An exploratory study of structural and microvascular changes in the skin following electrical shaving using optical coherence topography.

BACKGROUND: Consumer products such as electrical shavers exert a combination of dynamic loading in the form of pressure and shear on the skin. This mechanical stimulus can lead to discomfort and skin tissue responses characterised as "Skin Sensitivity". To minimise discomfort following shaving, there is a need to establish specific stimulus-response relationships using advanced tools such as optical coherence tomography (OCT). OBJECTIVE: To explore the spatial and temporal changes in skin morphology and microvascular function following an electrical shaving stimulus. METHODS: Ten healthy male volunteers were recruited. The study included a 60-s electrical shaving stimulus on the forearm, cheek and neck. Skin parameters were recorded at baseline, 20 min post stimulus and 24 h post stimulus. Structural and dynamic skin parameters were estimated using OCT, while transepidermal water loss (TEWL) was recorded to provide reference values for skin barrier function. RESULTS: At baseline, six of the eight parameters revealed statistically significant differences between the forearm and the facial sites, while only surface roughness (Rq) and reflectivity were statistically different (p < 0.05) between the cheek and neck. At 20 min post shaving, there was a significant increase in the TEWL values accompanied by increased blood perfusion, with varying magnitude of change dependent on the anatomical site. Recovery characteristics were observed 24 h post stimulus with most parameters returning to basal values, highlighting the transient influence of the stimulus. CONCLUSIONS: OCT parameters revealed spatial and temporal differences in the skin tissue response to electrical shaving. This approach could inform shaver design and prevent skin sensitivity.

Quantifying skin sensitivity caused by mechanical insults: A review.

BACKGROUND: Skin sensitivity (SS) is a commonly occurring response to a range of stimuli, including environmental conditions (e.g., sun exposure), chemical irritants (e.g., soaps and cosmetics), and mechanical forces (e.g., while shaving). From both industry and academia, many efforts have been taken to quantify the characteristics of SS in a standardised manner, but the study is hindered by the lack of an objective definition. METHODS: A review of the scientific literature regarding different parameters attributed to the loss of skin integrity and linked with exhibition of SS was conducted. Articles included were screened for mechanical stimulation of the skin, with objective quantification of tissue responses using biophysical or imaging techniques. Additionally, studies where cohorts of SS and non-SS individuals were reported have been critiqued. RESULTS: The findings identified that the structure and function of the stratum corneum and its effective barrier properties are closely associated with SS. Thus, an array of skin tissue responses has been selected for characterization of SS due to mechanical stimuli, including: transepidermal water loss, hydration, redness, temperature, and sebum index. Additionally, certain imaging tools allow quantification of the superficial skin layers, providing structural characteristics underlying SS. CONCLUSION: This review proposes a multimodal approach for identification of SS, providing a means to characterise skin tissue responses objectively. Optical coherence tomography (OCT) has been suggested as a suitable tool for dermatological research with clinical applications. Such an approach would enhance the knowledge underlying the multifactorial nature of SS and aid the development of personalised solutions in medical and consumer devices.

Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation.

In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics. Starting out from a reference geometry in which myofiber orientation had no transmural component, two new geometries were defined with either a 27 % decrease in LV short- to long-axis ratio, or a 16 % decrease of RV length, but identical LV and RV cavity and wall volumes. These variations in geometry caused differences in both local myofiber and global pump work below 6 %. Variation of fiber orientation was induced through adaptive myofiber reorientation that caused an average change in fiber orientation of [Formula: see text] predominantly through the formation of a component in transmural direction. Reorientation caused a considerable increase in local myofiber work [Formula: see text] and in global pump work [Formula: see text] in all three geometries, while differences between geometries were below 5 %. The findings suggest that implementing a realistic myofiber orientation is at least as important as defining a patient-specific geometry. The model for remodeling of myofiber orientation seems a useful approach to estimate myofiber orientation in the absence of accurate patient-specific information.

In vivo electromechanical assessment of heart failure patients with prolonged QRS duration.

BACKGROUND: Combined measurement of electrical activation and mechanical dyssynchrony in heart failure (HF) patients is scarce but may contain important mechanistic and diagnostic clues. OBJECTIVE: The purpose of this study was to characterize the electromechanical (EM) coupling in HF patients with prolonged QRS duration. METHODS: Ten patients with QRS width >120 ms underwent left ventricular (LV) electroanatomic contact mapping using the Noga® XP system (Biosense Webster). Recorded voltages during the cardiac cycle were converted to maps of depolarization time (TD). Electrode positions were tracked and converted into maps of time-to-peak shortening (TPS) using custom-made deformation analysis software. Correlation analysis was performed between the 2 maps to quantify EM coupling. Simulations with the CircAdapt cardiovascular system model were performed to mechanistically unravel the observed relation between TD and TPS. RESULTS: The delay between earliest LV electrical activation and peak shortening differed considerably between patients (TPSmin-TDmin = 360 ± 73 ms). On average, total mechanical dyssynchrony exceeded total electrical activation (ΔTPS = 177 ± 47 ms vs ΔTD = 93 ± 24 ms, P <.001), but a large interpatient variability was observed. The TD and TPS maps correlated strongly in all patients (median R = 0.87, P <.001). These correlations were similar for regions with unipolar voltages above and below 6mV (Mann-Whitney U test, P = .93). Computer simulations revealed that increased passive myocardial stiffness decreases ΔTPS relative to ΔTD and that lower contractility predominantly increases TPSmin-TDmin. CONCLUSION: EM coupling in HF patients is maintained, but the relationship between TD and TPS differs strongly between patients. Intra-individual and inter-individual differences may be explained by local and global differences in passive and contractile myocardial properties.

Assessment and comparison of left ventricular shear in normal and situs inversus totalis hearts by means of magnetic resonance tagging.

Situs inversus totalis (SIT) is characterized by complete mirroring of gross cardiac anatomy and position combined with an incompletely mirrored myofiber arrangement, being normal at the apex but inverted at the base of the left ventricle (LV). This study relates myocardial structure to mechanical function by analyzing and comparing myocardial deformation patterns of normal and SIT subjects, focusing especially on circumferential-radial shear. In nine control and nine SIT normotensive human subjects, myocardial deformation was assessed from magnetic resonance tagging (MRT) image sequences of five LV short-axis slices. During ejection, no significant difference in either circumferential shortening (εcc) or its axial gradient (Δεcc) is found between corresponding LV levels in control and SIT hearts. Circumferential-radial shear (εcr) has a clear linear trend from apex-to-base in controls, while in SIT it hovers close to zero at all levels. Torsion as well as axial change in εcr (Δεcr) is as in controls in apical sections of SIT hearts but deviates significantly towards the base, changing sign close to the LV equator. Interindividual variability in torsion and Δεcr values is higher in SIT than in controls. Apex-to-base trends of torsion and Δεcr in SIT, changing sign near the LV equator, further substantiate a structural transition in myofiber arrangement close to the LV equator itself. Invariance of εcc and Δεcc patterns between controls and SIT subjects shows that normal LV pump function is achieved in SIT despite partial mirroring of myocardial structure leading to torsional and shear patterns that are far from normality.

Patient-specific modelling of cardiac electrophysiology in heart-failure patients.

AIMS: Left-ventricular (LV) conduction disturbances are common in heart-failure patients and a left bundle-branch block (LBBB) electrocardiogram (ECG) type is often seen. The precise cause of this pattern is uncertain and is probably variable between patients, ranging from proximal interruption of the left bundle branch to diffuse distal conduction disease in the working myocardium. Using realistic numerical simulation methods and patient-tailored model anatomies, we investigated different hypotheses to explain the observed activation order on the LV endocardium, electrogram morphologies, and ECG features in two patients with heart failure and LBBB ECG. METHODS AND RESULTS: Ventricular electrical activity was simulated using reaction-diffusion models with patient-specific anatomies. From the simulated action potentials, ECGs and cardiac electrograms were computed by solving the bidomain equation. Model parameters such as earliest activation sites, tissue conductivity, and densities of ionic currents were tuned to reproduce the measured signals. Electrocardiogram morphology and activation order could be matched simultaneously. Local electrograms matched well at some sites, but overall the measured waveforms had deeper S-waves than the simulated waveforms. CONCLUSION: Tuning a reaction-diffusion model of the human heart to reproduce measured ECGs and electrograms is feasible and may provide insights in individual disease characteristics that cannot be obtained by other means.

Ureter smooth muscle cell orientation in rat is predominantly longitudinal.

In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.

Effects of activation pattern and active stress development on myocardial shear in a model with adaptive myofiber reorientation.

It has been hypothesized that myofiber orientation adapts to achieve a preferred mechanical loading state in the myocardial tissue. Earlier studies tested this hypothesis in a combined model of left ventricular (LV) mechanics and remodeling of myofiber orientation in response to fiber cross-fiber shear, assuming synchronous timing of activation and uniaxial active stress development. Differences between computed and measured patterns of circumferential-radial shear strain E(cr) were assumed to be caused by limitations in either the LV mechanics model or the myofiber reorientation model. Therefore, we extended the LV mechanics model with a physiological transmural and longitudinal gradient in activation pattern and with triaxial active stress development. We investigated the effects on myofiber reorientation, LV function, and deformation. The effect on the developed pattern of the transverse fiber angle α(t,0) and the effect on global pump function were minor. Triaxial active stress development decreased amplitudes of E(cr) towards values within the experimental range and resulted in a similar base-to-apex gradient during ejection in model computed and measured E(cr). The physiological pattern of mechanical activation resulted in better agreement between computed and measured strain in myofiber direction, especially during isovolumic contraction phase and first half of ejection. In addition, remodeling was favorable for LV pump and myofiber function. In conclusion, the outcome of the combined model of LV mechanics and remodeling of myofiber orientation is found to become more physiologic by extending the mechanics model with triaxial active stress development and physiological activation pattern.

Computational model for estimating the short- and long-term cardiac response to arteriovenous fistula creation for hemodialysis.

Creation of an arteriovenous fistula (AVF) for hemodialysis may result in cardiac failure due to dramatic increases in cardiac output. To investigate the quantitative relations between AVF flow, changes in cardiac output, myocardial stress and strain and resulting left ventricular adaptation, a computational model is developed. The model combines a one-dimensional pulse wave propagation model of the arterial network with a zero-dimensional one-fiber model of cardiac mechanics and includes adaptation rules to capture the effect of the baro-reflex and long-term structural remodelling of the left ventricle. Using generic vascular and cardiac parameters based on literature, simulations are done that illustrate the model's ability to quantitatively reproduce the clinically observed increase in brachial flow and cardiac output as well as occurence of eccentric hypertrophy. Patient-specific clinical data is needed to investigate the value of the computational model for personalized predictions.

Why SIT works: normal function despite typical myofiber pattern in Situs Inversus Totalis (SIT) hearts derived by shear-induced myofiber reorientation.

The left ventricle (LV) of mammals with Situs Solitus (SS, normal organ arrangement) displays hardly any interindividual variation in myofiber pattern and experimentally determined torsion. SS LV myofiber pattern has been suggested to result from adaptive myofiber reorientation, in turn leading to efficient pump and myofiber function. Limited data from the Situs Inversus Totalis (SIT, a complete mirror image of organ anatomy and position) LV demonstrated an essential different myofiber pattern, being normal at the apex but mirrored at the base. Considerable differences in torsion patterns in between human SIT LVs even suggest variation in myofiber pattern among SIT LVs themselves. We addressed whether different myofiber patterns in the SIT LV can be predicted by adaptive myofiber reorientation and whether they yield similar pump and myofiber function as in the SS LV. With a mathematical model of LV mechanics including shear induced myofiber reorientation, we predicted myofiber patterns of one SS and three different SIT LVs. Initial conditions for SIT were based on scarce information on the helix angle. The transverse angle was set to zero. During reorientation, a non-zero transverse angle developed, pump function increased, and myofiber function increased and became more homogeneous. Three continuous SIT structures emerged with a different location of transition between normal and mirrored myofiber orientation pattern. Predicted SIT torsion patterns matched experimentally determined ones. Pump and myofiber function in SIT and SS LVs are similar, despite essential differences in myocardial structure. SS and SIT LV structure and function may originate from same processes of adaptive myofiber reorientation.

A numerical method of reduced complexity for simulating vascular hemodynamics using coupled 0D lumped and 1D wave propagation models.

A computational method of reduced complexity is developed for simulating vascular hemodynamics by combination of one-dimensional (1D) wave propagation models for the blood vessels with zero-dimensional (0D) lumped models for the microcirculation. Despite the reduced dimension, current algorithms used to solve the model equations and simulate pressure and flow are rather complex, thereby limiting acceptance in the medical field. This complexity mainly arises from the methods used to combine the 1D and the 0D model equations. In this paper a numerical method is presented that no longer requires additional coupling methods and enables random combinations of 1D and 0D models using pressure as only state variable. The method is applied to a vascular tree consisting of 60 major arteries in the body and the head. Simulated results are realistic. The numerical method is stable and shows good convergence.

Patient-specific computational modeling of upper extremity arteriovenous fistula creation: its feasibility to support clinical decision-making.

INTRODUCTION: Inadequate flow enhancement on the one hand, and excessive flow enhancement on the other hand, remain frequent complications of arteriovenous fistula (AVF) creation, and hamper hemodialysis therapy in patients with end-stage renal disease. In an effort to reduce these, a patient-specific computational model, capable of predicting postoperative flow, has been developed. The purpose of this study was to determine the accuracy of the patient-specific model and to investigate its feasibility to support decision-making in AVF surgery. METHODS: Patient-specific pulse wave propagation models were created for 25 patients awaiting AVF creation. Model input parameters were obtained from clinical measurements and literature. For every patient, a radiocephalic AVF, a brachiocephalic AVF, and a brachiobasilic AVF configuration were simulated and analyzed for their postoperative flow. The most distal configuration with a predicted flow between 400 and 1500 ml/min was considered the preferred location for AVF surgery. The suggestion of the model was compared to the choice of an experienced vascular surgeon. Furthermore, predicted flows were compared to measured postoperative flows. RESULTS: Taken into account the confidence interval (25(th) and 75(th) percentile interval), overlap between predicted and measured postoperative flows was observed in 70% of the patients. Differentiation between upper and lower arm configuration was similar in 76% of the patients, whereas discrimination between two upper arm AVF configurations was more difficult. In 3 patients the surgeon created an upper arm AVF, while model based predictions allowed for lower arm AVF creation, thereby preserving proximal vessels. In one patient early thrombosis in a radiocephalic AVF was observed which might have been indicated by the low predicted postoperative flow. CONCLUSIONS: Postoperative flow can be predicted relatively accurately for multiple AVF configurations by using computational modeling. This model may therefore be considered a valuable additional tool in the preoperative work-up of patients awaiting AVF creation.

Control of whole heart geometry by intramyocardial mechano-feedback: a model study.

Geometry of the heart adapts to mechanical load, imposed by pressures and volumes of the cavities. We regarded preservation of cardiac geometry as a homeostatic control system. The control loop was simulated by a chain of models, starting with geometry of the cardiac walls, sequentially simulating circulation hemodynamics, myofiber stress and strain in the walls, transfer of mechano-sensed signals to structural changes of the myocardium, and finalized by calculation of resulting changes in cardiac wall geometry. Instead of modeling detailed mechano-transductive pathways and their interconnections, we used principles of control theory to find optimal transfer functions, representing the overall biological responses to mechanical signals. As biological responses we regarded tissue mass, extent of contractile myocyte structure and extent of the extra-cellular matrix. Mechano-structural stimulus-response characteristics were considered to be the same for atrial and ventricular tissue. Simulation of adaptation to self-generated hemodynamic load rendered physiologic geometry of all cardiac cavities automatically. Adaptation of geometry to chronic hypertension and volume load appeared also physiologic. Different combinations of mechano-sensors satisfied the condition that control of geometry is stable. Thus, we expect that for various species, evolution may have selected different solutions for mechano-adaptation.

Determinants of left ventricular shear strain.

Mathematical models of cardiac mechanics can potentially be used to relate abnormal cardiac deformation, as measured noninvasively by ultrasound strain rate imaging or magnetic resonance tagging (MRT), to the underlying pathology. However, with current models, the correct prediction of wall shear strain has proven to be difficult, even for the normal healthy heart. Discrepancies between simulated and measured strains have been attributed to 1) inadequate modeling of passive tissue behavior, 2) neglecting active stress development perpendicular to the myofiber direction, or 3) neglecting crossover of myofibers in between subendocardial and subepicardial layers. In this study, we used a finite-element model of left ventricular (LV) mechanics to investigate the sensitivity of midwall circumferential-radial shear strain (E(cr)) to settings of parameters determining passive shear stiffness, cross-fiber active stress development, and transmural crossover of myofibers. Simulated time courses of midwall LV E(cr) were compared with time courses obtained in three healthy volunteers using MRT. E(cr) as measured in the volunteers during the cardiac cycle was characterized by an amplitude of approximately 0.1. In the simulations, a realistic amplitude of the E(cr) signal could be obtained by tuning either of the three model components mentioned above. However, a realistic time course of E(cr), with virtually no change of E(cr) during isovolumic contraction and a correct base-to-apex gradient of E(cr) during ejection, could only be obtained by including transmural crossover of myofibers. Thus, accounting for this crossover seems to be essential for a realistic model of LV wall mechanics.

Computational modeling of volumetric soft tissue growth: application to the cardiac left ventricle.

As an initial step to investigate stimulus-response relations in growth and remodeling (G&R) of cardiac tissue, this study aims to develop a method to simulate 3D-inhomogeneous volumetric growth. Growth is regarded as a deformation that is decomposed into a plastic component which describes unconstrained growth and an elastic component to satisfy continuity of the tissue after growth. In current growth models, a single reference configuration is used that remains fixed throughout the entire growth process. However, considering continuous turnover to occur together with growth, such a fixed reference is unlikely to exist in reality. Therefore, we investigated the effect of tissue turnover on growth by incrementally updating the reference configuration. With both a fixed reference and an updated reference, strain-induced cardiac growth in magnitude of 30% could be simulated. However, with an updated reference, the amplitude of the stimulus for growth decreased over time, whereas with a fixed reference this amplitude increased. We conclude that, when modeling volumetric growth, the choice of the reference configuration is of great importance for the computed growth.

Computational analysis of the myocardial structure: adaptation of cardiac myofiber orientations through deformation.

Deformation and structure of the cardiac wall can be assessed non-invasively by imaging techniques such as magnetic resonance imaging. Understanding the (patho-)physiology that underlies the observed deformation and structure is critical for clinical diagnosis. However, much about the genesis of deformation and structure is unknown. In the present computational model study, we hypothesize that myofibers locally adapt their orientation to achieve minimal fiber-cross fiber shear strain during the cardiac cycle. This hypothesis was tested in a 3D finite element model of left ventricular (LV) mechanics by computation of tissue deformations and subsequent adaptation of initial myofiber orientations towards those in the deformed tissue. As a consequence of adaptation, local tissue peak stress, strain during ejection and stroke work density were all found to increase by at least 10%, as well as to become 50% more homogeneous throughout the wall. Global LV work (peak systolic pressure, stroke volume and stroke work) increased significantly as well (>9%). The model-predicted myofiber orientations were found to be similar to those in experiments. To the best of our knowledge the presented model is the first that is able to simultaneously predict a realistic myocardial structure as well as to account for the experimentally observed homogeneity in local mechanics.

Left ventricular apical torsion and architecture are not inverted in situs inversus totalis.

Occasionally, individuals have a complete, mirror-image reversal of their internal organ position, called situs inversus totalis (SIT). Whereas gross anatomy is mirror-imaged in SIT, this might not be the case for the internal architecture of organs, e.g. the myofiber pattern in the left cardiac ventricle. We performed a Magnetic Resonance Tagging study in nine controls and in eight subjects with SIT to assess the deformation pattern in the apical half of the LV wall. It appeared that both groups had the same LV apical deformation pattern. This implies that not only the superficial LV apical layers in SIT follow a normal, not inverted pattern, but the deeper layers as well. Apparently, the embryonic L/R controlling genetic pathway does determine situs-specific gross anatomy morphogenesis but it is not the only factor regulating fiber architecture within the apical part of the LV wall. We propose that mechanical forces generated in the not-inverted molecular structure of the basic right-handed helical contractile components of the sarcomere play a role in shaping the LV apex.

Structure and torsion of the normal and situs inversus totalis cardiac left ventricle. I. Experimental data in humans.

In 1926, the famous American pediatric cardiologist, Dr. Helen B. Taussig, observed that in situs inversus totalis (SIT) main gross anatomical structures and the deep muscle bundles of the ventricles were a mirror image of the normal structure, while the direction of the superficial muscle bundles remained unchanged (H. B. Taussig, Bull Johns Hopkins Hosp 39: 199-202, 1926). She and we wondered about the implication of this observation for left ventricular (LV) deformation in SIT. We used magnetic resonance tagging to obtain information on LV deformation, rotation, and torsion from a series of tagged images in five evenly distributed, parallel, short-axis sections of the heart of nine controls and eight persons with SIT without other structural (cardiac) defect. In the controls, during ejection, the apex rotated counterclockwise with respect to the base, when looking from the apex. Furthermore, the base-to-apex gradient in rotation (torsion) was negative and similar at all longitudinal levels of the LV. In SIT hearts, torsion was positive near the base, indicating mirrored myofiber orientations compared with the normal LV. Contrary to expectations, torsion in the apical regions of SIT LVs was as in normal ones, reflecting a normal internal myocardial architecture. The transition zone with zero torsion, found between the apex and base, suggests that the heart structure in SIT is essentially different from that in the normal heart. This provides a unique possibility to study regulatory mechanisms for myocardial fiber orientation and mechanical load, which has been dealt with in the companion paper by Kroon et al.

Structure and torsion in the normal and situs inversus totalis cardiac left ventricle. II. Modeling cardiac adaptation to mechanical load.

Mathematical models provide a suitable platform to test hypotheses on the relation between local mechanical stimuli and responses to cardiac structure and geometry. In the present model study, we tested hypothesized mechanical stimuli and responses in cardiac adaptation to mechanical load on their ability to estimate a realistic myocardial structure of the normal and situs inversus totalis (SIT) left ventricle (LV). In a cylindrical model of the LV, 1) mass was adapted in response to myofiber strain at the beginning of ejection and to global contractility (average systolic pressure), 2) cavity volume was adapted in response to fiber strain during ejection, and 3) myofiber orientations were adapted in response to myofiber strain during ejection and local misalignment between neighboring tissue parts. The model was able to generate a realistic normal LV geometry and structure. In addition, the model was also able to simulate the instigating situation in the rare SIT LV with opposite torsion and transmural courses in myofiber direction between the apex and base [Delhaas et al. (6)]. These results substantiate the importance of mechanical load in the formation and maintenance of cardiac structure and geometry. Furthermore, in the model, adapted myocardial architecture was found to be insensitive to fiber misalignment in the transmural direction, i.e., myofiber strain during ejection was sufficient to generate a realistic transmural variation in myofiber orientation. In addition, the model estimates that, despite differences in structure, global pump work and the mass of the normal and SIT LV are similar.