An Animal Model for In Vivo Imaging of Human Coronaries: A New Tool to Evaluate Emerging Technologie

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An Animal Model for In Vivo Imaging of Human
Coronaries A New Tool to Evaluate Emerging
Technologies to Detect Vulnerable Plaques

• Sergio Waxman1, Kamal R. Khabbaz1, Raymond J.
  Connolly1, Jing Tang2, Alexandra Dabreo1, Lara
  Egerhei1, James E. Muller2, Guillermo J. Tearney3.

1 Tufts-New England Medical Center- Boston, MA 2
InfraRedX, Inc. Cambridge, MA 3 Wellman
Laboratories, MGH- Boston, MA
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Presenter Disclosure Information
The following relationships exist related to this
presentation
Sergio Waxman Research Support, Consultant
InfraRedX Inc Kamal R. Khabbaz No
relationships to disclose Raymond J. Connolly No
relationships to disclose Jing Tang
Scientific officer, InfraRedX, Inc. Alexandra
Dabreo No relationships to disclose Lara
Egerhei No relationships to disclose James E.
Muller CEO, InfraRedX, Inc Guillermo J. Tearney
Consultant, InfraRedX, Inc.
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Background I

• Detection of coronary vulnerable plaques remains
  a challenge.
• The thin cap fibroatheroma (TCFA) may be the most
  common type of VP.
• Catheter-based imaging technologies hold promise
  for detection of TCFA based on identification of
  certain morphologic features
• Deformability
• Spectral composition
• Ultrasound wave reflection
• OCT pattern
• MR signal

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Background II

• However, a number of obstacles must be overcome
  in the development and testing of novel imaging
  technologies
• Lack of animal models of vulnerable plaque
• Effects of coronary and myocardial motion
• Effects of blood flow
• We designed an animal model that allows imaging
  of human coronaries under physiologic
  conditions.

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The Tearney Model Conceptualization
Human cadaver-to-porcine coronary xenograft model
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Objective

• To prove the feasibility of the human-to-porcine
  coronary xenograft model.
• To determine that conditions of coronary flow and
  motion similar to those encountered in humans can
  be reproduced using this model.
• To perform imaging of human coronaries in this
  model under such conditions using angiography and
  IVUS.

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Methods IHuman Coronary Prescreening

• Adult cadaver hearts were obtained at autopsy.
• Angiography with manual contrast injection was
  performed to determine
• Coronary patency.
• Angiographic evidence of CAD.
• Vessel tortuosity.

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Methods II Human Coronary Graft Preparation

• Segments of the coronary arteries were mapped and
  prosected en block with surrounding muscle and
  epicardial fat to preserve architecture and
  preserved in cold saline.
• Major sidebranches were ligated.
• Standard Luer lock connectors were attached to
  each end.

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Postmortem angiography
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Four different human coronary grafts
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Methods IIIGraft Implantation

• Anesthetized Yorkshire pigs (45-50 Kg)
• Median sternotomy
• Aorta and right atrium cannulated and attached in
  and end-to-end fashion to the human coronary
  xenograft, forming an aorto-atrial conduit.
• Graft tacked down to the anterior wall of the
  heart to mechanically couple the graft to the
  beating heart.

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Methods IVGraft Implantation

• Flow meter connected distal to the graft.
• A Y connector with a valve and sideport are
  attached proximal to the graft to
• Measure pressure.
• Allow contrast/saline injection.
• Introduce imaging catheter.

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Methods VGraft Imaging

• Graft angiography was performed.
• IVUS of each graft using motorized pullback at a
  constant speed of 0.5 mm/sec.
• A second xenograft was implanted if the animal
  tolerated the procedure.
• Histology was performed.

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Photograph of implanted coronary xenograft
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Results I
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Results II
Reasons for discarding tissue Occlusive disease,
tortuous anatomy, small caliber vessels.
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Results IIIHemodynamic parameters
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Results IVLaboratory Parameters
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Graft angiography and IVUS
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Graft angiography and IVUS
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Pulsatile flow in implanted coronary xenograft
Systolic LA 10.1 1.5 mm2
Diastolic LA 9.6 1.2 mm2
? 5.2
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Histology
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Histology
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Conclusions

• This is the first demonstration of a non-survival
  animal model for imaging of human coronaries
  reproducing conditions of coronary blood flow and
  motion that are encountered in vivo.
• Imaging of human coronary pathology under such
  conditions is possible.

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Advantages

• This human-to-porcine xenograft model provides an
  opportunity to evaluate imaging technologies that
  rely on morphology, composition, and
  biomechanical properties of atherosclerotic
  plaques.
• Histologic correlations are readily available.
• The model allows testing of same diagnostic and
  therapeutic devices that would be used in humans
  and facilitates preclinical testing and training.

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Applicable VP Diagnostics
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Limitations

• Only useful for technologies that rely on
  structural or biochemical features of plaques
  (graft is not viable).
• Proper registration between imaging window and
  histology sample may still be an issue.
• Postmortem changes that occur in tissue may alter
  acquisition signals.
• Availability of human tissue may be limited.

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Acknowledgements

• Center for Translational Cardiovascular Research,
  Tufts-NEMC
• Alexandra Dabreo
• Eric Weiss
• Fumiyuki Ishibashi, MD
• Surgical Research Laboratories, Tufts-NEMC
• Raymond J Connolly, PhD
• Lara Egerhei
• Barbara Murphy
• Kamal R Khabbaz, MD

• InfraRedX, Inc.
• Jing Tang, MD
• Jay Caplan
• Tara Dunn
• James E. Muller MD
• Wellman Lab, MGH
• Gary J Tearney, MD PhD

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Schematic representation