External validation of cerebral aneurysm rupture probability model with data from two patient cohorts

Detmer, Felicitas J.; Fajardo, Daniel; Mut, Fernando; Juchler, Norman; Hirsch, Sven; Pereira, Vítor Mendes; Bijlenga, Philippe; Cebral, Juan R.

doi:10.1007/s00701-018-3712-8

Cited by 12 publications

(14 citation statements)

References 39 publications

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“…conditions needed for the flow simulations are determined reasonably (see separate reviews on this topic in this issue). Although several studies have demonstrated how CFD can be used to differentiate ruptured and unruptured IAs with reasonable accuracy 18 (as well as separate publications on the topic in this issue), from the biological point of view it is worth noting that many human IA walls have regions that have completely lost the endothelium. 27 This will significantly impair the normal mechanobiological coupling between flow and wall remodeling, 10,48 and raises questions as to whether such an IA wall is sensitive to flow-induced remodeling at all.…”

Section: Figmentioning

confidence: 99%

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms

Frösén

Cebral

Robertson

et al. 2019

Neurosurgical Focus

215

162

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OBJECTIVEUnruptured intracranial aneurysms (UIAs) are relatively common lesions that may cause devastating intracranial hemorrhage, thus producing considerable suffering and anxiety in those affected by the disease or an increased likelihood of developing it. Advances in the knowledge of the pathobiology behind intracranial aneurysm (IA) formation, progression, and rupture have led to preclinical testing of drug therapies that would prevent IA formation or progression. In parallel, novel biologically based diagnostic tools to estimate rupture risk are approaching clinical use. Arterial wall remodeling, triggered by flow and intramural stresses and mediated by inflammation, is relevant to both.METHODSThis review discusses the basis of flow-driven vessel remodeling and translates that knowledge to the observations made on the mechanisms of IA initiation and progression on studies using animal models of induced IA formation, study of human IA tissue samples, and study of patient-derived computational fluid dynamics models.RESULTSBlood flow conditions leading to high wall shear stress (WSS) activate proinflammatory signaling in endothelial cells that recruits macrophages to the site exposed to high WSS, especially through macrophage chemoattractant protein 1 (MCP1). This macrophage infiltration leads to protease expression, which disrupts the internal elastic lamina and collagen matrix, leading to focal outward bulging of the wall and IA initiation. For the IA to grow, collagen remodeling and smooth muscle cell (SMC) proliferation are essential, because the fact that collagen does not distend much prevents the passive dilation of a focal weakness to a sizable IA. Chronic macrophage infiltration of the IA wall promotes this SMC-mediated growth and is a potential target for drug therapy. Once the IA wall grows, it is subjected to changes in wall tension and flow conditions as a result of the change in geometry and has to remodel accordingly to avoid rupture. Flow affects this remodeling process.CONCLUSIONSFlow triggers an inflammatory reaction that predisposes the arterial wall to IA initiation and growth and affects the associated remodeling of the UIA wall. This chronic inflammation is a putative target for drug therapy that would stabilize UIAs or prevent UIA formation. Moreover, once this coupling between IA wall remodeling and flow is understood, data from patient-specific flow models can be gathered as part of the diagnostic workup and utilized to improve risk assessment for UIA initiation, progression, and eventual rupture.

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Section: Figmentioning

confidence: 99%

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms

Frösén

Cebral

Robertson

et al. 2019

Neurosurgical Focus

215

162

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“…The US data were collected from hospitals mainly in the US and consist of 1631 aneurysms in 1061 patients. Details of the data set can be found in Detmer et al 6 The two European cohorts consist of a total of 249 aneurysms in 203 patients and were composed of the AneuX data set and the publicly available AneuRisk data set (see Detmer et al 7 for details). The Finnish data set consists of 102 IAs in 71 patients treated at Kuopio University Hospital.…”

Section: Patient and Image Datamentioning

confidence: 99%

“…When evaluating the model using two external European cohorts, it showed good predictive performance, indicating that it generalizes to patient cohorts other than the one used for model training. 7 The results of several studies have suggested that Finnish and Japanese populations have a higher risk of aneurysmal SAH than other populations. 11,22 Comparison of aneurysm-related and patient-related characteristics between these two high-risk aneurysm populations and other aneurysm patient populations may provide insight into what causes the higher risk of aneurysmal SAH in the Finnish and Japanese.…”

mentioning

confidence: 99%

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Extending statistical learning for aneurysm rupture assessment to Finnish and Japanese populations using morphology, hemodynamics, and patient characteristics

Detmer¹,

Hadad²,

Chung

et al. 2019

Neurosurgical Focus

Self Cite

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OBJECTIVEIncidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors’ goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data.METHODSPatient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm’s shape and hemodynamics. Next, the previously developed model’s discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data.RESULTSThe US model’s AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10.CONCLUSIONSDeveloping an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

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“…A very recent study in cerebral aneurysms showed adverse morphology and hemodynamics to be related to aneurysm rupture 22 . The corresponding statistical model of rupture probability was then successfully validated 23 . These results combined with our findings…”

Section: Limitationmentioning

confidence: 99%

A Cohort Longitudinal Study Identifies Morphology and Hemodynamics Predictors of Abdominal Aortic Aneurysm Growth

et al. 2019

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Abdominal aortic aneurysms (AAA) are localized, commonly occurring aortic dilations. Following rupture only immediate treatment can prevent morbidity and mortality. AAA maximal diameter and growth are the current metrics to evaluate the associated risk and plan intervention. Although these criteria alone lack patient specificity, predicting their evolution would improve clinical decision. If the disease is known 1 to be associated with altered morphology and blood flow, intraluminal thrombus deposit and clinical symptoms, the growth mechanisms are yet to be fully understood. In this retrospective longitudinal study of 138 scans, morphological analysis and blood flow simulations for 32 patients with clinically diagnosed AAAs and several follow-up CT-scans, are performed and compared to 9 control subjects. Several metrics stratify patients between healthy, low and high risk groups. Local correlations between hemodynamic metrics and AAA growth are also explored but due to their high inter-patient variability, do not explain AAA heterogeneous growth. Finally, high-risk predictors trained with successively clinical, morphological, hemodynamic and all data, and their link to the AAA evolution are built from supervise learning. Predictive performance is high for morphological, hemodynamic and all data, in contrast to clinical data. The morphology-based predictor exhibits an interesting effort-predictability tradeoff to be validated for clinical translation.

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External validation of cerebral aneurysm rupture probability model with data from two patient cohorts

Cited by 12 publications

References 39 publications

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms

Extending statistical learning for aneurysm rupture assessment to Finnish and Japanese populations using morphology, hemodynamics, and patient characteristics

A Cohort Longitudinal Study Identifies Morphology and Hemodynamics Predictors of Abdominal Aortic Aneurysm Growth

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