Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Physics of blood flow in arteries and its relation to intra-luminal thrombus and atherosclerosis
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics. (vascuMECH)
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Vascular pathologies such as Abdominal Aortic Aneurysm (AAA) and atherosclerosis are complex vascular diseases involving biological, mechanical, and fluid-dynamical factors. This thesis follows a multidisciplinary approach and presents an integrated fluid-chemical theory of ILT growth and analyzes the shear-induced migration of red blood cells (RBCs) in large arteries with respect to hypoxia and its possible role in atherosclerosis. The concept of Vortical Structures (VSs) is employed, with which a theory of uid-chemically-driven ILT growth is formulated. The theory proposes that VSs play an important role in convecting and activating platelets in the aneurysmatic bulge. In particular, platelets are convected toward the distal aneurysm region inside vortex cores and are activated via a combination of high residence times and relatively high shear stress at the vortex boundary. After vortex breakup, platelets are free to adhere to the thrombogenic wall surface. VSs also convect thrombin, a potent procoagulant enzyme, captured in their core, through the aneurysmatic lumen and force its accumulation in the distal portion of the AAA. This framework is in line with the clinical observation that the thickest ILT is usually seen in the distal AAA region. The investigation of the fluid-dynamics in arteries led to the study of the shear-induced migration of RBCs in large vessels such as the abdominal aorta and the carotid artery. Marked RBCs migration is observed in the region of the carotid sinus and in the iliac arteries, regions prone to atherogenesis. This leads to the hypothesis that oxyhemoglobin availability can decrease in the near-wall region thus contributing to wall hypoxia, a factor implicated in atherosclerosis. The thesis proposes a new potential mechanism of ILT growth, driven by fluid and chemical stimuli, which can be used to study ILT progression over physiologically relevant timeframes and be used as a framework to test new hypotheses; the thesis also provides new insights on the oxyhemoglobin availability in the near-wall region with direct inuence on atherosclerosis.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2013. , 43 p.
Series
Trita-HFL. Report / Royal Institute of Technology, Solid Mechanics, ISSN 1654-1472 ; 0546
National Category
Other Mechanical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-125810ISBN: 978-91-7501-836-2 (print)OAI: oai:DiVA.org:kth-125810DiVA: diva2:640492
Public defence
2013-08-22, sal F3, Lindstedtsvägen 26, KTH, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20130813

Available from: 2013-08-13 Created: 2013-08-13 Last updated: 2013-08-13Bibliographically approved
List of papers
1. Hemodynamics of the Normal Aorta Compared to Fusiform and Saccular Abdominal Aortic Aneurysms with Emphasis on a Potential Thrombus Formation Mechanism
Open this publication in new window or tab >>Hemodynamics of the Normal Aorta Compared to Fusiform and Saccular Abdominal Aortic Aneurysms with Emphasis on a Potential Thrombus Formation Mechanism
Show others...
2010 (English)In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 38, no 2, 380-390 p.Article in journal (Refereed) Published
Abstract [en]

Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau-Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.

Keyword
Intra-luminal thrombus, Aortic aneurysm, Computational Fluid Dynamics, Saccular, Fusiform, Aorta, fluid-structure interaction, intraluminal thrombus, wall stress, rupture, flow, biomechanics, blood, diameter, models, tissue
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-19176 (URN)10.1007/s10439-009-9843-6 (DOI)000274237000014 ()2-s2.0-77249088121 (Scopus ID)
Funder
Swedish Research Council, 20067568
Note

QC 20110124

Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
2. Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intraluminal thrombus formation
Open this publication in new window or tab >>Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intraluminal thrombus formation
2011 (English)In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 8, no 63, 1449-1461 p.Article in journal (Refereed) Published
Abstract [en]

Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the lambda(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

Keyword
coherent vortices, intra-luminal thrombus, aortic aneurysm, platelets, computational fluid dynamics, aorta
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-39504 (URN)10.1098/rsif.2011.0041 (DOI)000294208100009 ()2-s2.0-80052252526 (Scopus ID)
Funder
Swedish Research Council, 2006-7568
Note

QC 20111024

Available from: 2011-09-26 Created: 2011-09-12 Last updated: 2017-12-08Bibliographically approved
3. An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms
Open this publication in new window or tab >>An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms
2012 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 3, no 266Article in journal (Refereed) Published
Abstract [en]

Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.

National Category
Other Mechanical Engineering
Identifiers
urn:nbn:se:kth:diva-125750 (URN)10.3389/fphys.2012.00266 (DOI)000209173000260 ()2-s2.0-84866444131 (Scopus ID)
Funder
Swedish Research Council, 2006-7568VINNOVA
Note

QC 20130813

Available from: 2013-08-13 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
4. Shear-induced migration of red blood cells in the abdominal aorta and thecarotid bifurcation: considerations on oxygen transport
Open this publication in new window or tab >>Shear-induced migration of red blood cells in the abdominal aorta and thecarotid bifurcation: considerations on oxygen transport
2013 (English)Report (Other academic)
Abstract [en]

Shear-induced migration of red blood cells (RBCs) is a well known phenomenon characterizing blood flow in the small vessels (micron to mm size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (mm to cm size), the extent of this migration has not been fully elucidated. RBCs migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface; this being of primary importance in, for example, intra-luminal thrombus (ILT) growth, atherosclerosis and intima hyperplasia. Phillips’ shear-induced particle migration model coupled to the Quemada viscosity model was employed to simulate the macroscopic behavior of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near wall region with a lowering of wall hematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and in the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, the inner curvature wall of the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall hematocrit are correlated with the near-wall shear layer and with the secondary flow induced by the vessel curvature. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus and, more in general, on the inner curvature wall. The lowering of wall hematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhemoglobin, hence contributing, with the lowered oxygen partial pressure, to local hypoxia.

Publisher
27 p.
Keyword
shear-induced migration, red blood cell, RBC, abdominal aorta, abdominal aortic aneurysm, AAA, carotid bifurcation, oxygen transport, hemoglobin, platelet, PLT
National Category
Other Mechanical Engineering
Identifiers
urn:nbn:se:kth:diva-125807 (URN)
Note

QC 20130813

Available from: 2013-08-13 Created: 2013-08-13 Last updated: 2013-08-13Bibliographically approved

Open Access in DiVA

fulltext(1524 kB)983 downloads
File information
File name FULLTEXT01.pdfFile size 1524 kBChecksum SHA-512
364c5082fb7cf0c2f2e778a9380a257b94880cc98480d916f0af720ed2486529a136778f8b97f1b38de0060da4bfe1210f6a86d9b13b223f5b9e5ef112e840f1
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Biasetti, Jacopo
By organisation
Biomechanics
Other Mechanical Engineering

Search outside of DiVA

GoogleGoogle Scholar
Total: 983 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 909 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf