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Quantification of 4D Left Ventricular Blood Flow in Health and Disease
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The main function of the heart is to pump blood throughout the cardiovascular system by generating pressure differences created through volume changes. Although the main purpose of the heart and vessels is to lead the flowing blood throughout the body, clinical assessments of cardiac function are usually based on morphology, approximating the flow features by viewing the motion of the myocardium and vessels. Measurement of three-directional, three-dimensional and time-resolved velocity (4D Flow) data is feasible using magnetic resonance (MR). The focus of this thesis is the development and application of methods that facilitate the analysis of larger groups of data in order to increase our understanding of intracardiac flow patterns and take the 4D flow technique closer to the clinical setting.

In the first studies underlying this thesis, a pathline based method for analysis of intra ventricular blood flow patterns has been implemented and applied. A pathline is integrated from the velocity data and shows the path an imaginary massless particle would take through the data volume. This method separates the end-diastolic volume (EDV) into four functional components, based on the position for each individual pathline at end-diastole (ED) and end-systole (ES). This approach enables tracking of the full EDV over one cardiac cycle and facilitates calculation of parameters such as e.g. volumes and kinetic energy (KE). Besides blood flow, pressure plays an important role in the cardiac dynamics. In order to study this parameter in the left ventricle, the relative pressure field was computed using the pressure Poisson equation. A comprehensive presentation of the pressure data was obtained dividing the LV blood pool into 17 pie-shaped segments based on a modification of the standard seventeen segment model. Further insight into intracardiac blood flow dynamics was obtained by studying the turbulent kinetic energy (TKE) in the LV. The methods were applied to data from a group of healthy subjects and patients with dilated cardiomyopathy (DCM). DCM is a pathological state where the cardiac function is impaired and the left ventricle or both ventricles are dilated.

The validation study of the flow analysis method showed that a reliable user friendly tool for intra ventricular blood flow analysis was obtained. The application of this tool also showed that roughly one third of the blood that enters the LV, directly leaves the LV again in the same heart beat. The distribution of the four LV EDV components was altered in the DCM group as compared to the healthy group; the component that enters and leaves the LV during one cardiac cycle (Direct Flow) was significantly larger in the healthy subjects. Furthermore, when the kinetic energy was normalized by the volume for each component, at time of ED, the Direct Flow had the highest values in the healthy subjects. In the DCM group, however, the Retained Inflow and Delayed Ejection Flow had higher values. The relative pressure field showed to be highly heterogeneous, in the healthy heart. During diastole the predominate pressure differences in the LV occur along the long axis from base to apex. The distribution and variability of 3D pressure fields differ between early and late diastolic filling phases, but common to both phases is a relatively lower pressure in the outflow segment. In the normal LV, TKE values are low. The highest TKE values can be seen during early diastole and are regionally distributed near the basal LV regions. In contrast, in a heterogeneous group of DCM patients, total diastolic and late diastolic TKE values are higher than in normals, and increase with the LV volume.

In conclusion, in this thesis, methods for analysis of multidirectional intra cardiac velocity data have been obtained. These methods allow assessment of data quality, intra cardiac blood flow patterns, relative pressure fields, and TKE. Using these methods, new insights have been obtained in intra cardiac blood flow dynamics in health and disease. The work underlying this thesis facilitates assessment of data from a larger population of healthy subjects and patients, thus bringing the 4D Flow MRI technique closer to the clinical setting.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. , 63 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1374
Keyword [en]
MRI, relative pressure, 4D flow, quantification, turbulent kinetic energy, dilated cardiomyopathy, magnetic resonance imaging, physiology, cardiac function, diastolic dysfunction
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-98786DOI: 10.3384/diss.diva-99958ISBN: 978-91-7519-542-1 (print)OAI: oai:DiVA.org:liu-98786DiVA: diva2:655926
Public defence
2013-11-22, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2013-10-14 Created: 2013-10-14 Last updated: 2014-04-23Bibliographically approved
List of papers
1. Semi-automatic quantification of 4D left ventricular blood flow
Open this publication in new window or tab >>Semi-automatic quantification of 4D left ventricular blood flow
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2010 (English)In: JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, ISSN 1097-6647, Vol. 12, no 9Article in journal (Refereed) Published
Abstract [en]

Background: The beating heart is the generator of blood flow through the cardiovascular system. Within the hearts own chambers, normal complex blood flow patterns can be disturbed by diseases. Methods for the quantification of intra-cardiac blood flow, with its 4D (3D+time) nature, are lacking. We sought to develop and validate a novel semi-automatic analysis approach that integrates flow and morphological data. Method: In six healthy subjects and three patients with dilated cardiomyopathy, three-directional, three-dimensional cine phase-contrast cardiovascular magnetic resonance (CMR) velocity data and balanced steady-state free-precession long- and short-axis images were acquired. The LV endocardium was segmented from the short-axis images at the times of isovolumetric contraction (IVC) and isovolumetric relaxation (IVR). At the time of IVC, pathlines were emitted from the IVC LV blood volume and traced forwards and backwards in time until IVR, thus including the entire cardiac cycle. The IVR volume was used to determine if and where the pathlines left the LV. This information was used to automatically separate the pathlines into four different components of flow: Direct Flow, Retained Inflow, Delayed Ejection Flow and Residual Volume. Blood volumes were calculated for every component by multiplying the number of pathlines with the blood volume represented by each pathline. The accuracy and inter- and intra-observer reproducibility of the approach were evaluated by analyzing volumes of LV inflow and outflow, the four flow components, and the end-diastolic volume. Results: The volume and distribution of the LV flow components were determined in all subjects. The calculated LV outflow volumes [ml] (67 +/- 13) appeared to fall in between those obtained by through-plane phase-contrast CMR (77 +/- 16) and Doppler ultrasound (58 +/- 10), respectively. Calculated volumes of LV inflow (68 +/- 11) and outflow (67 +/- 13) were well matched (NS). Low inter- and intra-observer variability for the assessment of the volumes of the flow components was obtained. Conclusions: This semi-automatic analysis approach for the quantification of 4D blood flow resulted in accurate LV inflow and outflow volumes and a high reproducibility for the assessment of LV flow components.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-54610 (URN)10.1186/1532-429X-12-9 (DOI)000275445000001 ()
Note

The original article is: Jonatan Eriksson, Carljohan Carlhäll, Petter Dyverfeldt, Jan Engvall, Ann F Bolger and Tino Ebbers, Semi-automatic quantification of 4D left ventricular blood flow, 2010, JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, (12), 9. http://dx.doi.org/10.1186/1532-429X-12-9

Available from: 2010-03-26 Created: 2010-03-26 Last updated: 2014-01-15Bibliographically approved
2. Quantification of presystolic blood flow organization and energetics in the human left ventricle
Open this publication in new window or tab >>Quantification of presystolic blood flow organization and energetics in the human left ventricle
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2011 (English)In: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, ISSN 0363-6135, Vol. 300, no 6, H2135-H2141 p.Article in journal (Refereed) Published
Abstract [en]

Intracardiac blood flow patterns are potentially important to cardiac pumping efficiency. However, these complex flow patterns remain incompletely characterized both in health and disease. We hypothesized that normal left ventricular (LV) blood flow patterns would preferentially optimize a portion of the end-diastolic volume (LVEDV) for effective and rapid systolic ejection by virtue of location near and motion towards the LV outflow tract (LVOT). Three-dimensional cine velocity and morphological data were acquired in 12 healthy persons and 1 patient with dilated cardiomyopathy using MRI. A previously validated method was used for analysis in which the LVEDV was separated into four functional flow components based on the bloods locations at the beginning and end of the cardiac cycle. Each components volume, kinetic energy (KE), site, direction, and linear momentum relative to the LVOT were calculated. Of the four components, the LV inflow that passes directly to outflow in a single cardiac cycle (Direct Flow) had the largest volume. At the time of isovolumic contraction, Direct Flow had the greatest amount of KE and the most favorable combination of distance, angle, and linear momentum relative to the LVOT. Atrial contraction boosted the late diastolic KE of the ejected components. We conclude that normal diastolic LV flow creates favorable conditions for ensuing ejection, defined by proximity and energetics, for the Direct Flow, and that atrial contraction augments the end-diastolic KE of the ejection volume. The correlation of Direct Flow characteristics with ejection efficiency might be a relevant investigative target in cardiac failure.

Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA, 2011
Keyword
phase-contrast magnetic resonance imaging, kinetic energy, heart, cardiac physiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69186 (URN)10.1152/ajpheart.00993.2010 (DOI)000291209300019 ()
Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2013-12-17
3. Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy
Open this publication in new window or tab >>Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy
2013 (English)In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 14, no 5, 417-424 p.Article in journal (Refereed) Published
Abstract [en]

Aims : Patients with mild heart failure (HF) who are clinically compensated may have normal left ventricular (LV) stroke volume (SV). Despite this, altered intra-ventricular flow patterns have been recognized in these subjects. We hypothesized that, compared with normal LVs, flow in myopathic LVs would demonstrate a smaller proportion of inflow volume passing directly to ejection and diminished the end-diastolic preservation of the inflow kinetic energy (KE).

Methods and results : In 10 patients with dilated cardiomyopathy (DCM) (49 ± 14 years, six females) and 10 healthy subjects (44 ± 17 years, four females), four-dimensional MRI velocity and morphological data were acquired. A previously validated method was used to separate the LV end-diastolic volume (EDV) into four flow components based on the blood's locations at the beginning and end of the cardiac cycle. KE was calculated over the cardiac cycle for each component. The EDV was larger (P = 0.021) and the ejection fraction smaller (P < 0.001) in DCM compared with healthy subjects; the SV was equivalent (DCM: 77 ± 19, healthy: 79 ± 16 mL). The proportion of the total LV inflow that passed directly to ejection was smaller in DCM (P = 0.000), but the end-diastolic KE/mL of the direct flow was not different in the two groups (NS).

Conclusion : Despite equivalent LVSVs, HF patients with mild LV remodelling demonstrate altered diastolic flow routes through the LV and impaired preservation of inflow KE at pre-systole compared with healthy subjects. These unique flow-specific changes in the flow route and energetics are detectable despite clinical compensation, and may prove useful as subclinical markers of LV dysfunction.

Place, publisher, year, edition, pages
Oxford University Press, 2013
Keyword
4D flow, Heart failure, Magnetic resonance imaging, Stroke volume
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-87616 (URN)10.1093/ehjci/jes159 (DOI)000318088300003 ()22879457 (PubMedID)
Available from: 2013-01-19 Created: 2013-01-19 Last updated: 2017-12-06
4. Spatial heterogeneity of 4D relative pressure fields in the human left ventricle
Open this publication in new window or tab >>Spatial heterogeneity of 4D relative pressure fields in the human left ventricle
2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Blood flow throughout the cardiovascular system is driven by pressure differences generated by the contraction and relaxation of the heart, where blood accelerates from high to low pressure areas. Absolute intracardiac pressure cannot be measured noninvasively, but relative pressure can be calculated. The aim of this study was to assess the spatial heterogeneity of the 4D relative pressure fields in the human left ventricle (LV).

Twelve healthy subjects underwent MRI examination where 4D flow as well as morphological data were acquired. The morphological data were segmented, and the segmentation used as boundary condition when computing relative pressure fields from the pressure Poisson equation using a multi grid solver. The LV lumen was divided according to a seventeen segment model in order to assess spatial heterogeneity and present the extensive amount of data in a comprehensive manner.

The basal anteroseptal segment shows a significantly lower median pressure than the opposite basal inferolateral segment during both early and late diastolic filling (p<0.0005 and p=0.0024, respectively). Along the long axis, the relative pressure in the apical segments are significantly higher relative to the basal segments (p<0.0005) along both the anteroseptal and inferolateral sides at and after the peaks of E-wave and A-wave.

During diastole the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences can also be found in the short-axis direction, and may also reflect important aspects of atrioventricular coupling.

Keyword
Relative pressure, Magnetic resonance, 4D flow, physiology, cardiac function
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-99956 (URN)
Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2014-04-23Bibliographically approved
5. Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
Open this publication in new window or tab >>Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
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2015 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 41, no 4, 1021-1029 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: To assess turbulent kinetic energy (TKE) within the left ventricle (LV) of healthy subjects using novel 4D flow MRI methods and to compare TKE values to those from a spectrum of patients with dilated cardiomyopathy (DCM).

Methods: 4D flow and morphological MRI-data were acquired in 11 healthy subjects and 9 patients with different degrees of diastolic dysfunction. TKELV was calculated within the LV at each diastolic time frame. At peak early (E) and late (A) diastolic filling, the TKELV was compared to transmitral peak velocity, LV diameter and mitral annular diameter.

Results: In the majority of all subjects, peaks in TKELV could be observed at E and A. Peak TKELV at E was not different between the groups, and correlated with mitral annular dimensions. Peak TKELV at A was higher in DCM patients compared to healthy subjects, and was related to LV diameter and transmitral velocity.

Conclusions: In normal LVs, TKE values are low. Values are highest during early diastole, and diminish with increasing LV size. In a heterogeneous group of DCM patients, late diastolic TKE values are higher than in healthy subjects. Kinetic energy loss due to elevated late diastolic TKE may reflect inefficient flow in dilated LVs.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
Keyword
Magnetic resonance imaging, blood flow, turbulent flow, cardiac function, diastolic dysfunction, heart failure
National Category
Medical Engineering Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-99957 (URN)10.1002/jmri.24633 (DOI)000351521700019 ()
Note

Contract grant sponsor: Swedish Heart-Lung Foundation; Contract grant sponsor: Swedish Research Council; Contract grant sponsor: European Research Council.

Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2017-12-06Bibliographically approved

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