Skip to main content
SpringerLink
Log in

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

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Bourantas, C. V., H. M. Garcia-Garcia, K. K. Naka, A. Sakellarios, L. Athanasiou, D. I. Fotiadis, L. K. Michalis, and P. W. Serruys. Hybrid intravascular imaging: current applications and prospective potential in the study of coronary atherosclerosis. J. Am. Coll. Cardiol. 61:1369–1378, 2013.

    Article  PubMed  Google Scholar 

  2. Brown, M. B., and A. B. Forsythe. Robust tests for equality of variances. J. Am. Stat. Assoc. 69:364–367, 1974.

    Article  Google Scholar 

  3. Brown, M. S., and J. L. Goldstein. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu. Rev. Biochem. 52:223–261, 1983.

    Article  CAS  PubMed  Google Scholar 

  4. Cao, H., F. Yu, Y. Zhao, N. Scianmarello, J. Lee, W. Dai, N. Jen, T. Beebe, R. Li, R. Ebrahimi, D. S. Chang, F. V. Mody, J. Pacella, Y. C. Tai, and T. Hsiai. Stretchable electrochemical impedance sensors for intravascular detection of lipid-rich lesions in New Zealand White rabbits. Biosens. Bioelectron. 54:610–616, 2014.

    Article  PubMed  Google Scholar 

  5. Castellanos, A., A. Ramos, A. González, N. G. Green, and H. Morgan. Electrohydrodynamics and dielectrophoresis in microsystems: scaling laws. J. Phys. D Appl. Phys. 36:2584–2597, 2003.

    Article  CAS  Google Scholar 

  6. Chang, J.H., Huang, R., Tai Y.C. High-density 256-channel chip integration with flexible parylene pocket. In: IEEE 16th International Conference on Solid-State Sensors, Actuators and Microsystems, 2011, pp. 378–381.

  7. Chang, J.H., Liu Y., Kang D., Tai Y.C. Reliable packaging for parylene-based flexible retinal implant. In: IEEE 17th International Conference on Solid-State Sensors, Actuators and Microsystems, 2013, pp. 2612–2615.

  8. Chinetti-Gbaguidi, G., M. Baron, M. A. Bouhlel, J. Vanhoutte, C. Copin, Y. Sebti, B. Derudas, T. Mayi, G. Bories, A. Tailleux, S. Haulon, C. Zawadzki, B. Jude, and B. Staels. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARgamma and LXRalpha pathways. Circ. Res. 108:985–995, 2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dunnett, C. W. A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50:1096–1121, 1955.

    Article  Google Scholar 

  10. Ebrahimi, A. P. Mechanical properties of normal and diseased cerebrovascular system. J. Vasc. Interv. Neurol. 2:155–162, 2009.

    PubMed  PubMed Central  Google Scholar 

  11. Ehara, S., M. Ueda, T. Naruko, K. Haze, A. Itoh, M. Otsuka, R. Komatsu, T. Matsuo, H. Itabe, T. Takano, Y. Tsukamoto, M. Yoshiyama, K. Takeuchi, J. Yoshikawa, and A. E. Becker. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 103:1955–1960, 2001.

    Article  CAS  PubMed  Google Scholar 

  12. Fakirov, S., M. Evstatiev, and S. Petrovich. Microfibrillar reinforced composites from binary and ternary blends of polyesters and nylon 6. Macromolecules 26:5219–5226, 1993.

    Article  CAS  Google Scholar 

  13. Geselowitz, D. B. An application of electrocardiophic lead theory to impedance plethysmography. IEEE Trans. Bio-Med. Eng. 18:38–41, 1971.

    Article  CAS  Google Scholar 

  14. Grimnes, S., and Ø. G. Martines. Sources of error in tetrapolar impedance measurements on biomaterials and other ionic conductors. Sources of error in tetrapolar impedance measurements on biomaterials and other ionic conductors. J. Phys. D Appl. Phys. 40:9, 2007.

    Article  CAS  Google Scholar 

  15. Jaffer, F. A., C. Vinegoni, M. C. John, E. Aikawa, H. K. Gold, A. V. Finn, V. Ntziachristos, P. Libby, and R. Weissleder. Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis. Circulation 118:1802–1809, 2008.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Koike, T., J. Liang, X. Wang, T. Ichikawa, M. Shiomi, H. Sun, T. Watanabe, G. Liu, and J. Fan. Enhanced aortic atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits expressing lipoprotein lipase. Cardiovasc. Res. 65:524–534, 2005.

    Article  CAS  PubMed  Google Scholar 

  17. Konings, M. K., W. P. Mali, and M. A. Viergever. Development of an intravascular impedance catheter for detection of fatty lesions in arteries. IEEE Trans. Med. Imaging 16:439–446, 1997.

    Article  CAS  PubMed  Google Scholar 

  18. Levene, H. Robust tests for equality of variances. In: Contributions to Probability and Statistics: Essays in Honor of Harold Hotelling, edited by I. Olkin, H. Hotelling. Stanford University Press, 1960, pp. 278–292.

  19. Li, X., T. Ma, J. Tian, P. Han, Q. Zhou, and K. K. Shung. Micromachined PIN-PMN-PT crystal composite transducer for high-frequency intravascular ultrasound (IVUS) imaging. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 61:1171–1178, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Libby, P. Mechanisms of acute coronary syndromes and their implications for therapy. N. Engl. J. Med. 368:2004–2013, 2013.

    Article  CAS  PubMed  Google Scholar 

  21. Libby, P., A. H. Lichtman, and G. K. Hansson. Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity 38:1092–1104, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin, J.C.H., Lam, G., Tai Y.C. Viscoplasticity of parylene-C film at body temperature. In: IEEE 25th International Conference on Micro Electro Mechanical Systems, 2012, pp. 476–479.

  23. Ma, T., M. Yu, J. Li, C. E. Munding, Z. Chen, C. Fei, K. K. Shung, and Q. Zhou. Multi-frequency intravascular ultrasound (IVUS) imaging. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 62:97–107, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ma, T., X. Zhang, C. T. Chiu, R. Chen, K. Kirk Shung, Q. Zhou, and S. Jiao. Systematic study of high-frequency ultrasonic transducer design for laser-scanning photoacoustic ophthalmoscopy. J. Biomed. Opt. 19:16015, 2014.

    Article  PubMed  Google Scholar 

  25. Marcu, L., M. C. Fishbein, J. M. Maarek, and W. S. Grundfest. Discrimination of human coronary artery atherosclerotic lipid-rich lesions by time-resolved laser-induced fluorescence spectroscopy. Arterioscler. Thromb. Vasc. Biol. 21:1244–1250, 2001.

    Article  CAS  PubMed  Google Scholar 

  26. Pelias, M. Z. Classics in arteriosclerosis research: On experimental cholesterin steatosis and its significance in the origin of some pathological processes by N. Anitschkow and S. Chalatow, 1913. Arteriosclerosis. 3:178–182, 1983.

    Article  Google Scholar 

  27. Sevanian, A., J. Hwang, H. Hodis, G. Cazzolato, P. Avogaro, and G. Bittolo-Bon. Contribution of an in vivo oxidized LDL to LDL oxidation and its association with dense LDL subpopulations. Arterioscler. Thromb. Vasc. Biol. 16:784–793, 1996.

    Article  CAS  PubMed  Google Scholar 

  28. Streitner, I., M. Goldhofer, S. Cho, R. Kinscherf, H. Thielecke, M. Borggrefe, T. Suselbeck, and F. Streitner. Cellular imaging of human atherosclerotic lesions by intravascular electric impedance spectroscopy. PLoS ONE 7:e35405, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Streitner, I., M. Goldhofer, S. Cho, H. Thielecke, R. Kinscherf, F. Streitner, J. Metz, K. K. Haase, M. Borggrefe, and T. Suselbeck. Electric impedance spectroscopy of human atherosclerotic lesions. Atherosclerosis. 206:464–468, 2009.

    Article  CAS  PubMed  Google Scholar 

  30. Suselbeck, T., H. Thielecke, J. Kochlin, S. Cho, I. Weinschenk, J. Metz, M. Borggrefe, and K. K. Haase. Intravascular electric impedance spectroscopy of atherosclerotic lesions using a new impedance catheter system. Basic Res. Cardiol. 100:446–452, 2005.

    Article  CAS  PubMed  Google Scholar 

  31. Worthley, S. G., G. Helft, V. Fuster, Z. A. Fayad, M. Shinnar, L. A. Minkoff, C. Schechter, J. T. Fallon, and J. J. Badimon. A novel nonobstructive intravascular MRI coil: in vivo imaging of experimental atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 23:346–350, 2003.

    Article  CAS  PubMed  Google Scholar 

  32. Xiao, H., M. Lu, T. Y. Lin, Z. Chen, G. Chen, W. C. Wang, T. Marin, T. P. Shentu, L. Wen, B. Gongol, W. Sun, X. Liang, J. Chen, H. D. Huang, J. H. Pedra, D. A. Johnson, and J. Y. Shyy. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility. Circulation 128:632–642, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yeo, W. H., Y. S. Kim, J. Lee, A. Ameen, L. Shi, M. Li, S. Wang, R. Ma, S. H. Jin, Z. Kang, Y. Huang, and J. A. Rogers. Multifunctional epidermal electronics printed directly onto the skin. Adv. Mater. 25:2773–2778, 2013.

    Article  CAS  PubMed  Google Scholar 

  34. Yu, F., X. Dai, T. Beebe, and T. Hsiai. Electrochemical impedance spectroscopy to characterize inflammatory atherosclerotic plaques. Biosens. Bioelectron. 30(165–173):2011, 2011.

    Google Scholar 

  35. Yu, F., J. Lee, N. Jen, X. Li, Q. Zhang, R. Tang, Q. Zhou, E. S. Kim, and T. K. Hsiai. Elevated electrochemical impedance in the endoluminal regions with high shear stress: implication for assessing lipid-rich atherosclerotic lesions. Biosens. Bioelectron. 43:237–244, 2013.

    Article  CAS  PubMed  Google Scholar 

  36. Yu, F., R. Li, L. Ai, C. Edington, H. Yu, M. Barr, E. S. Kim, and T. K. Hsiai. Electrochemical impedance spectroscopy to assess vascular oxidative stress. Ann. Biomed. Eng. 39:287–296, 2011.

    Article  PubMed  Google Scholar 

  37. Zeibig, S., Z. Li, S. Wagner, H. P. Holthoff, M. Ungerer, A. Bultmann, K. Uhland, J. Vogelmann, T. Simmet, M. Gawaz, and G. Munch. Effect of the oxLDL binding protein Fc-CD68 on plaque extension and vulnerability in atherosclerosis. Circ. Res. 108:695–703, 2011.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present work was funded by National Institutes of Health grants HL118650 (T.K.H.), HL083015 (T.K.H.), HD069305 (T.K.H.), HL111437 (T.K.H.), T32HL007895 (R.R.S.P.) and the UCLA STAR program (R.R.S.P.).

Conflict of interest

The authors have no conflict of interest to disclose.

Author information

Author notes

    Authors and Affiliations

    1. Division of Cardiology, Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, 90073, USA

      René R. Sevag Packard, Jianguo Ma, Linda L. Demer, Rongsong Li & Tzung K. Hsiai

    2. Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, CA, 90073, USA

      René R. Sevag Packard, Nelson Jen, Jianguo Ma, Linda L. Demer & Tzung K. Hsiai

    3. Department of Molecular, Cellular and Integrative Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90073, USA

      René R. Sevag Packard, Linda L. Demer & Tzung K. Hsiai

    4. Electrical and Mechanical Engineering, California Institute of Technology, Pasadena, CA, USA

      XiaoXiao Zhang, Yuan Luo & Yu-Chong Tai

    5. Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA

      Teng Ma & Qifa Zhou

    6. Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA

      James W. Sayre

    Authors
    1. René R. Sevag Packard
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. XiaoXiao Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yuan Luo
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Teng Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Nelson Jen
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Jianguo Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Linda L. Demer
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Qifa Zhou
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. James W. Sayre
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Rongsong Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Yu-Chong Tai
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Tzung K. Hsiai
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Tzung K. Hsiai.

    Additional information

    Associate Editor Scott I. Simon oversaw the review of this article.

    René R. Sevag Packard, XiaoXiao Zhang, and Yuan Luo have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Packard, R.R.S., Zhang, X., Luo, Y. et al. Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques. Ann Biomed Eng 44, 2695–2706 (2016). https://doi.org/10.1007/s10439-016-1559-9

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10439-016-1559-9

    Keywords

    Search

    Navigation