Correlation of MRI-derived adipose tissue measurements and anthropometric markers with prevalent hypertension in the community.

OBJECTIVES: To compare the correlations of MRI-derived adipose tissue measurements and anthropometric markers, respectively, with prevalent hypertension in a community-based sample, free of clinical cardiovascular disease. METHODS: MRI-derived adipose tissue measurements were obtained in 345 participants (143 women; age 39-73 years) of the KORA FF4 survey from Southern Germany using a 3-Tesla machine and included total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SCAT), hepatic fat fraction (HFF), pancreatic fat fraction (PFF) as well as pericardial adipose tissue (PAT). In addition, the anthropometric markers body mass index, waist circumference, hip circumference, waist-hip ratio (WHR) and waist-height ratio (WHtR) as well as blood pressure measurements were obtained. RESULTS: The prevalence of hypertension was 33.6% (women: 28%, men: 38%). VAT and PAT had the highest area under the curve (AUC) values for identifying individuals with prevalent hypertension (AUC: 0.75; 0.73, respectively), whereas WHtR and waist circumference were best performing anthropometric markers (AUC: 0.72; 0.70, respectively). A 1SD increment of TAT was associated with the highest odd for hypertension in the age-adjusted and sex-adjusted model (OR = 2.20, 95% CI 1.67-2.91, P < 0.001) and in the fully adjusted model (OR = 1.97, 95% CI 1.45-2.66, P < 0.001). TAT was the only MRI-derived adipose tissue measurement that was associated with hypertension independently of the best performing anthropometric marker waist circumference in the fully adjusted model (OR = 1.93, 95% CI 1.00-3.72, P = 0.049). CONCLUSION: MRI-derived adipose tissue measurements perform similarly in identifying prevalent hypertension compared with anthropometric markers. Especially, TAT, VAT and PAT as well as WHtR and waist circumference were highly correlated with prevalent hypertension.

The role of visceral and subcutaneous adipose tissue measurements and their ratio by magnetic resonance imaging in subjects with prediabetes, diabetes and healthy controls from a general population without cardiovascular disease.

OBJECTIVE: To study the relationship of area- and volumetric-based visceral and subcutaneous adipose tissue (VAT and SAT) by MRI and their ratio in subjects with impaired glucose metabolism from the general population. METHODS: Subjects from a population-based cohort with established prediabetes, diabetes and healthy controls without prior cardiovascular diseases underwent 3 T MRI. VAT and SAT were assessed as total volume and area on a single slice, and their ratio (VAT/SAT) was calculated. Clinical covariates and cardiovascular risk factors, such as hypertension and glycemic state were assessed in standardized fashion. Univariate and adjusted analyses were conducted. RESULTS: Among 384 subjects (age: 56.2 ± 9.2 years, 58.1% male) with complete MRI data available, volumetric and single-slice VAT, SAT and VAT/SAT ratio were strongly correlated (all >r = 0.89). Similarly, VAT/SATvolume ratio was strongly correlated with VATvolume but not with SAT (r = 0.72 and r = -0.21, respectively). Significant higher levels of VAT, SAT and VAT/SAT ratio were found in subjects with impaired glucose metabolism (all p ≤ 0.01). After adjustment for potential cardiovascular confounders, VATvolume and VAT/SATvolume ratio remained significantly higher in subjects with impaired glucose metabolism (VATvolume = 6.9 ± 2.5 l and 3.4 ± 2.3 l; VAT/SATvolume ratio = 0.82 ± 0.34 l and 0.49 ± 0.29 l in patients with diabetes and controls, respectively, all p < 0.02), whereas the association for SATvolume attenuated. Additionally, there was a decreasing effect of glycemic status on VAT/SATvolume ratio with increasing body mass index and waist circumference (p < 0.05). CONCLUSIONS: VATvolume and VAT/SATvolume ratio are associated with impaired glucose metabolism, independent of cardiovascular risk factors or MRI-based quantification technique, with a decreasing effect of VAT/SATvolume ratio in obese subjects. Advances in knowledge: Quantification of VATvolume and VAT/SATvolume ratio by MRI represents a reproducable biomarker associated with cardiometabolic risk factors in subjects with impaired glucose metabolism, while the association of VAT/SATvolume ratio with glycemic state is attenuated in obese subjects.

Myocardial tissue characterization by contrast-enhanced cardiac magnetic resonance imaging in subjects with prediabetes, diabetes, and normal controls with preserved ejection fraction from the general population.

Aims: To characterize changes in the myocardium in subjects with prediabetes, diabetes, and healthy controls with preserved left ventricular ejection fraction (LVEF) by using cardiac magnetic resonance imaging (CMR) in a sample from the general population. Methods and results: Subjects without history of cardiovascular disease and preserved LVEF but established diabetes, prediabetes, and controls from a population-based cohort underwent contrast-enhanced CMR. Obtained parameters included left ventricular (LV) function and morphology, late gadolinium enhancement as well as T1-mapping and derivation of extracellular volume fraction (ECV) by modified Look-Locker inversion recovery for diffuse fibrosis in a subset of patients. Fibrosis volume and cell volume were calculated and LV remodelling index was calculated by dividing the LV mass by its end-diastolic volume. Among 343 subjects (56.1 ± 9.2 years, 57% males), 47 subjects were classified as diabetes, 78 as prediabetes, and 218 as controls. Haematocrit values and thus ECV parameters were available in 251 subjects. LV remodelling index was significantly higher in participants with prediabetes and diabetes, independent of body mass index (BMI), hypertension, age, and sex. ECV was decreased in subjects with prediabetes and diabetes compared with healthy controls (23.1 ± 2.4% and 22.8 ± 3.0%, both P < 0.007). In contrast, cell volume was significantly higher in subjects with prediabetes and diabetes as compared with controls (109.1 ± 23.8 and 114.9 ± 32.3 mL vs. 96.5 ± 26.9 mL, both P < 0.03, respectively). However, differences in ECV and cell volume attenuated after the adjustment for cardiometabolic risk factors, including age, sex, BMI, and hypertension. Conclusion: Subjects with prediabetes and diabetes but preserved LVEF had higher LV remodelling indices, suggesting early detectable changes in the disease process, while diffuse myocardial fibrosis appears to be less relevant at this stage.

Pancreatic fat content by magnetic resonance imaging in subjects with prediabetes, diabetes, and controls from a general population without cardiovascular disease.

BACKGROUND/OBJECTIVE: Despite the relevance of pancreatic fat content in the development of metabolic diseases, its association with impaired glucose metabolism, diabetes, and other adipose tissue compartments remains unclear. Thus, we determined differences in pancreatic fat content by magnetic resonance imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in a cohort from the general population. METHODS: Subjects without history of cardiovascular disease with established diabetes or prediabetes as well as normal controls were included and underwent whole-body MRI on a 3T scanner. Pancreatic fat content was quantified by measuring the proton-density fat fraction (PDFFpanc) using a 3D multi-echo GRE sequence (increment: 1.23 ms, 6 echoes) by placing ROIs in the pancreatic head, body, and tail by independent readers. In addition, hepatic fat content as well as abdominal subcutaneous and visceral adipose tissue (SAT and VAT) were measured by multi-echo GRE and 3D 2-point volume-interpolated DIXON MRI, respectively. Univariate and multivariate analyses were employed to determine associations. RESULTS: A total of 385 subjects were included in the analysis (median age: 57 years, 58.2% males), of them 53 were classified as subjects with diabetes, 95 as prediabetes, and 237 as controls (13.8%, 24.7%, and 61.6%; respectively). The median PDFFpanc was 5.2% [IQR 3.3-9.4], and significantly higher in subjects with prediabetes and diabetes as compared to controls (PDFFpanc: 6.2% [IQR: 3.5-12] vs. 8.6% [IQR: 4.3-17.5] vs. 4.9% [3.1-7.4], p<0.001, respectively). After adjusting for age, gender and BMI the association was attenuated (all p>0.12). While in univariate analysis BMI, PDFFhepatic, SAT and VAT were associated with PDFFpanc (all p<0.05), only VAT predicted PDFFpanc independently (ß: 0.02, 95%-confidence interval: 0.01-0.04, p<0.001). CONCLUSION: While pancreatic fat content differs significantly between subjects with prediabetes, diabetes and controls, this association may be confounded by age, gender, and the amount of VAT in this cross-sectional study.

Population-based imaging biobanks as source of big data.

Advances of computational sciences over the last decades have enabled the introduction of novel methodological approaches in biomedical research. Acquiring extensive and comprehensive data about a research subject and subsequently extracting significant information has opened new possibilities in gaining insight into biological and medical processes. This so-called big data approach has recently found entrance into medical imaging and numerous epidemiological studies have been implementing advanced imaging to identify imaging biomarkers that provide information about physiological processes, including normal development and aging but also on the development of pathological disease states. The purpose of this article is to present existing epidemiological imaging studies and to discuss opportunities, methodological and organizational aspects, and challenges that population imaging poses to the field of big data research.

Malarial anemia: digestive vacuole of Plasmodium falciparum mediates complement deposition on bystander cells to provoke hemophagocytosis.

The digestive vacuole (DV) of Plasmodium falciparum, which is released into the bloodstream upon rupture of each parasitized red blood cell (RBC), was recently discovered to activate the alternative complement pathway. In the present work, we show that C3- and C5-convertases assembling on the parasitic organelle are able to provoke deposition of activated C3 and C5b-9 on non-infected bystander erythrocytes. Direct contact of DVs with cells is mandatory for the effect, and bystander complement deposition occurs focally, possibly at the sites of contact. Complement opsonization promotes protracted erythrophagocytosis by human macrophages, an effect that is magnified when ring-stage infected RBCs with reduced CD55 and CD59, or paroxysmal nocturnal hemoglobinuria (PNH)-RBCs lacking these complement inhibitors are employed as targets. Bystander attack can also directly induce lysis of PNH-RBCs. Direct evidence for complement activation and bystander attack mediated by DVs was obtained through immunohistochemical analyses of brain paraffin sections from autopsies of patients who had died of cerebral malaria. C3d and the assembled C5b-9 complex could be detected in all sections, colocalizing with and often extending locally beyond massive accumulations of DVs that were identified under polarized light. This is the first demonstration that a complement-activating particle can mediate opsonization of bystander cells to promote their antibody-independent phagocytosis. The phenomenon may act in concert with other pathomechanisms to promote the development of anemia in patients with severe malaria.

Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation.

Severe Plasmodium falciparum malaria evolves through the interplay among capillary sequestration of parasitized erythrocytes, deregulated inflammatory responses, and hemostasis dysfunction. After rupture, each parasitized erythrocyte releases not only infective merozoites, but also the digestive vacuole (DV), a membrane-bounded organelle containing the malaria pigment hemozoin. In the present study, we report that the intact organelle, but not isolated hemozoin, dually activates the alternative complement and the intrinsic clotting pathway. Procoagulant activity is destroyed by phospholipase C treatment, indicating a critical role of phospholipid head groups exposed at the DV surface. Intravenous injection of DVs caused alternative pathway complement consumption and provoked apathy and reduced nociceptive responses in rats. Ultrasonication destroyed complement-activating and procoagulant properties in vitro and rendered the DVs biologically inactive in vivo. Low-molecular-weight dextran sulfate blocked activation of both complement and coagulation and protected animals from the harmful effects of DV infusion. We surmise that in chronic malaria, complement activation by and opsonization of the DV may serve a useful function in directing hemozoin to phagocytic cells for safe disposal. However, when the waste disposal system of the host is overburdened, DVs may transform into a trigger of pathology and therefore represent a potential therapeutic target in severe malaria.