Louis J. Kim, MD, MBA
Early detection and treatment of aneurysms can prevent hemorrhagic stroke. Developments in understanding the genomics of aneurysm growth and rupture coupled with the development of a minimally invasive endovascular method of obtaining endothelial cells from aneurysms and other healthy blood vessels have opened new avenues for research. Endothelial cell genetics have been proposed to play a critical role in aneurysm formation, growth and rupture. To access these cells for analyses, we have optimized a recently developed minimally-invasive endovascular endothelial cell collection technique to obtain aneurysmal endothelial cells during cerebral angiography. This is important in an era when most aneurysms are treated with endovascular techniques and research has relied on surgical specimens. This novel technique can be used to obtain cells from both aneurysm and healthy tissue samples.
The goal of this research is to build genomic transcriptome profiles of key vascular factors from both aneurysmal and non-pathological tissue. These expression profiles will be compared between low- or high-risk aneurysms (scored using PHASES) in both ruptured and unruptured states. Preliminary results suggest that distinctive transcriptome profiles for individual aneurysms will be obtained, which can be used to identify aneurysms at low- and- high risk of rupture, thus facilitating treatment decisions that are personalized for the individual patient and aneurysm of interest.
- Aim 1: Collect endothelial cells during endovascular treatment of low-risk and high-risk aneurysms (as defined by PHASES score).
- To date, we have collected coils and cells from 15 patients with both unruptured and ruptured aneurysms without any adverse clinical events.
- Aim 2: Perform targeted transcriptome measurement of collected endothelial cells by single-cell RNA sequencing (RNA-Seq).
- Completed for current collected cells.
- Aim 3: Compare the differential profile of key vascular factors of aneurysmal endothelial cells in unruptured, ruptured, low- and high-risk aneurysms.
- In progress.
Edgar A Samaniego MD, MS, FSVIN
This project is a collaborative effort between the Departments of Neurology, Radiology and Neurosurgery. Our group has been working for the last 10 years in aneurysm characterization. We have used different imaging methods and pioneered new techniques to better identify aneurysms that are at risk of rupture. As technology continues to evolve, we have more opportunities to find aneurysms as little as 3 mm. We can study the walls of these aneurysms and identify changes that cause the aneurysm to rupture. The aim of the research that The Bee Foundation has funded is to continue our exploration into high resolution aneurysm wall imaging with 3T and 7T scans. We would like to establish a “Gold Standard” in brain aneurysm imaging. The second part of the research is to correlate that imaging with known predictors of brain aneurysm rupture such as size, morphology and location.
- Determine the best way to quantify aneurysm wall enhancement in HR-VWI.
- Validate 7T vessel wall imaging with 3T.
- Quantify aneurysm wall enhancement in unruptured intracranial aneurysms with HR-VWI.
- Determine characteristics of aneurysm instability.
We have determined the best way to measure signal intensity (SI) as a surrogate marker of aneurysm inflammation in 7T and applied this to subject with 3T imaging. Next we have adopted a standard method and quantification of SI. As a result of this experience we were able to analyze 96unruptured intracranial aneurysms and determine that the use of aspirin is related to decreased SI. This addressed Aims 1, 2, & 3. In addition to working on Aim 4, we are refining the methodology and coding of a software that will allow semi-automated quantification of SI. This is a pivotal step in using SI as a surrogate biomarker of aneurysm instability and risk of rupture.