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Non-invasive imaging for improved cardiovascular diagnostics: Shear wave elastography, relative pressure estimation, and tomographic reconstruction
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.ORCID iD: 0000-0003-1002-2070
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Throughout the last century, medical imaging has come to revolutionise the way we diagnose disease, and is today an indispensable part of virtually any clinical practice. In cardiovascular care imaging is extensively utilised, and the development of novel techniques promises refined diagnostic abilities: ultrasound elastography allows for constitutive tissue assessment, 4D flow magnetic resonance imaging (MRI) enables full-field flow mapping, and micro-Computed Tomography (CT) permits high-resolution imaging at pre-clinical level. However, following the complex nature of cardiovascular disease, refined methods are still very much needed to accurately utilise these techniques and to effectively isolate disease developments.

The aim of this thesis has been to develop such methods for refined cardiovascular image diagnostics. In total eight studies conducted over three separate focus areas have been included: four on vascular shear wave elastography (SWE), three on non-invasive cardiovascular relative pressure estimations, and one on tomographic reconstruction for pre-clinical imaging.

In Study I-IV, the accuracy and feasibility of vascular SWE was evaluated, with particular focus on refined carotid plaque characterisation. With confined arterial or plaque tissue restricting acoustic wave propagation, analysis of group and phase velocity was performed with SWE output validated against reference mechanical testing and imaging. The results indicate that geometrical confinement has a significant impact on SWE accuracy, however that a combined group and phase velocity approach can be utilised to identify vulnerable carotid plaque lesions in-vivo.

In Study V-VII, a non-invasive method for the interrogation of relative pressure from imaged cardiovascular flow was developed. Using the concept of virtual work-energy, the method was applied to accurately assess relative pressures throughout complex, turbulence-inducing, branching vasculatures. The method was also applied on a dilated cardiomyopathy cohort, indicating arterial hemodynamic changes in cardiac disease.

Lastly, in Study VIII a method for multigrid image reconstruction of tomographic data was developed, utilising domain splitting and operator masking to accurately reconstruct high-resolution regions-of-interests at a fraction of the computational cost of conventional full-resolution methods.

Together, the eight studies have incorporated a range of different imaging modalities, developed methods for both constitutive and hemodynamic cardiovascular assessment, and utilised refined pre-clinical imaging, all with the same purpose: to refine current state cardiovascular imaging and to improve our ability to non-invasively assess cardiovascular disease. With promising results reached, the studies lay the foundation for continued clinical investigations, advancing the presented methods and maturing their usage for an improved future cardiovascular care.

Abstract [sv]

Medicinsk avbildning utgör idag en central del av modern klinisk diagnostik, och bildgivande diagnostikverktyg har kommit att i grunden förändra sättet på vilket dagligt kliniskt arbete utförs. Medicinsk bildteknik används också i stor utsträckning inom hjärt-kärldiagnostik, och i takt med att nya tekniker utvecklas kan förfinad information inhämtas: ultraljudsbaserad elastografi möjliggör avbildning av vävnaders mekaniska egenskaper, fyrdimensionella blodflödesmönster kan kartläggas genom 4D flödes-magnetresonanstomografi (MRI), och mikro-Datortomografi (mikro-CT) möjliggör preklinisk avbildning i mikrometerupplösning. För att kunna dra nytta av dessa teknikers potential i ett kliniskt sammanhang behövs dock förfinade och validerade analysverktyg, särskilt med tanke på hjärt-kärlsjukdomars komplexa och multifaktoriella natur.

Syftet med följande avhandling har varit att utveckla sådana metoder för förbättrad hjärt-kärlavbildning. Avhandlingen innehåller totalt åtta delarbeten fördelat över tre fokusområden: fyra inom vaskulär skjuvvågselastografi (SWE), tre inom icke-invasiv tryckfallsmätning, och en inom pre-klinisk tomografisk bildrekonstruktion.

I studie I-IV utvärderades vaskulär SWE, med särskilt fokus på teknikens potential för förfinad karaktärisering av karotisplack. I alla studier undersöktes SWE grupp- och fashastighet, med estimerade hastigheter och styvheter validerade mot mekanisk referensmätning eller kompletterande avbildning. Resultaten visar hur spatialt avgränsade kärl eller plack har en tydlig inverkan på SWE:s noggrannhet, men indikerar även hur rupturbenägna plack kan identifieras genom en kombination av grupp- och fashastighetsanalys.

I studie V-VII utvecklades en ny metod för icke-invasiv tryckfallsmätning baserad uteslutande på uppmätt 4D-flödesdata. Genom en komplett flödesmekanisk beskrivning i kombination med ett virtuellt flödesfält kan exakta och robusta tryckfallsmätningar genomföras genom komplexa, turbulensinducerande, och kliniskt relevant kardiovaskulära strukturer. Metoden användes också för att analysera en klinisk kohort med dilaterad kardiomyopati, där tydliga förändringar i arteriellt blodtrycksbeteende detekterades.

I studie VIII utvecklades en metod för multidimensionell bildrekonstruktion av tomografisk mikro-CT-data. Genom domän- och operatorseparering visar resultaten hur högupplöst rekonstruktion av en subdomän kan uppnås till en bråkdel av den totala tids- eller minnesåtgången som annars fordras för en fullupplöst bildrekonstruktion.

Tillsammans har de åtta delstudierna använt ett antal olika avbildningsmodaliteter, applicerat både vävnadsbaserat och hemodynamisk utvärdering av hjärt-kärlsystemet, och slutligen inkluderat preklinisk avbildning, allt för att uppnå samma mål: att förbättra klinisk hjärt-kärlavbildning och ge en fördjupad förståelse av olika hjärt-kärlsjukdomars kliniska manifestation genom icke-invasiv avbildning. Avhandlingen utgör också grunden för fortsatta vetenskapliga studier, där de utvärderade metoderna kan komma att förfinas ytterligare som del av en mer omfattande klinisk implementering.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2019. , p. 192
Series
TRITA-CBH-FOU ; 2019: 38
Keywords [en]
Medical imaging, Cardiovascular disease, Atherosclerosis, Hemodynamics, Ultrasound, Shear Wave Elastography (SWE), Magnetic Resonance Imaging (MRI), 4D flow MRI, Relative Pressure, Virtual Work-Energy, micro-Computed Tomography (micro-CT), Tomographic reconstruction, Pre-clinical imaging
Keywords [sv]
Medicinsk avbildning, Hjärt-kärlsjukdomar, Ateroskleros, Hemodynamik, Ultraljud, Skjuvvågselastografi (SWE), Magnetresonanstomografi (MRI), 4D flödes-MRI, Tryckfall, Virtuellt flöde, mikro-Datortomografi (mikro-CT), Tomografisk rekonstruktion, Preklinisk avbildning
National Category
Medical Engineering Medical Image Processing
Research subject
Medical Technology
Identifiers
URN: urn:nbn:se:kth:diva-256321ISBN: 978-91-7873-251-7 (print)OAI: oai:DiVA.org:kth-256321DiVA, id: diva2:1344648
Public defence
2019-09-20, T2, Hälsovägen 11C, Huddinge, 09:00 (English)
Opponent
Supervisors
Note

Karolinska Institutet-KTH joint degree doctoral thesis in in medical technology and medical sciences

Available from: 2019-08-23 Created: 2019-08-21 Last updated: 2019-08-23Bibliographically approved
List of papers
1. ARTERIAL STIFFNESS ESTIMATION BY SHEAR WAVE ELASTOGRAPHY: VALIDATION IN PHANTOMS WITH MECHANICAL TESTING
Open this publication in new window or tab >>ARTERIAL STIFFNESS ESTIMATION BY SHEAR WAVE ELASTOGRAPHY: VALIDATION IN PHANTOMS WITH MECHANICAL TESTING
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2016 (English)In: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 42, no 1, p. 308-321Article in journal (Refereed) Published
Abstract [en]

Arterial stiffness is an independent risk factor found to correlate with a wide range of cardiovascular diseases. It has been suggested that shear wave elastography (SWE) can be used to quantitatively measure local arterial shear modulus, but an accuracy assessment of the technique for arterial applications has not yet been performed. In this study, the influence of confined geometry on shear modulus estimation, by both group and phase velocity analysis, was assessed, and the accuracy of SWE in comparison with mechanical testing was measured in nine pressurized arterial phantoms. The results indicated that group velocity with an infinite medium assumption estimated shear modulus values incorrectly in comparison with mechanical testing in arterial phantoms (6.7 +/- 0.0 kPa from group velocity and 30.5 +/- 0.4 kPa from mechanical testing). To the contrary, SWE measurements based on phase velocity analysis (30.6 +/- 3.2 kPa) were in good agreement with mechanical testing, with a relative error between the two techniques of 8.8 +/- 6.0% in the shear modulus range evaluated (40-100 kPa). SWE by phase velocity analysis was validated to accurately measure stiffness in arterial phantoms.

Keywords
Accuracy, Arterial phantom, Arterial stiffness, Group velocity, Lamb waves, Mechanical testing, Phase velocity, Poly(vinyl alcohol), Shear modulus, Shear wave elastography
National Category
Medical Image Processing
Identifiers
urn:nbn:se:kth:diva-181377 (URN)10.1016/j.ultrasmedbio.2015.08.012 (DOI)000367733800032 ()26454623 (PubMedID)2-s2.0-84957007046 (Scopus ID)
Funder
VINNOVA, 2011-01365Swedish Research Council, 2012-2795
Note

QC 20160203

Available from: 2016-02-03 Created: 2016-02-01 Last updated: 2019-08-21Bibliographically approved
2. Plaque characterization using shear wave elastography-evaluation of differentiability and accuracy using a combined ex vivo and in vitro setup
Open this publication in new window or tab >>Plaque characterization using shear wave elastography-evaluation of differentiability and accuracy using a combined ex vivo and in vitro setup
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2018 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 63, no 23, article id 235008Article in journal (Refereed) Published
Abstract [en]

Ultrasound elastography has shown potential for improved plaque risk stratification. However, no clear consensus exists on what output metric to use, or what imaging parameters would render optimal plaque differentiation. For this reason we developed a combined ex vivo and in vitro setup, in which the ability to differentiate phantom plaques of varying stiffness was evaluated as a function of plaque geometry, push location, imaging plane, and analysed wave speed metric. The results indicate that group velocity or phase velocity >= 1 kHz showed the highest ability to significantly differentiate plaques of different stiffness, successfully classifying a majority of the 24 analysed plaque geometries, respectively. The ability to differentiate plaques was also better in the longitudinal views than in the transverse view. Group velocity as well as phase velocities <1 kHz showed a systematic underestimation of plaque stiffness, stemming from the confined plaque geometries, however, despite this group velocity analysis showed lowest deviation in estimated plaque stiffness (0.1 m s(-1) compared to 0.2 m s(-1) for phase velocity analysis). SWE results were also invariant to SWE push location, albeit apparent differences in signal-to-noise ratio (SNR) and generated plaque particle velocity. With that, the study has reinforced the potential of SWE for successful plaque differentiation; however the results also highlight the importance of choosing optimal imaging settings and using an appropriate wave speed metric when attempting to differentiate different plaque groups.

Place, publisher, year, edition, pages
IOP PUBLISHING LTD, 2018
Keywords
shear wave elastography, elastography, ultrasound, atherosclerosis, plaque characterization
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-239984 (URN)10.1088/1361-6560/aaec2b (DOI)000451049000003 ()30468683 (PubMedID)2-s2.0-85057084601 (Scopus ID)
Note

QC 20181211

Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2019-08-21Bibliographically approved
3. An ex-vivo setup for characterization of atherosclerotic plaque using shear wave elastography and micro-computed tomography
Open this publication in new window or tab >>An ex-vivo setup for characterization of atherosclerotic plaque using shear wave elastography and micro-computed tomography
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2016 (English)In: IEEE International Ultrasonics Symposium, IUS, IEEE conference proceedings, 2016, article id 7728810Conference paper, Published paper (Refereed)
Abstract [en]

Quantification of the mechanical properties of atherosclerotic plaque has shown to be important in assessing carotid artery plaque vulnerability. For such, shear wave elastography (SWE) has been applied on both in-vitro and in-vivo setups. The aim of this study was to build an ex-vivo setup for combined evaluation of plaque characteristics using SWE and micro-computed tomography (μCT). As a proof-of-concept of the constructed experimental setup, a single human carotid plaque specimen was extracted during carotid endarterectomy. The plaque was imaged in the μCT system, and subsequently imaged using SWE. For the SWE measurement, group and phase velocity was extracted from the obtained in-phase/quadrature data, with its spatial distribution being compared to anatomical features visible in the μCT images. The results indicated wave velocity changes at boundaries identified in the μCT, with group velocity data slightly increasing when entering a calcified nodule. Additionally, μCT images seemed to provide good contrast between several plaque constituens using the defined imaging settings. Overall, the study represents a proof-of-concept for detailed ex-vivo plaque analysis using combined SWE and μCT, with obtained wave speed and shear modulus values falling within observed values for atherosclerotic plaque tissue. With an experimental setup defined, future studies on carotid plaque behaviour both in SWE and μCT is enabled, where a large-scale plaque study could be performed to investigate the ability of SWE to differentiate between different plaque types.

Place, publisher, year, edition, pages
IEEE conference proceedings, 2016
Keywords
Atherosclerosis, Carotid, micro-Computed Tomography, Plaque, Shear Wave Elastography, Computerized tomography, Medical imaging, Shear waves, Tomography, Wave propagation, Microcomputed tomography, Shear flow
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-202279 (URN)10.1109/ULTSYM.2016.7728810 (DOI)2-s2.0-84996486771 (Scopus ID)9781467398978 (ISBN)
Conference
2016 IEEE International Ultrasonics Symposium, IUS 2016; Tours; France; 18 September 2016 through 21 September 2016
Note

Correspondence Address: Larsson, D.; Department of Medical Engineering, KTH Royal Institute of Technology, Hälsovägen 11C, Sweden; email: david.larsson@sth.kth.se. QC 20170221

Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2019-08-23Bibliographically approved
4. Shear wave elastography enables detection of vulnerable carotid plaques – MRI-validation of combined spatiotemporal and frequency-dependent wave analysis
Open this publication in new window or tab >>Shear wave elastography enables detection of vulnerable carotid plaques – MRI-validation of combined spatiotemporal and frequency-dependent wave analysis
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(English)Manuscript (preprint) (Other academic)
National Category
Medical Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-256315 (URN)
Note

QC 20190823

Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-23Bibliographically approved
5. Estimation of Cardiovascular Relative Pressure Using Virtual Work-Energy
Open this publication in new window or tab >>Estimation of Cardiovascular Relative Pressure Using Virtual Work-Energy
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 1375Article in journal (Refereed) Published
Abstract [en]

Many cardiovascular diseases lead to local increases in relative pressure, reflecting the higher costs of driving blood flow. The utility of this biomarker for stratifying the severity of disease has thus driven the development of methods to measure these relative pressures. While intravascular catheterisation remains the most direct measure, its invasiveness limits clinical application in many instances. Non-invasive Doppler ultrasound estimates have partially addressed this gap; however only provide relative pressure estimates for a range of constricted cardiovascular conditions. Here we introduce a non-invasive method that enables arbitrary interrogation of relative pressures throughout an imaged vascular structure, leveraging modern phase contrast magnetic resonance imaging, the virtual work-energy equations, and a virtual field to provide robust and accurate estimates. The versatility and accuracy of the method is verified in a set of complex patient-specific cardiovascular models, where relative pressures into previously inaccessible flow regions are assessed. The method is further validated within a cohort of congenital heart disease patients, providing a novel tool for probing relative pressures in-vivo.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-246401 (URN)10.1038/s41598-018-37714-0 (DOI)000457616300263 ()30718699 (PubMedID)2-s2.0-85061047544 (Scopus ID)
Note

QC 20190321

Available from: 2019-03-21 Created: 2019-03-21 Last updated: 2019-08-21Bibliographically approved
6. Non-invasive estimation of relative pressure in turbulent flow using virtual work-energy
Open this publication in new window or tab >>Non-invasive estimation of relative pressure in turbulent flow using virtual work-energy
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(English)Manuscript (preprint) (Other academic)
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-256318 (URN)
Note

QC 20190823

Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-23Bibliographically approved
7. Altered aortic hemodynamics and relative pressure in patients with dilated cardiomyopathy
Open this publication in new window or tab >>Altered aortic hemodynamics and relative pressure in patients with dilated cardiomyopathy
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(English)Manuscript (preprint) (Other academic)
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-256319 (URN)
Note

QC 20190823

Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-23Bibliographically approved
8. Multigrid reconstruction in tomographic imaging
Open this publication in new window or tab >>Multigrid reconstruction in tomographic imaging
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-256320 (URN)
Note

QC 20190823

Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-23Bibliographically approved

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  • apa
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  • Other style
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  • nn-NO
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