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Computational prediction of cerebral perfusion pressure and blood flow: patient-specific modelling of the cerebral collateral circulation in carotid artery stenosis and during aortic arch surgery
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.ORCID iD: 0009-0008-9145-7052
2026 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Beräkningsbaserad prediktion av cerebralt perfusionstryck och blodflöde : patientspecifik modellering av cerebral kollateralcirkulation vid karotisstenos och under aortabågskirurgi (Swedish)
Abstract [en]

Vascular surgery may involve manipulation and occlusion of arteries supplying blood to the brain. Obstructions in these feeding arteries can disturb cerebral blood flow, risking hypoperfusion and ischemic brain injury. To maintain balanced cerebral perfusion, the cerebral vasculature contains alternative pathways that can perfuse territories affected by an obstruction, known as the cerebral collateral circulation. However, collateral capacity varies among individuals, meaning that surgical risk is patient-specific. Currently, no reliable method exists for predicting an individual patient’s cerebral collateral capacity during vascular surgery. Computational modelling of hemodynamics offers a powerful tool for assessing patient-specific blood flow and perfusion pressure. This type of modelling provides a predictive dimension to the analysis and could potentially be used to assess intraoperative cerebral collateral circulation to inform preoperative planning and decision-making in vascular surgery.

This work aimed to develop and evaluate a computational method combining computational fluid dynamics (CFD) with segmented arterial trees from computed tomography angiography (CTA) and arterial flow rates from magnetic resonance imaging (MRI), to predict patient-specific cerebral hemodynamics during vascular surgery.

As cerebrovascular resistance is a key parameter in computational predictions of cerebral hemodynamics, we first studied 48 patients with stroke or transient ischemic attack, with and without symptomatic carotid stenosis (mean age 71 years). The aim was to assess patient-specific resistances and evaluate whether they are affected by feeding artery obstruction due to carotid stenosis. Territorial cerebrovascular resistances were estimated based on the simulated cerebral perfusion pressure in the major cerebral arteries and the MRI-measured arterial flow rates. Total cerebrovascular resistance was also compared with that of 56 controls (mean age 74 years). No differences were observed between patients and controls, nor between hemispheres in patients with symptomatic carotid stenosis (Paper I).

To test the predictive capabilities of our model, we next studied a prospective cohort of 20 patients (mean age 67 years) scheduled for elective aortic arch surgery with selective antegrade cerebral perfusion (SACP). Surgery with SACP presents a highly relevant scenario in which the cerebral collateral capacity is crucial for maintaining brain perfusion. SACP can be applied unilaterally, relying on the collateral circulation, or bilaterally, perfusing both hemispheres directly but requiring additional arterial manipulation. There is no consensus on a preferred technique, although neurological injury might be minimized if SACP use was tailored to the patient’s collateral capacity. Our method simulated perfusion pressure in the arterial tree using measured surgical parameters, for each patient obtained during both techniques, as well as downstream vascular resistances. First, a feasibility study (N=5) showed that predictions were possible but were sensitive to arterial size (Paper II). The full prediction analysis (N=19) showed no difference between measured and predicted left-side perfusion pressure for bilateral SACP, while it was slightly underestimated for unilateral SACP. Measured and predicted pressures were highly correlated for both techniques (Paper III). To make the modelling workflow more clinically feasible, these same patients also underwent time-of-flight magnetic resonance angiography (TOF-MRA) (Paper IV). Using the same segmentation method as for CTA, a signal intensity threshold was identified that produced arterial geometries similar to the CTA-based segmentations (N=19). Subsequent simulations showed no difference between modalities in simulated baseline perfusion pressure or pressure laterality during unilateral brain inflow. However, simulations were for both modalities sensitive to segmentation of the collateral arteries.

In summary, we presented a method to determine cerebrovascular resistances and found that carotid stenosis had minimal effect on global or local cerebrovascular resistance in stroke and TIA patients. Using surgical input data, we then proposed a method for computing cerebral perfusion pressure during unilateral and bilateral SACP in aortic arch surgery. The method showed acceptable accuracy in predicting left-side cerebral perfusion pressure, with predicted values highly correlated with measured values. Finally, TOF-MRA offers a promising alternative to CTA, reducing imaging requirements and improving clinical feasibility. These studies demonstrate the potential of hemodynamic modelling to predict cerebral collateral capacity and support individualized clinical decision-making in vascular surgery. 

Abstract [sv]

Vaskulär kirurgi kan innebära att artärer som förser hjärnan med blod tillfälligt manipuleras eller stängs av. Eftersom hjärnan är beroende av en konstant blodtillförsel finns risken att detta leder till syrebrist i hjärnan och i värsta fall stroke. Hjärnan har dock ett system av alternativa flödesvägar, den så kallade cerebrala kollateralcirkulationen, som kan hjälpa till att kompensera om blodflödet minskar i någon av de huvudsakliga artärerna. Hur väl detta fungerar varierar mellan individer, och i nuläget är det svårt att förutsäga vilka patienter vars kollateralcirkulation kan kompensera ett tillfälligt avbrott i blodflödet.

Om denna förmåga kunde bedömas i förväg skulle kirurgiska ingrepp kunna anpassas efter varje patient och därmed minska risken för neurologiska skador. Hemodynamisk modellering, matematiska modeller av blodflöde och blodtryck, kan användas för att studera kroppens cirkulation och simulera hur blodflödet förändras under olika förhållanden. I denna avhandling utvecklades en metod som kombinerar sådana modeller med medicinska bilder för att uppskatta enskilda patienters blodcirkulation i hjärnan och förutsäga effekterna av förändrat blodflöde.

Till att börja med undersöktes 48 patienter med stroke eller transitorisk ischemisk attack (TIA), med eller utan symptomgivande karotisstenos (förträngning i halspulsådern). För dessa beräknade vi den vaskulära resistansen, flödesmotståndet, i hjärnan genom att kombinera flödesmätningar samt tryck från trycksimuleringar. Dessa resistanser är en viktig parameter som används flitigt vid beräkningar av hjärnans blodcirkulation.

Metodens prediktiva förmåga undersöktes sedan i 20 patienter som var planerade för aortabågskirurgi, ett kliniskt relevant exempel där kollateralförmågan kan vara kritisk. Vid denna typ av operation kan blodflödet till hjärnan säkerställas genom att leda blod via slangar till ena eller båda sidorna av kroppen. Om man använder enbart ena sidan måste man förlita sig på patientens kollateralcirkulation. Alternativet är att skapa en ytterligare väg för blodflödet, men det innebär samtidigt en risk för neurologiska skador eftersom ytterligare manipulation av blodkärl kan leda till komplikationer. Än idag debatteras vilken av dessa tekniker som bör användas, och när. I studien användes våra beräkningsmodeller för att förutsäga trycket i hjärnans kärl under båda dessa tekniker, då låga tryck kan indikera ett otillräckligt blodflöde. När blodflödet leddes via båda sidor stämde modellernas beräkningar väl överens med de tryck som mättes under operationen. Vid flöde via enbart ena sidan underskattade modellerna trycket något. Korrelationen mellan beräknade och uppmätta värden var stark för båda teknikerna. Resultaten tyder på att metoden skulle kunna användas för att i förväg förutsäga hur hjärnans blodförsörjning bäst bör säkerställas under operationen, det vill säga via ena eller båda sidorna. Slutligen undersöktes patienterna även med en särskild magnetkamerateknik för att avbilda blodkärlen. Denna jämfördes med skiktröntgen som hittills har använts i modellen, i syfte att ersätta skiktröntgen och minska antalet undersökningar i metodens arbetsflöde. Jämförelser av kärlträdens anatomi och modelleringsresultat visade att den föreslagna magnetkameratekniken skulle kunna fungera som ett alternativ till skiktröntgen i vår modellering.

Sammanfattningsvis presenterar denna avhandling en patientspecifik beräkningsmetod som kan karakterisera flödesmotståndet i hjärnans territorier och därefter anpassas för att förutsäga förmågan hos patientens cerebrala kollateralcirkulation vid vaskulär kirurgi. Flödesmotstånden i hjärnans territorier beräknades med vår metod, och förträngningar i halspulsådern hade till synes ingen effekt på fördelningen. Vidare visade vi att metoden hade en god förmåga att återskapa uppmätta tryck från aortabågskirurgi. Slutligen kunde vi visa att metoden är genomförbar med kärlavbildning via magnetkamera i stället för skiktröntgen. Genom att möjliggöra utvärdering av patientens kollateralförmåga skulle denna metod potentiellt kunna bidra till kirurgisk planering och minskad risk för neurologiska skador under operation.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2026. , p. 83
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2421
Keywords [en]
cerebral perfusion, cerebral collateral circulation, aortic arch surgery, hemodynamic modeling, computational fluid dynamics, 4D flow MRI
National Category
Medical Modelling and Simulation Surgery Cardiology and Cardiovascular Disease
Research subject
Thoracic and Cardivascular Suregery; Numerical Analysis
Identifiers
URN: urn:nbn:se:umu:diva-251463ISBN: 978-91-8070-986-6 (print)ISBN: 978-91-8070-987-3 (electronic)OAI: oai:DiVA.org:umu-251463DiVA, id: diva2:2048852
Public defence
2026-04-29, Stora Hörsalen 5b, Norrlands Universitetssjukhus, Daniel Naezéns väg, 907 37, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2026-04-08 Created: 2026-03-26 Last updated: 2026-03-30Bibliographically approved
List of papers
1. Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI
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2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 14585Article in journal (Refereed) Published
Abstract [en]

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Neurosciences Physiology and Anatomy Medical Imaging Computational Mathematics
Identifiers
urn:nbn:se:umu:diva-227152 (URN)10.1038/s41598-024-65431-4 (DOI)001255006800068 ()2-s2.0-85196758949 (Scopus ID)
Funder
Swedish Research Council, 2015-05616Swedish Research Council, 2017-04949Region VästerbottenSwedish Heart Lung FoundationSwedish Foundation for Strategic Research
Available from: 2024-06-25 Created: 2024-06-25 Last updated: 2026-03-26Bibliographically approved
2. Non-invasive assessment of cerebral perfusion pressure: Applied towards preoperative planning of aortic arch surgery with selective antegrade cerebral perfusion
Open this publication in new window or tab >>Non-invasive assessment of cerebral perfusion pressure: Applied towards preoperative planning of aortic arch surgery with selective antegrade cerebral perfusion
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2025 (English)In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 179, article id 112459Article in journal (Refereed) Published
Abstract [en]

Selective antegrade cerebral perfusion (SACP) is a protective procedure to ascertain adequate brain perfusion during aortic arch surgeries requiring moderate hypothermic circulatory arrest. SACP entails catheterization of arteries feeding the brain, which can be done bilaterally (bSACP) or unilaterally (uSACP), but there is no consensus on when to use each approach. bSACP may increase the risk of embolization, while uSACP risks hypoperfusion due to insufficient perfusion pressure in the contralateral hemisphere, since a single catheter must perfuse both hemispheres. We developed and tested the feasibility of a new method for predicting cerebral perfusion pressures (CPP) during SACP, which could potentially aid clinicians in preoperatively identifying which SACP approach to use. Feasibility of the method was evaluated in five patients eligible for aortic arch surgery (65 ± 7 years, 3 men). Patients were investigated preoperatively with computed tomography angiography (CTA) and 4D flow magnetic resonance imaging (MRI) to assess patient-specific arterial anatomy and blood flows. From the imaging, computational fluid dynamics (CFD) simulations estimated the patients' vascular resistances. Applying these resistances and intraoperative SACP pressure/flow settings to the model's boundary conditions allowed for predictions of contralateral CPP during SACP. Predicted pressures were compared to corresponding intraoperative pressure measurements. The method showed promise for predicting contralateral CPP during both uSACP (median error (range): 2.4 (−0.2–18.0) mmHg) and bSACP (0.8 (−3.3–5.4) mmHg). Predictions were most sensitive to collateral artery size. This study showed the feasibility of CPP predictions of SACP, and presents key features needed for accurate modelling.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
4D flow MRI, Aortic arch surgery, Cerebral perfusion pressure, Computational fluid dynamics, Selective antegrade cerebral perfusion
National Category
Surgery Physiology and Anatomy
Identifiers
urn:nbn:se:umu:diva-233313 (URN)10.1016/j.jbiomech.2024.112459 (DOI)001383269200001 ()39662261 (PubMedID)2-s2.0-85211374967 (Scopus ID)
Funder
Region Västerbotten
Available from: 2025-01-03 Created: 2025-01-03 Last updated: 2026-03-26Bibliographically approved
3. Predicting intraoperative cerebral perfusion pressure in unilateral and bilateral selective antegrade cerebral perfusion during aortic arch surgery
Open this publication in new window or tab >>Predicting intraoperative cerebral perfusion pressure in unilateral and bilateral selective antegrade cerebral perfusion during aortic arch surgery
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(English)Manuscript (preprint) (Other academic)
National Category
Surgery Medical Modelling and Simulation Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:umu:diva-251461 (URN)
Available from: 2026-03-26 Created: 2026-03-26 Last updated: 2026-03-30Bibliographically approved
4. CTA versus TOF-MRA for circle of Willis segmentation: implications for hemodynamic modelling
Open this publication in new window or tab >>CTA versus TOF-MRA for circle of Willis segmentation: implications for hemodynamic modelling
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(English)Manuscript (preprint) (Other academic)
National Category
Radiology and Medical Imaging Medical Modelling and Simulation
Identifiers
urn:nbn:se:umu:diva-251462 (URN)
Available from: 2026-03-26 Created: 2026-03-26 Last updated: 2026-03-30Bibliographically approved

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