the role of optical coherence tomography in vascular medicine

10
http://vmj.sagepub.com/ Vascular Medicine http://vmj.sagepub.com/content/14/1/63 The online version of this article can be found at: DOI: 10.1177/1358863X08095153 2009 14: 63 Vasc Med Muhammad U Farooq, Atul Khasnis, Arshad Majid and Mounzer Y Kassab The role of optical coherence tomography in vascular medicine Published by: http://www.sagepublications.com On behalf of: Society for Vascular Medicine can be found at: Vascular Medicine Additional services and information for http://vmj.sagepub.com/cgi/alerts Email Alerts: http://vmj.sagepub.com/subscriptions Subscriptions: http://www.sagepub.com/journalsReprints.nav Reprints: http://www.sagepub.com/journalsPermissions.nav Permissions: http://vmj.sagepub.com/content/14/1/63.refs.html Citations: by guest on May 10, 2011 vmj.sagepub.com Downloaded from

Upload: independent

Post on 30-Apr-2023

0 views

Category:

Documents


0 download

TRANSCRIPT

http://vmj.sagepub.com/Vascular Medicine

http://vmj.sagepub.com/content/14/1/63The online version of this article can be found at:

 DOI: 10.1177/1358863X08095153

2009 14: 63Vasc MedMuhammad U Farooq, Atul Khasnis, Arshad Majid and Mounzer Y KassabThe role of optical coherence tomography in vascular medicine

  

Published by:

http://www.sagepublications.com

On behalf of: 

  Society for Vascular Medicine

can be found at:Vascular MedicineAdditional services and information for     

  http://vmj.sagepub.com/cgi/alertsEmail Alerts:

 

http://vmj.sagepub.com/subscriptionsSubscriptions:  

http://www.sagepub.com/journalsReprints.navReprints:  

http://www.sagepub.com/journalsPermissions.navPermissions:  

http://vmj.sagepub.com/content/14/1/63.refs.htmlCitations:  

by guest on May 10, 2011vmj.sagepub.comDownloaded from

The role of optical coherence tomography in vascular medicine

Muhammad U Farooq1, Atul Khasnis2, Arshad Majid1,3 and Mounzer Y Kassab1,3

Abstract: Optical coherence tomography (OCT) is an emerging imaging modality that

provides high-resolution, microstructural information on atherosclerotic plaques in

biological systems. Intracoronary OCT can identify thin-cap fibroatheroma and other

vulnerable plaques that may be responsible for acute coronary events. These charac-

teristics make OCT helpful in guiding coronary management and interventions,

including stent apposition and early identification of procedure-related complications.

OCT is being assessed for its potential role in carotid plaque characterization and in

the diagnosis of peripheral arterial atherosclerosis. Its current use in studying carotid

and cerebral vasculature and in the diagnosis of peripheral arterial diseases is limited

and ill defined, but it is finding increasing application in these areas. Its performance

can be further improved by increasing the signal to noise ratio and by using dynamic

focus tracking techniques. It can potentially be used to monitor the progression and

regression of atherosclerosis in the coronary, cerebral and peripheral vasculature.

New indications for its use in vascular medicine are emerging as its technology con-

tinues to improve over time.

Key words: carotid; coronary; optical coherence tomography; peripheral vasculature;

vulnerable plaques

Introduction

Optical coherence tomography (OCT) is a novel tech-nology for cross-sectional and three-dimensionalimaging in biological systems with ultra high resolu-tion approaching that of histology.1–3 It was firstintroduced by Huang, et al.4 in 1991 and was origi-nally designed for use in transparent tissues such asthose present in the eye.5 It integrates a wide range ofdisciplines, including fiber optics, interferometry,biomedical imaging, in vitro and in vivo studies andclinical medicine.6 OCT is a promising tool for thegenesis of biomedical images, which enables tissuepathology to be imaged in situ and in real time.7This rapidly developing technique has applicationsin a wide range of clinical specialties and has evolvedas a very useful diagnostic technique over the last

decade. It is now being used with great success toimage non-transparent tissues, including skin andgastrointestinal tract.2,4,8–11

This article discusses the valuable implication ofthis promising modality in the diagnosis and treat-ment of different atherosclerotic vascular disorders.We have mainly focused on the role of OCT in thediagnosis of vulnerable plaque in the coronary,carotid and peripheral vasculature. OCT is used tovisualize and characterize atherosclerotic plaques incoronary and carotid vasculature leading to betterrisk stratification of patients and consequentlyresulting in appropriate therapy.1,2,12,13 Its role incoronary plaque characterization is well establishedas compared to that of carotid plaque.13 It hasemerging indications in the diagnosis of peripheralvascular atherosclerosis and functional imaging ofthe brain as well.14,15

Basic principle

Optical technique using near-infrared lightOCT is an optical technique, which combines theprinciples of ultrasound with the imaging perfor-mance of a microscope. It measures the intensity ofback-reflected near-infrared light to measure thethickness of different biological tissues, which isanalogous to B-mode ultrasound imaging, except

1Department of Neurology and Ophthalmology, MichiganState University, East Lansing, Michigan, USA; 2Departmentof Rheumatology, Cleveland Clinic Foundation, Cleveland,Ohio, USA; 3Department of Neurology and Ophthalmology,Division of Cerebrovascular Diseases and InterventionalNeurology, Michigan State University, East Lansing,Michigan, USA

Correspondence to: Mounzer Kassab, A-217 Clinical Center,Michigan State University, East Lansing, MI 48824, USA.Email: [email protected]

Figures 1 and 2 are available to view in color online athttp://vmj.sagepub.com

Vascular Medicine 2009; 14: 63–71

© 2009 SAGE Publications, Los Angeles, London, New Delhi and Singapore 10.1177/1358863X08095153

by guest on May 10, 2011vmj.sagepub.comDownloaded from

that it uses light instead of sound. Sound waves areeasily transmitted in most of the biological tissuesand the deep structures in the body can be imagedusing an ultrasound technique. Ultrasound imagingdepends on the reflection of sound waves and theresolution of its measurement depends on the fre-quency of the sound waves. For a typical ultrasoundsystem, sound wave frequencies are approximately10 mHz, which yield spatial resolution of approxi-mately 150 μm. OCT uses light, which provides asignificantly higher spatial resolution than that ofany ultrasound technique. OCT images can haveaxial resolution of 10 μm, which is 10–20 timesgreater than standard B-mode ultrasound imaging.However, light used in OCT is scattered or absorbedin most of the biological tissues and it is difficult toimage deep structures in the body, which can beimaged using an ultrasound technique. These deepstructures can only be imaged if they are accessibleusing devices such as catheters or endoscopes. OCTuses an optical fiber-based design that can be readilyintegrated into catheters and endoscopes, which arecurrently being used in different specialties such ascardiology and gastroenterology.

Low coherence interferometryThe velocity of light is extremely high and muchgreater than that of sound; direct electronic detec-tion of this short time delay is impossible. OCT isbased on ‘low-coherence interferometry’, which is aspecial technique for obtaining high-resolutioncross-sectional images.2,4,6 Near-infrared light isdelivered to the imaging site through a single opticalfiber. This light enters a fiber-optic beam-splitter ora partially reflecting mirror where it is split equallyinto a reflected and transmitted beam, also calledsample arm and reference arm respectively. Thereflected light from a tissue consists of multiple ech-oes that give information about the distance andthickness of different structures in that tissue. Thesecond light beam is reflected from a reference mir-ror, which is at a known spatial position. The back-reflected reference optical beam travels back to thebeam-splitter where it combines with the opticalbeam reflected from a tissue. The light pulsereflected from the reference mirror will coincidewith the light pulse reflected from a given structurein a tissue only if both pulses arrive at the same time.In order to measure the time delays of light echoesfrom different structures within a tissue, the positionof the reference mirror is varied so that the timedelay of the reference light is adjusted accordingly.These two light pulses, as mentioned above, coin-cide and give rise to an interference pattern that ismeasured by a photodetector. It can measure dis-tances to objects with high precision by measuringthe echo time delay of the light reflected from tissues

(sample arm) and correlating it with the light thattravels a known reference path (reference arm).

Generation of OCT imagesIn this process, OCT images are generated bythe measurement of echo time delay of optical back-scattering in the tissue as a function of transverseposition. The axial resolution is measured by thecoherence length of the light source. In order to pro-duce cross-sectional tomographic images, the lightbeam is scanned across the tissue to produce two- andthree-dimensional data sets. Image resolutions of10–15 μm can be achieved.6 The output is measuredby a Michelson interferometer, which is required toextract the reflected optical signals from the infraredlight source. The output is computer processed toproduce real-time high-resolution cross-sectionalimages at near histological resolution of plaques inblood vessels. The basic OCT set up is shown inFigure 1.The technology is improving over time. The

frequency domain OCT has shown advantages inimaging speed and signal-to-noise ratio (SNR) overthe time domain OCT. High-speed image acquisitionby video-rated OCT can be achieved by using othertechniques such as piezoelectric fiber stretchersand rapid scanning phase-control delay lines. TheOCT systems can now be fiber-optically coupled to

Figure 1 Basic schematic diagram of optical coherencetomography (OCT). A broadband light source provideslow coherence light to the fiber-optic beam splitter. Thislight is spit into two arms: the sample arm and the refer-ence arm. These separate paths of light will ultimately bereflected back to the fiber-optic beam-splitter and com-bined. The light pulse reflected from the reference mirrorcoincides with the light pulse reflected from the tissue,only if both pulses arrive at the same time. The positionof the mirror is translated to alter the time delays of thetransmitted echoes of light. This translational feature pro-vides for a complex measurement of tissue depth. Whenthese two light pulses coincide an interference pattern isgenerated which can be measured by a photodetector. Itis then amplified, digitalized, and passed on to a com-puter for OCT image reconstruction.

64 MU Farooq et al.

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from

endoscopes and catheters imaging luminal structuresinside the body. Vascular OCT probes/catheters areavailable but still not approved by the Food andDrug Administration.

What makes plaques vulnerable?

The concept of ‘vulnerable plaque’ is central tocoronary and carotid vessel stenosis in the settingof atherosclerotic disease. The vulnerable plaques,which might usually account for minimal to moder-ate arterial stenosis from the nidus for thrombo-embolic events that precipitate most cases ofmyocardial infarction and stroke. These are charac-terized as having a lipid core laden with oxidizedLDL-activated macrophages, intense inflamma-tion, reduced collagen synthesis, local over-expression of collagenase, and smooth muscleapoptosis predisposing these plaques to ruptureresulting in emboli formation.16–19 Postmortemstudies have shown that most of the coronary events(~80%) are due to a type of vulnerable plaque calledthe thin-cap fibroatheroma (TCFA).20–22 TheTCFA are characterized by thin fibrous cap, largeamounts of lipids and active macrophages near orwithin the fibrous cap.20,21 (For in vivo OCT imagesof TCFA with circumferential lipid pool andplatelet-rich thrombus in coronary vessels refer toFigure 3C.) Plaque rupture occurs especially in theregion of the shoulders of the fibrotic cap due todifferent biomechanical factors resulting in therelease of tissue factor (TF, Factor III) and otherprocoagulant substances which ultimately result inthrombosis of the artery.23 Coronary plaques char-acterized by erosions and superficial calcifiednodules (see Figure 3B) can also predispose tothrombosis and sudden blockage of coronaryvasculature.16,20,21 Identifying these plaques beforethey proceed to rupture and thrombosis resulting inarterial occlusion has serious implications and pro-vides a window for possible prevention. The searchfor an optimal cardiovascular and cerebrovascularimaging modality that can best serve this purposehas led to the use of OCT as one of the most prom-ising modalities. Its ability to characterize themicroscopic features of vulnerable plaques makesit a unique imaging modality.

OCT in cardiovascular diseases

Review of currently available modalitiesSome of the more commonmodalities used to imagethe coronary circulation include conventionalangiography, intravascular ultrasound (IVUS) andangioscopy. Conventional angiography is touted as

the gold standard but has been criticized for its lim-itations of a two-dimensional nature of the imagesand its inability to characterize plaque composition.This inability of conventional angiography to char-acterize plaques makes it unable to delineate vulner-able plaques. Gossl, et al.24 reviewed the role ofangiography in the detection of vulnerable plaquesand suggested that when used with pharmacologicprovocation to identify one major criterion (stenosis> 90%) and one minor criterion (endothelial dys-function), it could have some role in defining thevulnerable plaque. It is still the most common inves-tigation for making a final diagnosis of epicardialcoronary artery disease.IVUS is another exciting technology for mapping

plaque morphology aiding prediction and decision-making in coronary atherosclerosis. Plaque mor-phology can be characterized based on ultrasoundappearance as lipid-laden (hypoechoic), fibromus-cular (low-intensity echoes), and fibrous or calcified(echogenic). The calcium content of the plaque mayresult in acoustic shadowing. IVUS technology hasbeen noted to be particularly useful for left maincoronary artery disease25 but is by no meansrestricted to this application in guiding coronaryintervention. IVUS is now routinely used in diagno-sis and interventional management of coronaryartery disease and has been used extensively in trialsevaluating the effects of lipid-lowering therapies oncoronary artery atherosclerotic plaques. The mainlimitations of IVUS are its low image resolutionand problems in its discriminatory ability in differ-entiating tissue echogenicity and texture fromechogenically similar lipid-rich lesions.26 In a studycomparing OCT and IVUS, IVUS had a specificityof 96% and 98% respectively for lipid-laden andcalcified plaques.27

Angioscopy involves direct visualization of thelumen of the coronary artery. Color coding is usedto identify plaques with a higher lipid content thatmay be more prone to rupture.28 It best evaluatesthe luminal surface of the artery; however, perturba-tions in the vessel wall remain unevaluated.

Where does OCT fit in coronary plaquecharacterization?OCT has been used regularly in ophthalmology, buthas found new uses in the domain of cardiovascularmedicine. It is an invasive microscopic imagingtechnique to identify vulnerable plaques in thearterial vasculature. Figures 2 and 3 show somein vivo and in vitro OCT images and correspondinghistology. The fibrous plaques are homogenous,signal-rich regions (Figures 2A,B; 3A), fibrocalcificplaques are signal-poor regions with sharp borders(Figures 2C,D) and lipid-rich plaques are signal-poor regions with diffuse borders (Figures 2E,F)

Optical coherence tomography in vascular medicine 65

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from

on ex vivo (Figure 2) and in vivo (Figure 3) OCTimages.29 The resolution of OCT is ten times thatof currently available IVUS. Yabushita, et al.reported sensitivity and specificity ranging from71% to 98% for fibrous plaques, 95% to 97% forfibrocalcific plaques, and 90% to 94% for lipid-richplaques among two OCT observers with good inter-observer variability (kappa = 0.83–0.84).30 OCT isnow being used for the detection of native coronaryartery disease as well as post-interventionevaluation.31,32 It is now well known and acceptedthat the microscopic composition of the plaqueholds the key to its behavior rather than its grossappearance by any imaging modality. Macrophagesare a sine qua non of atherosclerotic plaques andplay an important role from birth of the plaque (asa fatty streak) to its growth and eventual rupture.An ideal imaging technique would be one that isable to provide inside information on plaque com-position, thus helping predict its future. OCT has

shown promise in evaluating cellular aspects ofatherosclerotic plaques in both qualitative (presenceof macrophages) and quantitative (number ofmacrophages) terms. Macrophage quantificationwas done using immunoperoxidase staining withCD68 and smooth muscle actin.33 A thin fibrouscap is another well-described characteristic thatpredisposes to plaque rupture; measurement of thefibrous cap thickness has also been possible withOCT.34 In addition, OCT can evaluate other consti-tuents of the plaque-like smooth muscle cells andcollagen. The polarization properties of collagenhave been used to measure its content usingpolarization-sensitive OCT (PS-OCT).35 Recentstudies with OCT have shown that the vulnerableplaque morphology is similar in men andwomen.36 This is of interest as epidemiologic studieshave shown sex differences in pathophysiology, clin-ical presentation and outcomes in acute coronarysyndromes.

Figure 3 OCT images of coronary plaques acquired from living human patients (obtained in vivo). (A) Fibrous plaque(Fib); (B) calcific nodule (Ca); (C) thin cap fibroatheroma with circumferential lipid pool (L) and a region consistent witha platelet-rich thrombus (arrowheads). The * represents guidewire artifacts. (Reprinted from ref. 29 with permission.)

Figure 2 OCT images and corresponding histology of fibrous (A,B), calcified (C,D), lipid-rich (E,F) plaque types(obtained ex vivo). In fibrous plaques, the OCT signal (Fib) is observed to be strong and homogeneous. In comparison,both calcified (arrows) and lipid-rich regions (L) appear as signal-poor regions within the vessel wall. Lipid-rich plaqueshave diffuse or poorly demarcated borders while the borders of calcific nodules are sharply delineated. (B,D) Hematox-ylin and eosin; (F) Masson’s trichome; original magnification 40×. Scale bars, thick marks, 500 μm. (Reprinted fromref. 29 with permission.)

66 MU Farooq et al.

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from

OCT: a panacea for coronary imaging?OCT is an optical-based technology, and is moreadvantageous as it produces less rotational distor-tion, especially when evaluating tortuous segmentsof a phantom coronary artery model.37 However,this study was performed in the era of mechanicallyrotated IVUS catheters, and this technical limita-tion of non-uniform rotational distortion (NURD)may no longer apply to newer electronic IVUScatheters. A comparative study of OCT and IVUSshowed that all plaques identified by IVUS werevisualized in corresponding OCT images, but cer-tain plaque characteristics like intimal hyperplasiaand echolucent regions were identified more fre-quently by OCT.38 OCT therefore not only identi-fies abnormal plaques but also characterizes thembetter in terms of composition. There is a suggestionthat combining OCT and IVUS may provide thebest means to firmly characterize TCFA.39

OCT and percutaneous coronary interventionOCT can be helpful in coronary interventions andaids with real-time stent apposition as demonstratedby Diaz-Sandoval, et al.,40 Regar, et al.,41 andSuzuki, et al.42 It has revealed some complications,which were missed by IVUS after use of the cuttingballoon.43 Regar, et al. successfully demonstratedthe application of OCT to assess the final stentarea and recoil in real-time in their study.41 Suzuki,et al. analyzed the interstrut angles after the deploy-ment of drug-eluting stents.42 Drug-eluting stentscan significantly limit neointimal growth. IVUScannot accurately visualize the neointimal tissue ifit consists of only a few cell layers. OCT providesmore precise information about neointimal prolifer-ation on drug-eluting struts and makes it possible toquantify the thickness of tissue on the surface of thestent struts.44,45 Moreover, sirolimus-eluting stentsare susceptible to late thrombosis due to delayedre-endothelialization over the stent struts, whichmay result in different complications includingacute myocardial infarction. OCT can visualize thestrut apposition to the vessel wall and neointimalcoverage on sirolimus-eluting stents struts.46 Thisinformation might be helpful to direct the need forprolonged antiplatelet or anticoagulation therapyafter these stent placements in patients with coro-nary artery disease and related disorders. Based onthe results of these studies, OCT is a potentiallypromising modality in stent design9 as well as forearly identification of procedure-related complica-tions and long-term management in these patients.The major limitations of OCT in coronary artery

application have been the ability to map only veryshort arterial segments at a time, the inability toassess coronary arterial wall remodeling (thatIVUS can), problems with signal attenuation by

red blood cells (owing to a mismatch of refractiveproperties between the red blood cells (RBCs) andserum), and the potential prolongation of myocar-dial ischemia (because of the employment of bal-loon occlusion or frequent saline flushes to clearthe visualized field of interest). The use of index-matching by infusing solutions that negate therefractive differences between RBCs and surround-ing media and optical frequency domain imaging(OFDI) may surmount some of these technical dif-ficulties leading to increased use and a wider appli-cation of OCT as an imaging modality in coronaryarterial diagnosis and therapeutics.

OCT in cerebrovascular diseases

Review of currently available modalitiesA large number of strokes are caused by previouslyasymptomatic vulnerable atherosclerotic plaques,the morphology and material composition ofwhich may be more important determinants ofacute cerebral events than the degree of stenosisitself. Spontaneous rupture of atheroscleroticcarotid plaques with subsequent thrombosis is oneof the important mechanisms of acute stroke.Because mortality and morbidity after acute strokeare high, the characterization of atherosclerotic pla-ques is assuming greater importance in determiningthe risk of cerebrovascular events, including tran-sient ischemic attacks. Better characterization ofthese vulnerable plaques may also be needed tostratify patients for further interventions such ascarotid endarterectomy or stenting.Carotid Doppler, CT angiography, magnetic res-

onance (MR) imaging and conventional four-vesselangiography are currently available vascular studiesbeing used in stroke patients. These studies do notprovide satisfactory characteristics of vascular pla-ques. B-mode ultrasound and some newer MR tech-niques may provide some help in this regard.Different studies have shown the efficacy of

B-mode ultrasound in predicting outcomes inpatients with carotid stenosis by studying differentplaque characteristics.47–50 Plaque components thathave been studied in this way include intra-plaquehemorrhage, lipids, fibrosis, necrosis, calcification,and mural thrombus. On ultrasound examination,echolucency and heterogenicity herald poor prog-nosis among patients with high-grade carotidstenosis.48,49 However, ultrasound has its own lim-itations and sometimes it is hard to differentiate var-ious plaque characteristics due to its limited imagingresolution.51

MR imaging techniques have been used in carotidplaque characterization and are highly sensitive andspecific in resolving lipid-rich necrotic core regions

Optical coherence tomography in vascular medicine 67

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from

and fibrous cap thickness.52–57 The ultra-smallsuperparamagnetic iron oxide particle (USPIO)contrast-enhanced MRI techniques identify carotidplaque characteristics.56,58,59 Gadolinium-basedcontrast agents can penetrate human atheroscleroticcarotid plaques, indicating the extent and size ofplaque neovascularization, which is an importantfeature of vulnerable plaques.56 MR of carotidarteries after USPIO injection can identify plaqueinflammation due to the accumulation of USPIOwithin macrophages in the carotid plaque.60 MRtechniques have made tremendous recent stridesalong with continuous refinement.Other imaging studies including CTA and con-

ventional angiograms do not give much informationabout plaques, which are not causing hemodynami-cally significant stenosis. Most of the vulnerableplaques cause mild to moderate stenosis and caneasily be missed by these imaging techniques.These techniques are also not very useful for thediscrimination of plaque composition thought tobe central to disease progression and overallprognosis.61,62

Where does OCT fit in carotid plaquecharacterization?OCT is being assessed for its potential use in theidentification of carotid stenosis and distinctionbetween stable and unstable atheroscleroticplaques.13,63 Its high resolution and non-invasiveexternal usage are promising features to be usedfor characterization of carotid plaques. It can behelpful in improving patient risk stratification anddecision-making for carotid endarterectomy.13

Prabhudesai, et al. conducted a pilot study to evalu-ate OCT as a non-invasive diagnostic technique toreveal the morphology of carotid plaques from theadventitial surface of carotid artery.13 Their studydemonstrated that OCT can reveal the main fea-tures of carotid stenosis but scanning from the exter-nal surface cannot assess the thickness of fibrous capand plaque vulnerability very reliably and preciselydue to the reduction in light penetration. Perfor-mance of OCT in carotid plaque characterizationfrom the external surface can be improved byincreasing the SNR, depth of focus of the samplingbeam and by using dynamic focus trackingtechniques.64 SNR indicates the ratio of the strengthof a signal to the strength of any background noisethat might be present at a given point in time. Thehigher the SNR, the more easily the signal can bedistinguished. The use of a dynamic focus trackingsystem helps to increase resolution of the imagesobtained by OCT in retinal imaging.65 This princi-ple can be applied to improve the quality of studyresults for carotid vessels.

OCT and cerebral aneurysmsEndovascular coil embolization is a promising tech-nique to treat cerebral aneurysms. These patientsrequire multiple follow-up angiographic studies afterinitial intervention. Thorell, et al. studied the potentialuse of OCT to see the neck of aneurysms created in ananimal model and treated with coil embolization.OCT images demonstrated changes that correlatedwith histological findings at the aneurysm neck. Thisstudy supports the potential use of OCT in follow-upmanagement of patients with cerebral aneurysmstreated with endovascular coil embolization. Thispromising technique might aid to understand thehealing process after endovascular intervention inthese cases. This data is based only on one animalstudy and further research is needed to explore thepotential benefit of OCT in vascular neurology.66Currently available vascular OCT probes need to beadapted for use in cerebral circulation.

OCT and brain microcirculation – functionalimaging of brainThe importance of the structural–functional corre-lation cannot be overemphasized when studying thecerebral vasculature. OCT has the potential to beused to study the three-dimensional configurationand cross-sectional structure of the cerebral-cortical microvessels. Satomura, et al., in their ani-mal study, demonstrated the potential of OCT infunctional imaging of the brain by observing themicrocirculation in the rat cerebral cortex.15 Thecross-sectional images of the cerebral cortex (up toabout 1 mm depth with longitudinal resolution upto 8 μm) were obtained in this study. OCT was ableto visualize the cross-sectional structure of the men-ingeal (dura and arachnoid matter along with pialmicrovessels) and cortical tissue through the cranialwindow. However, the lumen of microvessels andthe microvessels running deeper within the corticaltissues were not clearly seen. Stimulus responses ofthe somatosensory cortices and velocity profilewithin microvessels were also studied. The surfaceof the somatosensory cortex was seen to rise whenthe hind paw of the study animal was electricallystimulated. The rise time is consistent with that offunctional hyperemia in response to neuronal acti-vation and the swelling of the cortical surface can bedue to the regional increase in blood volume.15 Thisstudy supports the usefulness and potential applica-tion of OCT in functional imaging of the brain andwarrants further studies.

OCT in peripheral vascular diseases

The composition of atherosclerotic plaque may beof interest for optimal treatment strategies in

68 MU Farooq et al.

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from

peripheral arteries with the introduction of newinterventional procedures such as cutting balloonangioplasty, intravascular cryoablation, and intra-vascular atherectomy.14 Currently, OCT is theonly imaging modality that has the potential to beused to characterize the nature of atheroscleroticplaque in peripheral vasculature. The underlyingpathophysiology of atherosclerosis involving theperipheral vasculature is assumed to be the sameas that of coronary and carotid arteries. Therewere no OCT-defined imaging criteria for periph-eral vasculature before the work of Meissner,et al., who studied the potential role of OCT inperipheral vascular diseases due to atherosclerosisand showed that their findings were comparablewith those reported for coronary arteries.14 TheOCT findings in their study were in agreementwith histopathologic findings of different athero-sclerotic plaque types. The interobserver andintraobserver reliabilities of OCT assessment werehigh (κ values of 0.84 and 0.87, respectively). Theintermethod agreement was 0.74 for consensusOCT versus consensus histology.14 There were afew limitations to this study, including the use ofarterial segments rather than patients and ex vivostudy of arteries from amputated extremities. How-ever, this was the first attempt to define the role ofOCT imaging criteria in studying the peripheralvasculature. OCT has the potential to be used tomonitor the progression or regression of peripheralarterial atherosclerosis in humans.14

Advantages and limitations of OCT

Advantages of OCT include high image resolutionand acquisition speed, reduced cost, portability, and,most importantly, its predictability of plaque behav-ior based on morphological plaque characteristics.1It has the ability to see beyond calcified plaques andvisualize the intima, which is a unique feature of thistechnology.38 The OCT catheter does not require atransducer and the imaging guidewire is small andinexpensive.8,9

OCT has its limitations as well. Image acquisitionby OCT is hampered by the presence of blood. Theblood flow may overwhelm techniques used to clearthe visualized field and result in problems withimage quality and interpretation. Index matchingtechnology has been used to allow better visualiza-tion through blood.67 One other limitation of OCTis its penetrability through the non-transparent tis-sues; with visualization limited to 2–3 mm.8,68 Thiscan substantially impede image quality in arteriescontaining significant necrotic debris. AdvancedOCT imaging techniques, including spectral radarand source-sweeped OCT, are being developed to

overcome this flaw of current OCT.69 The sampletemperature can affect the OCT measurementsand this effect should be kept in mind while inter-preting the readings.70

Overall, OCT is a lucrative technology and yieldsinvaluable information about plaque morphologyenabling better invasive and non-invasive assess-ment and management of native and post-intervention coronary and carotid artery disease.With the passage of time, OCT technology is likelyto advance, providing more useful information andcomplementing other modalities of studying athero-sclerotic plaques.

References

1 Tearney, GJ, Brezinski, ME, Bouma, BE, et al. In vivoendoscopic optical biopsy with optical coherence tomogra-phy. Science 1997; 276: 2037–2039.

2 Brezinski, ME, Tearney, GJ, Bouma, BE, et al. Opticalcoherence tomography for optical biopsy. Properties anddemonstration of vascular pathology. Circulation 1996;93: 1206–1213.

3 Fujimoto, JG, Pitris, C, Boppart, SA, Brezinski, ME.Optical coherence tomography: an emerging technologyfor biomedical imaging and optical biopsy. Neoplasia2000; 2: 9–25.

4 Huang, D, Swanson, EA, Lin, CP, et al. Optical coherencetomography. Science 1991; 254: 1178–1181.

5 Swanson, EA. In vivo retinal imaging by optical coherencetomography. Optics Lett 1993; 18: 1864–1866.

6 Fujimoto, JG. Optical coherence tomography for ultrahighresolution in vivo imaging. Nat Biotechnol 2003; 21: 1361–1367.

7 Fujimoto, JG, Brezinski, ME, Tearney, GJ, et al. Opticalbiopsy and imaging using optical coherence tomography.Nat Med 1995; 1: 970–972.

8 Brezinski, ME, Tearney, GJ, Weissman, NJ, et al. Asses-sing atherosclerotic plaque morphology: comparison ofoptical coherence tomography and high frequency intravas-cular ultrasound. Heart 1997; 77: 397–403.

9 Pinto, TL, Waksman, R. Clinical applications of opticalcoherence tomography. J Interv Cardiol 2006; 19: 566–573.

10 Welzel, J, Lankenau, E, Birngruber, R, Engelhardt, R.Optical coherence tomography of the human skin. J AmAcad Dermatol 1997; 37: 958–963.

11 Li, XD, Boppart, SA, Van Dam, J, et al. Optical coherencetomography: advanced technology for the endoscopicimaging of Barrett’s esophagus. Endoscopy 2000; 32: 921–930.

12 Tearney, GJ, Brezinski, ME, Boppart, SA, et al. Images incardiovascular medicine. Catheter-based optical imaging ofa human coronary artery. Circulation 1996; 94: 3013.

13 Prabhudesai, V, Phelan, C, Yang, Y, Wang, RK, Cowling,MG. The potential role of optical coherence tomography inthe evaluation of vulnerable carotid atheromatous plaques:a pilot study. Cardiovasc Intervent Radiol 2006; 29: 1039–1045.

14 Meissner,OA,Rieber, J, Babaryka,G, et al. Intravascular opti-cal coherence tomography: comparison with histopathology in

Optical coherence tomography in vascular medicine 69

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from

atherosclerotic peripheral artery specimens. J Vasc IntervRadiol 2006; 17: 343–349.

15 Satomura, Y, Seki, J, Ooi, Y, Yanagida, T, Seiyama, A. Invivo imaging of the rat cerebral microvessels with opticalcoherence tomography. Clin Hemorheol Microcirc 2004;31: 31–40.

16 Farb, A, Burke, AP, Tang, AL, et al. Coronary plaque ero-sion without rupture into a lipid core. A frequent cause ofcoronary thrombosis in sudden coronary death. Circulation1996; 93: 1354–1363.

17 Naghavi, M, Libby, P, Falk, E, et al. From vulnerable pla-que to vulnerable patient: a call for new definitions and riskassessment strategies: Part I. Circulation 2003; 108: 1664–1672.

18 Kolodgie, FD, Virmani, R, Burke, AP, et al. Pathologicassessment of the vulnerable human coronary plaque.Heart 2004; 90: 1385–1391.

19 Libby, P. Current concepts of the pathogenesis of the acutecoronary syndromes. Circulation 2001; 104: 365–372.

20 Kolodgie, FD, Burke, AP, Farb, A, et al. The thin-capfibroatheroma: a type of vulnerable plaque: the major pre-cursor lesion to acute coronary syndromes. Curr Opin Car-diol 2001; 16: 285–292.

21 Virmani, R, Kolodgie, FD, Burke, AP, Farb, A, Schwartz,SM. Lessons from sudden coronary death: a comprehensivemorphological classification scheme for atheroscleroticlesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262–1275.

22 Davies, MJ. Stability and instability: two faces of coronaryatherosclerosis. The Paul DudleyWhite lecture 1995.Circu-lation 1996; 94: 2013–2020.

23 Cheng, GC, Loree, HM, Kamm, RD, Fishbein, MC, Lee,RT. Distribution of circumferential stress in ruptured andstable atherosclerotic lesions. A structural analysis with his-topathological correlation. Circulation 1993; 87: 1179–1187.

24 Gossl, M, Versari, D, Hildebrandt, H, et al. Vulnerable pla-que: detection and management. Med Clin North Am 2007;91: 573–601.

25 Nissen, SE, Yock, P. Intravascular ultrasound: novelpathophysiological insights and current clinical applica-tions. Circulation 2001; 103: 604–616.

26 Vaina, S, Stefanadis, C. Detection of the vulnerable coro-nary atheromatous plaque. Where are we now. Int J Cardi-ovasc Intervent 2005; 7: 75–87.

27 Rieber, J, Meissner, O, Babaryka, G, et al. Diagnosticaccuracy of optical coherence tomography and intravascu-lar ultrasound for the detection and characterization of ath-erosclerotic plaque composition in ex-vivo coronary speci-mens: a comparison with histology. Coron Artery Dis 2006;17: 425–430.

28 Ishibashi, F, Aziz, K, Abela, GS, Waxman, S. Update oncoronary angioscopy: review of a 20-year experience andpotential application for detection of vulnerable plaque.J Interv Cardiol 2006; 19: 17–25.

29 Tearney, GJ, Jang, IK, Bouma, BE. Optical coherencetomography for imaging the vulnerable plaque. J BiomedOpt 2006; 11: 021002.

30 Yabushita, H, Bouma, BE, Houser, SL, et al. Characteriza-tion of human atherosclerosis by optical coherence tomog-raphy. Circulation 2002; 106: 1640–1645.

31 Shite, J, Matsumoto, D, Yokoyama, M. Sirolimus-elutingstent fracture with thrombus, visualization by opticalcoherence tomography. Eur Heart J 2006; 27: 1389.

32 Gupta, R, Raffel, OC, Jang, IK. Severe intimal hyperplasiaafter sirolimus eluting stent deployment: evaluation by opti-cal coherence tomography. Heart 2007; 93: 754.

33 Tearney, GJ, Yabushita, H, Houser, SL, et al. Quantifica-tion of macrophage content in atherosclerotic plaques byoptical coherence tomography. Circulation 2003; 107:113–119.

34 Kume, T, Akasaka, T, Kawamoto, T, et al. Measurementof the thickness of the fibrous cap by optical coherencetomography. Am Heart J 2006; 152: 755.e1–4.

35 Giattina, SD, Courtney, BK, Herz, PR, et al. Assessment ofcoronary plaque collagen with polarization sensitive opticalcoherence tomography (PS-OCT). Int J Cardiol 2006; 107:400–409.

36 Chia, S, Christopher Raffel, O, Takano, M, Tearney, GJ,Bouma, BE, Jang, IK. In-vivo comparison of coronary pla-que characteristics using optical coherence tomography inwomen vs. men with acute coronary syndrome. CoronArtery Dis 2007; 18: 423–427.

37 Nadkarni, SK, Pierce, MC, Park, BH, et al. Measurementof collagen and smooth muscle cell content in atheroscle-rotic plaques using polarization-sensitive optical coherencetomography. J Am Coll Cardiol 2007; 49: 1474–1481.

38 Jang, IK, Bouma, BE, Kang, DH, et al. Visualization ofcoronary atherosclerotic plaques in patients using opticalcoherence tomography: comparison with intravascularultrasound. J Am Coll Cardiol 2002; 39: 604–609.

39 Sawada, T, Shite, J, Garcia-Garcia, HM, et al. Feasibilityof combined use of intravascular ultrasound radiofre-quency data analysis and optical coherence tomographyfor detecting thin-cap fibroatheroma. Eur Heart J 2008;29: 1136–1146.

40 Diaz-Sandoval, LJ, Bouma, BE, Tearney, GJ, Jang, IK.Optical coherence tomography as a tool for percutaneouscoronary interventions. Catheter Cardiovasc Interv 2005;65: 492–496.

41 Regar, E, Schaar, J, Serruys, PW. Images in cardiology.Acute recoil in sirolimus eluting stent: real time, in vivoassessment with optical coherence tomography. Heart2006; 92: 123.

42 Suzuki, Y, Ikeno, F, Yeung, AC. Drug-eluting stent strutdistribution: a comparison between Cypher and Taxus byoptical coherence tomography. J Invasive Cardiol 2006;18: 111–114.

43 Ito, S, Itoh, M, Suzuki, T. Intracoronary imaging with opti-cal coherence tomography after cutting balloon angioplastyfor in-stent restenosis. J Invasive Cardiol 2005; 17: 369–370.

44 Kume, T, Akasaka, T, Kawamoto, T, et al. Visualization ofneointima formation by optical coherence tomography. IntHeart J 2005; 46: 1133–1136.

45 Matsumoto, D, Shite, J, Shinke, T, et al. Neointimal cover-age of sirolimus-eluting stents at 6-month follow-up: evalu-ated by optical coherence tomography. Eur Heart J 2007;28: 961–967.

46 Yao, ZH, Matsubara, T, Inada, T, Suzuki, Y, Suzuki, T.Neointimal coverage of sirolimus-eluting stents 6 monthsand 12 months after implantation: evaluation by opticalcoherence tomography. Chin Med J 2008; 121: 503–507.

47 AbuRahma, AF, Kyer 3rd, PD, Robinson, PA, Hannay,RS. The correlation of ultrasonic carotid plaque morphol-ogy and carotid plaque hemorrhage: clinical implications.Surgery 1998; 124: 721–726.

70 MU Farooq et al.

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from

48 Aburahma, AF, Thiele, SP, Wulu Jr, JT. Prospective con-trolled study of the natural history of asymptomatic 60% to69% carotid stenosis according to ultrasonic plaque mor-phology. J Vasc Surg 2002; 36: 437–442.

49 Gronholdt, ML, Nordestgaard, BG, Schroeder, TV,Vorstrup, S, Sillesen, H. Ultrasonic echolucent carotid pla-ques predict future strokes. Circulation 2001; 104: 68–73.

50 Schulte-Altedorneburg, G, Droste, DW, Haas, N, et al.Preoperative b-mode ultrasound plaque appearance com-pared with carotid endarterectomy specimen histology.Acta Neurol Scand 2000; 101: 188–194.

51 Eliasziw, M, Rankin, RN, Fox, AJ, Haynes, RB, Barnett,HJ. Accuracy and prognostic consequences of ultrasonog-raphy in identifying severe carotid artery stenosis. NorthAmerican Symptomatic Carotid Endarterectomy Trial(NASCET) group. Stroke 1995; 26: 1747–1752.

52 Hatsukami, TS, Ross, R, Polissar, NL, Yuan, C. Visualiza-tion of fibrous cap thickness and rupture in human athero-sclerotic carotid plaque in vivo with high-resolution magneticresonance imaging. Circulation 2000; 102: 959–964.

53 Coombs, BD, Rapp, JH, Ursell, PC, Reilly, LM, Saloner,D. Structure of plaque at carotid bifurcation: high-resolution MRI with histological correlation. Stroke 2001;32: 2516–2521.

54 Yuan, C, Mitsumori, LM, Ferguson, MS, et al. In vivoaccuracy of multispectral magnetic resonance imaging foridentifying lipid-rich necrotic cores and intraplaque hemor-rhage in advanced human carotid plaques. Circulation2001; 104: 2051–2056.

55 Adame, IM, de Koning, PJ, Lelieveldt, BP, Wasserman,BA, Reiber, JH, van der Geest, RJ. An integrated auto-mated analysis method for quantifying vessel stenosis andplaque burden from carotid MRI images: combined post-processing of MRA and vessel wall MR. Stroke 2006; 37:2162–2164.

56 Kawahara, I, Morikawa, M, Honda, M, et al. High-resolution magnetic resonance imaging using gadolinium-based contrast agent for atherosclerotic carotid plaque.Surg Neurol 2007; 68: 60–65.

57 Cai, J, Hatsukami, TS, Ferguson, MS, et al. In vivo quan-titative measurement of intact fibrous cap and lipid-richnecrotic core size in atherosclerotic carotid plaque: compar-ison of high-resolution, contrast-enhanced magneticresonance imaging and histology. Circulation 2005; 112:3437–3444.

58 Howarth, S, Li, ZY, Trivedi, RA, et al. Correlation of mac-rophage location and plaque stress distribution usingUSPIO-enhanced MRI in a patient with symptomatic

severe carotid stenosis: a new insight into risk stratification.Br J Neurosurg 2007; 21: 396–398.

59 Tang, TY, Howarth, SP, Li, ZY, et al. Correlation ofcarotid atheromatous plaque inflammation with bio-mechanical stress: utility of USPIO enhanced MR imagingand finite element analysis. Atherosclerosis 2008; 196: 879–887.

60 Trivedi, RA, Mallawarachi, C. U-King-Im, JM, et al.Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arter-ioscler Thromb Vasc Biol 2006; 26: 1601–1606.

61 Gronholdt, ML, Wagner, A, Wiebe, BM, et al. Spiral com-puted tomographic imaging related to computerized ultra-sonographic images of carotid plaque morphology andhistology. J Ultrasound Med 2001; 20: 451–458.

62 Walker, LJ, Ismail, A, McMeekin, W, Lambert, D,Mendelow, AD, Birchall, D. Computed tomographyangiography for the evaluation of carotid atheroscleroticplaque: correlation with histopathology of endarterectomyspecimens. Stroke 2002; 33: 977–981.

63 Zimarino, M, Prati, F, Stabile, E, et al. Optical coherencetomography accurately identifies intermediate atheroscle-rotic lesions – an in vivo evaluation in the rabbit carotidartery. Atherosclerosis 2007; 193: 94–101.

64 Divetia, A, Hsieh, T, Zhang, J, Chen, Z, Bachman, M, Li,G. Dynamically focused optical coherence tomography forendoscopic applications. Appl Phys Lett 2005; 86: 103902.

65 Pircher, M, Gotzinger, E, Hitzenberger, CK. Dynamicfocus in optical coherence tomography for retinal imaging.J Biomed Opt 2006; 11: 054013.

66 Thorell, WE, Chow, MM, Prayson, RA, et al. Opticalcoherence tomography: a new method to assess aneurysmhealing. J Neurosurg 2005; 102: 348–354.

67 Kawase, Y, Suzuki, Y, Ikeno, F, et al. Comparison of non-uniform rotational distortion between mechanical IVUSand OCT using a phantom model. Ultrasound Med Biol2007; 33: 67–73.

68 Stamper, D, Weissman, NJ, Brezinski, M. Plaque charac-terization with optical coherence tomography. J Am CollCardiol 2006; 47: C69–C79.

69 Brezinski, M, Saunders, K, Jesser, C, Li, X, Fujimoto, J.Index matching to improve optical coherence tomographyimaging through blood. Circulation 2001; 103: 1999–2003.

70 Van der Meer, FJ, Faber, DJ, Cilesiz, I, van Gemert, MJ,van Leeuwen, TG. Temperature-dependent optical proper-ties of individual vascular wall components measured byoptical coherence tomography. J Biomed Opt 2006; 11:041120.

Optical coherence tomography in vascular medicine 71

Vascular Medicine 2009; 14: 63–71

by guest on May 10, 2011vmj.sagepub.comDownloaded from