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4D flow MRI and modelling to assess cerebral arterial hemodynamics: method development and evaluation, with implementation in patients with symptomatic carotid stenosis
Umeå University, Faculty of Medicine, Department of Radiation Sciences.ORCID iD: 0000-0002-1315-7010
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Blood flow measurements are important for understanding the development of cerebrovascular diseases. With 4D flow magnetic resonance imaging (4D flow MRI), simultaneous velocity measurements are obtained in all cerebral arteries in a scan of about ten minutes. However, 4D flow MRI is a relatively new technique. For usefulness in both clinics and research, detailed knowledge is needed about its accuracy and precision for flow quantification. In patients with stroke or transient ischemic attack (TIA) from a symptomatic carotid stenosis, the stenosis may generate a difference in blood pressure and flow between the left and right cerebral hemispheres. Such a hemispheric pressure difference could be an early marker of to what extent a stenosis is affecting cerebral hemodynamics, which could be useful in the planning of carotid surgery. 

The overall aim of the thesis was to determine the accuracy of 4D flow MRI to measure cerebral arterial blood flow, and to develop and evaluate an approach combining 4D flow MRI and computational fluid dynamics (CFD) to characterize the cerebral arterial hemodynamics, with implementation in patients with symptomatic carotid stenosis. The thesis is based on four papers, investigating two cohorts.

The first cohort consisted of 35 elderly volunteers (mean age 79 years) and was studied in paper I-II. Blood flow rates were measured in nine cerebral arteries with 4D flow MRI and 2D phase-contrast MRI as reference. Three different flow quantification methods for 4D flow MRI were evaluated and optimized: one clustering approach and two threshold-based methods. The proposed new method, based on a locally adapted threshold, outperformed the previously suggested methods in flow rate quantification. For the clustering method, flow rates were systematically underestimated. 4D flow MRI was also evaluated to assess different arterial pulsatility measures, and a Windkessel model was used to estimate reference values for cerebrovascular resistance and cerebral arterial compliance in elderly.

The second cohort consisted of 28 stroke and TIA patients (mean age 73 years) with symptomatic carotid stenosis and was studied in paper III-IV. With 4D flow MRI and CFD, the preoperative hemispheric pressure laterality was quantified in the patients. The pressure laterality was compared to hemispheric flow lateralities. Estimating the hemispheric pressure laterality was a promising physiological biomarker for grading the cerebral arterial hemodynamic disturbances in patients with symptomatic carotid stenosis. A CFD model was also developed to predict carotid stump pressure, i.e., the important pressure measured in the clamped carotid artery during surgical removal of the stenosis. The predicted stump pressures were correlated with the pressures measured during surgery. Stump pressure prediction was promising and could be a potential tool in the preoperative planning in order to avoid hypoperfusion during surgery. 

In summary, post-processing methods were successfully developed and evaluated for accurate assessment of mean and pulsatile cerebral blood flow rates with 4D flow MRI. Thereby, this thesis provided knowledge about possibilities and limitations of how 4D flow MRI can be used with respect to cerebral arterial blood flow rate assessment. By contributing with models combining 4D flow MRI and CFD, specifically developed for analysis of pressure distributions in cerebral arteries, novel methods were proposed for assessing patients with symptomatic carotid stenosis in the planning of carotid surgery.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2021. , p. 69
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2128
Keywords [en]
4D flow MRI, carotid stenosis, cerebral blood flow, cerebral arterial compliance, cerebrovascular resistance, circleof Willis, computational fluid dynamics, magnetic resonance imaging, stroke, vascular disease
National Category
Medical Imaging Neurology
Research subject
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-182250ISBN: 978-91-7855-509-3 (print)ISBN: 978-91-7855-510-9 (electronic)OAI: oai:DiVA.org:umu-182250DiVA, id: diva2:1544281
Public defence
2021-05-12, Betula, Norrlands universitetssjukhus + Zoom, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2021-04-21 Created: 2021-04-14 Last updated: 2025-02-09Bibliographically approved
List of papers
1. Accuracy of blood flow assessment in cerebral arteries with 4D flow MRI: Evaluation with three segmentation methods
Open this publication in new window or tab >>Accuracy of blood flow assessment in cerebral arteries with 4D flow MRI: Evaluation with three segmentation methods
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2019 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 50, no 2, p. 511-518Article in journal (Refereed) Published
Abstract [en]

Background: Accelerated 4D flow MRI allows for high‐resolution velocity measurements with whole‐brain coverage. Such scans are increasingly used to calculate flow rates of individual arteries in the vascular tree, but detailed information about the accuracy and precision in relation to different postprocessing options is lacking.

Purpose: To evaluate and optimize three proposed segmentation methods and determine the accuracy of in vivo 4D flow MRI blood flow rate assessments in major cerebral arteries, with high‐resolution 2D PCMRI as a reference.

Study Type: Prospective.

Subjects: Thirty‐five subjects (20 women, 79 ± 5 years, range 70–91 years).

Field Strength/Sequence: 4D flow MRI with PC‐VIPR and 2D PCMRI acquired with a 3 T scanner.

Assessment: We compared blood flow rates measured with 4D flow MRI, to the reference, in nine main cerebral arteries. Lumen segmentation in the 4D flow MRI was performed with k‐means clustering using four different input datasets, and with two types of thresholding methods. The threshold was defined as a percentage of the maximum intensity value in the complex difference image. Local and global thresholding approaches were used, with evaluated thresholds from 6–26%.

Statistical Tests: Paired t‐test, F‐test, linear correlation (P < 0.05 was considered significant) along with intraclass correlation (ICC).

Results: With the thresholding methods, the lowest average flow difference was obtained for 20% local (0.02 ± 15.0 ml/min, ICC = 0.97, n = 310) or 10% global (0.08 ± 17.3 ml/min, ICC = 0.97, n = 310) thresholding with a significant lower standard deviation for local (F‐test, P = 0.01). For all clustering methods, we found a large systematic underestimation of flow compared with 2D PCMRI (16.1–22.3 ml/min).

Data Conclusion: A locally adapted threshold value gives a more stable result compared with a globally fixed threshold. 4D flow with the proposed segmentation method has the potential to become a useful reliable clinical tool for assessment of blood flow in the major cerebral arteries.

Level of Evidence: 2

Technical Efficacy: Stage 2

Keywords
magnetic resonance imaging, cerebral arteries, phase‐contrast MRI, 4D flow MRI, cerebral blood flow, Circle of Willis
National Category
Medical Imaging
Identifiers
urn:nbn:se:umu:diva-147255 (URN)10.1002/jmri.26641 (DOI)000475681600017 ()30637846 (PubMedID)2-s2.0-85059966858 (Scopus ID)
Funder
Swedish Research Council, 2015–05616, 2017-04949Swedish Heart Lung Foundation, 20140592
Note

Originally included in thesis in manuscript form with title "Blood flow assessment in cerebral arteries with 4D flow MRI, concordance with 2D PCMRI"

Available from: 2018-04-30 Created: 2018-04-30 Last updated: 2025-02-09Bibliographically approved
2. Assessment of Cerebral Blood Flow Pulsatility and Cerebral Arterial Compliance With 4D Flow MRI
Open this publication in new window or tab >>Assessment of Cerebral Blood Flow Pulsatility and Cerebral Arterial Compliance With 4D Flow MRI
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2020 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 51, no 5, p. 1516-1525Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Four-dimensional flow magnetic resonance imaging (4D flow MRI) enables efficient investigation of cerebral blood flow pulsatility in the cerebral arteries. This is important for exploring hemodynamic mechanisms behind vascular diseases associated with arterial pulsations.

PURPOSE: To investigate the feasibility of pulsatility assessments with 4D flow MRI, its agreement with reference two-dimensional phase-contrast MRI (2D PC-MRI) measurements, and to demonstrate how 4D flow MRI can be used to assess cerebral arterial compliance and cerebrovascular resistance in major cerebral arteries.

STUDY TYPE: Prospective.

SUBJECTS: Thirty-five subjects (20 women, 79 ± 5 years, range 70-91 years).

FIELD STRENGTH/SEQUENCE: 4D flow MRI (PC-VIPR) and 2D PC-MRI acquired with a 3T scanner.

ASSESSMENT: Time-resolved flow was assessed in nine cerebral arteries. From the pulsatile flow waveform in each artery, amplitude (ΔQ), volume load (ΔV), and pulsatility index (PI) were calculated. To reduce high-frequency noise in the 4D flow MRI data, the flow waveforms were low-pass filtered. From the total cerebral blood flow, total PI (PItot ), total volume load (ΔVtot ), cerebral arterial compliance (C), and cerebrovascular resistance (R) were calculated.

STATISTICAL TESTS: Two-tailed paired t-test, intraclass correlation (ICC).

RESULTS: There was no difference in ΔQ between 4D flow MRI and the reference (0.00 ± 0.022 ml/s, mean ± SEM, P = 0.97, ICC = 0.95, n = 310) with a cutoff frequency of 1.9 Hz and 15 cut plane long arterial segments. For ΔV, the difference was -0.006 ± 0.003 ml (mean ± SEM, P = 0.07, ICC = 0.93, n = 310) without filtering. Total R was 11.4 ± 2.41 mmHg/(ml/s) (mean ± SD) and C was 0.021 ± 0.009 ml/mmHg (mean ± SD). ΔVtot was 1.21 ± 0.29 ml (mean ± SD) with an ICC of 0.82 compared with the reference. PItot was 1.08 ± 0.21 (mean ± SD).

DATA CONCLUSION: We successfully assessed 4D flow MRI cerebral arterial pulsatility, cerebral arterial compliance, and cerebrovascular resistance. Averaging of multiple cut planes and low-pass filtering was necessary to assess accurate peak-to-peak features in the flow rate waveforms.

LEVEL OF EVIDENCE: 2

Technical Efficacy Stage: 2

Place, publisher, year, edition, pages
Wiley-Blackwell, 2020
Keywords
2D PC-MRI, 4D flow MRI, cerebral arterial compliance, cerebrovascular resistance, circle of Willis, pulsatility index
National Category
Medical Engineering
Identifiers
urn:nbn:se:umu:diva-165203 (URN)10.1002/jmri.26978 (DOI)000495792500001 ()31713964 (PubMedID)2-s2.0-85075025588 (Scopus ID)
Funder
Swedish Research Council, 2015–05616Swedish Heart Lung Foundation, 20140592Swedish Research Council, 2017-04949
Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2023-03-24Bibliographically approved
3. Middle cerebral artery pressure laterality in patients with symptomatic ICA stenosis
Open this publication in new window or tab >>Middle cerebral artery pressure laterality in patients with symptomatic ICA stenosis
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2021 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 1, article id e0245337Article in journal (Refereed) Published
Abstract [en]

An internal carotid artery (ICA) stenosis can potentially decrease the perfusion pressure to the brain. In this study, computational fluid dynamics (CFD) was used to study if there was a hemispheric pressure laterality between the contra- and ipsilateral middle cerebral artery (MCA) in patients with a symptomatic ICA stenosis. We further investigated if this MCA pressure laterality (ΔPMCA) was related to the hemispheric flow laterality (ΔQ) in the anterior circulation, i.e., ICA, proximal MCA and the proximal anterior cerebral artery (ACA). Twenty-eight patients (73±6 years, range 59–80 years, 21 men) with symptomatic ICA stenosis were included. Flow rates were measured using 4D flow MRI data (PC-VIPR) and vessel geometries were obtained from computed tomography angiography. The ΔPMCA was calculated from CFD, where patient-specific flow rates were applied at all input- and output boundaries. The ΔPMCA between the contra- and ipsilateral side was 6.4±8.3 mmHg (p<0.001) (median 3.9 mmHg, range -1.3 to 31.9 mmHg). There was a linear correlation between the ΔPMCA and ΔQICA (r = 0.85, p<0.001) and ΔQACA (r = 0.71, p<0.001), respectively. The correlation to ΔQMCA was weaker (r = 0.47, p = 0.011). In conclusion, the MCA pressure laterality obtained with CFD, is a promising physiological biomarker that can grade the hemodynamic disturbance in patients with a symptomatic ICA stenosis.

Place, publisher, year, edition, pages
Public Library of Science, 2021
National Category
Medical Imaging Neurology
Identifiers
urn:nbn:se:umu:diva-182247 (URN)10.1371/journal.pone.0245337 (DOI)000630020100027 ()33417614 (PubMedID)2-s2.0-85099353130 (Scopus ID)
Funder
Swedish Research Council, 2015–05616Swedish Research Council, 2017-04949Swedish Research Council, 2016-07213Swedish Heart Lung Foundation, 20140592
Available from: 2021-04-14 Created: 2021-04-14 Last updated: 2025-02-09Bibliographically approved
4. Computational fluid dynamics for prediction of measured carotid stump pressure during carotid endarterectomy
Open this publication in new window or tab >>Computational fluid dynamics for prediction of measured carotid stump pressure during carotid endarterectomy
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(English)Manuscript (preprint) (Other academic)
National Category
Medical Imaging Neurology
Identifiers
urn:nbn:se:umu:diva-182249 (URN)
Available from: 2021-04-14 Created: 2021-04-14 Last updated: 2025-02-09

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