Shape as Biomarker for Aneurysm Disease
Intracranial aneurisms are weak spots on blood vessels in the brain that balloon out and fill with blood. They are mostly quiescent and asymptomatic, but potentially lethal. There is currently no tool available to help predict aneurysm development or treatment outcomes. The scientists involved in AneuX aim to change this by using shape as a biomarker for aneurysm diagnosis.
Aneurysm is a disease of the vessel wall resulting in the deformation and enlargement of the vascular lumen. If the process of deformation remains active, the vessel wall may either: rupture and produce a hemorrhage, or thrombosis and ischemia may occur. All vessels may be affected but systemic and intracranial aneurysms are separate entities with a different epidemiology, underlying causes and management.
The Project AneuX focuses entirely on intracranial aneurysms. The occurrence of the disease is high, with three percent of the population affected. Although intracranial aneurysms are mostly benign, a rupture is likely to cause severe brain damage or death, resulting in a high socio-economic impact. An increasing number of patients are incidentally diagnosed with asymptomatic aneurysms. Most of these remain stable, but the criteria used to recommend intervention are controversial. Despite the increasing quality of imaging data, physicians still lack the adequate tools for safe decision making and for balancing benefits and risks at the individual level.
The objective of this project is to test the hypothesis that aneurysm 3D-shape can be used as proxy for disease status, and provide tools that properly quantify and analyze 3D-shape to the medical community. Such tools will improve the disease progression prediction and clinical decision making.
Developing a predictive tool
The AneuX Project’s starting point is the hypothesis that aneurysm 3D-shape can be used as an image biomarker. The involved partners follow a dual strategy centered on shape characterization:
- The biological track integrates the basic biological findings of mechano-biological transduction into a vessel-remodeling simulator. The simulations are validated with an experimental animal model of growing aneurysms.
- The clinical track collects and organises clinical evidence, using machine-learning techniques to consider shape descriptors.
Combined, these approaches will improve both the prediction of disease progression and clinical decision-making. The goal is to generate an integrated mathematical model able to predict disease trajectory and treatment outcomes, which will be validated in a subsequent clinical trial.
The main tasks of AneuX are divided in five subprojects and involve:
- Collection and integration of quantitative datasets in a single information “observatory” including: a) clinical observations, treatments and outcomes, b) millimetric and submillimetric scale 3D imaging in humans and animals, c) immune-histopathological human and animal microscopic explorations of the vessel wall and aneurysm domes, d) information about cellular behavior according to wall shear stress and circumferential wall tension measured in vitro e) analysis of molecular biomarkers and biochemical networks in vessel wall tissue and blood.
- Performing data-driven patterns analysis using all available datasets to identify predictive signature for aneurysm growth and rupture. Predictive power of the latest developed clinical score to predict aneurysm rupture will be tested. A clinical trial will be designed to test the predictive power of the disease model resulting from the project.
- The generation of an integrated mathematical model predicting disease trajectory and treatment outcome.