Intracoronary Optical Coherence Tomography

• A new technology for performing high-resolution cross sectional imaging.

• Analogous to IVUS imaging, uses light instead of sound.

• Provides cross sectional images of tissue structure on the micron scale in situ and in real time.

• A type of Optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time.

• OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures.

INTRODUCTION

• Huang et al. in 1991.

• The light source used for OCT imaging is in the Near-infrared range, around 1,300-nm wavelength, selected to achieve both penetration and delineation of vascular structures[tissue penetration is limited to 1 to 3 mm as compared with 4 to 8 mm achieved by intravascular ultrasound].

• Cross-sectional images are generated by measuring the Echo time delay and Intensity of light that is reflected or backscattered from internal structures in tissue .

• The Echo time delay cannot be measured directly [speed of light (3x108 m/s) is much faster than that of sound (1,500 m/s)--- direct quantification cannot be achieved on such a time scale.

• Correlation or Interferometry techniques.

Principles of operation

• Interferometry measures the echo time delay and intensity of backscattered light by interfering it with light that has travelled a known reference path length and time delay.

• Michelson-type interferometer.

• The interferometer splits the emitted light source into a Reference and Sample beam; the reference beam is directed to a reference mirror at known distance, the sample beam is directed to the structures of interest.

• The backscattered light from the sample is interfered with reflected light from the reference arm and their interference fringes are detected by a photodetector.

• When the back-reflected optical intensity of the two arms (interference signal) is measured and compared, the optical properties of the tissue can be deduced .

• The intensity of the back-reflected light can be measured and quantified digitally in grey scale, enabling the creation of a digital image.

• The imaging depth of TD-OCT is approximately 1.5–2.0 mm with an axial and lateral resolution of 15 mm and 25mm, respectively

• Blood strongly scatters light-- intravascular OCT requires a blood-free field lasting several seconds to allow imaging.

OCT Image Acquisition

•Injecting continuous saline/ contrast flushes through the guiding or delivery catheters.

•Proximal balloon occlusion of the vessel with distal saline/contrast injection.

•Time-consuming

• Require a high degree of operator expertise

•FD OCT systems do not require proximal occlusion

•Bolus injection of saline, contrast, or otherSolution, injected at rates of 2 to 4 ml/s, and an automated 20 mm/s pullback within a monorail rapid exchange catheter allows imaging of a 6-cm-long coronary segment during a 3-s injection

TD-OCT FD- OCT

• The OCT Image Wire-- guidewire-like profile.

• Inserted using an over-the-wire balloon catheter (Helios).

• The Helios balloon--- maximum external diameter of 1.5 mm---- compatible with large 6-F guiding catheters (0.071-inch inner diameter).

• Advanced distally to the segment of interest over a conventional angioplasty guidewire (0.014-inch).

• The guidewire is exchanged with the OCT Image Wire---occlusion balloon is pulled back ------ repositioned in a healthy proximal segment.

• The balloon is inflated at pressure that allows totally clean imaging from blood, usually between 0.4 to 0.7 atm ----- dedicated inflator.

• A contrast injector pump with a warming cuff is set at 0.5 cc/s infusion ---- can be increased to up to 1.0 cc/s until blood is completely cleared.

• The solution injected through the distal port of the occlusion balloon catheter----- start several seconds before balloon occlusion.

• The pullback speed adjusted from 0.5 to 3.0 mm/s, and the entire image wire is pulled from distal to proximal along the coronary artery.

• FD-OCT systems

Imaging --- without balloon occlusion.

The pullback speed can reach up to 20 to 40 mm/s and is performed during contrast injection (4 cc/s) to assure complete blood clearance.

Imaging of 4 to 6 cm of coronary artery segments can be achieved with <15 cc of contrast per pullback.

For non occlusion techniques, iodinated contrast media is preferred over saline or ringer’s lactate because of the advantage of high viscosity solutions in completely removing blood.

• The applied energies in OCT are low --- no functional or structural damage to the tissue.

• One study evaluated the safety and feasibility of OCT in 76 patients using the occlusive technique.

• Vessel occlusion time was 48 . 3 Sec.

• The most frequent complication was the presence of transient events, such as chest discomfort, brady - or tachycardia, and ST-T changes on ECG, all of which resolved immediately after the procedure.

• No major complications, including myocardial infarction, emergency revascularisation, death, acute vessel occlusion, dissection, thrombus formation, embolism, or vasospasm along the procedure related artery were observed.

Safety of OCT

• Introduction of the non-occlusive technique ----- reduction in the procedural time ---- rate of chest pain and ECG changes during image acquisition.

• New systems with high speed pullbacks ----- Permit coronary imaging in a few seconds.

Clinical Application

• ACS ------ Rupture of a coronary plaque .

• Detection of lesions at high risk of rupture (so called ‘‘vulnerable plaques’’) is of major importance for the prevention of future ACS.

• OCT --- one of the most promising --- provides unique information about the plaque composition, the presence of macrophages, and the thickness of the fibrous cap

Plaque Characterization

• The propensity to destabilise and rupture is highly dependent on Plaque composition.

• In comparison with histology, OCT has been shown to be highly sensitive and specific for characterising different types of atherosclerotic plaques.

• Yabushita et al analysed 357 diseased carotid and coronary segments ex vivo and classified them as fibrous, fibro- calcific, and lipid-rich plaques.

oFibrous plaques -- homogeneous, signal-rich regions

oFibro - calcific plaques --- signal-poor regions/ sharp borders

oLipid-rich plaques ---signal-poor regions with diffuse borders

Plaque composition

FIBROUS PLAQUE

FIBROCALCIFIC PLAQUE

LIPID RICH PLAQUE

SENSITIVITY

71–79% 95–96%

90–94%

SPECIFICITY

97–98% 97% 90–92%

comparison with histology

• Ex vivo validations --- OCT superior to conventional and integrated backscatter IVUS for the characterisation of coronary atherosclerotic plaque composition.

• In vivo, OCT is superior for the identification of lipid pools.

• OCT appearance of coronary plaques in different groups of patients:

lipid-rich plaque was identified in 90% of ST-segment elevation myocardial infarction (STEMI) and 75% of non–ST-segment elevation myocardial infarction (NSTEMI), as compared with < 60% of stable angina pectoris (SAP) lesions.

• Thin capped fibroatheromas (TCFA) - defined pathologically by the triad of:

Lipid core.

Fibrous cap with a thickness < 65 micron m.

Cell infiltration of the fibrous cap.

• OCT for in vivo assessment of fibrous cap thickness ---- Unique ability to image superficial detail.

Characterization of fibrous cap thickness

• In the ACS patients, TCFA was observed in 72 % STEMI and 50 % NSTEMI culprit lesions as compared with 20 % SAP lesions (p =0.01) [Jang I-K, Tearney GJ, MacNeill BD, et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation 2005;111:1551–5]

• The same groups exhibited mean fibrous cap thicknesses of 47, 54, and 103 micron m , respectively.

• Similar findings have been reported by subsequent studies (77% to 83% STEMI, 46% NSTEMI, and 3% to 25% SAP; p=0.001)[Kubo T et al. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J Am Coll Cardiol 2007;50:933–9].

• Potential for using OCT measurements of fibrous cap thickness as a possible marker of plaque vulnerability.

• In a single-center prospective study, cap thickness has been shown to increase in a statin-treated group [Takarada S,, Kubo T, et al. Effect of statin therapy on coronary fibrous-cap thickness in patients with acute coronary syndrome: assessment by optical coherence tomography study. Atherosclerosis 2009;202:491–7].

• In a smaller observational study, patients on statins had fewer plaque ruptures (8% vs. 36%) and had a trend toward increased fibrous cap thickness (78 micron m vs. 49 micron m) compared with those not taking statin. [Chia S,et al. Association of statin therapy with reduced coronary plaque rupture: an optical coherence tomography study. Coron Artery Dis 2008;19:237– 42]

• Plaque rupture/ Subsequent thrombosis ----- ACS.

• OCT can identify intracoronary thrombus and plaque rupture with high accuracy.

• Kubo et al evaluated the ability of OCT to assess the culprit lesion morphology in acute myocardial infarction in comparison with IVUS and angioscopy.

• Incidence of plaque rupture by OCT of 73%, significantly higher than that detected by both angioscopy (47%, p = 0.035) and IVUS (40%, p = 0.009).

• Intracoronary thrombus was observed in all cases by OCT and angioscopy, but was identified in only 33% of patients by IVUS.

Plaque rupture and intracoronary thrombusidentification

• Kume et al --- OCT distinguish between white and red thrombus. Red thrombus appears as a high backscattering structure with signal-free shadowing while white thrombus appears as a low backscattering structure.

• Intense infiltration of the fibrous cap is another of the features of vulnerable plaques.

• Study by Tearney et al ---- OCT was able to quantify macrophages within the fibrous cap.

• In vivo---- unstable patients present a significantly higher macrophage density detected by OCT in the culprit lesion than stable patients.

• The sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites.

Identification of intralesional macrophages

• Fine resolution at a superficial depth, OCT allows a uniquely detailed image of the effects of stent implantation on the vessel wall.

• OCT allows:

Examination of the target vessel both pre- and post-intervention

Defining stent struts readily

Tissue prolapse between stent struts immediately

Tissue characterization of plaque before and after stent placement

OCT and Percutaneous Coronary Intervention

• Tissue prolapse, or protrusion of tissue between stent struts without apparent surface disruption ----- depth of protrusion is >50micron m.

• Observed universally (97.5%) at some point along the stented segment

• IVUS-verified prolapse of 18% to 35%, suggesting OCT is both sensitive and specific.

• clinical significance ---- unclear, given that it occurs so frequently, and has not been associated with early clinical events.

Tissue prolapse

• Disruption of the vessel surface with dissection flap, or association with an underlying cavity

• 86.3% of stented vessels show a dissection flap and 68.8% show an underlying cavity at some point along their length.

• Significance—if any—remains to be established.

• Edge dissections were present less commonly (26.3%), with no associated clinical events.

Intrastent dissection

• The degree of stent strut apposition extensively evaluated using OCT by a number of investigators

[Raffel OC, Akasaka T, Jang IK. Cardiac optical coherence tomography. Heart 2008;94:1200 –10]

• Leading edge of stent struts.

• Lumen–vessel wall interface.

Stent strut apposition/coverage

• 3-point classification defines stent strut apposition.

Embedded ----- the leading edge is buried within the intima by more than one-half its thickness

Protrusion --- stent strut is apposed but not embedded

Malapposed ---- there is no intimal contact

• Another classification, describes whether or not the stent strut appears covered with tissue, and whether struts are well apposed or Malapposed . Stent struts are, therefore, classified as:

Well apposed and covered

well apposed and not covered

Malapposed and not covered

Malapposed but covered

• In a small series of OCT examinations after drug-eluting stent (DES) implantation 6,000 stent struts were examined : [Tanigawa J, Di Mario et al. The influence of strut thickness and cell design on immediate apposition of drug-eluting stents assessed by optical coherence tomography. Int J Cardiol 2009;134:180 – 8]

57.1% ---- Embedded

33.8%------Protruding

9.1% ------ Malapposed

The clinical relevance of these findings remains unclear.

• IVUS studies in late stent thrombosis after DES implantation ---- high prevalence of incomplete stent apposition.

• persistent or acquired (not present after stent implantation)

• (1) expansive vessel remodelling

• (2) chronic stent recoil

• (3) dissolution of thrombus trapped between the stent and the vessel wall in patients undergoing primary PCI for acute myocardial infarction

• (4) the resolution of an intramural haematoma created by vessel dissection during PCI

Stent apposition at follow-up

• Prevalence of Malapposed struts by OCT is higher in sirolimus eluting stents (SES) than in BMS.

• In another study that evaluated 57 SES at 6 months follow-up, 79 out of the 6840 struts visualised by OCT showed malapposition and were more often located in areas of SES overlap

• Xie et al compared the neointimal coverage at 3 months follow-up in 16 patients treated with BMS and 24 patients who underwent SES implantation.

• The neointimal thickness per strut[ 248 mm Vs 39 mm] and the percentage of neointimal thickness area per cross section[ 45.0 % vs. 10.0 %] were higher in the BMS group than in the SES group.

• The frequency of uncovered struts and Malapposed struts was higher in the SES group than in the BMS group (15% vs. 0.1%, p<0.0001, and 15% vs. 1.1%, p<0.0001, respectively).

• Matsumoto et al studied 34 patients (57 SES) with IVUS and OCT at 6 months follow-up. The authors reported that 64% of the struts were covered by thin neointima undetectable by IVUS .

• The most powerful histological predictor of stent thrombosis.

• DES inhibits neointimal proliferation to such an extent that it may not be detectable by IVUS. The higher resolution of OCT allows the visualisation and measurement of tiny layers of tissue covering the stent struts.

• A study in a carotid rabbit model evaluated the usefulness of OCT for identifying strut coverage after stenting. No differences in the mean neointimal thickness measured by histology and OCT. (The intra-and inter-observer reproducibility of neointimal thickness measurements by OCT was excellent.)

Strut coverage following DES implantation

• DES type may also influence stent coverage.

• Paclitaxel - and Zotarolimus -eluting stents exhibit fewer exposed stent struts compared with sirolimus.

• 1 study has demonstrated a stent strut exposure rate of 0.3% at 9 months with zotarolimus compared with 12% for sirolimus . [Kim J-S et al. Comparison of neointimal coverage of sirolimus-eluting stents and paclitaxel-eluting stents using optical coherence tomography at 9 months after implantation. Circ J 2010; 74:320 – 6.]

• Zotarolimus - eluting stents may also have low rates of uncovered stent struts comparable to BMS in the setting of STEMI [Guagliumi G et al. Optical coherence tomography assessment of in vivo vascular response after implantation of overlapping bare-metal and drug-eluting stents. J Am Coll Cardiol Intv 2010;3:531–9]

• Another study evaluated the strut coverage in SES at 6 and 12 months follow-up.

• Forty-six SES (6561 struts) were studied in 36 patients.

• The authors reported that only four SES at 6 months (18.2%) and 10 SES at 12 months (41.7%) were fully covered by tissue.

• Yamamoto et al evaluated the long term follow up of SES in 21 patients. Overall the frequency of uncovered struts was 5%, and 81% of the patients presented uncovered struts at 2 years follow-up.

• The presence of uncovered struts was more frequent at side branches and at overlapping segments.

• Useful in the evaluation of the causes that contribute to restenosis after DES implantation, such as incomplete coverage of lesion or gaps between stents.

• Stent fracture (defect of local drug delivery) has been related to restenosis in DES and could be visualised with OCT.

• Non-uniform distribution of stent struts could affect the drug delivery and therefore have an influence on restenosis in DES.

Assessment of restenosis

• OCT has not been able to distinguish if the tissue covering the struts is neointimal tissue or fibrin.

• the presence of tissue covering the strut does not prove that normal endothelial function in the area has been restored.

• Pathological and functional studies are needed to understand the real meaning of the OCT findings in strut coverage

• Fully biodegradable stents---- promising future stents--- they may avoid the potential complications of metallic DES----- late and very late stent thrombosis and the need for prolonged dual antiplatelet treatment.

• ABSORB TRIAL ---- feasibility of implantation of the Bioabsorbable Everolimus eluting coronary stent composed of a poly-L-lactic acid backbone coated with a degradable polymer/Everolimus matrix.

• In 13 patients, OCT was performed after stent implantation and at 6 months follow-up.

• OCT allowed a very precise characterisation of the stent apposition ,coverage, and also demonstrated structural changes in the Bioabsorbable DES over time.

• At baseline, 738 struts were visualised ----follow-up only 671 could be identified.

• optical properties of the remaining struts changed from baseline to follow-up ----- probably related to the partial absorption process.

• OCT appears to be the best available tool for the assessment of absorption of stent struts.

Evaluation of future DES

• Residual blood --- Attenuates the OCT light beam ---- defocus the beam if red cell density is high.

• This reduces brightness of the vessel wall, especially at large radial distances from the Image Wire.

• Mistakenly labelling residual blood artifact as thrombus or some other specific intra-vascular finding.

Artifacts

• Artifacts related to eccentric wire position

Eccentricity of the image wire in the vessel lumen image influence interpretation.

The reflection from metallic stent struts align toward the imaging wire, akin to sunflowers aligning to the sun or a “sunflower” effect or “merry-go-round” effect .

• Saturation Artifact

Occurs when light reflected from a highly specular surface (usually stent struts) produces signals with amplitudes that exceed the dynamic range of the data acquisition system

• Sew-up Artifactis

Result of rapid artery or imaging wire movement leading to misalignment of the lumen border

• Bubble Artifact

Result of air bubbles in the Image Wire sheath.

It attenuates the signal along a region of the vessel wall, and images with this artifact are not suitable for tissue characterization.

• Fold-over Artifactis

specific to the new generation of FD-OCT.

The longitudinal view demonstrates that the cross section is located at the level of a side branch.

when structure signals are reflected from outside the system’s field of view. Typical examples are side branch and large vessels.

• Need to displace blood or dilute the hematocrit, either with saline or contrast flush injection, or a combination of the two.

• Shallow image penetration of 1 to 2.5 mm. This prevents assessments of cross-sectional plaque area ---- OCT has only a limited role in the assessment of left main stem and Saphenous vein graft atherosclerosis severity.

• The differentiation of calcific areas from lipid pools can be problematic . both result in a low attenuation signal.

• Image artifacts

Limitations

Future Trends

• Fusion of IVUS and OCT would provide ideal imaging of luminal and vessel wall pathology.

• IVUS ---Increased penetration allow assessment of plaque burden and identification of positive or negative remodeling.

• High-resolution OCT ---- Permits assessment of luminal morphology, accurate estimation of fibrous cap thickness, identification of thrombus, and detection of plaque erosion and rupture.

• The combined information provided by both modalities would permit a more precise characterization of the type of plaque.

Combination of IVUS and OCT

• Sawada et al reported how the combined use of IVUS-VH analysis and OCT improved the accuracy for TCFA detection.

• 56 patients with angina (126 plaques) were included in the study.

• Of the 61 plaques diagnosed initially as TCFA by IVUS-VH analysis criteria, only 28 had a thin fibrous cap as measured by OCT, so they were considered as definite TCFAs.

• 8 OCT derived TCFAs did not have necrotic core in the IVUS-VH analysis, mainly due to the misreading in OCT caused by dense calcium.

• combination of the information provided by different methods could be essential for better identification of high risk coronary lesions

• A catheter combining an IVUS with an OCT probe would also be useful in planning and assessing the outcome of percutaneous coronary intervention.

• IVUS would provide information about the correct stent diameter (on the basis of the media-adventitia dimensions) ----- OCT would permit a detailed evaluation of the final result and detection of dissections, stent malapposition, or the presence of thrombus.

• There is currently no such catheter for clinical applications.

• 3D reconstruction of OCT images---- Automatically detect and quantify features of interest as

Shape of lumen

MLA

Stent strut malapposition and Thrombus volume.

• Combination of FD-OCT and Spectroscopic technique—allow for detailed analysis of the cellular and biochemical composition of Vulnerable plaque.

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