1 Application of Doppler Ultrasound to the Study of Intimal Hyperplasia Development Mauro Grigioni 1 , Carla Daniele 1 , Giuseppe D’Avenio 1 , Roberto Formigari 2 , Luigi Ballerini 2 , and Vincenzo Barbaro 1 Abstract - Modern ultrasound techniques enable the real- time measurement of velocity profiles in vivo. Thus, it is becoming possible to correlate reliably endothelium modifications with local haemodynamics alterations. In the present paper, the importance of the wall shear rate (mean value and oscillation) on the development of intima hyperplasia is emphasized using the Moncada model for aterosclerosis as the in vivo experimental theatre. Key words - Ultrasound, intima hyperplasia, wall shear rate I. INTRODUCTION Vessel wall remodeling is one of the principal mechanisms involved in several important vascular diseases (atherosclerosis, intimal hyperplasia (IH), hypertension), found e.g. in aged and prosthetic implanted population. This mechanism represents an adaptive behaviour to pathological states in arterial haemodynamics and several researches suggest that mechanical stimuli such as cyclic strain and flow- derived stresses induce the release of endothelium-derived vasoactive factors. [1-10] To date the development of IH is considered to be correlated with mechanical stretch, flow-induced wall shear stress, lipid metabolism and inflammatory response; there is, however, a general lack of information about the actual local haemodynamics, apart from in-vitro set-ups of limited applicability to the general case. [11-15] Evidences there are about the role of endothelial cells as mechanical receptors in in-vitro experiments and that the shear stress exerted by flowing blood on the endothelial surface (wall shear stress, WSS) affects the morphology of vascular wall and the release of vasoactive substances and growth factors by the wall. It is well known that shear rate or shear stress orients the endothelial cells in the prevailing direction of flowing blood [12], inducing the production of endothelium-derived relaxing factor [13] and prostacyclin [14], and also K+ channels can be activated [15]. Some evidences were found also that the endothelial cells can distinguish between cyclic strain and shear stress to produce autacoids; as an example cyclic strain enhances the production of endothelin-1 [15], whereas its production is found to be suppressed by shear stress [16]. In the past, IH was obtained after endothelium damage produced by means of catheter, but the role of hemodynamics cannot be studied in this way. In this paper we focus on wall shear rate (WSR) changes due to the vasomotor tone modification; since the wall shear stress is equal to the dynamic viscosity of blood multiplied by the WSR, the results can be easily interpreted in terms of WSS. These haemodynamical modifications, that can be correlated with the resulting IH, are produced under pulsatile flow conditions without any endothelium damage. The Moncada model [17] of collar insertion on New Zealand rabbit carotid artery was selected. Vessel flow was studied by means of the DOP1000 real-time Ultrasound profilometer, and the estimation of the WSR at the vessel wall was provided. The altered flow dynamics and distensibility provided by the carotid’s perivascular manipulation elicited a rapid development of IH (14 days) where WSR oscillation were higher. This result confirms the predominant role of the WSR in the physiology and pathology of the vascular endothelium as a mechanical stimulus to endothelium to promote changes in the mass transfer and the production of specific substances (of vasomotor type). II. MATERIALS AND METHODS New Zealand rabbits were selected for the experimental model as in Ref. 18. The haemodynamics of the carotid arteries was chronically altered by means of the insertion of Silastic collars around the vessels, after detachment from the muscular planes. Following the scheme of Ref. 17, the collars were large enough to enable the free expansion of the carotid in their inner space, with a marked deviation from the physiological condition, when the vessel is tethered by the surrounding tissue. In the experiments both rabbit carotid arteries were exposed surgically, and the right carotid artery was enclosed by a non- occlusive, biologically inert Silastic collar of 1.0 cm length and internal diameter of 3.5 mm. The controlateral carotid from the same animal was used as a control (sham-operated control). Carotid artery morphological investigation was performed, before each flow profile acquisition session, by means of Echo Doppler (ESAOTE) with linear probe (7.5 MHz), to allow for the correct positioning of the pulsed Doppler probe, 1. Laboratory of Biomedical Engineering, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy 2. Ospedale “Bambino Gesù”, Roma, Italy 0-7803-6468-6/00/$10.00 (c)2000 IEEE