3-D Electrochemical Impedance Spectroscopy Mapping of Arteries to Detect Metabolically Active but Angiographically Invisible Atherosclerotic Lesions

We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120° were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (Ω). By virtue of the distinctive impedimetric signature of metabolically active atherosclerotic lesions, a detailed impedance map was acquired, with the 15 EIS permutations uncovering early stages of disease characterized by fatty streak lipid accumulation in the New Zealand White rabbit model of atherosclerosis. Both the equivalent circuit and statistical analyses corroborated the 3-D EIS permutations to detect small, angiographically invisible, lipid-rich lesions, with translational implications for early atherosclerotic disease detection and prevention of acute coronary syndromes or strokes

Three-Dimensional Impedance Tomographic Mapping of Metabolically Active Endolumen

Real-time detection of vulnerable atherosclerotic lesions, characterized by a high content of oxidized low-density lipoprotein (oxLDL)-laden macrophages or foam cells, remains an unmet clinical need. While fractional flow reserve (FFR)-guided revascularization in angiographically intermediate stenoses is utilized to assess hemodynamic significance, in vivo detection of oxLDL-rich plaques may provide a new paradigm for treating metabolically unstable lesions. Herein, we have demonstrated endoluminal mapping of lipid-laden lesions using 3-D electrical impedance spectroscopy-derived impedance tomography (EIT) in a pre-clinical swine model. We performed surgical banding of the right carotid arteries of Yucatan mini-pigs, followed by 16 weeks of high-fat diet, to promote the development of lipid-rich lesions. We implemented an intravascular sensor combining an FFR pressure transducer with a 6-point micro-electrode array for electrical impedance spectroscopy (EIS) measurements. 3-D EIT mapping was achieved using an EIS-based reconstruction algorithm. We demonstrated that EIT mapping corresponds to endoluminal histology for oxLDL-laden lesions. We further used computational models to theoretically predict and validate EIS measurements. Thus, our 3-D EIS-derived EIT provides in vivo detection of metabolically active plaques with the goal of guiding optimal intravascular intervention

Intravascular Ultrasound

Intravascular ultrasound (IVUS) is a cardiovascular imaging technology using a specially designed catheter with a miniaturized ultrasound probe for the assessment of vascular anatomy with detailed visualization of arterial layers. Over the past two decades, this technology has developed into an indispensable tool for research and clinical practice in cardiovascular medicine, offering the opportunity to gather diagnostic information about the process of atherosclerosis in vivo, and to directly observe the effects of various interventions on the plaque and arterial wall. This book aims to give a comprehensive overview of this rapidly evolving technique from basic principles and instrumentation to research and clinical applications with future perspectives

Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques

Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 µm in diameter and separated by 400 µm was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy

Development of a Focused Broadband Ultrasonic Transducer for High Resolution Fundamental and Harmonic Intravascular Imaging

Intravascular ultrasound (IVUS) is increasingly employed for detection and evaluation of coronary artery diseases. Tissue Harmonic Imaging provides different tissue information that could additionally be used to improve diagnostic accuracy. However, current IVUS systems, with their unfocussed transducers, may not be capable of operating in harmonic imaging mode. Thus, there is a need to develop suitable transducers and appropriate techniques to allow imaging in multi modes for complementary diagnostic information. Focused PVDF TrFE transducers were developed using MEMS (Micro-Electro-Mechanical-Systems) compatible protocols. The transducers were characterized using pulse-echo techniques and exhibited broad bandwidth (110 at -6dB) with axial resolutions of Such promising results suggest that focused, broadband PVDF TrFE transducers have opened up the potential to incorporate harmonic imaging modality in IVUS and also improve the image quality. In addition, the transducer\u27s multimodality imaging capability, not possible with the current systems, could enhance the functionality and thereby the clinical use of IVU

Development of a Focused Broadband Ultrasonic Transducer for High Resolution Fundamental and Harmonic Intravascular Imaging

Intravascular ultrasound (IVUS) is increasingly employed for detection and evaluation of coronary artery diseases. Tissue Harmonic Imaging provides different tissue information that could additionally be used to improve diagnostic accuracy. However, current IVUS systems, with their unfocussed transducers, may not be capable of operating in harmonic imaging mode. Thus, there is a need to develop suitable transducers and appropriate techniques to allow imaging in multi modes for complementary diagnostic information. Focused PVDF TrFE transducers were developed using MEMS (Micro-Electro-Mechanical-Systems) compatible protocols. The transducers were characterized using pulse-echo techniques and exhibited broad bandwidth (110 at -6dB) with axial resolutions of Such promising results suggest that focused, broadband PVDF TrFE transducers have opened up the potential to incorporate harmonic imaging modality in IVUS and also improve the image quality. In addition, the transducer\u27s multimodality imaging capability, not possible with the current systems, could enhance the functionality and thereby the clinical use of IVU