Zahra Keshavarz-Motamed

Endovascular shear strain elastography for the detection and characterization of the severity of atherosclerotic plaques: in vitro validation and in vivo evaluation

This work explores the potential of shear strain elastograms to identify vulnerable atherosclerotic plaques. The Lagrangian speckle model estimator (LSME) elasticity imaging method was further developed to estimate shear strain elasticity (SSE). Three polyvinyl alcohol cryogel vessel phantoms were imaged with an intravascular ultrasound (IVUS) scanner. The estimated SSE maps were validated against finite-element results. Atherosclerosis was induced in carotid arteries of eight Sinclair mini-pigs using a combination of surgical techniques, diabetes and a high-fat diet. IVUS images were acquired in vivo in 14 plaques before euthanasia and histology. All plaques were characterized by high magnitudes in SSE maps that correlated with American Heart Association atherosclerosis stage classifications (r = 0.97, p < 0.001): the worse the plaque condition the higher was the absolute value of SSE, i.e. |SSE| (e.g., mean |SSE| was 3.70 ± 0.40% in Type V plaques, whereas it was reduced to 0.11 ± 0.01% in normal walls). This study indicates the feasibility of using SSE to highlight atherosclerotic plaque vulnerability characteristics.

A new approach for the evaluation of the severity of coarctation of the aorta using Doppler velocity index and effective orifice area: In vitro validation and clinical implications

Early detection and accurate estimation of COA severity are the most important predictors of successful long-term outcome. However, current clinical parameters used for the evaluation of the severity of COA have several limitations and are flow dependent. The objectives of this study are to evaluate the limitations of current existing parameters for the evaluation of the severity of coarctation of the aorta (COA) and suggest two new parameters: COA Doppler velocity index and COA effective orifice area. Three different severities of COAs were tested in a mock flow circulation model under various flow conditions and in the presence of normal and stenotic aortic valves. Catheter trans-COA pressure gradients and Doppler echocardiographic trans-COA pressure gradients were evaluated. COA Doppler velocity index was defined as the ratio of pre-COA to post-COA peak velocities measured by Doppler echocardiography. COA Doppler effective orifice area was determined using continuity equation. The results show that peak-to-peak trans-COA pressure gradient significantly increased with flow rate (from 83% to 85%). Peak Doppler pressure gradient also significantly increased with flow rate (80-85%). A stenotic or bicuspid aortic valve increased peak Doppler pressure gradient by 20-50% for a COA severity of 75%. Both COA Doppler velocity index and COA effective orifice area did not demonstrate significant flow dependence or dependence upon aortic valve condition. As a conclusion, COA Doppler velocity index and COA effective orifice area are flow independent and do not depend on aortic valve conditions. They can, then, more accurately predict the severity of COA.

Modeling the impact of concomitant aortic stenosis and coarctation of the aorta on left ventricular workload

Coarctation of the aorta (COA) is an obstruction of the aorta and is usually associated with bicuspid and tricuspid aortic valve stenosis (AS). When COA coexists with AS, the left ventricle (LV) is facing a double hemodynamic load: a valvular load plus a vascular load. The objective of this study was to develop a lumped parameter model, solely based on non-invasive data, allowing the description of the interaction between LV, COA, AS and the arterial system. First, a formulation describing the instantaneous net pressure gradient through the COA was introduced and the predictions were compared to in vitro results. The model was then used to determine LV work induced by coexisting AS and COA with different severities. The results show that LV stroke work varies from 0.98J (no-AS; no-COA) up to 2.15J (AS: 0.61cm(2)+COA: 90%). Our results also show that the proportion of the total flow rate that will cross the COA is significantly reduced with the increasing COA severity (from 85% to 40%, for a variation of COA severity from 0% to 90%, respectively). Finally, we introduced simple formulations capable of, non-invasively, estimating both LV peak systolic pressure and workload. As a conclusion, this study allowed the development of a lumped parameter model, based on non-invasive measurements, capable of accurately investigating the impact of coexisting AS and COA on LV workload. This model can be used to optimize the management of patients with COA and AS in terms of the sequence of lesion repair.

3D pulsatile flow in a curved tube with coexisting model of aortic stenosis and coarctation of the aorta

Coarctation of the aorta is a congenital heart disease defined as an obstruction of the aorta distal to the left subclavian artery (between the aortic arch and descending aorta). It is usually associated with other diseases such as bicuspid and tricuspid aortic stenosis. If the coarctation remains uncorrected it can lead to hypertension, left ventricular failure and aortic dissection. Numerous investigations pointed out that there is a relationship between the genesis and the progression of cardiovascular disease and the locally irregular flow occurring at the diseased zone. Therefore, to examine the relationship between arterial disease and hemodynamics conditions, detailed quantitative studies on flow dynamics in arterial models are clearly inquired. In this study we numerically investigate pulsatile blood flow in a simplified model of the aorta (curved pipe) with coexisting coarctation of the aorta and aortic stenosis. Three severities of aortic stenoses (0.61 cm(2), 1.0 cm(2) and 1.5 cm(2)) coexisting with aortic coarctations (50%, 75% and 90% by area) are investigated. An experimentally validated numerical model from literature is used and baseline results are validated against it. To ensure having a physiologically relevant model using this geometry, flow properties are set so that the Dean number falls in the physiological range for the aorta. The results show that the coexistence of these pathologies significantly modifies the flow in a curved pipe. The maximal velocity is shifted towards the outer wall and can reach values as high as 5m/s just downstream of the coarctation. The wall shear stress distribution is significantly modified compared to the normal, unobstructed case. Finally, a clinically significant pressure gradient is induced by the curvature of the tube (up to 36 mmHg). This can lead to an overestimation of the severity of the coarctation using catheterization.

Non-Invasive Determination of Left Ventricular Workload in Patients with Aortic Stenosis Using Magnetic Resonance Imaging and Doppler Echocardiography

Early detection and accurate estimation of aortic stenosis (AS) severity are the most important predictors of successful long-term outcomes in patients. Current clinical parameters used for evaluation of the AS severity have several limitations including flow dependency. Estimation of AS severity is specifically challenging in patients with low-flow and low transvalvular pressure gradient conditions. A proper diagnosis in these patients needs a comprehensive evaluation of the left ventricle (LV) hemodynamic loads. This study has two objectives: (1) developing a lumped-parameter model to describe the ventricular-valvular-arterial interaction and to estimate the LV stroke work (SW); (2) introducing and validating a new index, the normalized stroke work (N-SW), to assess the global hemodynamic load imposed on the LV. N-SW represents the global hemodynamic load that the LV faces for each unit volume of blood ejected. The model uses a limited number of parameters which all can be measured non-invasively using current clinical imaging modalities. The model was first validated by comparing its calculated flow waveforms with the ones measured using Cardiovascular Magnetic Resonance (CMR) in 49 patients and 8 controls. A very good correlation and concordance were found throughout the cycle (median root mean square: 12.21 mL/s) and between the peak values (r = 0.98; SEE = 0.001, p<0.001). The model was then used to determine SW using the parameters measured with transthoracic Doppler-echocardiography (TTE) and CMR. N-SW showed very good correlations with a previously-validated index of global hemodynamic load, the valvular arterial impedance (), using data from both imaging modalities (TTE: r = 0.82, SEE = 0.01, p<0.001; CMR: r = 0.74, SEE = 0.01, p<0.001). Furthermore, unlike , N-SW was almost independent from variations in the flow rate. This study suggests that considering N-SW may provide incremental diagnostic and prognostic information, beyond what standard indices of stenosis severity and provide, particularly in patients with low LV outflow.

Fluid Dynamics of Coarctation of the Aorta and Effect of Bicuspid Aortic Valve

Up to 80% of patients with coarctation of the aorta (COA) have a bicuspid aortic valve (BAV). Patients with COA and BAV have elevated risks of aortic complications despite successful surgical repair. The development of such complications involves the interplay between the mechanical forces applied on the artery and the biological processes occurring at the cellular level. The focus of this study is on hemodynamic modifications induced in the aorta in the presence of a COA and a BAV. For this purpose, numerical investigations and magnetic resonance imaging measurements were conducted with different configurations: (1) normal: normal aorta and normal aortic valve; (2) isolated COA: aorta with COA (75% reduction by area) and normal aortic valve; (3) complex COA: aorta with the same severity of COA (75% reduction by area) and BAV. The results show that the coexistence of COA and BAV significantly alters blood flow in the aorta with a significant increase in the maximal velocity, secondary flow, pressure loss, time-averaged wall shear stress and oscillatory shear index downstream of the COA. These findings can contribute to a better understanding of why patients with complex COA have adverse outcome even following a successful surgery.

Coronary artery atherectomy reduces plaque shear strains: An endovascular elastography imaging study

Mechanical response and properties of the arterial wall can be used to identify the biomechanical instability of plaques and predict their vulnerability to rupture. Shear strain elastography (SSE) is proposed to identify vulnerable plaque features attributed to mechanical structural heterogeneities. The aims of this study were: 1) to report on the potential of SSE to identify atherosclerotic plaques; and 2) to use SSE maps to highlight biomechanical changes in lesion characteristics after directional coronary atherectomy (DCA) interventions. For this purpose, SSE was imaged using in vivo intravascular ultrasound (IVUS) radio-frequency data collected from 12 atherosclerotic patients before and after DCA intervention. Coronary atherosclerotic plaques (pre-DCA) showed high SSE magnitudes with large affected areas. There were good correlations between SSE levels and soft plaque content (i.e., cellular fibrosis, thrombosis and fibrin) (mean |SSE| vs. soft plaque content: r = 0.82, p < 0.01). Significant differences were noticed between SSE images before and after DCA. Stable arteries (post-DCA) exhibited lower values than pre-DCA vessels (e.g., pre-DCA: mean |SSE| = 3.9 ± 0.2% vs. 1.1 ± 0.2% post-DCA, p < 0.001). Furthermore, SSE magnitude was statistically higher in plaques with a high level of inflammation (e.g., mean |SSE| had values of 4.8 ± 0.4% in plaques with high inflammation, whereas it was reduced to 1.8 ± 0.2% with no inflammation, p < 0.01). This study demonstrates the potential of the IVUS-based SSE technique to detect vulnerable plaques in vivo.

The role of aortic compliance in determination of coarctation severity: Lumped parameter modeling, in vitro study and clinical evaluation

Early detection and accurate estimation of the extent of coarctation of the aorta (COA) is critical to long-term outcome. Peak-to-peak trans-coarctation pressure gradient (PKdP) higher than 20mmHg is an indication for interventional/surgical repair. Patients with COA have reduced proximal and distal aortic compliances. A comprehensive study investigating the effects of variations of proximal COA and systemic compliances on PKdP, and consequently on the COA severity evaluation has never been done. This study evaluates the effect of aortic compliance on diagnostic accuracy of PKdP. Lumped parameter modeling and in vitro experiments were performed for COA severities of 50%, 75% and 90% by area. Modeling and in vitro results were validated against retrospective clinical data of PKdP, measured in 54 patients with COA. Modeling and in vitro. PKdP increases with reduced proximal COA compliance (+36%, +38% and +53% for COA severities of 50%, 75% and 90%, respectively; p<0.05), but decreases with reduced systemic compliance (-62%, -41% and -36% for COA severities of 50%, 75% and 90%, respectively; p<0.01). Clinical study. PKdP has a modest correlation with COA severity (R=0.29). The main determinants of PKdP are COA severity, stroke volume index and systemic compliance. Systemic compliance was found to be as influential as COA severity in PKdP determination (R=0.30 vs. R =0.34). In conclusion, PKdP is highly influenced by both stroke volume index and arterial compliance. Low values of PKdP cannot be used to exclude the severe COA presence since COA severity may be masked by reduced systemic compliance and/or low flow conditions.

Mathematical, numerical and experimental study in the human aorta with coexisting models of bicuspid aortic stenosis and coarctation of the aorta

Coarctation of the aorta is an obstruction of the aorta and is usually associated with other concomitant cardiovascular abnormalities especially with bicuspid aortic valve stenosis. The objectives of this study are, (1) to investigate the effects of coarctation on the hemodynamics in the aorta to gain a better understanding of the cause of certain post-surgical coarctation problems, (2) to develop and introduce a new lumped parameter model, mainly based on non-invasive data, allowing the description of the interaction between left ventricle, coarctation of the aorta, aortic valve stenosis, and the arterial system.

Hemodynamic changes following aortic valve bypass: a mathematical approach.

Aortic valve bypass (AVB) has been shown to be a viable solution for patients with severe aortic stenosis (AS). Under this circumstance, the left ventricle (LV) has a double outlet. The objective was to develop a mathematical model capable of evaluating the hemodynamic performance following the AVB surgery. A mathematical model that captures the interaction between LV, AS, arterial system, and AVB was developed. This model uses a limited number of parameters that all can be non-invasively measured using patient data. The model was validated using in vivo data from the literature. The model was used to determine the effect of different AVB and AS configurations on flow proportion and pressure of the aortic valve and the AVB. Results showed that the AVB leads to a significant reduction in transvalvular pressure gradient. The percentage of flow through the AVB can range from 55.47% to 69.43% following AVB with a severe AS. LV stroke work was also significantly reduced following the AVB surgery and reached a value of around 1.2 J for several AS severities. Findings of this study suggest: 1) the AVB leads to a significant reduction in transvalvular pressure gradients; 2) flow distribution between the AS and the AVB is significantly affected by the conduit valve size; 3) the AVB leads to a significant reduction in LV stroke work; and 4) hemodynamic performance variations can be estimated using the model.