Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects.

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants' smoking and sporting habits were measured by a questionnaire. Physical inactivity was associated with a reduction of left ventricular ejection fraction (LV-EF), stroke volume, early diastolic peak filling rate and peak ejection rate of the left ventricle as well as right ventricular stroke volume. LV-EF was reduced in subjects with almost no physical activity compared to subjects with regular physical activity (68.4%, 95%CI 66.8-70.1% vs. 70.8%, 95%CI 69.2-72.3%, p < 0,05). Smokers had lower right ventricular end-diastolic volumes (80.6 ml/m², 95%CI 76.7-84.5 ml/m²; never-smokers: 85.5 ml/m², 95%CI 82.6-88.3 ml/m²; p < 0.05) but higher extracellular volume fractions (ECV) and fibrosis volumes (34.3 ml, 95%CI 32.5-36.0 ml, vs. 31.0 ml, 95%CI 29.6-32.3 ml, p < 0.01). We conclude that asymptomatic individuals without known cardiovascular diseases show differences in cardiac function and structure depending on their physical activity and smoking habits. This underlines the importance of prevention and health education.

Hepatic fat is superior to BMI, visceral and pancreatic fat as a potential risk biomarker for neurodegenerative disease.

OBJECTIVES: Prior studies relating body mass index (BMI) to brain volumes suggest an overall inverse association. However, BMI might not be an ideal marker, as it disregards different fat compartments, which carry different metabolic risks. Therefore, we analyzed MR-based fat depots and their association with gray matter (GM) volumes of brain structures, which show volumetric changes in neurodegenerative diseases. METHODS: Warp-based automated brain segmentation of 3D FLAIR sequences was obtained in a population-based study cohort. Associations of temporal lobe, cingulate gyrus, and hippocampus GM volume with BMI and MR-based quantification of visceral adipose tissue (VAT), as well as hepatic and pancreatic proton density fat fraction (PDFFhepatic and PDFFpanc, respectively), were assessed by linear regression. RESULTS: In a sample of 152 women (age 56.2 ± 9.0 years) and 199 men (age 56.1 ± 9.1 years), we observed a significant inverse association of PDFFhepatic and cingulate gyrus volume (p < 0.05) as well as of PDFFhepatic and hippocampus volume (p < 0.05), when adjusting for age and sex. This inverse association was further enhanced for cingulate gyrus volume after additionally adjusting for hypertension, smoking, BMI, LDL, and total cholesterol (p < 0.01) and also alcohol (p < 0.01). No significant association was observed between PDFFhepatic and temporal lobe and between temporal lobe, cingulate gyrus, or hippocampus volume and BMI, VAT, and PDFFpanc. CONCLUSIONS: We observed a significant inverse, independent association of cingulate gyrus and hippocampus GM volume with hepatic fat, but not with other obesity measures. Increased hepatic fat could therefore serve as a marker of high-risk fat distribution. KEY POINTS: • Obesity is associated with neurodegenerative processes. • In a population-based study cohort, hepatic fat was superior to BMI and visceral and pancreatic fat as a risk biomarker for decreased brain volume of cingulate gyrus and hippocampus. • Increased hepatic fat could serve as a marker of high-risk fat distribution.

Alcohol consumption, but not smoking is associated with higher MR-derived liver fat in an asymptomatic study population.

BACKGROUND: The aim of our study was to determine the relation of alcohol consumption and cigarette smoking on continuous-measured hepatic fat fraction (HFF) in a population free of cardiovascular disease. We suggested a direct correlation of alcohol consumption with HFF and increased HFF in former smokers compared to current smokers. METHODS: Data from 384 subjects (mean age: 56 years, 58% men) of a population-based cohort study (KORA) were included in a cross-sectional design. Liver fat was assessed by 3 Tesla magnetic resonance imaging (MRI) using a multi-echo Dixon sequence and T2-corrected single voxel multi-echo spectroscopy (1H-MRS). Smoking status was classified as never, former or current smoker and alcohol consumption as non-, moderate (0.1-39.9 g/day for men and 0.1-19.9 g/day for women), or heavy drinker (≥ 40 g/day for men and ≥ 20 g/day for women). Fatty liver disease was defined as HFF≥5.56%. RESULTS: Average HFF was 8.8% by 1H-MRS and 8.5% by MRI. Former smokers showed a higher HFF (MRI: ß = 2.64; p = 0.006) and a higher FLD prevalence (MRI: OR = 1.91; p = 0.006) compared to never smokers. Current smokers showed decreased odds for FLD measured by 1H-MRS after multivariable adjustment (OR = 0.37; p = 0.007) with never smoker as reference. Heavy drinking was positively associated with HFF (1H-MRS: ß = 2.99; p = 0.003) and showed highest odds for FLD (1H-MRS: OR = 3.05; p = 0.008) with non-drinker as reference. Moderate drinking showed a positive association with HFF (1H-MRS: ß = 1.54; p = 0.061 and MRI: ß = 1.75; p = 0.050). CONCLUSIONS: Our data revealed lowest odds for FLD in current smokers, moderate drinkers showing higher HFF than non-drinkers and heavy drinkers showing highest HFF and odds for FLD. These findings partly conflict with former literature and underline the importance of further studies to investigate the complex effects on liver metabolism.

Qualitative and Quantitative Evaluation of Structural Myocardial Alterations by Grating-Based Phase-Contrast Computed Tomography.

OBJECTIVES: Grating-based phase-contrast computed tomography (gb-PCCT) relies on x-ray refraction instead of absorption to generate high-contrast images in biological soft tissue. The aim of this study was to evaluate the potential of gb-PCCT for the depiction of structural changes in heart disease. MATERIALS AND METHODS: Four human heart specimens from patients with hypertensive disease, ischemic disease, dilated heart disease, and cardiac lipomatosis were examined. The gb-PCCT setup consisted of an x-ray tube (40 kV, 70 mA), grating-interferometer, and detector, and allowed simultaneous acquisition of phase- and absorption-contrast data. With histopathology as the standard of reference, myocardium (MC), fibrotic scar (FS), interstitial fibrosis (IF), and fatty tissue (FT) were visually and quantitatively evaluated. Systematic differences in absorption- and phase-contrast Hounsfield units (HUabs and HUp) were assessed. RESULTS: Thirteen corresponding cross-sections were included, and MC, FS, IF, and FT were found in 13 (100%), 4 (30.8%), 7 (53.8%), and 13 (100%) cross-sections, respectively. Mean HUp/HUabs were 52.5/54.1, 86.6/69.7, 62.4/62.3, and -38.6/-258.9 for MC, FS, IF, and FT, respectively. An overlap in HUabs was observed for MC and IF (P = 0.84) but not for HUp (P < 0.01). Contrast-to-noise ratios were significantly higher in phase- than in absorption-contrast for MC/FT (35.4 vs 7.8; P < 0.01) and for MC/FS (12.3 vs 0.2; P < 0.01). CONCLUSIONS: Given its superior soft tissue contrast, gb-PCCT is able to depict structural changes in different cardiomyopathies, which can currently not be obtained by x-ray absorption-based imaging methods. If current technical limitations can be overcome, gb-PCCT may evolve as a powerful tool for the anatomical assessment of cardiomyopathy.

Dark-field imaging in coronary atherosclerosis.

OBJECTIVES: Dark-field imaging based on small angle X-ray scattering has been shown to be highly sensitive for microcalcifications, e.g. in breast tissue. We hypothesized (i) that high signal areas in dark-field imaging of atherosclerotic plaque are associated with microcalcifications and (ii) that dark-field imaging is more sensitive for microcalcifications than attenuation-based imaging. METHODS: Fifteen coronary artery specimens were examined at an experimental set-up consisting of X-ray tube (40kV), grating-interferometer and detector. Tomographic dark-field-, attenuation-, and phase-contrast data were simultaneously acquired. Histopathology served as standard of reference. To explore the potential of dark field imaging in a full-body CT system, simulations were carried out with spherical calcifications of different sizes to simulate small and intermediate microcalcifications. RESULTS: Microcalcifications were present in 10/10 (100%) cross-sections with high dark-field signal and without evidence of calcifications in attenuation- or phase contrast. In positive controls with high signal areas in all three modalities, 10/10 (100%) cross-sections showed macrocalcifications. In negative controls without high signal areas, no calcifications were detected. Simulations showed that the microcalcifications generate substantially higher dark-field than attenuation signal. CONCLUSIONS: Dark-field imaging is highly sensitive for microcalcifications in coronary atherosclerotic plaque and might provide complementary information in the assessment of plaque instability.

Increase of Intra-abdominal Adipose Tissue in Pediatric Crohn Disease.

BACKGROUND AND OBJECTIVE: Recent evidence points toward an active immunological role of intra-abdominal adipose tissue in Crohn disease (CD). We quantified the abdominal adipose tissue compartments using magnetic resonance imaging (MRI) in 27 pediatric patients with CD compared with 14 controls undergoing MRI examination for other reasons. METHODS: Total (TAAT), subcutaneous (SCAT) and intra-abdominal (IAAT) adipose tissue areas were measured by semiautomatic segmentation on a transverse slice centered on the umbilicus (mean ±â€Šstandard deviation in square centimeter) using standard T1-weighted sequences. IAAT/TAAT and IAAT/height ratios were calculated and analyzed for associations with disease duration, phenotype, or therapy. RESULTS: Patients with CD (median age 15.0 years, range 7.7-17.9, 18/27 boys, median disease duration 29 months, range 0-136) compared to controls (median age 13.9 years, range 3.3-17.8, 4/14 boys) had higher IAAT area (42.3 ±â€Š21.0 vs 28.7 ±â€Š11.6, P = 0.0494) but similar SCAT and TAAT areas (104.6 ±â€Š72.8 vs 96.5 ±â€Š50.8, P = 0.8170 and 146.9 ±â€Š87.3 vs 125.3 ±â€Š61.5, P = 0.7417, respectively). IAAT/TAAT ratio was higher in patients with CD compared to controls (0.32 ±â€Š0.10 vs 0.24 ±â€Š0.04, P = 0.0081). Patients with disease duration >2 years (n = 14) had higher IAAT/TAAT ratio than those with shorter disease and controls (0.35 ±â€Š0.10 vs 0.28 ±â€Š0.08, P = 0.0288 and 0.24 ±â€Š0.04, P = 0.0009, respectively). In these patients, increased IAAT/height ratio was associated with complicated disease (P = 0.043, r = 0.573). No association was found between IAAT/TAAT ratio and actual disease activity or therapy. CONCLUSIONS: IAAT is increased in pediatric CD and correlates with disease duration. Assessment of IAAT accumulation may be considered in future MRI scores for inflammation and bowel damage in CD and during follow-up of different therapeutic interventions.

Differences in the serum nonesterified Fatty Acid profile of young women associated with a recent history of gestational diabetes and overweight/obesity.

BACKGROUND: Nonesterified fatty acids (NEFA) play pathophysiological roles in metabolic syndrome and type 2 diabetes (T2D). In this study, we analyzed the fasting NEFA profiles of normoglycemic individuals at risk for T2D (women with a recent history of gestational diabetes (GDM)) in comparison to controls (women after a normoglycemic pregnancy). We also examined the associations of NEFA species with overweight/obesity, body fat distribution and insulin sensitivity. SUBJECTS AND METHODS: Using LC-MS/MS, we analyzed 41 NEFA species in the fasting sera of 111 women (62 post-GDM, 49 controls). Clinical characterization included a five-point oral glucose tolerance test (OGTT), biomarkers and anthropometrics, magnetic resonance imaging (n = 62) and a food frequency questionnaire. Nonparametric tests with Bonferroni correction, binary logistic regression analyses and rank correlations were used for statistical analysis. RESULTS: Women after GDM had a lower molar percentage of total saturated fatty acids (SFA; 38.55% vs. 40.32%, p = 0.0002) than controls. At an explorative level of significance several NEFA species were associated with post-GDM status (with and without adjustment for body mass index (BMI) and HbA1c): The molar percentages of 14:0, 16:0, 18:0 and 18:4 were reduced, whereas those of 18:1, 18:2, 20:2, 24:4, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and total n-6 NEFA were increased. BMI and the amount of body fat correlated inversely with several SFA and MUFA and positively with various PUFA species over the whole study cohort (abs(ρ)≥0.3 for all). 14:0 was inversely and BMI-independently associated with abdominal visceral adiposity. We saw no correlations of NEFA species with insulin sensitivity and the total NEFA concentration was similar in the post-GDM and the control group. CONCLUSION: In conclusion, we found alterations in the fasting NEFA profile associated with a recent history of gestational diabetes, a risk marker for T2D. NEFA composition also varied with overweight/obesity and with body fat distribution, but not with insulin sensitivity.

Feasibility of dynamic CT-based adenosine stress myocardial perfusion imaging to detect and differentiate ischemic and infarcted myocardium in an large experimental porcine animal model.

The purpose of the study is feasibility of dynamic CT perfusion imaging to detect and differentiate ischemic and infarcted myocardium in a large porcine model. 12 Country pigs completed either implantation of a 75 % luminal coronary stenosis in the left anterior descending coronary artery simulating ischemia or balloon-occlusion inducing infarction. Dynamic CT-perfusion imaging (100 kV, 300 mAs), fluorescent microspheres, and histopathology were performed in all models. CT based myocardial blood flow (MBFCT), blood volume (MBVCT) and transit constant (Ktrans), as well as microsphere's based myocardial blood flow (MBFMic) were derived for each myocardial segment. According to histopathology or microsphere measurements, 20 myocardial segments were classified as infarcted and 23 were ischemic (12 and 14 %, respectively). Across all perfusion states, MBFCT strongly predicted MBFMic (ß 0.88 ± 0.12, p < 0.0001). MBFCT, MBVCT, and Ktrans were significantly lower in ischemic/infarcted when compared to reference myocardium (all p < 0.01). Relative differences of all CT parameters between affected and non-affected myocardium were higher for infarcted when compared to ischemic segments under rest (48.4 vs. 22.6 % and 46.1 vs. 22.9 % for MBFCT, MBVCT, respectively). Under stress, MBFCT was significantly lower in infarcted than in ischemic myocardium (67.8 ± 26 vs. 88.2 ± 22 ml/100 ml/min, p = 0.002). In a large animal model, CT-derived parameters of myocardial perfusion may enable detection and differentiation of ischemic and infarcted myocardium.

Translation of atherosclerotic plaque phase-contrast CT imaging from synchrotron radiation to a conventional lab-based X-ray source.

OBJECTIVES: Phase-contrast imaging is a novel X-ray based technique that provides enhanced soft tissue contrast. The aim of this study was to evaluate the feasibility of visualizing human carotid arteries by grating-based phase-contrast tomography (PC-CT) at two different experimental set-ups: (i) applying synchrotron radiation and (ii) using a conventional X-ray tube. MATERIALS AND METHODS: Five ex-vivo carotid artery specimens were examined with PC-CT either at the European Synchrotron Radiation Facility using a monochromatic X-ray beam (2 specimens; 23 keV; pixel size 5.4 µm), or at a laboratory set-up on a conventional X-ray tube (3 specimens; 35-40 kVp; 70 mA; pixel size 100 µm). Tomographic images were reconstructed and compared to histopathology. Two independent readers determined vessel dimensions and one reader determined signal-to-noise ratios (SNR) between PC-CT and absorption images. RESULTS: In total, 51 sections were included in the analysis. Images from both set-ups provided sufficient contrast to differentiate individual vessel layers. All PCI-based measurements strongly predicted but significantly overestimated lumen, intima and vessel wall area for both the synchrotron and the laboratory-based measurements as compared with histology (all p<0.001 with slope >0.53 per mm(2), 95%-CI: 0.35 to 0.70). Although synchrotron-based images were characterized by higher SNRs than laboratory-based images; both PC-CT set-ups had superior SNRs compared to corresponding conventional absorption-based images (p<0.001). Inter-reader reproducibility was excellent (ICCs >0.98 and >0.84 for synchrotron and for laboratory-based measurements; respectively). CONCLUSION: Experimental PC-CT of carotid specimens is feasible with both synchrotron and conventional X-ray sources, producing high-resolution images suitable for vessel characterization and atherosclerosis research.

Multiple stent fractures at the site of coronary artery bypass insertion.

Drug eluting stents have led to a substantial reduction of in-stent restenosis. Stent fracture (SF) is an important cause for the cases of restenosis which still occur. Sites of increased vessel movement, long stents, and overlapping stents have been observed to be more prone to fracture. We report the case of a patient with multiple drug eluting SFs at the site of coronary artery bypass insertion. The decision to implant stents at the site of bypass insertion should be made carefully. SF should be considered when gaps between previously implanted stents are observed.

Endovascular optical coherence tomography ex vivo: venous wall anatomy and tissue alterations after endovenous therapy.

Endovascular optical coherence tomography (OCT) is a new imaging modality providing histology-like information of the venous wall. Radiofrequency ablation (RFA) and laser therapy (ELT) are accepted alternatives to surgery. This study evaluated OCT for qualitative assessment of venous wall anatomy and tissue alterations after RFA and ELT in bovine venous specimens. One hundred and thirty-four venous segments were obtained from ten ex-vivo bovine hind limbs. OCT signal characteristics for different wall layers were assessed in 180/216 (83%) quadrants from 54 normal venous cross-sections. Kappa statistics (kappa) were used to calculate intra- and inter-observer agreement. Qualitative changes after RFA (VNUS-Closure) and ELT (diode laser 980 nm, energy densities 15 Joules (J)/cm, 25 J/cm, 35 J/cm) were described in 80 venous cross-sections. Normal veins were characterized by a three-layered appearance. After RFA, loss of three-layered appearance and wall thickening at OCT corresponded with circular destruction of tissue structures at histology. Wall defects after ELT ranged from non-transmural punctiform damage to complete perforation, depending on the energy density applied. Intra- and inter-observer agreement for reading OCT images was very high (0.90 and 0.88, respectively). OCT allows for reproducible evaluation of normal venous wall and alterations after endovenous therapy. OCT could prove to be valuable for optimizing endovenous therapy in vivo.