Towards the use of geometric parameters and blood-borne species concentration in the prediction of cerebral aneurysm growth and rupture

The r upture of a c erebral a neurysm can ha ve de vastating effects, with hi gh rates of morbidity a nd mo rtality a ssociated w ith th e event. A pproximately 1 2% o f p atients who s uffer a s ubarachnoid ha emorrhage due t o t he r upture of a n a neurysm di e immediately, a further 40% die within one month and one third of those that survive are l eft w ith n eurological d efects. Although t he e xact m echanisms behind t he formation, growth and rupture of a neurysms a re unknow n, i t i s b elieved t hat a combination of geometric, morphological an d haemodynamic f actors may p lay an important role. The primary aim of this research was to investigate the links between geometric features and the mass transport of blood-borne species, and their combined relationship with cerebral aneurysm growth and rupture potential. Improved imaging techniques have allowed for better detection of unruptured cerebral aneurysms. However, the management of unruptured aneurysms, which are estimated to af fect 5 -8% of t he po pulation, is di sputed and current i ntervention methods carry substantial risks for the patient. Currently, the decision to treat patients is based on the likelihood of a neurysm rupture, thus i dentifying f actors t hat can ad equately i ndicate aneurysm rupture potential is paramount to distinguishing patients at need of surgical or endovascular i ntervention f rom those who can undergo observation. However, a n issue w ith m any of t he pa rameters pr eviously shown t o ha ve a r elationship w ith rupture i s t hat t hey c annot be di rectly m easured u sing t ypical i maging t echniques. Consequently, t his s tudy investigated t he i nfluence of r adiologically r elevant a nd measurable pa rameters on a neurysm r upture i n or der t o de termine i f g eometric features could be used to predict aneurysm rupture potential. A study of 168 pa tientspecific c erebral an eurysms s uggested t hat aneurysm r upture r isk i s i ncreased f or aneurysms of the posterior circulation, bifurcating in shape, with increasing tilt angle and with increasing aspect ratio. Computational fluid dynamics has become a popular tool for haemodynamic studies of cerebral a neurysms. C urrent s tudies f ocus m ainly on f actors s uch a s i nflow j ets, impingement sites, wall shear stress and oscillatory shear index: however, few studies address t he i nfluence of t he m ass transport of bl ood-borne s pecies o n a neurysm rupture. C omputational a nalysis of m ass t ransport of t he bl ood-borne s pecies adenosine triphosphate carried out on a sample set of 12 patient-specific aneurysms of both l ateral and b ifurcating s hape. A s pecies concentration t hreshold i s introduced, which indicates the amount of the aneurysm dome that is exposed to concentrations at iii 1%, 5% , 10% a nd 20 % l ess t han t he i nlet c oncentration, s uggesting a n unde rexpression of vi tal bl ood-borne s pecies. T he c omputational a nalysis id entified aneurysms t hat d emonstrated ar eas o f r educed co ncentration as a r esult o f t heir geometric configuration. Statistical analysis was carried out on the results and rupture probability equations were developed based on t he species threshold values, allowing for t he pr ediction of t he r upture s tatus of a n a neurysm t o be m ade ba sed on t he concentration distribution seen within the dome. Results from the geometric and mass transport studies were tested on a n independent cohort of ten patient-specific aneurysms, where the rupture status of 8/10 (80%) of the cohort were correctly predicted by the rupture probability equation based on a species threshold of 1% . F urthermore, a c ombined r upture pr obability equation, de veloped based o n g eometric f eatures a nd t he 1% s pecies c oncentration t hreshold l ed t o t he rupture status of 7/10 (70%) of the aneurysms being correctly predicted. In pr evious C FD s tudies, i dealised m odels were i nitially us ed t o i dentify general trends in aneurysm haemodynamics. Idealised models can neglect s ignificant aspects of the geometry such as aneurysmal blebs and irregularities of the aneurysm wall, and so i n r ecent years a s hift has been m ade t owards t he u se o f patient-specific models. Patient-specific s imulations can b e computationally expensive a nd require l arge amounts of medical imaging and flow data, and so in this study it was investigated if representative m odels a re a v iable alternative. T hese r epresentative models w ere developed based on key geometric measurements taken from patient-specific models, and w ere ba sed on t wo l ocations w ithin t he C oW: t he oph thalmic s egment of t he internal carotid artery, representing typical lateral shaped aneurysms, and the sylvian bifurcation, r epresenting bi furcation/terminal t ype a neurysms. R esults from ma ss transport a nalyses w ithin i dealised, pa tient-specific an d r epresentative m odels demonstrated th at while r epresentative mo dels may neglect a spects o f the p atientspecific geometry such as aneurysmal blebs o r undulations, improved information is gained compared to simplified, idealised models in the mass transport of blood-borne species within cerebral aneurysms. Overall, t his s tudy i ndicates t hat aneurysm rupture r isk m ay b e i nfluenced b y t he amount of the aneurysm dome that is exposed to a species concentration less than 1% of the inlet concentration. The results and conclusions presented throughout this thesis contribute a dvancements t o r esearch i n bot h e xperimental a nd c omputational