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Novel preclinical method for evaluating the efficacy of a percutaneous treatment in human ex vivo calcified plaque

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Abstract

The lack of suitable atherosclerotic calcification models and testing strategies inhibits preclinical efficacy testing of existing and novel percutaneous devices. The goal of this study is to develop a preclinical testing method for quantitatively and qualitatively evaluating the efficacy of noncompliant balloon angioplasty (NC BA) treatment in human ex vivo calcified plaque (CP). NC BA using a 3- and 4-mm diameter balloon was performed on an ex vivo tibial calcified vessel obtained from an amputation. Three-dimensional microcomputed tomography (μ-CT) imaging was performed pre- and post-BA to compare crack density in the CP. Comparing the pre- and posttreatment three-dimensional μ-CT images showed a glass-like cracking that occurred in the CP due to the BA procedure. Expansion of the 3-mm balloon showed little tissue deformation and no CP cracking. Although expansion of the 4-mm balloon occurred nonuniformly along balloon length and across the perpendicular projections, the balloon generated cracking throughout the CP, which allowed the surrounding elastic tissue to be dilated. This combined X-ray microscopy and μ-CT technique is a useful preclinical tool for quantifying the efficacy of percutaneous treatments for CP. Because of its nondestructive nature, the CP structure can be visualized pre- and posttreatment to determine the treatment effect.

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Abbreviations

NC BA:

noncompliant balloon angioplasty

CP:

calcified plaque

IC:

intimal calcification

IVUS:

intravascular ultrasound

MC:

medial calcification

MCTA:

multi-slice computed tomography angiography

μ-CT:

microcomputed tomography

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Acknowledgments

The authors acknowledge the University of Michigan College of Engineering for financial support, the Michigan Center for Materials Characterization for use of the instruments and staff assistance (especially Nancy Senabulya), and the Michigan Pathology Lab.

Funding

This work was supported by State of Michigan Economic Development Corporation Fast Forward Medical Innovation MTrac (CASE-244578, Lansing, MI) and NIH Center for Accelerated Innovations at Cleveland Clinic Grant (U54HL119810, Cleveland, OH).

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, University of Michigan at Ann Arbor, 2350 Hayward St, Ann Arbor, MI, 48109, USA

    Robert S. Chisena & Albert J. Shih

  2. Department of Biomedical Engineering, University of Michigan at Ann Arbor, 2200 Bonisteel Blvd, Ann Arbor, MI, 48109, USA

    Jordan Sengenberger

  3. Department of Internal Medicine, University of Michigan Health System at Ann Arbor, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA

    Hitinder Gurm

Authors
  1. Robert S. Chisena
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Corresponding author

Correspondence to Robert S. Chisena.

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Conflict of interest

Drs. Chisena, Shih, and Gurm have financial interests in Amplitude Vascular Systems, Inc. (formerly known as Calcium Solutions, Inc.), a company that is developing a novel, mechanical lithotripsy-based BA treatment. These authors are inventors on the following patents: US No. 62/656,699 and No. 16/654,073 and PCT/US2019/027139. The remaining authors have no conflicts to disclose.

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Appendix

Appendix

Figure 8 shows two-dimensional X-ray microscopy images during BA with a 3-mm and 4-mm balloon of the tibial CP. Incremental pressure steps are shown with normal projection images. During the expansion of the 3-mm balloon, the balloon displaces the artery’s endothelial layer but does not affect the calcified portion of the vessel. During the expansion of the 4-mm balloon, the balloon does affect the calcified portion of the vessel. Table 1 shows statistical information of the balloon’s diameter during the BA treatment.

Fig. 8
figure 8

Two-dimensional X-ray microscopy images during BA of a tibial CP. From top to bottom, the grid shows an increase in balloon pressure from 2 to 14 ATM, a return to 2 ATM, and then vacuum. Zero degree and 90° images for the 3- and 4-mm balloons are shown. See Video 2 in the journal for each 1 ATM pressure increment image

Full size image
Table 1 The 3-mm and 4-mm mean, median, minimum, maximum, and standard deviation balloon diameters during each pressurization step for the 0° and 90° projections
Full size table

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Chisena, R.S., Sengenberger, J., Shih, A.J. et al. Novel preclinical method for evaluating the efficacy of a percutaneous treatment in human ex vivo calcified plaque. Med Biol Eng Comput 59, 799–811 (2021). https://doi.org/10.1007/s11517-021-02334-w

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  • DOI: https://doi.org/10.1007/s11517-021-02334-w

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