Traction mechanical characterization of porcine mitral valve annulus.

The Mitral Annulus (MA) is an anisotropic, fibrous, flexible and dynamical structure. While MA dynamics are well documented, its passive mechanical properties remain poorly investigated to complete the design of adequate prostheses. Mechanical properties in traction on four sections of the MA (aortic, left, posterior and right segments) were assessed using a traction test system with a 30 N load cell and pulling jaws for sample fixation. Samples were submitted to a 1.5 N pre-load, 10 pre-conditioning cycles. Three strain rates were tested (5 %/min, 7 %/min and 13 %/min), the first two up to 10 % strain and the last until rupture. High-resolution diffusion-MRI provided microstructural mapping of fractional anisotropy and mean diffusion within muscle and collagen fibres. Ten MA from porcine hearts were excised resulting in 40 tested samples, out of which 28 were frozen prior to testing. Freezing samples significantly increased Young Moduli for all strain rates. No significant differences were found between Young Moduli at different strain rates (fresh samples 2.4 ± 1.1 MPa, 3.8 ± 2.2 MPa and 3.1 ± 1.8 MPa for increasing strain rates in fresh samples), while significant differences were found when comparing aortic with posterior and posterior with lateral (p < 0.012). Aortic segments deformed the most (24.1 ± 9.4 %) while lateral segments endured the highest stress (>0.3 MPa), corresponding to higher collagen fraction (0.46) and fractional anisotropy. Passive machinal properties differed between aortic and lateral segments of the MA. The process of freezing samples altered their mechanical properties. Underlying microstructural differences could be linked to changes in strain response.

Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study.

BACKGROUND: Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D). We hypothesized that empaglifozin (EMPA) could modulate ectopic fat stores and myocardial energetics in high-fat-high-sucrose (HFHS) diet mice and in type 2 diabetics (T2D). METHODS: C57BL/6 HFHS mice (n = 24) and T2D subjects (n = 56) were randomly assigned to 12 weeks of treatment with EMPA (30 mg/kg in mice, 10 mg/day in humans) or with placebo. A 4.7 T or 3 T MRI with 1H-MRS evaluation-myocardial fat (primary endpoint) and liver fat content (LFC)-were performed at baseline and at 12 weeks. In humans, standard cardiac MRI was coupled with myocardial energetics (PCr/ATP) measured with 31P-MRS. Subcutaneous (SAT) abdominal, visceral (VAT), epicardial and pancreatic fat were also evaluated. The primary efficacy endpoint was the change in epicardial fat volume between EMPA and placebo from baseline to 12 weeks. Secondary endpoints were the differences in PCr/ATP ratio, myocardial, liver and pancreatic fat content, SAT and VAT between groups at 12 weeks. RESULTS: In mice fed HFHS, EMPA significantly improved glucose tolerance and increased blood ketone bodies (KB) and ß-hydroxybutyrate levels (p < 0.05) compared to placebo. Mice fed HFHS had increased myocardial and liver fat content compared to standard diet mice. EMPA significantly attenuated liver fat content by 55%, (p < 0.001) but had no effect on myocardial fat. In the human study, all the 56 patients had normal LV function with mean LVEF = 63.4 ± 7.9%. Compared to placebo, T2D patients treated with EMPA significantly lost weight (- 2.6 kg [- 1.2; - 3.7]) and improved their HbA1c by 0.88 ± 0.74%. Hematocrit and EPO levels were significantly increased in the EMPA group compared to placebo (p < 0.0001, p = 0.041). EMPA significantly increased glycosuria and plasma KB levels compared to placebo (p < 0.0001, p = 0.012, respectively), and significantly reduced liver fat content (- 27 ± 23 vs. - 2 ± 24%, p = 0.0005) and visceral fat (- 7.8% [- 15.3; - 5.6] vs. - 0.1% [- 1.1;6.5], p = 0.043), but had no effect on myocardial or epicardial fat. At 12 weeks, no significant change was observed in the myocardial PCr/ATP (p = 0.57 between groups). CONCLUSIONS: EMPA effectively reduced liver fat in mice and humans without changing epicardial, myocardial fat or myocardial energetics, rebutting the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors. Trial registration NCT, NCT03118336. Registered 18 April 2017, https://clinicaltrials.gov/ct2/show/NCT03118336.

Quantification of diffuse myocardial fibrosis using CMR extracellular volume fraction and serum biomarkers of collagen turnover with histologic quantification as standard of reference.

PURPOSE: To compare the assessment of diffuse interstitial myocardial fibrosis in valvular diseases using cardiac magnetic resonance (CMR) extracellular volume fraction (ECV) quantification and serum biomarkers of collagen turnover using results of myocardial biopsy as standard of reference. MATERIALS AND METHODS: This prospective monocentric study included consecutive patients before aortic valvular replacement. All patients underwent: i), 1.5T CMR with pre and post contrast T1 mapping sequence and ECV computation; ii), serum quantification of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) and iii), myocardial biopsies were collected during surgery to assess collagen volume fraction (CVF). Patients with coronary artery disease were excluded. Correlation between native T1, ECV, CVF and serum biomarkers were assessed using Pearson correlation test. Agreement between basal anteroseptal ECV with global ECV was assessed using Bland-Altman test. RESULTS: Twenty-one patients, 16 with aortic stenosis and 5 with aortic regurgitation were included. There were 12 men and 9 women with a mean age of 74.1±6.8 (SD) years (range: 32-84 years). Mean global ECV value was 26.7±2.7 (SD) % (range: 23.4-32.5%) and mean CVF value was 12.4±9.7% (range: 3.2-25.7%). ECV assessed at the basal anteroseptal segment correlated moderately with CVF (r=0.6; P=0.0026). There was a strong correlation and agreement between basal anteroseptal ECV and global ECV, (r=0.8; P<0.0001; bias 5.4±6.1%) but no correlation between global ECV and CVF (r=0.5; P=0.10). Global ECV poorly correlated with serum TIMP-1 (r=0.4; P=0.037) and MMP-2 (r=0.4; P=0.047). No correlation was found between serum biomarkers and basal anteroseptal- ECV or native T1. CONCLUSION: In patients with severe aortic valvulopathy, diffuse myocardial fibrosis assessed by anterosepto-basal ECV correlates with histological myocardial fibrosis. Anteroseptobasal ECV strongly correlates with global ECV, which poorly correlates with TIMP-1 and MMP-2, serum biomarkers involved in the progression of heart failure.

Quantification of right ventricular extracellular volume in pulmonary hypertension using cardiac magnetic resonance imaging.

PURPOSE: The purpose of this prospective study was to assess the value of biventricular extracellular volume (ECV) in pre-capillary pulmonary hypertension (PH) obtained using cardiac magnetic resonance imaging (CMR) and to correlate ECV with markers of prognosis such as strain echocardiography and blood biomarkers of fibrosis. MATERIALS AND METHODS: Twelve patients with PH (6 men, 6 women; mean age=50±16 [SD] years; age range: 22-73 years) underwent the same day: (i), transthoracic echocardiography including measurement of right ventricular (RV) fractional shortening (RVfs), tricuspid annular plane systolic excursion (TAPSE), maximal tricuspid annular velocity, RV global and segmental deformation; (ii), right heart catheterization measuring pulmonary arterial pressures (inmmHg) and cardiac output (inL/min); (iii), CMR at 1.5-T measuring RV volumes and ejection fraction; (iv), native and 15min post-contrast T1 mapping using modified look-locker inversion-recovery sequence; and (v), serum quantification of two biomarkers of collagen turnover and hematocrit. Non-parametric Mann-Whitney tests were used to search for differences between categorical variables. Spearman correlation test was used for search for correlation between quantitative values. RESULTS: Global RV ECV was 34%±4.2 (SD) for our entire population. A significant correlation was found between RV ECV and RVfs (r=0.6; P=0.026), S wave velocity (r=0.7; P=0.009), TAPSE (r=0.6; P=0.040) and RV systolic ejection fraction on CMR (r=0.6; P=0.04). There were no correlations between the ECV values in the lateral wall of the RV and in the septum (r=0.4; P=0.206). A significant correlation was found between septal ECV and 2D septal strain (r=0.7; P=0.013). CONCLUSION: ECV in PH as obtained using CMR appears to correlate with known echocardiographic prognostic markers and more specifically with the markers, which assess RV systolic function.

Distribution of left ventricular trabeculation across age and gender in 140 healthy Caucasian subjects on MR imaging.

PURPOSE: The purpose of this study was to quantify the distribution of trabeculated (T) and compact (C) left ventricular (LV) myocardium masses in a healthy Caucasian population against age, gender and LV parameters, and to provide normal values for T, C and T/C. MATERIALS AND METHODS: One hundred and forty healthy subjects were prospectively recruited and underwent cardiac MRI at 1.5T with a stack of short-axis cine sequences covering the entire LV. End-diastolic volume (EDV), C and T masses were quantified using a semi-automatic method. Ejection fraction (EF) and T/C ratio were computed. RESULTS: We included 70 men and 70 women with a mean age of 44±14 (SD) years (range: 20-69 years). The mean EF was 63.7±6.3 (SD) % (range: 50.7-82.0%), the mean EDV was 75.9±16.2 (SD) mL/m2 (range: 36.4-112.2mL/m2), the mean C mass was 53.9±11.2 (SD) g/m2 (range: 26.5-93.4g/m2) and the mean T mass was 4.9±2.4 (SD) g/m2 (range: 1.1-11.4g/m2). The T/C ratio was 9.2±4.5% (range: 2.0-29.4%). Multivariate ANOVA test showed that the compact mass was influenced by EDV (P<0.0001), EF (P=0.001) and gender (P<0.0001), and the trabeculated mass depended on EDV (P<0.0001), gender (P=0.002) and age (P<0.0001), while the T/C ratio was only influenced by age (P=0.0003). Spearman test showed a correlation between EDV and C (r=0.60; P<0.0001),T (r=0.46; P<0.0001) and T/C ratio (r=0.26; P=0.0023).T and T/C ratio correlated with EF (r=-0.18, P=0.0373; r=-0.18, P=0.0321, respectively). CONCLUSION: While the compact and trabeculated myocardium masses appear to relate separately to the cardiac function, age and gender, their ratio T/C appears to only decrease with age. Furthermore, we propose here normal values for T, C and T/C in a cohort of healthy Caucasians subjects.

Feasibility of automated pancreas segmentation based on dynamic MRI.

OBJECTIVE: MRI-guided radiotherapy is particularly attractive for abdominal targets with low CT contrast. To fully utilize this modality for pancreas tracking, automated segmentation tools are needed. A hybrid gradient, region growth and shape constraint (hGReS) method to segment two-dimensional (2D) upper abdominal dynamic MRI (dMRI) is developed for this purpose. METHODS: 2D coronal dynamic MR images of two healthy volunteers were acquired with a frame rate of 5 frames per second. The regions of interest (ROIs) included the liver, pancreas and stomach. The first frame was used as the source where the centres of the ROIs were manually annotated. These centre locations were propagated to the next dMRI frame. Four-neighborhood region transfer growth was performed from these initial seeds before refinement using shape constraints. RESULTS from hGReS and two other automated segmentation methods using integrated edge detection and region growth (IER) and level set, respectively, were compared with manual contours using Dice's index (DI). RESULTS: For the first patient, the hGReS resulted in the organ segmentation accuracy as a measure by the DI (0.77) for the pancreas, superior to the level set method (0.72) and IER (0.71). The hGReS was shown to be reproducible on the second subject, achieving a DI of 0.82, 0.92 and 0.93 for the pancreas, stomach and liver, respectively. Motion trajectories derived from the hGReS were highly correlated to respiratory motion. CONCLUSION: We have shown the feasibility of automated segmentation of the pancreas anatomy on dMRI. ADVANCES IN KNOWLEDGE: Using the hybrid method improves segmentation robustness of low-contrast images.

PCATMIP: enhancing signal intensity in diffusion-weighted magnetic resonance imaging.

Diffusion-weighted MRI studies generally lose signal intensity to physiological motion, which can adversely affect quantification/diagnosis. Averaging over multiple repetitions, often used to improve image quality, does not eliminate the signal loss. In this article, PCATMIP, a combined principal component analysis and temporal maximum intensity projection approach, is developed to address this problem. Data are first acquired for a fixed number of repetitions. Assuming that physiological fluctuations of image intensities locally are likely temporally correlated unlike random noise, a local moving boxcar in the spatial domain is used to reconstruct low-noise images by considering the most relevant principal components in the temporal domain. Subsequently, a temporal maximum intensity projection yields a high signal-intensity image. Numerical and experimental studies were performed for validation and to determine optimal parameters for increasing signal intensity and minimizing noise. Subsequently, a combined principal component analysis and temporal maximum intensity projection approach was used to analyze diffusion-weighted porcine liver MRI scans. In these scans, the variability of apparent diffusion coefficient values among repeated measurements was reduced by 59% relative to averaging, and there was an increase in the signal intensity with higher intensity differences observed at higher b-values. In summary, a combined principal component analysis and temporal maximum intensity projection approach is a postprocessing approach that corrects for bulk motion-induced signal loss and improves apparent diffusion coefficient measurement reproducibility.

Interpolation of vector fields from human cardiac DT-MRI.

There has recently been increased interest in developing tensor data processing methods for the new medical imaging modality referred to as diffusion tensor magnetic resonance imaging (DT-MRI). This paper proposes a method for interpolating the primary vector fields from human cardiac DT-MRI, with the particularity of achieving interpolation and denoising simultaneously. The method consists of localizing the noise-corrupted vectors using the local statistical properties of vector fields, removing the noise-corrupted vectors and reconstructing them by using the thin plate spline (TPS) model, and finally applying global TPS interpolation to increase the resolution in the spatial domain. Experiments on 17 human hearts show that the proposed method allows us to obtain higher resolution while reducing noise, preserving details and improving direction coherence (DC) of vector fields as well as fiber tracking. Moreover, the proposed method perfectly reconstructs azimuth and elevation angle maps.