Patient specific cerebral arterial blood flow modelling

Many cerebrovascular diseases are complex and treatment is often based on experience and relatively small studies. A mathematical blood flow model might aid in better treatment decisions and might lead to more personalised healthcare. In this thesis we set out to develop a clinical applicable cerebrovascular blood flow model. Initially we developed a complex 3D blood flow model which was tested in two retrospective patients treated by proximal and distal occlusion for complex cerebral aneurysms. Results matched well with follow-up data. This pilot study confirms the potential of a complex 3D model. However, it also showed the complexity in these 3D models which limits clinical applicability. Hence, we set out to develop a simplified model. In a narrative literature survey, we identified important causes that might hamper development of such a model and presented possible solutions. One of such difficulties lies in distal boundary conditions (peripheral resistance). One solution to estimate distal boundary conditions is the usage of branching patterns to generate structured arterial trees which can serve as replacing resistances. However, data on branching patterns in the cerebral circulation were scarce. Hence, we validated and used a method based on 7T MRI and 9.4T MRI scanning of plastic cerebral arterial casts to acquire cerebrovascular branching patterns. Additionally, manual measurements were used. The branching patterns showed a broad distribution. Further, it was confirmed that on average the cerebral arterial tree complies to the principle of minimum work as defined in Murray’s Law. A simplified mathematical blood flow model of the cerebral arterial circulation was produced based on linear Hagen-Poiseuille equations. Blood pressure cuff measurement served as a simple accessible proximal boundary condition. A semi-automatic method was used to generate patient-specific morphology of the larger cerebral arteries based on MRI data. Distal boundary conditions were based on branching patterns combined with a simplified autoregulatory model. Calculated flow values were compared to phase-contrast MRI based measurements acquired using the Noninvasive Optimal Vessel Analysis (NOVA) software. Data of 10 healthy subjects was used to optimize parameters of distal boundary conditions. Data of 20 additional healthy subjects were used to compare calculated and NOVA measured flow to validate the model. The model showed to be accurate in a range that might proof feasible for clinical use. For some specific purposes more complex 3D models are likely required, especially when information on flow patterns and wall stresses are needed. However, based on the current thesis and literature, simplified models show great potential. Hence, studies developing a patient-specific blood flow model for a specific clinical question should whenever possible first consider the usage of such a simplified model

Patient specific cerebral arterial blood flow modelling

Many cerebrovascular diseases are complex and treatment is often based on experience and relatively small studies. A mathematical blood flow model might aid in better treatment decisions and might lead to more personalised healthcare. In this thesis we set out to develop a clinical applicable cerebrovascular blood flow model. Initially we developed a complex 3D blood flow model which was tested in two retrospective patients treated by proximal and distal occlusion for complex cerebral aneurysms. Results matched well with follow-up data. This pilot study confirms the potential of a complex 3D model. However, it also showed the complexity in these 3D models which limits clinical applicability. Hence, we set out to develop a simplified model. In a narrative literature survey, we identified important causes that might hamper development of such a model and presented possible solutions. One of such difficulties lies in distal boundary conditions (peripheral resistance). One solution to estimate distal boundary conditions is the usage of branching patterns to generate structured arterial trees which can serve as replacing resistances. However, data on branching patterns in the cerebral circulation were scarce. Hence, we validated and used a method based on 7T MRI and 9.4T MRI scanning of plastic cerebral arterial casts to acquire cerebrovascular branching patterns. Additionally, manual measurements were used. The branching patterns showed a broad distribution. Further, it was confirmed that on average the cerebral arterial tree complies to the principle of minimum work as defined in Murray’s Law. A simplified mathematical blood flow model of the cerebral arterial circulation was produced based on linear Hagen-Poiseuille equations. Blood pressure cuff measurement served as a simple accessible proximal boundary condition. A semi-automatic method was used to generate patient-specific morphology of the larger cerebral arteries based on MRI data. Distal boundary conditions were based on branching patterns combined with a simplified autoregulatory model. Calculated flow values were compared to phase-contrast MRI based measurements acquired using the Noninvasive Optimal Vessel Analysis (NOVA) software. Data of 10 healthy subjects was used to optimize parameters of distal boundary conditions. Data of 20 additional healthy subjects were used to compare calculated and NOVA measured flow to validate the model. The model showed to be accurate in a range that might proof feasible for clinical use. For some specific purposes more complex 3D models are likely required, especially when information on flow patterns and wall stresses are needed. However, based on the current thesis and literature, simplified models show great potential. Hence, studies developing a patient-specific blood flow model for a specific clinical question should whenever possible first consider the usage of such a simplified model

A Laser-Assisted Anastomotic Technique : Feasibility on Human Diseased Coronary Arteries

OBJECTIVE: Atherosclerotic disease might hamper the efficacy of the Excimer laser-assisted Trinity Clip anastomotic connector in coronary arteries. Therefore, its efficacy was evaluated on human diseased coronary arteries (study 1). In addition, the acute laser effects onto the coronary wall were assessed (study 2). METHODS: Thirty-eight anastomoses were constructed on ex vivo human hearts. Atherosclerosis was histopathologically determined and subsequently related to the success of the technique (ie, connector positioning and laser punching; study 1). In addition, 20 anastomoses were constructed in an ex vivo (porcine, n = 8) and an in vivo [rabbit (n = 9) and porcine (n = 3)] model. Subsequently, the coronary was histologically studied on the presence of laser-induced damage (study 2). RESULTS: In 13 of 38 anastomoses (study 1), the connector was malpositioned, 3 because of a severely diseased coronary wall and 10 because of an inner diameter less than the intended target range. The laser-punch success rates on coronary arteries with an early and advanced lesion were 100% (16/16) and 89% (8/9; lesions were located in the inferolateral wall), respectively. In one case, an advanced lesion (ie, fibrocalcified plaque) was located in the superolateral wall and caused a laser-punch failure. No histological signs of laser-induced damage were observed, in case of correct use (study 2). CONCLUSIONS: This study demonstrates the feasibility of an anastomotic connector on human diseased coronary arteries and shows that lasering does not induce coronary wall damage. However, careful selection of the coronary, regarding the target inner diameter and disease status, will prevent construction failures. This connector could facilitate less invasive coronary artery bypass grafting

A patient-specific cerebral blood flow model

In clinical practice, many complex choices in treatment of complex cerebrovascular diseases have to be made. A patient-specific mathematical blood flow could aid these decisions. For certain cases, less accuracy is required and more simplistic models might be feasible. The current study is aiming to validate a patient-specific simplistic blood flow model in 20 healthy subjects. All subjects underwent MRI and Noninvasive Optimal Vessel Analysis (NOVA) to obtain patient-specific vascular morphology and flow measurements of all major cerebral arteries for validation. The mathematical model used was based on the Hagen-Poiseuille equations. Proximal boundary conditions were patient-specific blood pressure cuff measurements. For distal boundary conditions, a structured tree and a simple autoregulatory model were applied. Autoregulatory parameters were optimized based on the data of 10 additional healthy subjects. A median percentual flow difference of −3% (interquartile range −36% to 17%) was found. Regression analysis to an identity line resulted in R2 values of 0.71 for absolute flow values. Bland-Altman plots showed a bias (levels of agreement) of 5% (-70 to 80%) for absolute flow. Based on these results the model proved to be accurate within a range that might be feasible for use in clinic. Major limitations to the model arise from the simplifications made compared to the actual physiological situation and limitations in the validation method. As the model is validated in healthy subjects only, further validation in actual patients is needed

High resolution 7T and 9.4T-MRI of human cerebral arterial casts enables accurate estimations of the cerebrovascular morphometry

Quantitative data on the morphology of the cerebral arterial tree could aid in modelling and understanding cerebrovascular diseases, but is scarce in the range between 200 micrometres and 1 mm diameter arteries. Traditional manual measurements are difficult and time consuming. 7T-MRI and 9.4T-MRI of human cerebral arterial plastic casts could proof feasible for acquiring detailed morphological data of the cerebral arterial tree in a time efficient method. One cast of the complete human cerebral arterial circulation embedded in gadolinium-containing gelatine gel was scanned at 7T-MRI (0.1 mm isotropic resolution). A small section of another cast was scanned at 9.4T-MRI (30 µm isotropic resolution). Subsequent 3D-reconstruction was performed using a semi-automatic approach. Validation of 7T-MRI was performed by comparing the radius calculated using MRI to manual measurements on the same cast. As manual measurement of the small section was not feasible, 9.4T-MRI was validated by scanning the small section both at 7T-MRI and 9.4T MRI and comparing the diameters of arterial segments. Linear regression slopes were 0.97 (R-squared 0.94) and 1.0 (R-squared 0.90) for 7T-MRI and 9.4T-MRI. This data shows that 7T-MRI and 9.4T-MRI and subsequent 3D reconstruction of plastic casts is feasible, and allows for characterization of human cerebral arterial tree morphology

Branching Pattern of the Cerebral Arterial Tree

Quantitative data on branching patterns of the human cerebral arterial tree are lacking in the 1.0–0.1 mm radius range. We aimed to collect quantitative data in this range, and to study if the cerebral artery tree complies with the principle of minimal work (Law of Murray). To enable easy quantification of branching patterns a semi-automatic method was employed to measure 1,294 bifurcations and 2,031 segments on 7 T-MRI scans of two corrosion casts embedded in a gel. Additionally, to measure segments with a radius smaller than 0.1 mm, 9.4 T-MRI was used on a small cast section to characterize 1,147 bifurcations and 1,150 segments. Besides MRI, traditional methods were employed. Seven hundred thirty-three bifurcations were manually measured on a corrosion cast and 1,808 bifurcations and 1,799 segment lengths were manually measured on a fresh dissected cerebral arterial tree. Data showed a large variation in branching pattern parameters (asymmetry-ratio, area-ratio, length-radius-ratio, tapering). Part of the variation may be explained by the variation in measurement techniques, number of measurements and location of measurement in the vascular tree. This study confirms that the cerebral arterial tree complies with the principle of minimum work. These data are essential in the future development of more accurate mathematical blood flow models. Anat Rec, 302:1434–1446, 2019

Added Value of Abnormal Lymph Nodes Detected with FDG-PET/CT in Suspected Vascular Graft Infection

Vascular graft and endograft infections (VGEI) cause a serious morbidity and mortality burden. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is frequently used in the diagnostic workup, but the additional value of abnormal (18F-FDG active and/or enlarged) locoregional lymph nodes is unknown. In this retrospective study, the additional diagnostic value of abnormal locoregional lymph nodes on 18F-FDG PET/CT imaging for VGEI was evaluated, including 54 patients with a culture-proven VGEI (defined according to the Management of Aortic Graft Infection [MAGIC] group classification) and 25 patients without VGEI. 18F-FDG PET/CT was qualitatively and quantitatively assessed for tracer uptake and pattern at the location of the vascular graft, and locoregional lymph node uptake and enlargement (>10 mm). 18F-FDG uptake intensity and pattern independently predicted the presence of VGEI by logistic regression (Χ2: 46.19, p < 0.001), with an OR of 7.38 (95% CI [1.65, 32.92], p = 0.009) and 18.32 (95% CI [3.95, 84.88], p < 0.001), respectively. Single visual assessment of abnormal locoregional lymph nodes predicted the presence of VGEI with a sensitivity of 35%, specificity of 96%, PPV of 95%, and NPV of 41%. The visual assessment of abnormal lymph nodes after qualitative assessment of 18F-FDG uptake intensity and pattern at the vascular graft location did not independently predict the presence of VGEI by logistic regression (Χ2: 3.60, p = 0.058; OR: 8.25, 95% CI [0.74, 63.37], p = 0.096). In conclusion, detection of abnormal locoregional lymph nodes on 18F-FDG PET/CT has a high specificity (96%) and PPV (95%) for VGEI. However, it did not add to currently used 18F-FDG PET/CT interpretation criteria

Added Value of Abnormal Lymph Nodes Detected with FDG-PET/CT in Suspected Vascular Graft Infection

Vascular graft and endograft infections (VGEI) cause a serious morbidity and mortality burden. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) imaging is frequently used in the diagnostic workup, but the additional value of abnormal ( 18F-FDG active and/or enlarged) locoregional lymph nodes is unknown. In this retrospective study, the additional diagnostic value of abnormal locoregional lymph nodes on 18F-FDG PET/CT imaging for VGEI was evaluated, including 54 patients with a culture-proven VGEI (defined according to the Management of Aortic Graft Infection [MAGIC] group classification) and 25 patients without VGEI. 18F-FDG PET/CT was qualitatively and quantitatively assessed for tracer uptake and pattern at the location of the vascular graft, and locoregional lymph node uptake and enlargement (>10 mm). 18F-FDG uptake intensity and pattern independently predicted the presence of VGEI by logistic regression (Χ 2: 46.19, p < 0.001), with an OR of 7.38 (95% CI [1.65, 32.92], p = 0.009) and 18.32 (95% CI [3.95, 84.88], p < 0.001), respectively. Single visual assessment of abnormal locoregional lymph nodes predicted the presence of VGEI with a sensitivity of 35%, specificity of 96%, PPV of 95%, and NPV of 41%. The visual assessment of abnormal lymph nodes after qualitative assessment of 18F-FDG uptake intensity and pattern at the vascular graft location did not independently predict the presence of VGEI by logistic regression (Χ 2: 3.60, p = 0.058; OR: 8.25, 95% CI [0.74, 63.37], p = 0.096). In conclusion, detection of abnormal locoregional lymph nodes on 18F-FDG PET/CT has a high specificity (96%) and PPV (95%) for VGEI. However, it did not add to currently used 18F-FDG PET/CT interpretation criteria

Branching Pattern of the Cerebral Arterial Tree

Quantitative data on branching patterns of the human cerebral arterial tree are lacking in the 1.0–0.1 mm radius range. We aimed to collect quantitative data in this range, and to study if the cerebral artery tree complies with the principle of minimal work (Law of Murray). To enable easy quantification of branching patterns a semi-automatic method was employed to measure 1,294 bifurcations and 2,031 segments on 7 T-MRI scans of two corrosion casts embedded in a gel. Additionally, to measure segments with a radius smaller than 0.1 mm, 9.4 T-MRI was used on a small cast section to characterize 1,147 bifurcations and 1,150 segments. Besides MRI, traditional methods were employed. Seven hundred thirty-three bifurcations were manually measured on a corrosion cast and 1,808 bifurcations and 1,799 segment lengths were manually measured on a fresh dissected cerebral arterial tree. Data showed a large variation in branching pattern parameters (asymmetry-ratio, area-ratio, length-radius-ratio, tapering). Part of the variation may be explained by the variation in measurement techniques, number of measurements and location of measurement in the vascular tree. This study confirms that the cerebral arterial tree complies with the principle of minimum work. These data are essential in the future development of more accurate mathematical blood flow models. Anat Rec, 302:1434–1446, 2019