 4.01 to 4.32 and cluster size from 64 to 171 voxels; p < 0.001). No associations were found for duration of exclusive breastfeeding. Additionally, none of the gray matter regions that were associated with the early life factors were associated with academic performance (all p > 0.05). Our results demonstrate that birth weight, birth length, and breastfeeding are predictive of gray matter volume of numerous brain structures that are involved in higher order cognition and emotion regulation, but how these results relate to measures of academic achievement remain a matter of speculation.

Assessment of real-time and quantitative changes in renal hemodynamics in healthy overweight males: Contrast-enhanced ultrasonography vs para-aminohippuric acid clearance.

OBJECTIVE: To determine the ability of renal contrast-enhanced ultrasonography (CEUS) to detect acute drug-induced changes in renal perfusion (using the glucagon-like peptide (GLP)-1 receptor agonist exenatide and nitric oxide [NO]-synthase inhibitor L-NG -monomethyl arginine [l-NMMA]), and assess its correlation with gold standard-measured effective renal plasma flow in humans. METHODS: In this prespecified exploratory analysis of a placebo-controlled cross-over study, renal hemodynamics was assessed in 10 healthy overweight males (aged 20-27 years; BMI 26-31 kg/m2 ) over two separate testing days; during placebo (isotonic saline) and subsequent exenatide infusion (Day-A), and during l-NMMA, and subsequent exenatide plus l-NMMA infusion (Day-B). Renal cortical microvascular blood flow was estimated following microbubble infusion and CEUS destruction-refilling-sequences. Renal cortical microvascular blood flow was compared with simultaneously measured effective renal plasma flow in humans, derived from para-aminohippuric acid-clearance methodology. RESULTS: On Day-A, effective renal plasma flow increased by 68 [26-197] mL/min/1.73 m2 during exenatide vs placebo infusion (+17%; P = .015). In parallel, exenatide increased renal cortical microvascular blood flow, from 2.42 × 10-4 [6.54 × 10-5 -4.66 × 10-4 ] AU to 4.65 × 10-4 [2.96 × 10-4 -7.74 × 10-4 ] AU (+92%; P = .027). On Day-B, effective renal plasma flow and renal cortical microvascular blood flow were reduced by l-NMMA, with no significant effect of concomitant exenatide on renal hemodynamic-indices assessed by either technique. Effective renal plasma flow correlated with renal cortical microvascular blood flow on Day-A (r = .533; P = .027); no correlation was found on Day-B. CONCLUSIONS: Contrast-enhanced ultrasonography can detect acute drug-induced changes human renal hemodynamics. CEUS-assessed renal cortical microvascular blood flow moderately associates with effective renal plasma flow, particularly when perfusion is in normal-to-high range. Renal CEUS cannot replace effective renal plasma flow measurements, but may be a complementary tool to characterize regional kidney perfusion.

Sex-specific associations between insulin resistance and bone parameters in overweight and obese older adults.

OBJECTIVES: To determine sex-specific associations between insulin resistance and bone parameters measured by peripheral quantitative computed tomography in overweight and obese community-dwelling older adults. STUDY DESIGN: Cross-sectional study of 79 community-dwelling overweight and obese adults (mean ± SD age 62.8 ± 7.9 years; body mass index 32.3 ± 6.1 kg/m2 ; 58% women). MAIN OUTCOME MEASURES: Peripheral quantitative computed tomography assessed distal radius and tibia trabecular volumetric bone mineral density (vBMD) and proximal radius and tibia cortical vBMD, periosteal circumference, endosteal circumference and stress-strain index. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated from fasting glucose and insulin values. Lean mass was assessed using dual-energy X-ray absorptiometry. Total minutes of moderate and vigorous physical activity (MVPA) were calculated using the Active Australia Survey. RESULTS: Men and women in this cohort had no significant differences in fasting glucose and insulin concentrations, HOMA-IR values and diabetes prevalence (all P > 0.05). In women, HOMA-IR was positively correlated with proximal radius periosteal and endosteal circumference (r = 0.331; P = 0.034 and r = 0.325; P = 0.038, respectively). These associations became nonsignificant in multivariable regression analyses; however, HOMA-IR was negatively associated with proximal radius cortical vBMD (B = -4.79; 95% CI -8.66, -0.92) after adjusting for age, lean mass and MVPA. All associations between HOMA-IR and bone parameters became nonsignificant in a sensitivity analysis excluding individuals with diabetes, or self-reported use of glucose-lowering medications. There were no associations between HOMA-IR and bone parameters in men. CONCLUSIONS: Homeostatic Model Assessment of Insulin Resistance was negatively associated with radial cortical vBMD in overweight and obese older women, but not in men. Further studies are needed to clarify sex-specific associations between insulin resistance and bone health in overweight and obese older adults.