- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan,
- Department of Endovascular Neurosurgery, Saitama Medical University, International Medical Center, Hidaka, Saitama, Japan,
- Division of Radiology, Sapporo Medical University Hospital, Sapporo, Hokkaido, Japan,
- Division of Radiology, Sapporo Shiroishi Memorial Hospital, Sapporo, Hokkaido, Japan,
- Department of Neurosurgery, Sapporo Shiroishi Memorial Hospital, Sapporo, Hokkaido, Japan.
Tomoyoshi Kuribara, Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan.
DOI:10.25259/SNI_439_2021Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Tomoyoshi Kuribara1, Takeshi Mikami1, Satoshi Iihoshi2, Toru Hirano3, Daisuke Sasamori4, Tadashi Nonaka5, Nobuhiro Mikuni1. Virtual test occlusion for assessing ischemic tolerance using computational fluid dynamics. 27-Jul-2021;12:378
How to cite this URL: Tomoyoshi Kuribara1, Takeshi Mikami1, Satoshi Iihoshi2, Toru Hirano3, Daisuke Sasamori4, Tadashi Nonaka5, Nobuhiro Mikuni1. Virtual test occlusion for assessing ischemic tolerance using computational fluid dynamics. 27-Jul-2021;12:378. Available from: https://surgicalneurologyint.com/surgicalint-articles/10992/
Background: Ischemic tolerance has been evaluated by the balloon test occlusion (BTO) for cerebral aneurysms and tumors that might require parent artery occlusion during surgery. However, because of its invasiveness, a non-invasive evaluation method is needed. In this study, we assessed the possibility of virtual test occlusion using computational fluid dynamics (CFD) as a non-invasive alternative to BTO for evaluating ischemic tolerance.
Methods: Twenty-one patients who underwent BTO were included in the study. Virtual test occlusion was performed using CFD analysis, and the flow rate (FR) and wall shear stress (WSS) of the middle cerebral artery on the occlusion side were calculated. The correlations between these parameters and examination data including the parameters of computed tomography perfusion during BTO were assessed and the cutoff value of CFD parameters for detecting the good collateral group was calculated.
Results: The FR was strongly correlated with mean transit time (MTT) during BTO and moderately correlated with collateral flow grade based on angiographic appearance. The WSS was moderately correlated with collateral flow grade, mean stump pressure (MSP), and MTT. Furthermore, the FR and WSS were strongly correlated with the total FR and the diameters of the inlet vessels. The cutoff value of FR for detecting the good collateral group was 126.2 mL/min, while that of the WSS was 4.54 Pa.
Keywords: Balloon test occlusion, Computational fluid dynamics, Computed tomography perfusion, Flow rate, Wall share stress
Ischemic tolerance has been evaluated by balloon test occlusion (BTO) for large and giant cerebral aneurysms[
Image-based computational fluid dynamics (CFD) are able to extract patient-specific hemodynamic information based on the imaging data obtained through CT angiography (CTA), 3-dimensional (3D) DSA, and magnetic resonance angiography.[
The study protocol was approved by the ethics committee of Sapporo Medical University Hospital. As this study had a retrospective design, patient consent was obtained with an opt-out policy using a website. From March 2015 to February 2020, consecutive patients who underwent BTO of the ICA at our hospital were enrolled in the study. The patients were diagnosed with cerebral aneurysms, head and neck tumors, and other conditions (intracranial infection) that might require parent artery occlusion during surgery. Patients under 10-years-old and those who required BTO of other arteries were excluded from the study. A total of 21 patients (seven males and 14 females) were examined. The median age (interquartile range) of the patients was 61.0 (50.0–69.5) years (range, 11–74 years). The diagnoses of the 21 patients included cerebral aneurysm in four; head and neck tumor in 15; and other in two.
All procedures were performed using single-plane DSA equipment (Infinix Celeve-i INFX-8000C, Canon Inc., Tokyo, Japan) as previously described.[
Stump pressure was measured using a 3.3-Fr MASAMUNE balloon catheter (Fuji Systems Corp., Tokyo, Japan) placed in the ICA on the lesion side. The ratio of the mean stump pressure (MSP) before and after the temporal occlusion adjusted by mean blood pressure taken from a cuff on the left upper arm was calculated as MSPBR ([MSP 10 min after occlusion/mean blood pressure 10 min after occlusion]/[MSP before occlusion/mean blood pressure before occlusion]) (BR; ratio before and after temporal occlusion).
The INVOS examination was performed during the temporary occlusion. The ratio of INVOS before versus after the temporal occlusion adjusted by INVOS on the contralateral side was calculated as INVOSBR = ([INVOS on the lesion side 10 min after the occlusion/INVOS on the contralateral side 10 min after the occlusion]/[INVOS on the lesion side before the occlusion/INVOS on the contralateral side before the occlusion]).
If the temporary occlusion was <10 min due to ischemic symptoms, MSP and INVOS values just before balloon deflation were used.
CT perfusion during BTO
CT perfusion was performed using interventional radiology CT equipment with 16 rows (Aquilion 16 LB; Canon Inc.). The CT perfusion scanning parameters were described previously.[
Virtual test occlusion based on CFD analysis
The CTA examination was performed before BTO using a multidetector-row CT scanner with 320 rows (Aquilion ONE; Canon Inc.). The 3D-CTA scanning parameters were as previously described.[
A case of left middle fossa tumor. Three-dimensional imaging data were obtained through CTA using a volume-rendering algorithm. (a) The white arrow shows the ICA on the lesion side. Extraction of the center lines and segmentation and labeling of the associated vessels were performed (b). ICA on the lesion side was set as a wall (white arrowhead), while that of the contralateral ICA and bilateral VA were set as the inlet, and the on-site analysis was run (c). After the analysis, the steam line contributing to M1 on the lesion side is shown (d). CTA: Computed tomography angiography, ICA: Internal carotid artery, M1: First segment of the middle cerebral artery, VA: vertebral artery.
In ZIOSTATION 2, the 3D image data were transformed to stereolithography (STL) format and Hemoscope Ver.1.5 (EBM Corp., Tokyo, Japan) was used for further image processing and analysis. In the vessel module, extraction of the center lines, segmentation, and labeling of the associating vessels (bilateral ICA, M1, A1, A2, VA, P1, P2, PcomA) were performed. These vascular geometries were filled with unstructured cells mainly consisting of hexahedrons approximately 0.25 mm in the far-wall regions and 0.125 mm (width) and 0.05 mm (height) in the near-wall regions. In the near-wall regions, the meshes were aligned to fit the boundary with three layers. The inlet (contralateral ICA, bilateral VA) and outlet vessels (bilateral M1, A2, P2) were extended as long as possible based on imaging data and trimmed their proximal and distal ends [
where Q, τ, µ, and D denote FR (mL/min), WSS (Pa), fluid viscosity, and vascular diameter, respectively. After total FR at the inflow vessels was calculated, the amount of FR was distributed at each outlet vessel according to equation;[
CFD analysis was performed using a finite volume method to solve the 3D unsteady Navier-Stokes equations and equation of continuity. Blood was assumed to be an incompressible and Newtonian fluid with a density of 1050 kg/m3 and a viscosity of 0.004 Pa s. The Euler and second-order upwind schemes were utilized to discern unsteady and convective acceleration terms. The convergent criteria were set to 10−4. Mean FR (mL/min) and mean WSS of the target vessels was obtained thorough this analysis, and the values (FR and WSS of M1 on the lesion side and FR of all inlet vessels) were evaluated. We named this simulation method virtual test occlusion. This method included vessels that were associated with perfusion on the lesion side. The virtual test occlusion with a steam line contributing to M1 on the lesion side is shown in [
The data are expressed as median (interquartile range). Spearman’s rank correlation coefficient was used to confirm the correlation between the parameters of virtual test occlusion and those of other modalities. A correlation coefficient (ρ) larger than 0.7, between 0.4 and 0.7, and between 0.2 and 0.4 indicated strong, moderate, and weak correlations, respectively. Receiver operating characteristic (ROC) curve analysis was used to determine the most suitable cutoff value of FR and WSS to detect good collateral groups based on the shortest distance from the curve to the upper left corner. Statistical analyses were performed using SPSS software (version 25; IBM Corporation, Armonk, NY, USA). P < 0.05 was considered statistically significant.
Correlations between parameters of virtual test occlusion and those of other modalities
Patient characteristics are shown in
A summary of the correlations is shown in
Scatter diagrams showing the correlations between FR and collateral flow grade (a), MTTAR obtained through CT perfusion (b) and MSPBR (c), WSS and collateral flow grade (d), and MTTAR (e) and MSPBR (f). CT: Computed tomography, FR: Flow rate; AR: Asymmetry ratio, BR: Ratio before and after temporal occlusion, MTT: Mean transit time; MSP: Mean stump pressure, WSS: Wall share stress.
We subsequently evaluated the anatomical factors that affect the parameters of M1 on the lesion side obtained through virtual test occlusion. The FR of M1 on the lesion side showed strong correlations with the diameter of the contralateral ICA (ρ = 0.709, P = 0.007), total diameter of the inlet vessels (ρ = 0.886, P < 0.001), and total FR of the inlet vessels (ρ = 0.962, P < 0.001) and moderate correlations with ICA diameter on the lesion side (ρ = 0.648, P = 0.012), diameter of M1 on the lesion side (ρ = 0.556, P = 0.039), and mean diameter of the bilateral VA (ρ = 0.567, P = 0.054). WSS of M1 on the lesion side showed strong correlations with total diameter of the inlet vessels (ρ = 0.833, P < 0.001) and total FR of the inlet vessels (ρ = 0.957, P < 0.001) and a moderate correlation with contralateral ICA diameter (ρ = 0.626, P = 0.022) and weak correlations with ICA diameter on the lesion side (ρ = 0.358, P = 0.208) and mean diameter of the bilateral VA (ρ = 0.354, P = 0.259) with the exception of M1 diameter on the lesion side (ρ = 0.059, P = 0.840). Regarding anatomical factors, total FR of the inlet vessels was most strongly correlated with FR and WSS of M1 on the lesion side. It was also obtained through virtual test occlusion depending on anatomical information.
ROC curve analysis of good collateral group
The good collateral group consisted of six patients, while the poor collateral group consisted of 15 patients. The ROC curve analysis of FR and WSS of M1 on the lesion side to detect the good collateral group is shown in [
Utility of virtual test occlusion for assessing ischemia
In this study, the CFD parameters were correlated with collateral flow grade, MSP, and MTT. Collateral angiographic appearance, stump pressure, and MTT obtained through CT perfusion during BTO are reportedly predictors of ischemic tolerance,[
Regarding the items influencing CFD parameters, FR and WSS might be reflected, particularly inlet vessel diameter. FR obtained through CFD analysis reportedly reflects actual cerebral hemodynamic condition depending on anatomical structures. Kataoka et al. reported that vessel diameter and FR of intracranial arteries might be controlled so WSS remains constant after bypass surgery.[
Indications for recanalization with parent artery occlusion
In the present study, the most suitable cutoff values of FR and WSS for detecting the good collateral group obtained through ROC curve analysis were 126.2 mL/min and 4.54 Pa, respectively. These values represent the requirement for good collateral screening, and not indicating the need for revascularization surgery. The quantification of ischemic tolerance with FR and WSS obtained through virtual test occlusion using CFD analysis is expected to indicate ICA occlusion without high-flow bypass. However, the indications for revascularization surgery should be considered carefully with an appropriate safety margin to avoid delayed ischemic stroke. Regarding the requirement for revascularization surgery, various parameters using BTO have been reported previously. Abud et al. reported that carotid sacrifice without bypass was possible when the delay between the venous drainage of the injected and occluded hemisphere was <3 s.[
Limitations and future work
This study has several limitations. First, visualization of the small vessels such as the AcomA and PcomA was difficult because of partial volume effect and transformation to an STL format. The mean diameters of the AcomA and PcomA were reportedly 1.5 mm and 1.4–1.6 mm, respectively,[
Among the parameters obtained through CFD analysis, FR and WSS were correlated with collateral flow grade and MSP in addition to MTT. The good collateral group could be distinguished using virtual test occlusion and might be treated by ICA occlusion without high-flow bypass, although prospective validation is needed to confirm this. Most researchers focus on angiographic appearance and clinical data during BTO for detecting delayed ischemic stroke after parent artery occlusion, with little research having been done on non-invasively analyzing hemodynamic mechanisms. Virtual test occlusion might be used to evaluate ischemic tolerance as a non-invasive alternative to BTO.
The authors certify that they have obtained all appropriate patient consent.
Grant support: This work was supported in part by JSPS KAKENHI grant Number 20K15933 (to T.K.).
There are no conflicts of interest.
I would like to thank Kei Miyata, Sangnyon Kim, Katsuya Komatsu, Yusuke Kimura, Rei Enatsu, and Yukinori Akiyama for helpful discussions.
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