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Editorial Slides
VP Watch, January 15, 2003, Volume 1, Issue 2
Can OCT Catheter See Plaque Macrophages?!
–Optical coherence tomography
(OCT) is analogous to ultrasound,
measuring the intensity of back-
reflected light (near infrared light)
rather than sound (acoustical waves).
–An OCT image represents a cross
sectional picture of the optical
reflectance properties of tissue. 4
–OCT originally developed to image
the transparent tissue of the eye with
unprecedented resolution.
 Brezinski, Tearney, Bouma,
Fujimoto, and colleagues in
1997 discussed the advantages
of OCT as following:
• High resolution,
• Broad dynamic range, and
• Ability to be delivered through
intravascular catheters 2
–In vitro studies have shown that the
resolution of OCT (10-20 micron) can
resolve the thin fibrous caps thought to
be responsible for plaque vulnerability. 1
–Catheter-based diagnostic techniques
can provide structural information with
higher resolution than non-invasive
methods. OCT achieves at least 10
times higher resolution than IVUS, and
can be adapted for catheter-based
imaging of vulnerable plaque. 3
IVUS OCT
Coronary IVUS vs Coronary OCT
Tearney, Boma, Chang et
 Tearney, Jang, and colleagues
showed that in vivo OCT imaging of
normal coronary arteries, intimal
dissections, and deployed stents in
swine is feasible, and allows
identification of clinically relevant
coronary artery morphology with high-
resolution and contrast. 4
• As highlighted in VP Watch of this
week, Tearney and colleagues showed
OCT can characterize structure of
atherosclerotic plaque ex-vivo.5
• They further showed that macrophage
content of plaque cap can be identified
by OCT. 5
• Ex vivo studies
– Plaque characterization
– Cap thickness
– Macrophage density
• In vivo studies
– Feasibility
– Post-MI
Fibrous
Calcific
LIPID
Yabushita, Tearney et al. Circulation, 2002
Plaque Characterization Study
• Evaluate diagnostic potential (lipid pools)
• Methods
– 357 diseased arterial segments from 90 cadavers
• 78 Coronary; 86 Carotid; 143 Aorta
– OCT imaging, histology processing, registration
– Correlation of OCT with histology
– Develop OCT criteria for characterization (training set,
n=50)
– Prospectively test OCT criteria (validation set, n = 307)
– Two OCT readers and two pathologists
Yabushita, Tearney et al. Circulation, 2002
Plaque Characterization
lp
lp
Homogeneous,
Signal-rich
Fibrous Lipid pool
Echolucent,
Diffuse Borders
Echolucent,
Sharp Borders
Calcific
OCT Criteria, training set (n=50)
500 µm
Plaque Characterization Results
SENS .79
SPEC .97
SENS .95
SPEC .97
SENS .90
SPEC .92
• Accuracy Statistics
• Fibrous
• Calcific
• Lipid pool
Interobserver κ = 0.88, Intraobserver κ = 0.91
Yabushita, Tearney et al. Circulation, 2002
• Technology development
• Ex vivo studies
– Plaque characterization
– Cap thickness
– Macrophage density
• In vivo studies
– Feasibility
– Post-MI
– Epidemiology
– Prospective trials
*Mφ produce proteases
Degrade collagen and matrix
Impair structural integrity of cap
CD68 Immunoperoxidase
Cap
Lipid
Tearney, Bouma et al. Circulation, 2003
Macrophage Study
• Can OCT quantify macrophage content?
• Methods
– 26 diseased arterial segments from 17 cadavers
• 7 Carotid; 19 Aorta
– OCT imaging
– Histology processing - CD68, SMA, trichrome
– Correlation of OCT with histology
– 500x125 µm ROI
– Histology - automatic segmentation - % area staining
– OCT - quantitative image analysis
NSD=
σ
Smax−Smin( )
Tearney, Bouma et al. Circulation, 2003
Macrophage Study
250 µm
OCT
CD68
Low Mφ High Mφ
Tearney, Bouma et al. Circulation, 2003
Linear NSD vs. CD68
CD68 % area > 10 % - NSD cutoff 6.2%
R = 0.84
P < 0.0001
Tearney, Bouma et al. Circulation, 2003
Human Coronary Artery In Vivo
P
G
L
F
G
2x
m
a
i
ieleel
F
OCT IVUS
Tearney, Bouma et al. Circulation, 2003
Calcified Plaques In Vivo
OCT IVUS
Tearney, Bouma et al. Circulation, 2003
Lipid-rich Plaque In Vivo
OCT IVUS
Tearney, Bouma et al. Circulation, 2003
Thrombus In Vivo
OCT IVUS
Tearney, Bouma et al. Circulation, 2003
Conclusion:
• Intracoronary OCT represents a new
technology for microscale imaging of
atherosclerotic plaque.
• In exvivo studies OCT can identify
macrophage intensity in plaque cap.
• Given above, OCT can be an important
addition to cardiovascular cat labs, may
completely replace IVUS catheter.
Questions:
I. Presence of blood induces artifacts
for OCT imaging, knowing the time
constraint in cath labs, the question
is how practically OCT catheter can
be utilized for screening vulnerable
plaques throughout total coronary
arteries?
Questions:
• Assuming the limited use of IVUS
(<20%) for plaque characterization in
cath labs is due to cost issue, would
OCT with equal price be cost effective?
• With the trend towards non-invasive
diagnosis, and using invasive
procedure only for therapy, how will
OCT be greeted by interventional
cardiologists?
ReferencesReferences
1- Fujimoto JG, Boppart SA, Tearney GJ, Bouma BE, Pitris C, Brezinski ME.; High resolution
in vivo intra-arterial imaging with optical coherence tomography.; Heart. 1999
Aug;82(2):128-33.
2- Brezinski ME, Tearney GJ, Weissman NJ, Boppart SA, Bouma BE, Hee MR, Weyman AE,
Swanson EA, Southern JF, Fujimoto JG.; Assessing atherosclerotic plaque morphology:
comparison of optical coherence tomography and high frequency intravascular
ultrasound. Heart. 1997 May;77(5):397-403.
3- Ik-Kyung Jang, Brett E. Bouma, Dong-Heon Kang, Seung-Jung Park, Seong-Wook Park, Ki-
Bae Seung, Kyu-Bo Choi, Milen Shishkov, Kelly Schlendorf, Eugene Pomerantsev et al.;
Visualization of coronary atherosclerotic plaques in patients using optical coherence
tomography: comparison with intravascular ultrasound, Pages 604-609 ; Journal of the
American College of Cardiology 2002; Volume 39(4): 604-609
4- Tearney GJ, Jang IK, Kang DH, Aretz HT, Houser SL, Brady TJ, Schlendorf K, Shishkov M,
BoumaBE. Porcine coronary imaging in vivo by optical coherence tomography. Acta
Cardiol. 2000 Aug;55(4):233-7.
5- Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence
Tomography Tearney Guillermo , Yabushita Hiroshi , Houser Stuart , Aretz H , Jang
Ik-kyung , Schlendorf Kelly , Kauffman Christopher , Shishkov Milen , Halpern Elkan ,
Bouma Brett ,
Circulation. 2003;107:113

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Esv3n2

  • 1. Editorial Slides VP Watch, January 15, 2003, Volume 1, Issue 2 Can OCT Catheter See Plaque Macrophages?!
  • 2. –Optical coherence tomography (OCT) is analogous to ultrasound, measuring the intensity of back- reflected light (near infrared light) rather than sound (acoustical waves). –An OCT image represents a cross sectional picture of the optical reflectance properties of tissue. 4 –OCT originally developed to image the transparent tissue of the eye with unprecedented resolution.
  • 3.  Brezinski, Tearney, Bouma, Fujimoto, and colleagues in 1997 discussed the advantages of OCT as following: • High resolution, • Broad dynamic range, and • Ability to be delivered through intravascular catheters 2
  • 4. –In vitro studies have shown that the resolution of OCT (10-20 micron) can resolve the thin fibrous caps thought to be responsible for plaque vulnerability. 1 –Catheter-based diagnostic techniques can provide structural information with higher resolution than non-invasive methods. OCT achieves at least 10 times higher resolution than IVUS, and can be adapted for catheter-based imaging of vulnerable plaque. 3
  • 5. IVUS OCT Coronary IVUS vs Coronary OCT Tearney, Boma, Chang et
  • 6.  Tearney, Jang, and colleagues showed that in vivo OCT imaging of normal coronary arteries, intimal dissections, and deployed stents in swine is feasible, and allows identification of clinically relevant coronary artery morphology with high- resolution and contrast. 4
  • 7. • As highlighted in VP Watch of this week, Tearney and colleagues showed OCT can characterize structure of atherosclerotic plaque ex-vivo.5 • They further showed that macrophage content of plaque cap can be identified by OCT. 5
  • 8. • Ex vivo studies – Plaque characterization – Cap thickness – Macrophage density • In vivo studies – Feasibility – Post-MI Fibrous Calcific LIPID Yabushita, Tearney et al. Circulation, 2002
  • 9. Plaque Characterization Study • Evaluate diagnostic potential (lipid pools) • Methods – 357 diseased arterial segments from 90 cadavers • 78 Coronary; 86 Carotid; 143 Aorta – OCT imaging, histology processing, registration – Correlation of OCT with histology – Develop OCT criteria for characterization (training set, n=50) – Prospectively test OCT criteria (validation set, n = 307) – Two OCT readers and two pathologists Yabushita, Tearney et al. Circulation, 2002
  • 10. Plaque Characterization lp lp Homogeneous, Signal-rich Fibrous Lipid pool Echolucent, Diffuse Borders Echolucent, Sharp Borders Calcific OCT Criteria, training set (n=50) 500 µm
  • 11. Plaque Characterization Results SENS .79 SPEC .97 SENS .95 SPEC .97 SENS .90 SPEC .92 • Accuracy Statistics • Fibrous • Calcific • Lipid pool Interobserver κ = 0.88, Intraobserver κ = 0.91 Yabushita, Tearney et al. Circulation, 2002
  • 12. • Technology development • Ex vivo studies – Plaque characterization – Cap thickness – Macrophage density • In vivo studies – Feasibility – Post-MI – Epidemiology – Prospective trials *Mφ produce proteases Degrade collagen and matrix Impair structural integrity of cap CD68 Immunoperoxidase Cap Lipid Tearney, Bouma et al. Circulation, 2003
  • 13. Macrophage Study • Can OCT quantify macrophage content? • Methods – 26 diseased arterial segments from 17 cadavers • 7 Carotid; 19 Aorta – OCT imaging – Histology processing - CD68, SMA, trichrome – Correlation of OCT with histology – 500x125 µm ROI – Histology - automatic segmentation - % area staining – OCT - quantitative image analysis NSD= σ Smax−Smin( ) Tearney, Bouma et al. Circulation, 2003
  • 14. Macrophage Study 250 µm OCT CD68 Low Mφ High Mφ Tearney, Bouma et al. Circulation, 2003
  • 15. Linear NSD vs. CD68 CD68 % area > 10 % - NSD cutoff 6.2% R = 0.84 P < 0.0001 Tearney, Bouma et al. Circulation, 2003
  • 16. Human Coronary Artery In Vivo P G L F G 2x m a i ieleel F OCT IVUS Tearney, Bouma et al. Circulation, 2003
  • 17. Calcified Plaques In Vivo OCT IVUS Tearney, Bouma et al. Circulation, 2003
  • 18. Lipid-rich Plaque In Vivo OCT IVUS Tearney, Bouma et al. Circulation, 2003
  • 19. Thrombus In Vivo OCT IVUS Tearney, Bouma et al. Circulation, 2003
  • 20. Conclusion: • Intracoronary OCT represents a new technology for microscale imaging of atherosclerotic plaque. • In exvivo studies OCT can identify macrophage intensity in plaque cap. • Given above, OCT can be an important addition to cardiovascular cat labs, may completely replace IVUS catheter.
  • 21. Questions: I. Presence of blood induces artifacts for OCT imaging, knowing the time constraint in cath labs, the question is how practically OCT catheter can be utilized for screening vulnerable plaques throughout total coronary arteries?
  • 22. Questions: • Assuming the limited use of IVUS (<20%) for plaque characterization in cath labs is due to cost issue, would OCT with equal price be cost effective? • With the trend towards non-invasive diagnosis, and using invasive procedure only for therapy, how will OCT be greeted by interventional cardiologists?
  • 23. ReferencesReferences 1- Fujimoto JG, Boppart SA, Tearney GJ, Bouma BE, Pitris C, Brezinski ME.; High resolution in vivo intra-arterial imaging with optical coherence tomography.; Heart. 1999 Aug;82(2):128-33. 2- Brezinski ME, Tearney GJ, Weissman NJ, Boppart SA, Bouma BE, Hee MR, Weyman AE, Swanson EA, Southern JF, Fujimoto JG.; Assessing atherosclerotic plaque morphology: comparison of optical coherence tomography and high frequency intravascular ultrasound. Heart. 1997 May;77(5):397-403. 3- Ik-Kyung Jang, Brett E. Bouma, Dong-Heon Kang, Seung-Jung Park, Seong-Wook Park, Ki- Bae Seung, Kyu-Bo Choi, Milen Shishkov, Kelly Schlendorf, Eugene Pomerantsev et al.; Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound, Pages 604-609 ; Journal of the American College of Cardiology 2002; Volume 39(4): 604-609 4- Tearney GJ, Jang IK, Kang DH, Aretz HT, Houser SL, Brady TJ, Schlendorf K, Shishkov M, BoumaBE. Porcine coronary imaging in vivo by optical coherence tomography. Acta Cardiol. 2000 Aug;55(4):233-7. 5- Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence Tomography Tearney Guillermo , Yabushita Hiroshi , Houser Stuart , Aretz H , Jang Ik-kyung , Schlendorf Kelly , Kauffman Christopher , Shishkov Milen , Halpern Elkan , Bouma Brett , Circulation. 2003;107:113

Notas del editor

  1. Calcific coronary plaque imaged in vivo by OCT (left) and IVUS (right). Left Image. This OCT image shows a well delineated, heterogeneous, signal-poor region corresponding to a macrocalcification (left image, arrow), also seen in the corresponding IVUS image (right image, arrow). A signal-rich fibrous band (left image, two arrowheads) overlying the calcification is easily identified in the OCT image but is obscured by a saturation artifact in the IVUS image. The borders of the guide wire (*) artifact are marked by dotted lines in A, C. Tick marks, 1 mm.
  2. Lipid-rich coronary plaque imaged in vivo by OCT (Left Image) and IVUS (Right Image). Left Image. This plaque demonstrates a homogeneous, signal-poor region (inset, arrow) by OCT that extends near the vessel lumen at the shoulder of the plaque (inset, arrowheads), possibly representing a vulnerable shoulder region. The minimum cap thickness at this region measured 20  3 µm by OCT. Right Image. The echolucent region (arrow) is also identified in the IVUS image from the same site, but the cap is difficult to visualize and its thickness cannot be measured. Tick marks, 1 mm.
  3. Calcific coronary plaque with an intraluminal thrombus imaged in vivo by OCT (Left Image) and IVUS (Right Image). Signal-rich calcifications (arrows) are seen in both OCT (Left Image) and IVUS (Right Image) images. An irregular, homogeneous tissue adherent to the vessel surface, consistent with a thrombus, is present in the OCT image adjacent to the calcifications (Left Image, inset). The inability of the IVUS reader to discriminate between intraluminal blood and thrombus in (B) may have been a result of the lack of flushing during IVUS imaging. Tick marks, 1 mm.