3-Dimensional electrical impedance spectroscopy for in situ endoluminal mapping of metabolically active plaques

Abstract

Electrical impedance spectroscopy (EIS) has been recognized to characterize oxidized low-density lipoprotein (oxLDL) in the metabolically active plaque. However, intravascular deployment of 3-D EIS-derived electrical impedance tomography (EIT) for endoluminal mapping of oxLDL-laden arterial walls remains an unmet clinical challenge. To this end, we designed the 6-point microelectrode arrays that were circumferentially configurated onto the balloon catheter for 15 intravascular EIS permutations. In parallel, we created the metabolically active plaques by performing partial ligation of right carotid artery in Yorkshire mini-pigs (n = 6 males), followed by demonstrating the plaque progression at baseline, 8 weeks, and 16 weeks of high-fat diet via computed tomography (CT) angiogram. Next, we deployed the 3-D EIS sensors to the right and left carotid arteries, and we demonstrated 3-D EIS mapping of metabolically active endolumen in the right but not left carotid arteries as evidenced by the positive E06 immunostaining for oxLDL-laden regions. By considering electrical conductivity (σ) and permittivity (ε) properties of collagen, lipid, and smooth muscle presence in the arterial wall, we further validated the 3-D EIS-derived EIT by reconstructing the histology of right and left carotid arteries for the finite element modeling of the oxLDL-laden endolumen, and we accurately predicted 3-D EIS mapping. Thus, we establish the capability of 3-D EIS-derived EIT to detect oxLDL-laden arterial walls with translational implication to predict metabolically active plaques prone to acute coronary syndromes or stroke.

Machine learning‐directed electrical impedance tomography to predict metabolically vulnerable plaques

“…Materials used in our EIS catheter, such as PtB, gold, polyimide (PI), and silicone, have all been found by previous studies to be safe for in vivo applications 20–23 . No adverse responses were observed in this study, and to the best of our knowledge, no immunogenic responses were reported in prior literature that tested similarly constructed EIS devices in vivo on animal models 24–27 . Despite the promising outlook of the materials implemented in our catheter, approval by the Food and Drug Administration (FDA) is still required to proceed with Phase I clinical study of our device 28 …”

“…Lastly, we were able to show similarities in impedimetric properties between the atherosclerotic components of pigs and that of ex vivo human arteries, whereas previous studies have largely been limited to animal models. [24][25][26][27] Thus, our study adds to the translational potential of intravascular EIS, paving the way towards its clinical application to predict plaque rupture in patients, in real time.…”

“…Copper (Cu) wires were also embedded within the PI substrate to establish a direct connection to the electrochemical workstation. By increasing the surface roughness of the electrodes at the nanoscopic level, electroplating serves to reduce the parasitic impedance at the low‐frequency regime (Figure 4e), which is primarily driven by the diffusion of ions at the electrode–tissue interface 27,31 . This phenomenon is known as the electrochemical double layer (Figure S7), and its impedimetric effects are modeled by Randle's equivalent circuit (Figure 4f).…”

“…[20][21][22][23] No adverse responses were observed in this study, and to the best of our knowledge, no immunogenic responses were reported in prior literature that tested similarly constructed EIS devices in vivo on animal models. [24][25][26][27] Despite the promising outlook of the materials implemented in our catheter, approval by the Food and Drug Administration (FDA) is still required to proceed with Phase I clinical study of our device. 28 It is also important to note that only male Yucatan mini-pigs were available during the time of experimentation.…”

A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy

“…Advances in vascular catheter-based deployment allow for implantation of biomedical devices such as arterial stents and bioprosthetic valves. Through a percutaneous incision to the femoral or radial arteries, catheter-based deployment obviates the need for thoracotomy for cardiac bypass surgery or valve replacement (30)(31)(32) and shortens recovery times and hospital stay (33)(34)(35)(36). Recently, artificial stent and electric blood vessels enable a small and implantable endovascular device for targeted control for localized therapy (37,38).…”