Purpose Biomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation of stem cells injected with the biomaterial into the infarcted heart. Methods A microstructural finite element model of a mid-wall infarcted myocardial region was developed from ex vivo microcomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (E inj ) ranging between 4.1 and 405,900 kPa. Results The transplanted cells’ deformation was largest for E inj = 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in E inj . The cell deformation was more sensitive to E inj changes for softer (E inj ≤ 738 kPa) than stiffer biomaterials. Conclusions Combining the microstructural and biventricular finite element models enables quantifying micromechanics and signalling of transplanted cells in the heart. The approach offers a broader scope for in silico investigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.

Intramyocardial delivery of biomaterials is a promising concept for treating myocardial infarction. The delivered biomaterial provides mechanical support and attenuates wall thinning and elevated wall stress in the infarct region. This study aimed at developing a biventricular finite element model of an infarcted rat heart with a microstructural representation of an in situ biomaterial injectate, and a parametric investigation of the effect of the injectate stiffness on the cardiac mechanics. A three-dimensional subject-specific biventricular finite element model of a rat heart with left ventricular infarct and microstructurally dispersed biomaterial delivered 1 week after infarct induction was developed from ex vivo microcomputed tomography data. The volumetric mesh density varied between 303 mm(-3) in the myocardium and 3852 mm(-3) in the injectate region due to the microstructural intramyocardial dispersion. Parametric simulations were conducted with the injectate's elastic modulus varying from 4.1 to 405,900 kPa, and myocardial and injectate strains were recorded. With increasing injectate stiffness, the end-diastolic median myocardial fibre and cross-fibre strain decreased in magnitude from 3.6% to 1.1% and from -6.0% to -2.9%, respectively. At end-systole, the myocardial fibre and cross-fibre strain decreased in magnitude from -20.4% to -11.8% and from 6.5% to 4.6%, respectively. In the injectate, the maximum and minimum principal strains decreased in magnitude from 5.4% to 0.001% and from -5.4% to -0.001%, respectively, at end-diastole and from 38.5% to 0.06% and from -39.0% to -0.06%, respectively, at end-systole. With the microstructural injectate geometry, the developed subject-specific cardiac finite element model offers potential for extension to cellular injectates and in silico studies of mechanotransduction and therapeutic signalling in the infarcted heart with an infarct animal model extensively used in preclinical research.

SummaryIn the past few years, dynamic computed tomography (CT) approaches or uninterrupted acquisitions of deforming materials have rapidly emerged as an essential technique to understand material evolution, facilitating in situ investigations ranging from mechanical deformation to fluid flow in porous materials and beyond. Developments at synchrotron facilities have led this effort, pointing to the future of the technique. In the laboratory, recent developments at TESCAN XRE have made it possible to image, reconstruct and inspect dynamic processes in the laboratory with a temporal resolution below 10 s, meaning that an entire acquisition from 0 to 360° is completed within 10 s. The aim of this study is to explore the challenges and innovations that have led to the ability to perform high speed, dynamic acquisitions. A unique horizontally rotating gantry based micro‐CT system was developed to facilitate complex in situ experiments. In doing so, the sample stays fixed while source and detector are uninterruptedly rotating around a vertical axis. In this work, the dynamic CT method with this rotating gantry based system will be described by two application examples: (1) deformation and collapse of a delicate beer foam and (2) in situ baking process of pastry. For the pastry baking process, an oven was needed to reach baking temperature. In a conventional micro‐CT system, where the sample rotates, it is not so obvious to rotate an oven with sensor and heating cables. On the other hand, the delicate foam of a collapsing beer head is able to rotate, but because of the tangential convection during fast rotation (<10 s), it could influence the bubble detachment and liquid drainage and thus also the foam degradation. To investigate both processes, a horizontally rotating gantry based micro‐CT is required. For both examples it was possible to quantify the key parameters such as pore size and distribution to better understand the rise and fall of porous foams. These examples will highlight the recent progress in adapting micro‐CT workflows to accommodate uninterrupted imaging of dynamic events and point to opportunities for future continued development.Lay DescriptionMicro‐CT allows the nondestructive visualisation of internal structures and is being used routinely in the field of Material Science, Geoscience, Life Science and more. Because of its nondestructive aspect, micro‐CT is optimal to take repetitive scans of the same sample over time. The combination of taking different scans over time is so called time‐resolved CT. By doing so, crucial insights can be obtained on how materials form, deform and perform over time or under certain external conditions. TESCAN XRE have made it possible to image, reconstruct and inspect dynamic processes in the laboratory with a temporal resolution below 10 s. The dynamic CT method will be described through the lens of two application examples: (1) deformation and collapse of a delicate beer foam and (2) in situ baking process of pastry. These examples will highlight the recent progress in adapting micro‐CT workflows to accommodate imaging of dynamic events and point to opportunities for future continued development.

Carotid artery stenting is emerging as an alternative technique to surgery for the treatment of symptomatic severe carotid stenosis. Clinical and experimental evidence demonstrates that both plaque morphology and biomechanical changes due to the device implantation can be possible causes of an unsuccessful treatment. In order to gain further insights of the endovascular intervention, a virtual environment based on structural finite element simulations was built to emulate the stenting procedure on generalized atherosclerotic carotid geometries which included a damage model to quantify the injury of the vessel. Five possible lesion scenarios were simulated by changing both material properties and vascular geometrical features to cover both presumed vulnerable and stable plaques. The results were analyzed with respect to lumen gain and wall stresses which are potentially related to the failure of the procedure according to previous studies. Our findings show that an elliptic lumen shape and a thinner fibrous cap with an underlying lipid pool result in higher stenosis reduction, while large calcifications and fibrotic tissue are more prone to recoil. The shielding effect of a thicker fibrous cap helps to reduce local compressive stresses in the soft plaque. The presence of a soft plaque reduces the damage in the healthy vascular structures. Contrarily, the presence of hard plaque promotes less damage volume in the fibrous cap and reduces stress peaks in this region, but they seem to increase stresses in the media-intima layer. Finally the reliability of the achieved results was put into clinical perspective.

High resolution X-ray computed tomography (CT), or microCT, is a promising and already widely used technique in various scientific fields. Also for histological purposes it has great potential. Although microCT has proven to be a valuable technique for the imaging of bone structures, the visualization of soft tissue structures is still an important challenge due to their low inherent X-ray contrast. One way to achieve contrast enhancement is to make use of contrast agents. However, contrary to light and electron microscopy, knowledge about contrast agents and staining procedures is limited for X-ray CT. The purpose of this paper is to identify useful X-ray contrast agents for soft tissue visualization, which can be applied in a simple way and are also suited for samples larger than (1 cm)3. And 28 chemical substances have been investigated. All chemicals were applied in the form of concentrated aqueous solutions in which the samples were immersed. First, strips of green Bacon were stained to evaluate contrast enhancement between muscle and adipose tissue. Furthermore it was also tested whether the contrast agents remained fixed in the tissue after staining by re-immersing them in water. Based on the results, 12 contrast agents were selected for further testing on postmortem mice hind legs, containing a variety of different tissues, including muscle, fat, bone, cartilage and tendons. It was evaluated whether the contrast agents allowed a clearer distinction between the different soft tissue structures present. Finally also penetration depth was measured. And 26 chemicals resulted in contrast enhancement between muscle and adipose tissue in the Bacon strips. Mercury(II)chloride (HgCl2), phosphotungstic acid (PTA), phosphomolybdic acid (PMA) and ammonium orthomolybdate ((NH4)2MoO4) remained fixed after re-immersion in water. The penetration tests showed that potassium iodide (KI) and sodium tungstate can be most efficiently used for large samples of the order of several tens of cm3. PMA, PTA, HgCl2 and also to a lesser extent Na2WO4 and (NH4)2MoO4 allowed a clearer distinction between the different soft tissue structures present.

The presented study details a combined experimental and computational method to assess and compare the mechanical behavior of the main body of 4 different stent graft designs. The mechanical response to a flat plate compression and radial crimping of the devices is derived and related to geometrical and material features of different stent designs. The finite element modeling procedure is used to complement the experimental results and conduct a solution sensitivity study. Finite element evaluations of the mechanical behavior match well with experimental findings and are used as a quantitative basis to discuss design characteristics of the different devices.

Studying structure and chemistry of wood and wood-based materials is the backbone of all wood research and many techniques are at hand to do so. A very valuable modality is X-ray computed tomography (CT), able to non-destructively probe the three-dimensional (3D) structure and composition. In this paper, we elaborate on the use of Nanowood, a flexible multi-resolution X-ray CT set-up developed at UGCT, the Ghent University Centre for X-ray Tomography. The technique has been used successfully in many different fields of wood science. It is illustrated how 3D structural and microdensitometrical data can be obtained using different scan set-ups and protocols. Its potential for the analysis of modified wood is exemplified, e.g. for the assessment of wood treated with hydrophobing agents, localisation of modification agents, pathway analysis related to functional tissues, dimensional changes due to thermal treatment, etc. Furthermore, monitoring of transient processes is a promising field of activity too.

The presented study details the virtual deployment of a bifurcated stent graft (Medtronic Talent) in an Abdominal Aortic Aneurysm model, using the finite element method. The entire deployment procedure is modeled, with the stent graft being crimped and bent according to the vessel geometry, and subsequently released. The finite element results are validated in vitro with placement of the device in a silicone mock aneurysm, using high resolution CT scans to evaluate the result. The presented work confirms the capability of finite element computer simulations to predict the deformed configuration after endovascular aneurysm repair (EVAR). These simulations can be used to quantify mechanical parameters, such as neck dilations, radial forces and stresses in the device, that are difficult or impossible to obtain from medical imaging.

Modelling of the hepatic circulation by combining vascular corrosion casting and micro-CT imagingIntroduction: Hepatic perfusion plays a crucial role in many liver-related research areas (e.g.living donor liver transplantation, machine perfusion preservation, cirrhosis).Nevertheless, liver perfusion remains relatively poorly understood, especially at the microcirculation level.It is thus essential to clarify the hepatic vascular morphology and hemodynamics.Therefore, we visualised the liver macro-towards microvasculature and performed computer simulations of the hepatic circulation. Methods and results:Vascular corrosion casting was applied to a human liver (discarded for transplantation) by simultaneous injections of resin (Batson's TM #17, Polysciences, USA) in the hepatic artery and portal vein.Data on the liver macrovasculature were gathered by a high resolution (110 µm) in globo micro-CT scan.Consecutive samples of different orders of magnitude were dissected from the cast and imaged at increasing resolutions, the most detailed scan (resolution 2.6 µm) obtained from a sample of ± 0.134 mm³.Image processing (Mimics, Materialise, Belgium) allowed segmentations and 3D reconstructions up to the sinusoidal network (Figure 1).These data were used to quantify branching topology and vessel features such as radii (up to 13 generations: range 13.2 to 0.08 mm; sinusoids: 6.63 µm) and lengths (range 74.4 to 0.74 mm).Sinusoidal porosity was found to be 0.15 ± 0.03.Various computational models (electrical network analogues, detailed 3D computational fluid dynamic models) were used to model pressure drops and flows throughout the liver (Figure 2; results of electrical liver model for natural blood flow and hypothermic machine perfusion).Microcirculatory flow simulations revealed anisotropic permeability characteristics within liver lobules (higher permeability parallel to the central vein; lower permeability in radial or circumferential directions). Conclusion:Combining vascular corrosion casting and micro-CT imaging allows (i) to quantify the hepatic vascular anatomy up to the microcirculation level, and (ii) to model hepatic perfusion.This approach may lead to novel insights into liver microcirculation, that can be used to study normal and pathological liver perfusion in the future.

s from the EASL – The International Liver Congress, Barcelona 2012 Propofol, but not sevorane, protects mitochondria and liver function after ischemiareperfusion injury F. Bellanti1, L. Mirabella2, N. Eronia2, G. Cinnella2, R. Tamborra1, M. Dambrosio2, E. Altomare1, G. Serviddio1 1Department of Medical and Occupational Sciences, C.U.R.E. Centre for Liver Diseases Research and Treatment, 2Department of Anaesthesiology, University of Foggia, Foggia, Italy Background and aims: Patients undergoing liver transplantation may face several problems related to ischemia-reperfusion (IR) injury, which can compromise graft function. Clinical trials proved that volatile anaesthetics are better than propofol in the protection of myocardial cells after IR injury during heart surgery. However, there are no studies investigating the post-operative outcomes of liver function after hepatic IR. Propofol has shown antioxidant properties, but no studies focused on its effects on liver surgery. Thus, we designed the present study to compare sevoflurane versus propofol anesthesia in a rodent model of hepatic IR. Mitochondrial function was evaluated as a key factor in IR injury. Data were then confirmed in liver from a group of patient after liver surgery. Methods: Sham-operated (S) and liver IR rats were randomly anaesthetised with intraperitoneal tiletamine/xylazine (S-CTRL and IRCTRL), inhaled sevoflurane (S-SEVO and IR-SEVO) or intravenous propofol (S-PROP and IRPROP). After surgery, rats were sacrificed and liver function tests (ALT and AST) were measured in the serum. Liver mitochondria were freshly isolated for measurement of bioenergetics parameters (oxygen uptake, membrane potential, respiratory complexes activity). Mitochondrial free radicals production was measured by evaluating H2O2 synthesis rate. Mitochondrial adducts formed by hydroxynonenal (HNE) and proteins were also measured. Results: In the IR groups, ALT and AST levels were significantly lower in rats anaestethised with propofol as compared to control and sevorane group. Moreover, oxygen uptake and respiratory activity from Complex I as well as membrane potential were severely impaired in IR-SEVO group but not in liver mitochondria isolated from IR-PROP. In addition, mitochondria H2O2 synthesis rate and HNE-protein adducts were considerably lower in IR-PROP as compared to IR-CTRL and IR-SEVO. Very interestingly, liver tests and mitochondrial function were also preserved in patients after liver surgery. Discussion: IR induces mitochondrial dysfunction that is not prevented by inhaled sevoflurane; propofol reduces liver damage and mitochondrial dysfunction by limiting mitochondrial free radicals production. The potential effect of propofol during liver surgery merits clinical investigation. Modelling of the hepatic circulation by combining vascular corrosion casting and micro-CT imaging C. Debbaut1, C. Casteleyn2, P. Cornillie3, D. Van Loo4,5, J. Vierendeels6, P. Segers1, D. Monbaliu7 1IBiTech bioMMeda, Ghent University, Gent, 2Applied Veterinary Morphology, University of Antwerp, Antwerpen, 3Department of Morphology, 4Centre for X-Ray Tomography, 5Department of Soil Management, 6Department of Flow, Heat and Combustion Mechanics, Ghent University, Gent, 7Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium Introduction: Hepatic perfusion plays a crucial role in many liver-related research areas (e.g. living donor liver transplantation, machine perfusion preservation, cirrhosis). Nevertheless, liver perfusion remains relatively poorly understood, especially at the microcirculation level. It is thus essential to clarify the hepatic vascular morphology and hemodynamics. Therefore, we visualised the liver macrotowards microvasculature and performed computer simulations of the hepatic circulation. Methods and results: Vascular corrosion casting was applied to a human liver (discarded for transplantation) by simultaneous injections of resin (Batson'sTM#17, Polysciences, USA) in the hepatic artery and portal vein. Data on the liver macrovasculature were gathered by a high resolution (110 μm) in globo micro-CT scan. Consecutive samples of different orders of magnitude were dissected from the cast and imaged at increasing resolutions, the most detailed scan (resolution 2.6 μm) obtained from a samAbstracts from the EASL, Barcelona, 2012 Transplantationsmedizin 2012, 24. Jahrgang 39s from the EASL, Barcelona, 2012 Transplantationsmedizin 2012, 24. Jahrgang 39 ple of ± 0.134 mm3. Image processing (Mimics, Materialise, Belgium) allowed segmentations and 3D reconstructions up to the sinusoidal network (Figure 1). These data were used to quantify branching topology and vessel features such as radii (up to 13 generations: range 13.2 to 0.08 mm; sinusoids: 6.63 μm) and lengths (range 74.4 to 0.74 mm). Sinusoidal porosity was found to be 0.15 ± 0.03. Various computational models (electrical network analogues, detailed 3D computational fluid dynamic models) were used to model pressure drops and flows throughout the liver (Figure 2; results of electrical liver model for natural blood flow and hypothermic machine perfusion). Microcirculatory flow simulations revealed anisotropic permeability characteristics within liver lobules (higher permeability parallel to the central vein; lower permeability in radial or circumferential directions). Conclusion: Combining vascular corrosion casting and micro-CT imaging allows (i) to quantify the hepatic vascular anatomy up to the microcirculation level, and (ii) to model hepatic perfusion. This approach may lead to novel insights into liver microcirculation, that can be used to study normal and pathological liver perfusion in the future. Acknowledgment: This research was supported by the Agency for Innovation by Science and Technology in Flanders (IWT), Belgium. Xanthohumol suppresses hepatic inflammatory response to acute liver injury C. Dorn1, J. Heilmann2, C. Hellerbrand1 1Department of Internal Medicine I, University Hospital Regensburg, 2Institute of Pharmacy, University of Regensburg, Regensburg, Germany Liver cell injury induced by stress such as ischemia-reperfusion (I/R) or toxins triggers an inflammatory response, which leads to reactive oxygen species (ROS) formation. ROS play a major role in the mechanisms, which lead to hepatic inflammation and hepatocellular damage. Xanthohumol, the major prenylated chalcone found in hops, is known for its anti-inflammatory and ROS-scavenging properties. Aim: The aim of this study was to investigate the effects of xanthohumol in two models of acute liver injury. Methods and results: Xanthohumol was applied to BALB/c mice orally at a dose of approximately 1mg/g body weight for 5 days via foodsupplementation. Control-mice received standard chow. Acute liver damage was induced either by injection of a single dose of carbon tetrachloride 72h prior to sample asservation or by clamping the vascular blood supply to the median and left lateral liver lobe for 1h (ischemic phase) followed by a 6h period of reperfusion. Histomorphology and serum levels of transaminases revealed considerable heFigure 1: (a) Vascular corrosion cast at the level of the hepatic microvasculature and (b) 3D reconstruction of a sinusoidal cube (0.15 x 0.15 x 0.15 mm3) Figure 2: Results of the computational liver model: (a) Pressure profile throughout the liver for natural blood flow; (b) hepatic arterial (HA), portal venous(PV) and hepatic venous (HV) blood flow in different conditions (natural blood flow, hypothermic machine perfusion (HMP)) 40 Transplantationsmedizin 2012, 24. Jahrgang Abstracts from the EASL, Barcelona, 2012 patocellular necrosis in both models, which was accompanied by significantly enhanced hepatic expression of pro-inflammatory cytokines and elevated NFkappaB activity. While acute liver damage related GSH-depletion and induction of hepatic HMOX-1 expression were significantly reduced in xanthohumol-fed mice compared to control-mice, the degree of overall hepatocellular damage did not significantly differ between these groups. However, pro-inflammatory hepatic gene expression as well as I-kappaB-alpha degradation and subsequent induction of NFkappaB activity were almost completely blunted in xanthohumol-fed mice. Conclusions: Our data suggest that xanthohumol is able to counter hepatic oxidative stress in vivo, and more importantly, block the inflammatory response to acute liver damage, presumable at least in part via decreasing NFkappaB activity. Thus, this study indicates the potential of xanthohumol application to prevent adverse inflammatory responses to acute liver damage of various etiologies as after intoxication or surgically related I/R injury. Post-transplantation metabolic syndrome: Is it only a therapeutic concern? M. D. Iadevaia, M. Giusto, V. Giannelli, Q. Lai, M. Rossi, P. Berloco, S. Ginanni Corradini, M. Merli Sapienza University of Rome, Rome, Italy Background and aims: Due to the improved survival after liver transplantation (LT), greater attention has been reserved to diseases occurring within the long term follow-up, such as PostTransplantation Metabolic Syndrome (PTMS). Several predictors for PTMS have been identified: higher age at transplant, male gender, pre-LT metabolic derangements, the etiology of hepatopathy and immunosuppression. This syndrome contributes to increase the cardiovascular risk in transplanted patients. Aim of the study was (1) to evaluate the prevalence and the incidence of the Post-Transplant Metabolic Syndrome (PTMS); (2) To evaluate risk factors and predictors for its development; (3) To verify its influence on patients' cardiovascular risk. Methods: We enrolled 156 patients (mean age 58±9 years, 76% male) who underwent LT during the last twenty years. Mean follow-up was 67±50 months (range 6-114 months). Personal and clinical data were collected retrospectively for each patients; PTMS was diagnosed according to modified NCEP ATPIII