Detecting Growth of Intracranial Aneurysms Using Non-Invasive Photon Counting CT in a Murine Model.

Abstract: Unruptured intracranial aneurysms (UIAs), particularly those between 3-7 mm in diameter, present significant clinical challenges due to their potential for growth and rupture. Early and accurate detection is critical for effective management, as current invasive interventions carry substantial risks and costs. Emerging evidence suggests that Aspirin (ASA) may be a viable, cost-effective alternative for mitigating the growth and rupture of UIAs, with its effectiveness varying by sex due to differences in enzymatic activity related to ASA metabolism. This project aims to leverage recent advances in Photon Counting CT (PCCT) imaging to enhance our understanding and treatment of UIAs in mouse models, addressing the critical need for noninvasive imaging techniques. In Aim 1, we will establish optimized PCCT protocols for mouse brain imaging using both blood pool and conventional contrast agents and focusing on achieving high-resolution, detailed visualization of cerebral arteries and aneurysm morphology. By optimizing parameters such as X-ray dose, detector settings, and image reconstruction algorithms, we aim to provide the best possible image quality for this challenging task. Aim 2 involves validating PCCT imaging (both in vivo and ex vivo) against histological analysis in the same subjects to ensure accurate multimodal characterization of UIAs. Direct comparison of imaging findings with actual tissue morphology will confirm the reliability of PCCT imaging and establish it as a non-invasive alternative for monitoring UIA growth. In Aim 3, we will conduct longitudinal PCCT studies to assess the efficacy of ASA in slowing UIA growth and maintaining wall integrity in male and female animal models. This aim will provide insights into sex-specific vulnerabilities and the differential effects of ASA treatment on UIAs. The expected outcomes include establishing PCCT as a reliable, non-invasive method for early detection, accurate characterization, and effective monitoring of UIAs. Additionally, this research will elucidate the sex-specific therapeutic effects of ASA, paving the way for personalized treatment strategies and reducing reliance on invasive procedures. By integrating cutting-edge imaging technology with advanced therapeutic approaches, this project has the potential to transform the management of UIAs and significantly improve patient outcomes. Furthermore, the innovative application of PCCT imaging in preclinical models will set new standards for non-invasive vascular imaging, offering unprecedented resolution and contrast for detailed cerebrovascular studies.