X-ray dark-field imaging of carotid hemodynamics enhanced by anisotropic IONP

__________________________________________________________________________________ Abstract Cerebrovascular disease (CVD) ranks 5th in the major causes of death and disability in the US. Along with plaque analysis in morphology and intra-plaque conditions, imaging-based hemodynamic analysis, e.g., wall shear (WS) rate, WS stress, and WS oscillation at the carotid bifurcation is of clinical relevance, especially in predicting plaque vulnerability, selecting patient for intervention (endarterectomy/stenting), and assessing therapeutic efficacy. Pulsed wave Doppler ultrasound and phase-encoded flow-sensitive 4D MRI are finding the clinical utility in correlating vascular pathologies with hemodynamic features, though still a few challenges must be overcome. Via time-density profiling-based analysis, digital subtraction angiography (DSA) under intra-arterial (IA) administration of contrast agents may provide subjective and semiquantitative information on the hemodynamics but cannot support analysis of WS rate, WSS and WS oscillation. We have been developing grating-based interferometric X-ray imaging, a novel modality that is reaching the scale for clinical applications, in which the dark-field (D-F) signal generated by micro/nano particles can be substantially larger than its conventional attenuation-based counterpart. We recently discovered that the D-F signal rising from the micro/nano particle contrast agents that have anisotropic shapes, such as iron oxide nanorods (IONR), varies substantially over the particles’ orientation. Notably, the rod-shaped particles may streamline, marginalize, or tumble in vascular flow and thus alter their orientation. These two phenomena drive us to explore the possibility that, if administered intravenously (IV) as contrast agent, the rod-shaped nanoparticles may generate X-ray D-F contrast that is strong enough to image the flow patterns (zones) in the carotid artery, which can support quantitative characterization of hemodynamic features, such as WS stress and WS oscillation for clinical CVD management. In this project, we propose two Aims: (1a) Optimize IONR’s morphology via simulation to maximize its D-F signal and orientational variation, (1b) Optimize aXRDF method’s temporal resolution for dynamic imaging of complex flow patterns/zones, (2a) Demonstrate the aXRDF method’s capability of imaging complex flow in dynamic stenotic flow phantom, and (2b) Verify the aXRDF method’s feasibility of imaging complex carotid flow patterns/zones in animal study. Project Number: 1R21NS142639-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Xiangyang Tang | Institution: EMORY UNIVERSITY, ATLANTA, GA | Award Amount: $430,375 | Activity Code: R21 | Study Section: Imaging Technology Development Study Section[ITD] View on NIH RePORTER: https://reporter.nih.gov/project-details/11374249