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Assessment of predicting blood flow and atherosclerosis in the aorta and renal arteries
KTH, School of Engineering Sciences (SCI), Engineering Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.ORCID iD: 0000-0003-0112-9271
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiovascular diseases (CVD) are the most common cause of death in large parts of the world. Atherosclerosis (AS) has a major part in most CVDs. AS is a slowly developingdisease which is dependent on multiple factors such as genetics and life style (food, smoking, and physical activities). AS is primarily a disease of the arterial wall and develops preferentially at certain locations (such as arterial branches and in certain vessels like thecoronary arteries). The close relation between AS sites and blood flow has been well established over the years. However, due to multi-factorial causes, there exist no early prognostic tools for identifying individuals that should be treated prophylactically or followed up. The underlying hypothesis of this thesis was to determine if it is possible to use bloodflow simulations of patient-specific cases in order to identify individuals with risk for developing AS. CT scans from patients with renal artery stenosis (RAS) were used to get the affected vessels geometry. Blood flow in original and “reconstructed” arteries were simulated. Commonly used wall shear stress (WSS) related indicators of AS were studied to assess their use as risk indicators for developing AS. Divergent results indicated urgent need to assess the impact ofsimulation related factors on results. Altogether, blood flow in the following vessels was studied: The whole aorta with branches from the aortic arch and the abdominal aorta, abdominal aorta as well as the renal arteries, and separately the thoracic aorta with the three main branching arteries from the aortic arch. The impact of geometrical reconstruction, employed boundary conditions (BCs), effects of flow-rate, heart-rate and models of blood viscosity as function of local hematocrit (red blood cell, RBC, concentration) and shear-rate were studied in some detail. In addition to common WSS-related indicators, we suggested the use of endothelial activation models as a further risk indicator. The simulations data was used to extract not only the WSS-related data but also the impact of flow-rate on the extent of retrograde flow in the aorta and close to its walls. The formation of helical motion and flow instabilities (which at high flow- and heart-rate lead to turbulence) was also considered.

Results:

A large number of simulations (more than 100) were carried out. These simulations assessed the use of flow-rate specified BCs, pressure based BCs or so called windkessel (WK) outlet BCs that simulate effects of peripheral arterial compliance. The results showed high sensitivity of the flow to BCs. For example, the deceleration phase of the flow-rate is more prone to flow instabilities (as also expressed in terms of multiple inflection points in the streamwise velocity profile) as well as leading to retrograde flow. In contrast, the acceleration phase leads to uni-directional and more stable flow. As WSS unsteadiness was found to be pro-AS, it was important to assess the effect flow-rate deceleration, under physiological and pathological conditions. Peaks of retrograde flow occur at local temporal minima in flow-rate. WK BCs require ad-hoc adjusted parameters and are therefore useful only when fully patient specific (i.e. all information is valid for a particular patient at a particular point of time) data is available. Helical flows which are considered as atheroprotective, are formed naturally, depending primarily on the geometry (due to the bends in the thoracic aorta). Helical flow was also observed in the major aortic branches. The helical motion is weaker during flow deceleration and diastole when it may locally also change direction. Most common existing blood viscosity models are based on hematocrit and shear-rate. These models show strong variation of blood (mixture) viscosity. With strong shear-rate blood viscosity is lowest and is almost constant. The impact of blood viscosity in terms of dissipation is counter balanced by the shear-rate; At low shear-rate the blood has larger viscosity and at high shear-rate it is the opposite. This effect and due to the temporal variations in the local flow conditions the effect of blood rheology on the WSS indicators is weak. Tracking of blood components and clot-models shows that the retrograde motion and the flow near branches may have so strong curvature that centrifugal force can become important. This effect may lead to the transport of a thrombus from the descending aorta back to the branches of the aortic arch and could cause embolic stroke. The latter results confirm clinical observation of the risk of stroke due to transport of emboli from the proximal part of the descending aorta upstream to the vessels branching from the aortic arch and which lead blood to the brain.

Conclusions:

The main reasons for not being able to propose an early predictive tool for future developmentof AS are four-folded:

i. At present, the mechanisms behind AS are not adequately understood to enable to define aset of parameters that are sensitive and specific enough to be predictive of its development.

ii. The lack of accurate patient-specific data (BC:s) over the whole physiological “envelop”allows only limited number of flow simulations which may not be adequate for patientspecificpredictive purposes.

iii. The shortcomings of current models with respect to material properties of blood andarterial walls (for patient-specific space- and time-variations) are lacking.

iv. There is a need for better simulation data processing, i.e. tools that enable deducinggeneral predictive atherosclerotic parameters from a limited number of simulations, throughe.g. extending reduced modeling and/or deep learning.

The results do show, however, that blood flow simulations may produce very useful data thatenhances understanding of clinically observed processes such as explaining helical- andretrograde flows and the transport of blood components and emboli in larger arteries.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2020.
Series
TRITA-SCI-FOU ; 2020:23
Keywords [sv]
Blodflödessimulering, Åderförkalkning, Väggskjuvspänning, Blodrehologiska modeller
National Category
Applied Mechanics
Research subject
Engineering Mechanics
Identifiers
URN: urn:nbn:se:kth:diva-276456ISBN: 978-91-7873-585-3 (print)OAI: oai:DiVA.org:kth-276456DiVA, id: diva2:1439999
Public defence
2020-08-28, Live-streaming via Zoom:https://kth-se.zoom.us/webinar/register/WN_c-F9jLngQHeqIggkBkYoGg If you lack computer or computer skills, contact Lisa Prahl Wittberg for information at prahl@mech.kth.se, Stockholm, 14:00 (English)
Opponent
Supervisors
Note

QC20200724

Available from: 2020-07-24 Created: 2020-06-12 Last updated: 2022-06-26Bibliographically approved
List of papers
1. Stenosis Indicators Applied to Patient-Specific Renal Arteries without and with Stenosis
Open this publication in new window or tab >>Stenosis Indicators Applied to Patient-Specific Renal Arteries without and with Stenosis
2019 (English)In: Fluids, E-ISSN 2311-5521, Vol. 4, no 1, article id 26Article in journal (Refereed) Published
Abstract [en]

Pulsatile flow in the abdominal aorta and the renal arteries of three patients was studied numerically. Two of the patients had renal artery stenosis. The aim of the study was to assess the use of four types of indicators for determining the risk of new stenosis after revascularization of the affected arteries. The four indicators considered include the time averaged wall shear stress (TAWSS), the oscillatory shear index (OSI), the relative reference time (RRT) and a power law model based in platelet activation modeling but applied to the endothelium, named endothelium activation indicator (EAI). The results show that the indicators can detect the existing stenosis but are less successful in the revascularized cases. The TAWSS and, more clearly, the EAI approach seem to be better in predicting the risk for stenosis relapse at the original location and close to the post-stenotic dilatation. The shortcomings of the respective indicators are discussed along with potential improvements to endothelial activation modeling and its use as an indicator for risks of restenosis.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
renal artery stenosis, blood flow simulation, atherosclerosis, reconstructed arteries, stenosis indicators
National Category
Fluid Mechanics
Identifiers
urn:nbn:se:kth:diva-251364 (URN)10.3390/fluids4010026 (DOI)000464457900001 ()2-s2.0-85063386762 (Scopus ID)
Note

QC 20190513

Available from: 2019-05-13 Created: 2019-05-13 Last updated: 2025-02-09Bibliographically approved
2. Pulsatile aortic blood flow – A critical assessment of boundary conditions
Open this publication in new window or tab >>Pulsatile aortic blood flow – A critical assessment of boundary conditions
2020 (English)In: ASME Journal of Engineering and Science in Medical Diagnostics and Therapy (JESMDT), ISSN 2572-7958Article in journal (Refereed) Published
Abstract [en]

Patient specific (PS) blood flow studies have become popular in recent years but have thus far had limited clinical impact. This is possibly due to uncertainties and errors in the underlying models and simulations set-up. This study focuses on the sensitivity of simulation results due to in- and outflow boundary conditions (BC:s). Nine different inlet- and seven different outlet BC:s were applied to two variants of a healthy subject’s thoracic aorta. Temporal development of the flow is essential for the formation and development of helical/spiralling flow where the commonly observed clockwise helical motion may change direction during the heart-cycle. The sensitivity to temporal and spatial variations in the inlet conditions is significant both when expressed in terms of mean and maximal wall shear stress (WSS) and its different averaged variables, e.g. Time-Averaged WSS (TAWSS), Oscillating Shear Index (OSI) and Relative Residence Time (RRT). The simulation results are highly sensitive to BC. For example, the maximal WSS may vary over 3 orders of magnitude (1 to 1000 Pa) depending on particular combinations of BC:s. Moreover, certain formulations of outlet boundary conditions may be inconsistent with the computed flow field if the underlying assumptions of the space-time dependence are violated. The results of this study show that CFD simulations can reveal flow details that can enhance understanding of blood flows. However, the results also demonstrate the potential difficulties in mimicking blood flow in clinical situations.

Place, publisher, year, edition, pages
ASME International, 2020
Keywords
Aorta, Boundary-value problems, Flow (Dynamics), Blood flow, Pressure, Simulation
National Category
Fluid Mechanics
Research subject
Speech and Music Communication
Identifiers
urn:nbn:se:kth:diva-278873 (URN)10.1115/1.4048978 (DOI)
Note

QC 20250303

Available from: 2020-08-05 Created: 2020-08-05 Last updated: 2025-03-03Bibliographically approved
3. Fluid mechanical aspects of blood flow in the thoracic aorta
Open this publication in new window or tab >>Fluid mechanical aspects of blood flow in the thoracic aorta
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Arterial blood flow contains structures known to be associated with arterial wall pathologies (such as atherosclerosis and aneurysms) but also with helical motion reported to be atheroprotective. Numerical simulation of the flow in a typical human thoracic aorta model was carried out for several heart- and flow-rates. The aim was to explore the presence and the underlying mechanism of the formation of helical flow, retrograde motion and the formation of smaller scale unsteady flow structures. The main findings of the paper are as follows:

- Retrograde flow is induced during flow deceleration. Reversed flow may persist throughout the cardiac cycle in parts of the descending aorta. Retrograde flow may lead enhanced risk of upstream transport of thrombi from the descending aorta to the branches of the aortic arch.

- Helical flows are induced by bend and torsion of the aorta and through non-uniformity in the spatial distribution of the inlet flow (aortic valve plane).

- Amplification of axial vorticity was shown to occur in the thoracic aorta. This convective instability is enhanced in the descending aorta.

- Transitional and turbulent flow may occur in the thoracic aorta under elevated flow- and heart-rate conditions also in healthy individuals.

- Under normal conditions, healthy individuals do not develop turbulent flow in the thoracic aorta.

A hypothesis for a possible mechanism for the atheroprotective effect of helical flow is suggested.

National Category
Fluid Mechanics
Research subject
Engineering Mechanics
Identifiers
urn:nbn:se:kth:diva-278874 (URN)
Note

QC 20200806

Available from: 2020-08-05 Created: 2020-08-05 Last updated: 2025-02-09Bibliographically approved
4. The impact of heart rate and cardiac output on the flow in the human thoracic aorta
Open this publication in new window or tab >>The impact of heart rate and cardiac output on the flow in the human thoracic aorta
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Purpose: The purpose of the study is to determine the effects of heart rate (HR) and cardiac output(CO), in the temporal variation of CO on flow structures and related biomechanical markers.

Methods: The pulsatile flow in the thoracic aorta was simulated for 15 combinations of HR (60-150 beats per minutes, BPM), CO and cardiac temporal profiles. In all cases, the Quemada viscositymodel was used. The results were analyzed in terms of biomechanical markers such as extent ofretrograde flow in the lumen and close to the wall, helicity parameters, commonly used wall shearstress (WSS) indicators along with proposed Endothelial Activation Indices (EAIs).

Results: The simulations demonstrated the presence of helical motion in all cases. The helicalmotion depends on the spatial distribution of the flow by the aortic valve. Time- and space-averagedhelicity indices were found to have smallest values in the aortic arch and largest in the descendingpart of the aorta. For all cases, retrograde flow was observed. The extent of separated flow close tothe aortic wall depended strongly on the rate of decelerating CO during late systole as well aspossible axial flow deceleration periods during diastole. At high HR and CO, small scale flowstructures developed, indicating transition to turbulence. Time averaged WSS-related indicatorswere less distinctive in assessing the spatial and temporal impact as compared to the EAI indicators(EAI_Nobili and EAI_Soares) accounting for both accumulated stress and the temporal behavior of thestress.

Conclusions: The results underpin the importance of temporal variation of the cardiac flowrate andthe impact of the deceleration phase of systole on retrograde flow and formation of helical flowstructures. As retrograde and helical flow has been found to be related to atherosclerosis, thetemporal contribution of the flowrate must be maintained, since time averaged biomechanicalindicators filter out information of potential diagnostic importance. Temporal flow behavior, up tocell response frequency, needs to be reflected by the biomechanical indicators as in the proposed EAI_Soares indicator.

Keywords
Aortic hemodynamics, retrograde- and helical-flow, wall shear-stress, CFD.
National Category
Fluid Mechanics
Research subject
Engineering Mechanics
Identifiers
urn:nbn:se:kth:diva-278875 (URN)
Note

QC 20200806

Available from: 2020-08-05 Created: 2020-08-05 Last updated: 2025-03-26Bibliographically approved
5. Blood rheology modeling effects in aortic flow simulations
Open this publication in new window or tab >>Blood rheology modeling effects in aortic flow simulations
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Purpose: The purpose of the study is to assess the importance of non-Newtonian rheological models onblood flow in the human thoracic aorta.Methods: The pulsatile flow in the aorta is simulated using the models of Casson, Quemada and Walburn-Schneck in addition to a case of fixed (Newtonian) viscosity. The impact of the four rheological models wasassessed with respect to the following quantities:

i. Magnitude of the viscosity relative to a reference value (the Newtonian case) and the relative mean deviation from that value.

ii. Mechanical kinetic energy,vorticity, viscous dissipation rate.

iii. WSS and its time derivative.

iv. WSS-related indicators; OSI, TAWSS and RRT.

Results: The flow in the thoracic aorta is characterized by shear-rates leading to an increase in viscosity by afactor of up to six. The different models had negligible impact on the kinetic energy and viscous dissipationrate. The effect on WSS related parameters was quantified and was found to be modest. Largest effect wasobserved for low shear-rates (below 100 s-2).

Conclusions: The choice of a non-Newtonian model is important whenever the flow is viscosity dominated.Blood flow in larger arteries is weakly dependent on viscosity and can be handled by a model with weakdependence on shear-rate (e.g. Quemada or Newtonian). Blood flows with regions with low shear-rate andstrong temporal variation requires rheological models that better account for low shear and explicitlyincludes temporal variation effects.

Keywords
Whole blood viscosity, non-Newtonian fluid, Thoracic aorta, Wall shear-stress, viscous losses.
National Category
Fluid Mechanics
Research subject
Engineering Mechanics
Identifiers
urn:nbn:se:kth:diva-278876 (URN)
Note

QC 20200806

Available from: 2020-08-05 Created: 2020-08-05 Last updated: 2025-02-09Bibliographically approved
6. On the modelling of cell and lipoprotein transport in the thoracic aorta
Open this publication in new window or tab >>On the modelling of cell and lipoprotein transport in the thoracic aorta
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Purpose: The purpose of the study is to compare and assess modeling of transport cells and lipoproteins by the blood in the human thoracic aorta.

Methods: In the continuum framework, three flux models were considered; Fickian, Zydney-Colton (Z-C) and Leighton-Acrivos (L-A). The transport of spherical particles (cells and lipoprotein of different sizes and densities) under pulsatile flow condition were simulated. The effect of local red blood cell (RBC) concentration (hematocrit) on blood viscosity wasconsidered through Quemada’s model. Lagrangian particle transport (LPT) was assessed and compared to the continuum models. Contribution to RBC flux (diffusion) due to gradients inhematocrit, mixture density and viscosity was assessed. Results were extracted in terms ofmean and variations in concentrations, residence time and path lengths of RBC and six othercells and lipoproteins.

Results: The effects of local hematocrit variations on the local blood viscosity is large (a factor of more than 2) but the effect on wall shear stress (WSS) indicators is much more modest (few percent). In terms of mean concentration, the three continuum transport modelsyield local viscosity that deviate by a factor between about 1.3 to 2, as compared to a constantviscosity case. The main contribution to the mass (RBC) flux in the L-A model is from the shear-rate gradient term, followed by the viscosity gradient term and least by the RBC concentration gradient term (low flow rate). The inflow and wall boundary conditions play an important role on the details of the mass transport. The LPT result do converge to the expected concentration at the different outflow boundaries. However, the convergence rate isslow and require more than 30 cardiac periods to get below 2% in outflow hematocrit.Detailed analysis of the RBC paths shows large variations. For the outlet from the thoracicaorta RBC path length and residence time ranging from 0.333 m to 0.0.791 m and from lessthan one to about four cardiac cycles, respectively. The corresponding values for the LCCA are about 0.2 m to more than 0.5 m and about a quarter to about four cardiac cycles,respectively. The LPT results also show that particles are subject to a lift force driven bystrong path curvature and particle to fluid density difference. A simulation with injection ofparticles in the descending aorta indicated the possibility of upstream transport of particlesinto the three main arteries branching from the aortic arch.

Conclusions: Continuum transport models depend strongly on calibrated model parametersand the imposed boundary conditions. Counter gradient diffusion may occur as the fluxes aredependent on gradients of shear rate, concentration, and viscosity. LPT has the advantage ofaccounting for temporal effect and are most appropriate for dilute particle suspensions such ascells (except for RBC) and lipoproteins. LPT though, may require substantially longercomputational time when statistical data is sought.

Keywords
Whole blood viscosity, non-Newtonian fluid, Thoracic aorta, LPT, cell and lipoprotein transport.
National Category
Fluid Mechanics
Research subject
Engineering Mechanics
Identifiers
urn:nbn:se:kth:diva-278877 (URN)
Note

QC 20200806

Available from: 2020-08-05 Created: 2020-08-05 Last updated: 2025-02-09Bibliographically approved

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