Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis.

Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery or sham surgery (n = 2 ligated, n = 2 sham). Flow was measured by transcranial Doppler ultrasonography, vessel geometry was determined by 3D angiography, and hemodynamics were quantified by computational fluid dynamics. 24 h post-surgery, the basilar artery and terminus were embedded for sectioning. Intima and media were separately microdissected from the sections, and whole transcriptomes were obtained by RNA-seq. Correlation analysis of expression across all possible intima-media gene pairs revealed potential remodeling signals. Carotid ligation increased flow in the basilar artery and terminus and caused differential expression of 194 intimal genes and 529 medial genes. 29,777 intima-media gene pairs exhibited correlated expression. 18 intimal genes had > 200 medial correlates and coded for extracellular products. Gene ontology of the medial correlates showed enrichment of organonitrogen metabolism, leukocyte activation/immune response, and secretion/exocytosis processes. This demonstrates correlative expression analysis of intimal and medial genes can reveal novel signals that may regulate flow-induced arterial remodeling.

Design and Physical Properties of 3-Dimensional Printed Models Used for Neurointervention: A Systematic Review of the Literature.

BACKGROUND: Three-dimensional (3D) printing has revolutionized training, education, and device testing. Understanding the design and physical properties of 3D-printed models is important. OBJECTIVE: To systematically review the design, physical properties, accuracy, and experimental outcomes of 3D-printed vascular models used in neurointervention. METHODS: We conducted a systematic review of the literature between January 1, 2000 and September 30, 2018. Public/Publisher MEDLINE (PubMed), Web of Science, Compendex, Cochrane, and Inspec databases were searched using Medical Subject Heading terms for design and physical attributes of 3D-printed models for neurointervention. Information on design and physical properties like compliance, lubricity, flow system, accuracy, and outcome measures were collected. RESULTS: A total of 23 articles were included. Nine studies described 3D-printed models for stroke intervention. Tango Plus (Stratasys) was the most common material used to develop these models. Four studies described a population-representative geometry model. All other studies reported patient-specific vascular geometry. Eight studies reported complete reconstruction of the circle of Willis, anterior, and posterior circulation. Four studies reported a model with extracranial vasculature. One prototype study reported compliance and lubricity. Reported circulation systems included manual flushing, programmable pistons, peristaltic, and pulsatile pumps. Outcomes included thrombolysis in cerebral infarction, post-thrombectomy flow restoration, surgical performance, and qualitative feedback. CONCLUSION: Variations exist in the material, design, and extent of reconstruction of vasculature of 3D-printed models. There is a need for objective characterization of 3D-printed vascular models. We propose the development of population representative 3D-printed models for skill improvement or device testing.

9.4T Magnetic Resonance Imaging of the Mouse Circle of Willis Enables Serial Characterization of Flow-Induced Vascular Remodeling by Computational Fluid Dynamics.

BACKGROUND: The neurovasculature dynamically responds to changes in cerebral blood flow by vascular remodeling processes. Serial imaging studies in mouse models could help characterize pathologic and physiologic flow-induced remodeling of the Circle of Willis (CoW). METHOD: We induced flow-driven pathologic cerebral vascular remodeling in the CoW of mice (n=3) by ligation of the left Common Carotid Artery (CCA), and the right external carotid and pterygopalatine arteries, increasing blood flow through the basilar and the right internal carotid arteries. One additional mouse was used as a wild-type control. Magnetic Resonance Imaging (MRI) at 9.4 Tesla (T) was used to serially image the mouse CoW over three months, and to obtain threedimensional images for use in Computational Fluid Dynamic (CFD) simulations. Terminal vascular corrosion casting and scanning electron microscope imaging were used to identify regions of macroscopic and microscopic arterial damage. RESULTS: We demonstrated the feasibility of detecting and serially measuring pathologic cerebral vascular changes in the mouse CoW, specifically in the anterior vasculature. These changes were characterized by bulging and increased vessel tortuosity on the anterior cerebral artery and aneurysm- like remodeling at the right olfactory artery origin. The resolution of the 9.4T system further allowed us to perform CFD simulations in the anterior CoW, which showed a correlation between elevated wall shear stress and pathological vascular changes. CONCLUSION: In the future, serial high-resolution MRI could be useful for characterizing the flow environments corresponding to other pathologic remodeling processes in the mouse CoW, such as aneurysm formation, subarachnoid hemorrhage, and ischemia.