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  • 1.
    Berg, Niclas
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strömningsfysik.
    Blood flow and cell transport in arteries and medical assist devices2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The cardiovascular system is responsible for transport of nutrients, oxygen, as well as the cells and molecules making up the immune system. Through the hemostatic system, the body maintains the integrity of the blood vessels, and prevents bleeding. The biochemical and physical processes governing the circulation interact, and take place at a large range of time and length scales - from those related to the individual cells up to the large scale flow structures. Dysfunctions of the heart or the circulatory system may have severe consequences. Cardiovascular diseases (CVD) is a heterogeneous group of diseases, responsible for about 50% of all death cases in the western world.

    Patients with severe but transient heart and/or lung disease may require the assistance of a heart-lung machine to bridge over the period required for the affected organ to recover. One such system is the Extracorporeal Membrane Oxygenator (ECMO) circuit, consting of a blood pump, a membrane oxygenator, cannulae and tubing system. While the therapy is life-saving, it is associated with relatively frequent thromboembolic (blood clotting and/or bleeding) events. Modeling of the flow in some components of the ECMO circuit was undertaken. The flow data was used together with models for platelet activation to assess the risk for thrombus formation. The results indicated locations of elevated risk of thrombosis in the centrifugal blood pump, the ECMO cannulae and the pipe connectors. The identified locations agreed well with clinical observations. The results lead to a direct recommendation to minimize the use of tube connectors. Further study of the sensitivity of the platelet activation models to uncertainties and errors was carried out. Some recommendations for improved modeling were proposed.

    Arteriosclerosis develops slowly over a long period of time (years or decades). It manifests initially at some common sites; arteries of certain sizes with relatively strong flow rate, as well as near artery bifurcations and locations of strong vessel curvature. The location specificity indicates that the blood flow plays a central role in the arteriosclerotic process. Being able to predict the future development of arteriosclerotic lesion and its location for an individual patient would imply that pre-emptive actions could be taken. This idea was the foundation of some of the numerical simulations in this thesis. A stenoted patient specific renal artery was considered, and was reconstructed to a non-pathological state by removing the stenosis using different segmentation methods. We could then evaluate if common stenosis markers based on functions of time-averages of the Wall Shear-Stress (WSS) could be use as predictive parameters. It was shown that these markers are not adequate as predictive tools. Furthermore, it was shown that the sensitivity to reconstruction technique was at least of the same order as the effect of the choice of blood rheology model. The rheology of blood was further studied through detailed simulations resolving the blood plasma flow and its interaction with the red blood cells (RBC) and the platelets. A hybrid Immersed boundary-Lattice Boltzmann method was applied, and the rheological data was compared to the Quemada model. It was found that the Quemada model could underpredict the effective viscosity by as much as 50%. The same methodology was applied to study the transport of RBCs and platelets, and the influence of RBC polydispersity. An increased degree of variability in RBC volume was found, under certain circumstances, to lead to an increase of the transport of platelets to the vessel wall (margination). 

  • 2.
    Berg, Niclas
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strömningsfysik.
    Fuchs, Laszlo
    KTH, Skolan för teknikvetenskap (SCI), Mekanik.
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Mekanik, Biomekanik.
    Blood flow simulations of the renal arteries - effect of segmentation and stenosis removalIngår i: Flow Turbulence and Combustion, ISSN 1386-6184, E-ISSN 1573-1987Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patient specic based simulation of blood flows in arteries has been proposed as a future approach for better diagnostics and treatment of arterial diseases.The outcome of theoretical simulations strongly depends on the accuracy in describing the problem (the geometry, material properties of the artery and of the blood, flow conditions and the boundary conditions). In this study, the uncertainties associated with the approach for a priori assessment of reconstructive surgery of stenoted arteries are investigated. It is shown that strong curvature in the reconstructed artery leads to large spatial- and temporal-peaks in the wall shear-stress. Such peaks can be removed by appropriate reconstruction that also handles the post-stenotic dilatation of the artery. Moreover, it is shown that the effects of the segmentation approach can be equally important as the effects of using advanced rheological models. Unfortunately, this fact has not been recognized in the literature up to this point, making patient specic simulations potentially less reliable.

  • 3.
    Berg, Niclas
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx.
    Fuchs, Laszlo
    KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW.
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. KTH Mech, Linne FLOW Ctr, BioMEx, SE-10044 Stockholm, Sweden..
    Blood Flow Simulations of the Renal Arteries - Effect of Segmentation and Stenosis Removal2019Ingår i: Flow Turbulence and Combustion, ISSN 1386-6184, E-ISSN 1573-1987, Vol. 102, nr 1, s. 27-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patient specific based simulation of blood flows in arteries has been proposed as a future approach for better diagnostics and treatment of arterial diseases. The outcome of theoretical simulations strongly depends on the accuracy in describing the problem (the geometry, material properties of the artery and of the blood, flow conditions and the boundary conditions). In this study, the uncertainties associated with the approach for a priori assessment of reconstructive surgery of stenoted arteries are investigated. It is shown that strong curvature in the reconstructed artery leads to large spatial- and temporal-peaks in the wall shear-stress. Such peaks can be removed by appropriate reconstruction that also handles the post-stenotic dilatation of the artery. Moreover, it is shown that the effects of the segmentation approach can be equally important as the effects of using advanced rheological models. This fact has not been recognized in the literature up to this point, making patient specific simulations potentially less reliable.

  • 4.
    Berg, Niclas
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strömningsfysik.
    Fuchs, Laszlo
    KTH, Skolan för teknikvetenskap (SCI), Mekanik.
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Mekanik, Biomekanik.
    Flow characteristics and coherent structures in a centrifugal blood pump2019Ingår i: Flow Turbulence and Combustion, ISSN 1386-6184, E-ISSN 1573-1987, Vol. 102, nr 2, s. 469-483Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Blood clot formation can be initiated by local flow conditions where regions of high shear and long residence time regions, such as flow separation and stagnation, have been identified as risk factors. This study highlights coherent structures,some of which not yet considered in the literature that may contribute to blood clot formation in the ECMO (Extra Corporeal Membrane Oxygenator) circuit. The centrifugal ECMO pump investigated in this study is compact and delivers adequate volume of blood with relatively high pressure in order to compensate for the large pressure drop in the membrane oxygenator. These requirements lead to regions with high shear in several different parts of the pump. In the narrow gap between the pump house and the impeller body (the magnet) a Taylor-Couette-like flow is observed with azimuthally aligned wavy vortices, which are also pushed towards the bottom of the pump-house by the flow generated by the blades. At the bottom gap between the impeller house and the pump house one finds spiraling flow structures, due to the rotation of the former structure. Separation bubbles are found near the tongue of the pump and at the lee sides of the blades. Such vortical structures have in literature been identified as regions where platelets may be activated whereby clots may develop.

  • 5.
    Berg, Niclas
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strömningsfysik.
    Fuchs, Laszlo
    KTH, Skolan för teknikvetenskap (SCI), Mekanik.
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strömningsfysik. KTH, Skolan för teknikvetenskap (SCI), Mekanik, Biomekanik.
    Influence of red blood cell polydispersity on blood rheology and platelet marginationManuskript (preprint) (Övrigt vetenskapligt)
  • 6.
    Fuchs, Alexander
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. Linköping Univ Hosp, Dept Radiol, SE-58185 Linköping, Sweden.
    Berg, Niclas
    KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW.
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx.
    Stenosis Indicators Applied to Patient-Specific Renal Arteries without and with Stenosis2019Ingår i: FLUIDS, ISSN 2311-5521, Vol. 4, nr 1, artikel-id 26Artikel i tidskrift (Refereegranskat)
    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.

  • 7.
    Fuchs, Gabriel
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Sundsvall Reg Hosp, Dept Cardiol, Sundsvall, Sweden..
    Berg, Niclas
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. KTH, Skolan för teknikvetenskap (SCI), Mekanik.
    Broman, L. Mikael
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Univ Hosp, ECMO Ctr Karolinska, Pediat Perioperat Med & Intens Care, Stockholm, Sweden..
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx.
    Flow-induced platelet activation in components of the extracorporeal membrane oxygenation circuit2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 13985Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Extracorporeal membrane oxygenation (ECMO) is used for rescue in severe respiratory and/or circulatory failure. The patient's blood is pumped over artificial surfaces in the ECMO circuit. A platelet activation model was applied to study the potential thrombogenicity of ECMO circuit components: the centrifugal blood pump, cannulae, and tubing connectors. Based on the accumulated effect of the scalar form of the stress acting on the platelet over time, the activation model enables assessment of platelet activation and pinpoints regions of elevated activation risk in a component. Numerical simulations of the flow in different components of the ECMO circuit was carried out where the activation level is a function of the impact of local stress and its history along the path that the platelets follow. The results showed that the pump carried the largest risk for platelet activation followed by the reinfusion cannula and lastly the connectors. Pump thrombogenicity was mainly due to long residence time and high shear-rate while the connector showed a high level of non-stationary shear-rate that in turn may contribute to the formation of aggregates through direct platelet activation or through high shear-rate modulation of the vWF multimers.

  • 8.
    Fuchs, Gabriel
    et al.
    Sundsvall Reg Hosp, Sundsvall, Sweden..
    Berg, Niclas
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW.
    Broman, Mikael
    Karolinska Hosp, ECMO Ctr, Stockholm, Sweden..
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW.
    Blood clots in the ECMO-system - a theoretical platelet activation study2017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 964-965Artikel i tidskrift (Övrigt vetenskapligt)
  • 9.
    Fuchs, Gabriel
    et al.
    Dept. of Physiology and Pharmacology, Karolinska Institutet ; Department of Cardiology, Sundsvall’s Hospital.
    Berg, Niclas
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strömningsfysik.
    Broman, Mikael
    Dept. of Physiology and Pharmacology, Karolinska Institutet ; ECMO Centre Karolinska, Pediatric Perioperative Medicine and Intensive Care, Karolinska University Hospital.
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW. KTH, Skolan för teknikvetenskap (SCI), Mekanik, Strömningsfysik. KTH, Skolan för teknikvetenskap (SCI), Mekanik, Biomekanik.
    Modeling sensitivity and uncertainties in platelet activation models applied on centrifugal pumps for extracorporeal life support2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 8809Artikel i tidskrift (Refereegranskat)
  • 10. Fuchs, Gabriel
    et al.
    Berg, Niclas
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW.
    Eriksson, Anders
    Prahl Wittberg, Lisa
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, Linné Flow Center, FLOW.
    Detection of Thrombosis in the Extracorporeal Membrane Oxygenation Circuit by Infrasound: Proof of Concept2017Ingår i: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 41, nr 6, s. 573-579Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    As of today, there exist no reliable, objective methods for early detection of thrombi in the extracorporeal membrane oxygenators (ECMO) system. Within the ECMO system, thrombi are not always fixed to a certain component or location in the circuit. Thus, clot fragments of different shapes and consistencies may circulate and give rise to vibrations and sound generation. By bedside sound measurements and additional laboratory experiments (although not detailed herein), we found that the presence of particles (clots or aggregates and fragments of clots) can be detected by analyzing the strength of infra-sound (< 20 Hz) modes of the spectrum near the inlet and outlet of the centrifugal pump in the ECMO circuit. For the few patients that were considered in this study, no clear false positive or negative examples were found when comparing the spectral approach with clinical observations. A laboratory setup provided insight to the flow in and out of the pump, confirming that in the presence of particles a low-amplitude low-frequency signal is strongly amplified, enabling the identification of a clot.

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