Large vessels as a tree of transmission lines incorporated in the CircAdapt whole-heart model:a computational tool to examine heart-vessel interaction

\u3cp\u3eWe developed a whole-circulation computational model by integrating a transmission line (TL) model describing vascular wave transmission into the established CircAdapt platform of whole-heart mechanics. In the present paper, we verify the numerical framework of our TL model by benchmark comparison to a previously validated pulse wave propagation (PWP) model. Additionally, we showcase the integrated CircAdapt–TL model, which now includes the heart as well as extensive arterial and venous trees with terminal impedances. We present CircAdapt–TL haemodynamics simulations of: 1) a systemic normotensive situation and 2) a systemic hypertensive situation. In the TL–PWP benchmark comparison we found good agreement regarding pressure and flow waveforms (relative errors ≤ 2.9% for pressure, and ≤ 5.6% for flow). CircAdapt–TL simulations reproduced the typically observed haemodynamic changes with hypertension, expressed by increases in mean and pulsatile blood pressures, and increased arterial pulse wave velocity. We observed a change in the timing of pressure augmentation (defined as a late-systolic boost in aortic pressure) from occurring after time of peak systolic pressure in the normotensive situation, to occurring prior to time of peak pressure in the hypertensive situation. The pressure augmentation could not be observed when the systemic circulation was lumped into a (non-linear) three-element windkessel model, instead of using our TL model. Wave intensity analysis at the carotid artery indicated earlier arrival of reflected waves with hypertension as compared to normotension, in good qualitative agreement with findings in patients. In conclusion, we successfully embedded a TL model as a vascular module into the CircAdapt platform. The integrated CircAdapt–TL model allows detailed studies on mechanistic studies on heart-vessel interaction.\u3c/p\u3

Monodisperse perfluorohexane emulsions for targeted ultrasound contrast imaging

Quantitative targeted ultrasound contrast imaging demands for contrast agents with a small monodisperse size and a high coverage of specific ligands for effective adhesion under physiological shear stress conditions. However, the particles should also be large enough to generate sufficient ultrasound reflection. Standard perfluorocarbon emulsions do not satisfy both requirements (adhesion and echogenicity). Therefore, we decided to develop a membrane emulsification technique to produce echogenic monodisperse perfluorohexane emulsions able to carry specific ligands for adhesion to the artery wall. In this work, we demonstrate that membrane emulsification is an excellent tool to create strictly monodisperse echogenic perfluorohexane emulsions with a preset droplet size. Perfluorohexane is emulsified in water using photolithographic microsieves. An ultrasound experiment demonstrates that the perfluorohexane emulsions clearly enhance echogenicity. The acoustic enhancement varies with droplet size and surface coverage. The emulsions, with a biotinylated fluoro-surfactant, are able to bind avidin coated SiO2 particles. This proves that these emulsions show a very promising potential to act as key species in the field of selective targeting, which can provide novel insights into the development and early detection of important vascular diseases, e.g. atherosclerosis

Noninvasive pulmonary transit time:a new parameter for general cardiac performance

\u3cp\u3eIntroduction: Pulmonary transit time (PTT) assessed with contrast-enhanced ultrasound (CEUS) is a novel tool to evaluate cardiac function. PTT represents the time for a bolus of contrast to pass from the right to the left ventricle, measured according to the indicator dilution principles using CEUS. We investigated the hypothesis that PTT is a measure of general cardiac performance in patient populations eligible for cardiac resynchronization therapy (CRT). Methods: The study population consisted of heart failure patients referred for CRT with NYHA class II–IV, left ventricular ejection fraction (LVEF)≤35% and QRS≥120 ms. CEUS, ECG, and blood were analyzed, and participants completed a quality of life questionnaire at baseline and 3 months after CRT implantation. Normalized PTT (nPTT) was calculated to compensate for the heart rate. Correlations were assessed with Pearson's or Spearman's coefficients and stratified for rhythm and NYHA class. Results: The study population consisted of 94 patients (67 men) with a mean age of 70±8.9 years. (n)PTT was significantly correlated with left ventricular parameters (r\u3csub\u3es\u3c/sub\u3e=−.487, P<.001), right ventricular parameters (r=−.282, P=.004), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r\u3csub\u3es\u3c/sub\u3e=.475, P<.001), and quality of life (r\u3csub\u3es\u3c/sub\u3e=.364, P<.001). Stronger significant correlations were found in patients in sinus rhythm. Conclusion: CEUS-derived PTT and nPTT correlate to a fair degree with measures of systolic and diastolic function, NT-pro-BNP, and quality of life. As CEUS-derived PTT can be obtained easily, noninvasively and at the bedside, it is a promising future measure of general cardiac performance.\u3c/p\u3

Pressure-dependence of arterial stiffness:potential clinical implications

BACKGROUND: \u3cbr/\u3eArterial stiffness measures such as pulse wave velocity (PWV) have a known dependence on actual blood pressure, requiring consideration in cardiovascular risk assessment and management. Given the impact of ageing on arterial wall structure, the pressure-dependence of PWV may vary with age.\u3cbr/\u3eMETHODS: \u3cbr/\u3eUsing a noninvasive model-based approach, combining carotid artery echo-tracking and tonometry waveforms, we obtained pressure-area curves in 23 hypertensive patients at baseline and after 3 months of antihypertensive treatment. We predicted the follow-up PWV decrease using modelled baseline curves and follow-up pressures. In addition, on the basis of these curves, we estimated PWV values for two age groups (mean ages 41 and 64 years) at predefined hypertensive (160/90 mmHg) and normotensive (120/80 mmHg) pressure ranges.\u3cbr/\u3eRESULTS: \u3cbr/\u3eFollow-up measurements showed a near 1 m/s decrease in carotid PWV when compared with baseline, which fully agreed with our model-prediction given the roughly 10 mmHg decrease in diastolic pressure. The stiffness-blood pressure-age pattern was in close agreement with corresponding data from the 'Reference Values for Arterial Stiffness' study, linking the physical and empirical bases of our findings.\u3cbr/\u3eCONCLUSION: \u3cbr/\u3eOur study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements.\u3cbr/\u3

In vivo high-resolution structural imaging of large arteries in small rodents using two-photon laser scanning microscopy

In vivo (molecular) imaging of the vessel wall of large arteries at subcellular resolution is crucial for unraveling vascular pathophysiology. We previously showed the applicability of two-photon laser scanning microscopy (TPLSM) in mounted arteries ex vivo. However, in vivo TPLSM has thus far suffered from in-frame and between-frame motion artifacts due to arterial movement with cardiac and respiratory activity. Now, motion artifacts are suppressed by accelerated image acquisition triggered on cardiac and respiratory activity. In vivo TPLSM is performed on rat renal and mouse carotid arteries, both surgically exposed and labeled fluorescently (cell nuclei, elastin, and collagen). The use of short acquisition times consistently limit in-frame motion artifacts. Additionally, triggered imaging reduces between-frame artifacts. Indeed, structures in the vessel wall (cell nuclei, elastic laminae) can be imaged at subcellular resolution. In mechanically damaged carotid arteries, even the subendothelial collagen sheet (~1 µm) is visualized using collagen-targeted quantum dots. We demonstrate stable in vivo imaging of large arteries at subcellular resolution using TPLSM triggered on cardiac and respiratory cycles. This creates great opportunities for studying (diseased) arteries in vivo or immediate validation of in vivo molecular imaging techniques such as magnetic resonance imaging (MRI), ultrasound, and positron emission tomography (PET)