Prediction of 60 day case-fatality after aneurysmal subarachnoid haemorrhage: results from the International Subarachnoid Aneurysm Trial (ISAT)

Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with substantial case-fatality. Our purpose was to examine which clinical and neuro-imaging characteristics, available on admission, predict 60 day case-fatality in aSAH and to evaluate performance of our prediction model. We performed a secondary analysis of patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomised multicentre trial to compare coiling with clipping in aSAH patients. Multivariable logistic regression analysis was used to develop a prognostic model to estimate the risk of dying within 60 days from aSAH based on clinical and neuro-imaging characteristics. The model was internally validated with bootstrapping techniques. The study population comprised of 2,128 patients who had been randomised to either endovascular coiling or neurosurgical clipping. In this population 153 patients (7.2%) died within 60 days. World Federation of Neurosurgical Societies (WFNS) grade was the most important predictor of case-fatality, followed by age, lumen size of the aneurysm and Fisher grade. The model discriminated reasonably between those who died within 60 days and those who survived (c statistic = 0.73), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.70). Several strong predictors are available to predict 60 day case-fatality in aSAH patients who survived the early stage up till a treatment decision; after external validation these predictors could eventually be used in clinical decision making

Prediction of two month modified Rankin Scale with an ordinal prediction model in patients with aneurysmal subarachnoid haemorrhage

Background. Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with a frequently disabling outcome. Our aim was to develop a prognostic model to predict an ordinal clinical outcome at two months in patients with aSAH. Methods. We studied patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomized multicentre trial to compare coiling and clipping in aSAH patients. Several models were explored to estimate a patient's outcome according to the modified Rankin Scale (mRS) at two months after aSAH. Our final model was validated internally with bootstrapping techniques. Results. The study population comprised of 2,128 patients of whom 159 patients died within 2 months (8%). Multivariable proportional odds analysis identified World Federation of Neurosurgical Societies (WFNS) grade as the most important predictor, followed by age, sex, lumen size of the aneurysm, Fisher grade, vasospasm on angiography, and treatment modality. The model discriminated moderately between those with poor and good mRS scores (c statistic = 0.65), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.64). Conclusion. We presented a calibrated and internally validated ordinal prognostic model to predict two month mRS in aSAH patients who survived the early stage up till a treatment decision.

Patient-specific modelling of the cerebral circulation for aneurysm risk assessment

Cerebral aneurysms are localised pathological dilatations of cerebral arteries, most commonly found in the circle of Willis. Although not all aneurysms are unstable, the major clinical concern involved is the risk of rupture. High morbidity and mortality rates are associated with the haemorrhage resulting from rupture. New indicators of aneurysm stability are sought, since current indicators based on morphological factors have been shown to be unreliable. Haemodynamical factors are known to be relevant in vascular wall remodelling, and therefore believed to play an important role in aneurysmdevelopment and stability. Studies suggest that intra-aneurysmal wall shear stress and flow patterns, for example, are candidate parameters in aneurysm stability assessment. These factors can be estimated if the 3D patient-specific intra-aneurysmal velocity is known, which can be obtained via a combination of in vivo measurements and computational fluid dynamics models. The main determinants of the velocity field are the vascular geometry and flow through this geometry. Over the last decade the extraction of the vascular geometry has become well established. More recently, there has been a shift of attention towards extracting boundary conditions for the 3D vascular segment of interest. The aim of this research is to improve the reliability of the model-based representation of the velocity field in the aneurysmal sac. To this end, a protocol is proposed such that patient-specific boundary conditions for the 3D segment of interest can be estimated without the need for added invasive procedures. This is facilitated by a 1D wave propagation model based on patient-specific geometry and boundary conditions measured non-invasively in more accessible regions. Such a protocol offers improved statistical reliability owing to the increased number of patients that can participate in studies aiming to identify parameters of interest in aneurysm stability assessment. In chapter 2 the intra-aneurysmal velocity field in an idealised aneurysm model is validated with particle image velocimetry experiments, after which the flow patterns are evaluated using a vortex identification method. Chapter 3 describes a 1D model wave propagation model of the cerebral circulation with a patient-specific vascular geometry. The resulting flow pulses at the boundaries of the 3D segment of interest are compared to those obtained with a patient-generic geometry. The influence of these different boundary conditions on the 3D intra-aneurysmal velocity field is evaluated in chapter 4 by prescribing the end-diastolic flows extracted from the 1D models. In order to measure blood flow with videodensitometric methods, an injection of contrast agent is required. The effect of this injection on the flow of interest is assessed in chapter 5. In chapter 6, pressure measurements in the internal carotid are used to evaluate the variability of pressure waveform and its effect on the boundary conditions for the 1D model. Finally, a protocol for full patient-specific modelling is discussed in chapter 7

Subarachnoid Haemorrhage: epidemiological studies on aetiology and outcome

Subarachnoid haemorrhage (SAH) is bleeding into the subarachnoid space ‒ the area between the arachnoid membrane and the pia mater surrounding the brain. SAH occurs spontaneously or can be caused by traumatic injury of the head. Spontaneous SAH is caused by rupture of an intracranial aneurysm in 85 percent of cases. In this thesis we consider both spontaneous SAH in general and in several studies aneurysmal SAH specifi cally. Reliable knowledge about the risks of (aneurysmal) SAH in diff erent populations will help in planning, screening and prevention strategies and in predicting the prognosis of individual patients. The overall incidence of SAH is in general between 5 and 10 per 100,000 person years. However, in Japan and Finland rates are as high as 20 per 100,000 person years. This can partly be explained by genetic and environmental diff erences between these and other countries. The incidence increases with age; and from midlife onwards incidence is higher in women than in men. The reasons for this higher incidence in women are not clear, but hormonal factors (including hormonal medication) have been suggested as a possible explanation

Morphodynamic analysis of cerebral aneurysm pulsation from time-resolved rotational angiography

This paper presents a technique to estimate and model patient-specific pulsatility of cerebral aneurysms over one/ncardiac cycle, using 3D rotational X-ray angiography (3DRA) acquisitions. Aneurysm pulsation is modeled as a time varying/n-spline tensor field representing the deformation applied to a reference volume image, thus producing the instantaneous/nmorphology at each time point in the cardiac cycle. The estimated deformation is obtained by matching multiple simulated projections of the deforming volume to their corresponding original projections. A weighting scheme is introduced to account for the relevance of each original projection for the selected time point. The wide coverage of the projections, together with the weighting scheme, ensures motion consistency in all directions. The technique has been tested on digital and physical phantoms that are realistic and clinically relevant in terms of geometry, pulsation and imaging conditions. Results from digital phantom/nexperiments demonstrate that the proposed technique is able to recover subvoxel pulsation with an error lower than 10% of the maximum pulsation in most cases. The experiments with the physical phantom allowed demonstrating the feasibility of pulsation estimation as well as identifying different pulsation regions under clinical conditions.This work was supported in part by Philips Healthcare, Best, The Netherlands, in part by/nthe CENIT-CDTEAM grant funded by the Spanish Ministry Of Science and Innovation (MICINN-CDTI), and partially generated in the framework of the/n@neurIST Integrated Project, which is co-financed by the European Commission (IST-027703)

Morphodynamic analysis of cerebral aneurysm pulsation from time-resolved rotational angiography

This paper presents a technique to estimate and model patient-specific pulsatility of cerebral aneurysms over one/ncardiac cycle, using 3D rotational X-ray angiography (3DRA) acquisitions. Aneurysm pulsation is modeled as a time varying/n-spline tensor field representing the deformation applied to a reference volume image, thus producing the instantaneous/nmorphology at each time point in the cardiac cycle. The estimated deformation is obtained by matching multiple simulated projections of the deforming volume to their corresponding original projections. A weighting scheme is introduced to account for the relevance of each original projection for the selected time point. The wide coverage of the projections, together with the weighting scheme, ensures motion consistency in all directions. The technique has been tested on digital and physical phantoms that are realistic and clinically relevant in terms of geometry, pulsation and imaging conditions. Results from digital phantom/nexperiments demonstrate that the proposed technique is able to recover subvoxel pulsation with an error lower than 10% of the maximum pulsation in most cases. The experiments with the physical phantom allowed demonstrating the feasibility of pulsation estimation as well as identifying different pulsation regions under clinical conditions.This work was supported in part by Philips Healthcare, Best, The Netherlands, in part by/nthe CENIT-CDTEAM grant funded by the Spanish Ministry Of Science and Innovation (MICINN-CDTI), and partially generated in the framework of the/n@neurIST Integrated Project, which is co-financed by the European Commission (IST-027703)