A brain aneurysm is a localized bulge or ballooning that forms in a blood vessel within the brain due to a weakened area in the vessel wall. An aneurysm poses a significant health risk because its rupture causes a Subarachnoid Hemorrhage (SAH), a type of stroke that is frequently fatal or causes long-term neurological disability. Early detection before rupture allows for monitoring or preventative treatment, which substantially reduces this catastrophic risk. However, a simple, routine blood test is not yet available to screen for an unruptured brain aneurysm.
Current Diagnostic Imaging Methods
Detecting a brain aneurysm relies on visualizing this structural defect, which requires specialized imaging techniques. Digital Subtraction Angiography (DSA) remains the benchmark for aneurysm diagnosis, offering the highest resolution and detail of the cerebral vasculature. This invasive method involves inserting a catheter into an artery, usually in the groin, and threading it up to the brain’s blood vessels to inject a contrast agent. Due to associated risks, such as minor stroke or arterial injury, DSA is typically reserved for confirming a diagnosis or planning treatment.
Computed Tomography Angiography (CTA) is a less invasive and faster alternative, utilizing X-rays and an injected contrast dye to generate detailed three-dimensional images of the blood vessels. CTA is often the preferred initial test in emergency settings, as it quickly provides the necessary clarity to detect aneurysms generally larger than three millimeters. Magnetic Resonance Angiography (MRA) is a non-invasive technique that uses magnetic fields and radio waves, avoiding the use of radiation and often contrast dye, which makes it suitable for repeated screening and monitoring of at-risk patients. Both CTA and MRA have high sensitivity and specificity, with CTA showing a slight diagnostic edge for some aneurysms.
The Search for Specific Aneurysm Biomarkers
The scientific community is actively searching for blood-based biomarkers that could signal the presence of an unruptured aneurysm, thereby offering a non-invasive screening tool. These markers fall into categories such as inflammatory proteins, molecules related to vessel wall degradation, and circulating nucleic acids.
One focus is on Matrix Metalloproteinases (MMPs), particularly MMP-2 and MMP-9, which are enzymes that break down the collagen and elastin that give the arterial wall its strength. Increased expression of MMPs has been observed in the tissue of aneurysm walls, leading to degradation. However, studies have shown that while MMP levels are highly elevated locally at the site of the aneurysm, the systemic plasma activity of MMP-9 does not significantly increase in the bloodstream of patients with unruptured aneurysms compared to healthy controls. This finding illustrates the challenge of detecting a localized structural defect from a peripheral blood sample.
Researchers are also exploring circulating microRNAs (miRNAs), small molecules that regulate gene expression and are shed into the blood by damaged cells. Specific microRNAs, such as miR-16 and miR-25, have been found to be differentially expressed in the plasma of patients with unruptured aneurysms. This suggests that changes in vascular cell function associated with aneurysm formation may be detectable through these circulating genetic fragments. Furthermore, proteomics analysis has identified specific protein candidates, such as the glycoprotein ORM1, that are significantly upregulated in the serum of unruptured aneurysm patients, offering another potential diagnostic target.
Blood Testing in Acute Rupture Situations
While blood tests cannot currently screen for an unruptured aneurysm, they play a procedural role in managing a patient after a suspected rupture has occurred. When a brain aneurysm bursts, the resulting subarachnoid hemorrhage (SAH) triggers a widespread systemic and neurological reaction. Standard blood tests are immediately utilized to assess the patient’s general health and manage complications.
These laboratory studies are used to assess general health and monitor systemic effects. They include:
- A complete blood count (CBC)
- Coagulation tests, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT)
- Comprehensive serum chemistries to monitor electrolyte balance, blood sugar levels, and liver function
If initial brain imaging is inconclusive for SAH, a lumbar puncture may be performed to analyze the Cerebrospinal Fluid (CSF). The presence of xanthochromia, the yellow discoloration caused by the breakdown products of blood, confirms that a hemorrhage has occurred.
Research Directions for Non-Invasive Screening
Future non-invasive screening focuses on combining advanced molecular analysis with computational power to develop risk-stratification tools. Genetic screening is a primary direction, as seven to 20 percent of brain aneurysms occur in individuals with a family history. Specific genetic syndromes, such as Polycystic Kidney Disease (PKD), carry a seven-fold increased risk of aneurysm development.
Large-scale genetic studies, using whole-genome sequencing, identify specific genetic variants that predispose individuals to aneurysm formation. This research aims to create a comprehensive genetic risk model that could identify high-risk individuals who would benefit most from ongoing imaging surveillance. In parallel, advanced proteomics and metabolomics are leveraging machine learning and Artificial Intelligence (AI) to analyze complex panels of molecules in a blood sample.
One study used an eight-protein model developed through high-throughput proteomics to predict aneurysm rupture risk with an accuracy exceeding 91 percent. This approach moves beyond single markers, using a combination of proteins to create a profile reflecting the underlying vascular disease. The integration of these advanced molecular panels with AI algorithms offers a promising path toward a future blood test capable of identifying the presence and assessing the rupture risk of an unruptured brain aneurysm.