Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on 18F-FDG PET/CT.

BACKGROUND: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified. METHODS: Two 18F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic-euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial 18F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT. RESULTS: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81-44.06] vs. 30.82 [21.48-38.02]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. CONCLUSIONS: 18F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D.

Modelling the skeletal muscle injury recovery using in vivo contrast-enhanced micro-CT: a proof-of-concept study in a rat model.

BACKGROUND: Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model. METHODS: Skeletal muscle injury was performed in 23 rats. Twenty animals were sorted into five groups to image lesion recovery at 2, 4, 7, 10, or 14 days after injury using contrast-enhanced micro-CT. Injury volumes were quantified using a semiautomatic image processing, and these values were used to build a prediction model. The remaining 3 rats were imaged at all monitoring time points as validation. Predictions were compared with Bland-Altman analysis. RESULTS: Optimal contrast agent dose was found to be 20 mL/kg injected at 400 µL/min. Injury volumes showed a decreasing tendency from day 0 (32.3 ± 12.0mm3, mean ± standard deviation) to day 2, 4, 7, 10, and 14 after injury (19.6 ± 12.6, 11.0 ± 6.7, 8.2 ± 7.7, 5.7 ± 3.9, and 4.5 ± 4.8 mm3, respectively). Groups with single monitoring time point did not yield significant differences with the validation group lesions. Further exponential model training with single follow-up data (R2 = 0.968) to predict injury recovery in the validation cohort gave a predictions root mean squared error of 6.8 ± 5.4 mm3. Further prediction analysis yielded a bias of 2.327. CONCLUSION: Contrast-enhanced CT allowed in vivo tracking of skeletal muscle injury recovery in rat.

Quantification of the detailed cardiac left ventricular trabecular morphogenesis in the mouse embryo.

During embryogenesis, a mammalian heart develops from a simple tubular shape into a complex 4-chamber organ, going through four distinct phases: early primitive tubular heart, emergence of trabeculations, trabecular remodeling and development of the compact myocardium. In this paper we propose a framework for standardized and subject-independent 3D regional myocardial complexity analysis, applied to analysis of the development of the mouse left ventricle. We propose a standardized subdivision of the myocardium into 3D overlapping regions (in our case 361) and a novel visualization of myocardial complexity, whereupon we: 1) extend the fractal dimension, commonly applied to image slices, to 3D and 2) use volume occupied by the trabeculations in each region together with their surface area, in order to quantify myocardial complexity. The latter provides an intuitive characterization of the complexity, given that compact myocardium will tend to occupy a larger volume with little surface area while high surface area with low volume will correspond to highly trabeculated areas. Using 50 mouse embryo images at 5 different gestational ages (10 subjects per gestational age), we demonstrate how the proposed representation and complexity measures describe the development of LV myocardial complexity. The mouse embryo data was acquired using high resolution episcopic microscopy. The complexity analysis per region was carried out using: 3D fractal dimension, myocardial volume, myocardial surface area and ratio between the two. The analysis of gestational ages was performed on embryos of 14.5, 15.5, 16.5, 17.5 and 18.5 embryonic days, and demonstrated that the regional complexity of the trabeculations increases longitudinally from the base to the apex, with a maximum around the middle. The overall complexity decreases with gestational age, being most complex at 14.5. Circumferentially, at ages 14.5, 15.5 and 16.5, the trabeculations show similar complexity everywhere except for the anteroseptal and inferolateral area of the wall, where it is smaller. At 17.5 days, the regions of high complexity become more localized towards the inferoseptal and anterolateral parts of the wall. At 18.5 days, the high complexity area exhibits further localization at the inferoseptal and anterior part of the wall.

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations.

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches use smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band, and papillary muscles. Four paired detailed and smoothed RV endocardium models (2 male and 2 female) were reconstructed from ex vivo human hearts high-resolution magnetic resonance images. Detailed models include structures with ≥1 mm2 cross-sectional area. Haemodynamic characterisation was done by computational fluid dynamics simulations with steady and transient inflows, using high-performance computing. The differences between the flows in smoothed and detailed models were assessed using Q-criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress. Results demonstrated that detailed endocardial structures increase the degree of intra-ventricular pressure drop, decrease the wall shear stress, and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity.

Left Ventricular Trabeculations Decrease the Wall Shear Stress and Increase the Intra-Ventricular Pressure Drop in CFD Simulations.

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10-2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.

Relationship between the left ventricular size and the amount of trabeculations.

Contemporary imaging modalities offer noninvasive quantification of myocardial deformation; however, they make gross assumptions about internal structure of the cardiac walls. Our aim is to study the possible impact of the trabeculations on the stroke volume, strain, and capacity of differently sized ventricles. The cardiac left ventricle is represented by an ellipsoid and the trabeculations by a tissue occupying a fixed volume. The ventricular contraction is modeled by scaling the ellipsoid whereupon the measurements of longitudinal strain, end-diastolic, end-systolic, and stroke volumes are derived and compared. When the trabeculated and nontrabeculated ventricles, having the same geometry and deformation pattern, contain the same amount of blood and contract with the same strain, we observed an increased stroke volume in our model of the trabeculated ventricle. When these ventricles contain and eject the same amount of blood, we observed a reduced strain in the trabeculated case. We identified that a trade-off between the strain and the amount of trabeculations could be reached with a 0.35- to 0.41-cm dense trabeculated layer, without blood filled recesses (for a ventricle with end-diastolic volume of about 150 mL). A trabeculated ventricle can work at lower strains compared to a nontrabeculated ventricle to produce the same stroke volume, which could be a possible explanation why athletes and pregnant women develop reversible signs of left ventricular noncompaction, since the trabeculations could help generating extra cardiac output. This knowledge might help to assess heart failure patients with dilated cardiomyopathies who often show signs of noncompaction.

Whole heart detailed and quantitative anatomy, myofibre structure and vasculature from X-ray phase-contrast synchrotron radiation-based micro computed tomography.

BACKGROUND: While individual cardiac myocytes only have a limited ability to shorten, the heart efficiently pumps a large volume-fraction thanks to a cell organization in a complex 3D fibre structure. Subclinical subtle cardiac structural remodelling is often present before symptoms arise. Understanding and early detection of these subtle changes is crucial for diagnosis and prevention. Additionally, personalized computational modelling requires knowledge on the multi-scale structure of the whole heart and vessels. METHODS AND RESULTS: We developed a rapid acquisition together with visualization and quantification methods of the integrated microstructure of whole in-vitro rodents hearts using synchrotron based X-ray phase-contrast tomography. These images are formed not only by X-ray absorption by the tissue but also by wave propagation phenomena, enhancing structural information, thus allowing to raise tissue contrast to an unprecedented level. We used a (ex-vivo) normal rat heart and fetal rabbit hearts suffering intrauterine growth restriction as a model of subclinical cardiac remodelling to illustrate the strengths and potential of the technique. For comparison, histology and diffusion tensor magnetic resonance imaging was performed. CONCLUSIONS: We have developed a novel, high resolution, image acquisition, and quantification approach to study a whole in-vitro heart at myofibre resolution, providing integrated 3D structural information at microscopic level without any need of tissue slicing and processing. This superior imaging approach opens up new possibilities for a systems approach towards analysing cardiac structure and function, providing rapid acquisition of quantitative microstructure of the heart in a near native state.

Patient independent representation of the detailed cardiac ventricular anatomy.

Reparameterization of surfaces is a widely used tool in computer graphics known mostly from the remeshing algorithms. Recently, the surface reparameterization techniques started to gain popularity in the field of medical imaging, but mostly for convenient 2D visualization of the information initially represented on 3D surfaces (e.g. continuous bulls-eye plot). However, by consistently mapping the 3D information to the same 2D domain, surface reparameterization techniques allow us to put into correspondence anatomical shapes of inherently different geometry. In this paper, we propose a method for anatomical parameterization of cardiac ventricular anatomies that include myocardium, trabeculations, tendons and papillary muscles. The proposed method utilizes a quasi-conformal flattening of the myocardial surfaces of the left and right cardiac ventricles and extending it to cover the interior of the cavities using the local coordinates given by the solution of the Laplace's equation. Subsequently, we define a geometry independent representation for the detailed cardiac left and right ventricular anatomies that can be used for convenient visualization and statistical analysis of the trabeculations in a population. Lastly we show how it can be used for mapping the detailed cardiac anatomy between different hearts, which is of considerable interest for detailed cardiac computational models or shape atlases.