Hybrid Intravascular Imaging Current Applications and Prospective Potential in the Study of Coronary Atherosclerosis

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Journal of the American College of Cardiology Vol. 61, No. 13, 2013 © 2013 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2012.10.057

STATE-OF-THE-ART PAPER

Christos V. Bourantas, MD, PHD,* Hector M. Garcia-Garcia, MD, PHD,* Katerina K. Naka, MD,† Antonios Sakellarios, BSC,‡ Lambros Athanasiou, BSC,‡ Dimitrios I. Fotiadis, PHD,‡ Lampros K. Michalis, MD,† Patrick W. Serruys, MD, PHD* Rotterdam, the Netherlands; and Ioannina, Greece

The miniaturization of medical devices and the progress in image processing have allowed the development of a multitude of intravascular imaging modalities that permit more meticulous examination of coronary pathology. However, these techniques have signiﬁcant inherent limitations that do not allow a complete and thorough assessment of coronary anatomy. To overcome these drawbacks, fusion of different invasive and noninvasive imaging modalities has been proposed. This integration has provided models that give a more detailed understanding of coronary artery pathology and have proved useful in the study of the atherosclerotic process. In this review, the authors describe the currently available hybrid imaging approaches, discuss the technological innova- tions and efﬁcient algorithms that have been developed to integrate information provided by different invasive techniques, and stress the advantages of the obtained models and their potential in the study of coronary atherosclerosis. (J Am Coll Cardiol 2013;61:1369–78) © 2013 by the American College of Cardiology Foundation

Coronary artery disease is the leading cause of death in the Atheroma burden and its composition seem to affect prog- developed world (1). Its prevalence has been attributed to nosis, as there is evidence that cardiovascular outcomes and population aging and sedentary lifestyles and is expected to the occurrence of acute coronary events depend not only on rise in the coming years. During the past decades, there has the severity of luminal narrowing but also on plaque been considerable progress in understanding the pathophys- characteristics and inflammation (2). To address these iology of coronary artery disease, while devices, imaging limitations and study in more detail the natural evolution of techniques, and therapeutic strategies have been developed atherosclerosis, considerable effort has been made in devel- aiming to optimize the treatment of patients with ischemic oping new imaging modalities that would permit the precise heart disease. These advances have made feasible the treat- evaluation of coronary pathology. Advances in signal pro- ment of complex lesions and high-risk patients, improving cessing and the miniaturization of medical devices have their prognosis and quality of life. allowed numerous intravascular imaging techniques to However, these developments have also created the need emerge (e.g., intravascular ultrasound [IVUS], optical co- for more detailed imaging of coronary anatomy and pathol- herence tomography [OCT], near-infrared spectroscopic ogy. It is apparent that contrast coronary angiography, [NIRS] imaging, intravascular magnetic spectroscopy, in- which is the traditional method for the visualization of travascular magnetic resonance imaging, Raman spectros- coronary artery disease, has significant limitations in assess- copy, intravascular photoacoustic [IVPA] imaging, near- ing the extent and severity of atherosclerosis, as it permits infrared fluorescence [NIRF] imaging, and time resolved only a 2-dimensional evaluation of luminal dimensions and fluorescence spectroscopic [TRFS] imaging), which have is unable to provide information regarding vessel walls. enriched our knowledge of coronary atherosclerosis by providing detailed visualization of luminal and plaque morphology and reliable quantification of the atheroma burden From the *Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; and its composition (Online Fig. 1)(3,4). Although these †Department of Cardiology, University of Ioannina, Ioannina, Greece; and the ‡Unit modalities offer a plethora of new data, each also has of Medical Technology and Intelligent Information Systems, Department of Mate- rials Science and Engineering, University of Ioannina, Ioannina, Greece. Dr. inherent limitations that do not allow complete evaluation Bourantas is supported by the Hellenic Heart Foundation. Dr. Michalis has received of the coronary arteries (Online Appendix). To address this research grants from Menarini. All other authors have reported that they have no drawback, hybrid imaging has been proposed. Hybrid im- relationships relevant to the contents of this paper to disclose. Manuscript received May 7, 2012; revised manuscript received October 6, 2012, aging is the combination of different imaging techniques accepted October 9, 2012. with complementary strengths into advanced images and 1370 Bourantas et al. JACC Vol. 61, No. 13, 2013 Applications of Hybrid Intravascular Imaging April 2, 2013:1369–78

Abbreviations models that allow more detai- include advanced visualization modules for comprehensive and Acronyms led and comprehensive coronary 3D coronary representation (Fig. 1)(13–15). Although visualization. these provide holistic and detailed coronary visualization, computed ؍ CTCA tomographic coronary The aims of this review are to they have applications only in research. This controversy has angiography describe the currently available been attributed to the facts that coronary reconstruction is intravascular intravascular-based hybrid imag- time consuming and requires specific expertise and that the ؍ IVPA photoacoustic ing modalities, cite the advantages additional information it provides cannot affect medical .intravascular of the provided images and mod- management ؍ IVUS ultrasound els, stress the methodological lim- Fusion of IVUS and computed tomography. The inte- near-infrared itations of each approach, and dis- gration of IVUS and x-ray may allow the evaluation of ؍ NIRF fluorescence cuss their potential value in the plaque distribution in a vessel, but it cannot include coro- -near-infrared study of coronary atherosclerosis. nary bifurcations and portray side branches. Two ap ؍ NIRS spectroscopic proaches have been proposed for this purpose, but both optical coherence Hybrid Intravascular Imaging: appear tedious and time consuming (16,17). This limitation ؍ OCT tomography Current Status was addressed by the method developed by van der Giessen quantitative et al. (18), who fused IVUS and computed tomographic ؍ QCA coronary angiography Fusion of IVUS and coronary coronary angiographic data. The proposed method used angiography. The fusion of ؍ 3D 3-dimensional computed tomographic coronary angiography (CTCA) to IVUS and x-ray angiography was -time-resolved define the centerline of the lumen and anatomical land ؍ TRFS fluorescence spectroscopic performed for the first time in 1992 marks seen on both IVUS and CTCA to identify the and was the first intravascular- position and the orientation of IVUS images onto the based hybrid imaging technique extracted centerline. Similar approaches have been recently (5). Although the proposed approach had significant method- proposed by Boogers et al. (19) and Voros et al. (20) ological limitations, it opened new horizons in coronary rep- (Online Fig. 2). resentation, as it combined information regarding vessel ge- Although these methods are restricted only to patients ometry (given by coronary angiography) and vessel wall who have undergone CTCA, coronary angiography, and pathology (provided by IVUS). In recent years, several more IVUS, they have attracted attention because they permit efficient methodologies have been introduced that have man- direct comparison of the estimations of IVUS and aged to overcome the limitations of this approach (e.g., CTCA. This erratic combination of invasive and nonin- unreliable extraction of the catheter path and orientation of the vasive techniques has broken the boundaries of conven- IVUS frames) and achieve reliable and complete coronary tional imaging and allowed the detailed evaluation of the representation (6–8). capabilities and limitations of CTCA in characterizing The obtained 3-dimensional (3D) models allow compre- coronary atheroma. Thus, these techniques have already hensive visualization of vessel geometry and plaque distri- been used to demonstrate that CTCA provides reliable bution and have been extensively used in research to study identification of plaque and accurate evaluation of the the association between local hemodynamic factors and the luminal, outer vessel wall, and plaque dimensions, but it progression of atherosclerosis. Thus, today it is known that has moderate capability in assessing the proportions of low and oscillatory shear stress have both atheropromoting different plaque types in its composition (19,21). and neointimal formation effects and contribute to the Combination of IVUS and NIRS imaging. IVUS has development of high-risk plaques (9–11). Recently, the limited capability in detecting the composition of the PREDICTION (Prediction of Progression of Coronary plaque, while the radiofrequency backscatter analysis of the Artery Disease and Clinical Outcome Using Vascular Pro- IVUS signal, which seems to provide more reliable plaque filing of Shear Stress and Wall Morphology) study was characterization, results in erroneous estimations about the reported, in which serial IVUS examinations were used to lipid tissue in stented segments and in areas behind calcified investigate the effect of blood flow on the natural evolution plaques (22). To address this drawback, a fusion of IVUS of atherosclerosis. In that study, the acquired IVUS data and NIRS imaging has been proposed. A new intravascular were fused with angiographic data to reconstruct the coro- imaging catheter has recently been developed, the TVC nary arteries of 502 patients at baseline and at 6-month to Imaging System (MC 7 system, InfraReDx, Burlington, 10-month follow-up. Blood flow simulation was performed Massachusetts), which has both an NIRS light source and in the baseline models, and endothelial shear stress was an IVUS probe on its tip, allowing the simultaneous estimated. It was found that low endothelial shear stress was acquisition of NIRS and IVUS data (Fig. 2). The feasibility associated with plaque progression and expansive remodel- of combined IVUS and NIRS imaging has already been ing and was an independent predictor of luminal narrowing tested, and currently this hybrid catheter is being used in the and of future culprit lesions (12). IBIS-3 (Integrated Biomarker and Imaging Study 3), which Currently, 3 systems are available that can integrate IVUS is examining the effect of rosuvastatin on lipid-rich coronary and x-ray angiography in a user-friendly environment and atherosclerotic plaques (23). JACC Vol. 61, No. 13, 2013 Bourantas et al. 1371 April 2, 2013:1369–78 Applications of Hybrid Intravascular Imaging

Figure 1 3-Dimensional Reconstruction of Coronary Anatomy Using ANGIOCARE Software

(A) Automated segmentation of the intravascular ultrasound sequence. (B) Extraction of the catheter path from 2 angiographic images. (C) Back-projection of the reconstructed model onto the angiographic image. (D) Three-dimensional visualization of the ﬁnal model; the outer vessel wall is portrayed in a transparent fashion to allow evaluation of the distribution of the plaque. (E) The user can interact with the ﬁnal model, select a segment of interest, and obtain quantitative data regarding its length and the luminal, outer vessel wall, and plaque dimensions that are displayed at the bottom left side of the screen. (F) Virtual endoscopy and assessment of vessel anatomy from inside.

Recently, this catheter has been used to fuse computed hemodynamic status. Some investigators have advocated tomographic coronary angiographic, IVUS, and NIRS data. that high shear and tensile stress may contribute to plaque This approach provides 3D models that permit the identi- destabilization and rupture (27,28). It is expected that the fication of the location of lipid-rich plaques, and thus it may integration of OCT with coronary angiography will provide prove useful in examining the associations among vessel the substrate to study in vivo the impact of blood flow on geometry, shear stress, and plaque composition (Fig. 3)(24). acute coronary syndromes (Online Fig. 3). Combination of OCT and coronary angiography. The fusion of OCT and coronary angiography aims to merge information regarding vessel geometry and plaque type in a Hybrid Intravascular Imaging: Future Trends single hybrid model. Two methodologies are currently avail- Combination of IVUS and OCT. Fusion of IVUS and able. The first approach uses the method applied to reconstruct OCT would provide ideal imaging of luminal and vessel the coronary arteries from IVUS and angiographic data, while wall pathology. IVUS with increased penetration would the other, which was introduced by Tu et al. (25), can integrate allow assessment of plaque burden and identification of quantitative coronary angiography (QCA) and OCT/IVUS positive or negative remodeling, while high-resolution (26). The latter method uses biplane QCA to reconstruct the OCT would permit assessment of luminal morphology, vessel and then uses anatomical landmarks seen on both QCA accurate estimation of fibrous cap thickness, identification and OCT/IVUS to register the frames onto the reconstructed of thrombus, and detection of plaque erosion and rupture. by QCA vessel. In contrast to the approach proposed by In addition, the combined information provided by both Bourantas et al. (26), this method can process frequency- modalities would permit a more precise characterization of domain OCT data, but it is unable to estimate the orientation the type of plaque, as IVUS can “see” behind lipid-rich of the OCT frames onto the 3D vessel. plaques, while OCT can penetrate calcium deposits (Online IVUS has helped us study the natural evolution of Fig. 4)(29). Recent studies have demonstrated that the atherosclerosis, but its low resolution did not allow detailed combined use of IVUS and OCT allows more accurate examination of the distribution of culprit lesions and inves- detection of high-risk plaques (30,31). In addition, a cath- tigation of the association between plaque rupture and local eter that would combine an IVUS with an OCT probe 1372 Bourantas et al. JACC Vol. 61, No. 13, 2013 Applications of Hybrid Intravascular Imaging April 2, 2013:1369–78

Figure 2 Data Acquired by a Combined IVUS and NIRS Catheter

The output of the near-infrared spectroscopic (NIRS) catheter is illustrated (A, chemogram; B, block chemogram). The yellow-red color-coded map illustrates the probability of the presence of a lipid core (yellow corresponds to high probability and red to low probability). (C) Coregistration of the intravascular ultrasound (IVUS) and NIRS data. The lilac and blue lines mark the anatomical position of frames (D) and (E) on IVUS and on the chemogram. (D, E) IVUS cross-sections with the corresponding chemogram obtained in a stented and a nonstented segment, respectively. The probability of the presence of a lipid-rich plaque is low in the stented segment but high in the frame portrayed in E (high probability between 1 and 7 o’clock). ep ϭ echolucent plaque; ss ϭ stent struts. §Area with insufficient NIRS signal. would also be useful in planning and assessing the outcome of demonstrated that this combination is feasible, and dual- percutaneous coronary intervention, as IVUS would provide modality systems have been developed that have already information about the correct stent diameter (on the basis of been tested in vitro (Fig. 4). However, further improve- the media-adventitia dimensions), and OCT would permit a ments are required before the technique can be used in detailed evaluation of the final result and detection of dissec- clinical practice, because the designed catheters have signif- tions, stent malapposition, or the presence of thrombus. icant limitations, such as increased size, difficulties in the Although the clinical and research value of combined coregistration of the IVUS and OCT images, low OCT and IVUS and OCT imaging is apparent, there is currently no IVUS image quality, and the slow image acquisition rate such catheter for clinical applications. Some studies have (32–36). JACC Vol. 61, No. 13, 2013 Bourantas et al. 1373 April 2, 2013:1369–78 Applications of Hybrid Intravascular Imaging

Figure 3 Fusion of IVUS, NIRS Imaging, and CTCA

Fusion of computed tomographic coronary angiography (CTCA) (A), intravascular ultrasound (IVUS), and near-infrared spectroscopy (NIRS) imaging (B). The obtained model (C) allows the assessment of vessel morphology and of plaque distribution and identiﬁcation of the location of lipid-rich plaques. (D) Shear stress distribution on the luminal surface portrayed in a color coded map. Reprinted, with permission, from Wentzel et al. (24).

Combination of IVUS and IVPA imaging. Although Combination of OCT and NIRF imaging. The fusion of IVPA imaging has not been implemented in clinical prac- molecular imaging with conventional intravascular imaging tice, there are already available catheters that combine an techniques such as IVUS or OCT is expected to provide a IVUS probe and a laser delivery system and permitting more thorough evaluation of plaque vulnerability, as it would hybrid IVUS-IVPA imaging (37). The first experimental permit the simultaneous evaluation of vessel anatomy and applications have created high expectations, and we antici- plaque inflammation. A dual modality OCT-NIRF catheter pate that these catheters will allow detailed assessment of has recently been presented that allows the acquisition and vessel wall pathology, as IVUS would provide evaluation of coregistration of OCT and NIRF data (38). In vitro and in vivo the lumen, plaque, and outer vessel wall morphology and studies have confirmed the feasibility and efficacy of this device dimensions, while IVPA imaging would allow characteriza- and demonstrated the great potential of the combined microstruc- tion of the type of plaque and identification of vessel wall tural and molecular functional imaging (Fig. 5). However, further inflammation. However, the safety of this hybrid imaging evaluation of the safety of NIRF imaging is required before technique must be proved, and further development is combined OCT and NIRF imaging can be used in humans. needed to reduce the acquisition time (currently Ͼ25 Combination of IVUS and TRFS imaging. Recently, s/frame) before being applied in clinical setting. Stephens et al. (39) developed a hybrid catheter that

Figure 4 In Vitro Application of a Hybrid IVUS and OCT Catheter

Histological cross-sections obtained from a human coronary artery stained with Movat’s pentachrome (A) and hematoxylin and eosin (B). A calciﬁed superﬁcial plaque is noted that spans from 6 to 9 o’clock. (C, D) Corresponding intravascular ultrasound (IVUS) and optical coherence tomographic (OCT) images obtained during examination with a 4-F hybrid IVUS-OCT system that allows simultaneous image acquisition. Image kindly provided by B. H. Li and B. K. Courtney. 1374 Bourantas et al. JACC Vol. 61, No. 13, 2013 Applications of Hybrid Intravascular Imaging April 2, 2013:1369–78

Figure 5 Dual-Modality OCT-NIRS Catheter

Fusion of optical coherence tomographic (OCT) and near-infrared fluorescence (NIRF) data acquired using a dual-modality catheter (A). An eccentric plaque is detected by OCT, extending from 2 to 10 o’clock, while NIRF imaging demonstrates increased inflammation (indicated with a white-yellow color). Staining of the corresponding histological cross-section with hematoxylin and eosin confirms the presence of an eccentric plaque (B), whereas immunohistochemistry shows an increased cathepsin B con- centration within the plaque (C). In contrast in (D), the atheroma burden and the recorded inflammation are minor. These findings are confirmed by histology (E, F). Reprinted, with permission, from Yoo et al. (38). combines an IVUS and a TRFS probe (Fig. 6)(40). graphic data provided by CTCA and perfusion information Although in vitro applications have demonstrated the fea- given by scintigraphy permits reliable diagnosis of hemody- sibility of this dual imaging approach, the large diameter of namically significant lesions (it is more accurate than the device (5.4 F) and the fact that there are difficulties in CTCA or scintigraphy), and it can be used to plan treat- acquiring TRFS data (the TRFS catheter requires steering ment as it allows identification of the stenosis that causes and must be pushed onto the vessel wall because the TRFS ischemia in patients with stable angina and multivessel signal has poor penetration) have not allowed its in vivo disease (42,43). implementation yet (41). Recently, Rogers et al. (44), in a feasibility study, demonstrated that fusion of fluorodeoxyglucose positron emis- Comparison With Noninvasive Hybrid Imaging sion tomography and CTCA permits the detection of Hybrid intravascular imaging currently has limited applica- coronary inflammation. This innovative approach has been tions only in research. This can be attributed to the invasive used to examine the effect of treatment on vascular inflam- nature of the fused techniques, the additional time required mation, but it has poor resolution and does not allow the to integrate the data, and the fact that the methods identification of the exact location of the high-risk lesion implemented for data fusion, or the combined catheters, are (45). Advances in molecular imaging and catheter design not available in most catheterization laboratories. In con- have led to the development of new invasive techniques that trast, recently emerged noninvasive fusion imaging tech- offer accurate evaluation of plaque biology (46). Multimo- niques have already proved useful not only in research but dality imaging catheters that provide detailed visualization also in clinical practice. For example, the fusion of angio- of plaque morphology and composition and simultaneous JACC Vol. 61, No. 13, 2013 Bourantas et al. 1375 April 2, 2013:1369–78 Applications of Hybrid Intravascular Imaging

Figure 6 Hybrid IVUS-TRFS Catheter

Hybrid intravascular ultrasound (IVUS) and time-resolved fluorescence spectroscopic (TRFS) catheter (A to D). The catheter consists of a sheathed IVUS mechanical rotating probe that operates at 30 to 40 MHz, a side-viewing optical fiber (SVOF/OF) (C, D) that is placed in a 0.7-mm water-flushing lumen that occupies the position of the IVUS monorail guidewire (GW), and a steering wire (SW) that is connected to the distal end of the hybrid catheter and can be pushed forward to steer the device toward the luminal surface of the region of interest (B, D). Bimodal analysis of a carotid atherosclerotic plaque using fluorescence lifetime imaging microscopy and high- resolution ultrasound. Fluorescence lifetime microscopy allows evaluation of the intimal molecular composition and provides a biochemical map of the superficial plaque (red corresponds to fibrous plaque, yellow to fibrolipid, and cyan to normal endothelium) (E). By overlaying the fluorescence lifetime microscopic image onto the ultrasound image, it is possible to coregister the intimal biochemical features with the underlying plaque morphology and microstructure (F). Reprinted, with permission, and adapted from Stephens et al. (39) and Sun et al. (40). detection of plaque inflammation are currently available detailed visualization of plaque pathology (47,48). In par- (e.g., catheters that permit concurrent IVUS and IVPA data allel, numerous hybrid modalities have emerged that appear acquisition or combined optical computed tomographic and able to address the drawbacks of the available intravascular NIRF imaging) and are expected to allow us to recognize approaches through the combination of imaging techniques mechanisms of vascular inflammation, understand its role in with complementary strengths and weaknesses (Table 1 plaque destabilization, investigate the effects of new phar- [41,49–57]). Most of the hybrid imaging systems are maceutical and invasive treatments, and probably predict currently in the hands of a few research groups and have not future culprit lesions. been incorporated in user-friendly commercial software that would permit their use in everyday practice. However, Future Perspectives in Intravascular Imaging things are likely to change in the future. Dual-modality It is very difficult to predict the evolution of intravascular catheters that provide simultaneous IVUS-NIRS, IVUS- imaging and foresee the dominant invasive imaging modal- IVPA, or IVUS-OCT data are expected to allow more ities of the future. Over the past few years, an effort has been accurate plaque characterization than IVUS, IVUS radio- made to overcome the limitations of the prominent intra- frequency backscatter analysis, or OCT, while the hybrid vascular techniques by developing new methodologies that IVUS-IVPA and OCT-NIRF systems are anticipated to be allow better processing of the acquired data (e.g., focal superior to OCT in the assessment of the association between acoustic computed tomography to improve the radial reso- plaque characteristics and vessel wall inflammation. The Achil- lution of IVUS, micro-OCT to visualize cellular and sub- les’ heel of multimodality imaging, which is the difficulty to cellular features associated with atherogenesis, polarized miniaturize intravascular devices and processes and integrate sensitive OCT to quantify plaque collagen) and more different information, is expected to be addressed by upcoming 1376 Bourantas et al. JACC Vol. 61, No. 13, 2013 Applications of Hybrid Intravascular Imaging April 2, 2013:1369–78

AdvantagesTable 1 andAdvantages Limitations and of Limitations the Available of the Hybrid Available Intravascular Hybrid Intravascular Imaging Techniques Imaging Techniques

Visualization Identification of Detection Representation of the Imaging and Features Associated of the Detection of Hybrid Intravascular of Vessel Distribution Quantification of Plaque With Increased Culprit Vessel Wall Imaging Modality Geometry of Plaque Atheroma Characterization Vulnerability Lesion Inflammation IVUS ϩ x-ray angiography ϩϩϩ (6–8) ϩϩϩ (13,14) ϩϩϩ (13) ϩ (49) ϩ (50) ϩ (51) — IVUS/RF-IVUS ϩ CTCA ϩϩϩ (18–20) ϩϩϩ (18–20) ϩϩϩ (19,20,52) ϩϩ (20,49,52) ϩϩ (50,53) ϩ (51) — IVUS ϩ NIRS imaging — — ϩϩϩ (52) ϩϩ (49,54) ϩϩ (50,54) ϩ (51) — IVUS ϩ NIRS imaging ϩ CTCA ϩϩϩ (24) ϩϩϩ (24) ϩϩϩ (24,52) ϩϩ (49,54) ϩϩ (50,54) ϩ (51) — OCT ϩ x-ray angiography ϩϩϩ (26) ϩ (26) ϩ (55) ϩϩ (49,55) ϩϩ (50,53,55) ϩϩϩ (51) ϩ (55) IVUS ϩ OCT — — ϩϩϩ (52) ϩϩϩ (30,31) ϩϩϩ (30,31) ϩϩϩ (51) ϩ (55) IVUS ϩ IVPA imaging* — — ϩϩϩ (52) ϩϩ (56) ϩϩ (56) ϩ (51) ϩϩ (56) OCT ϩ NIRF imaging* — — ϩ (55) ϩϩ (49,55) ϩϩ (50,53,55) ϩϩϩ (51) ϩϩϩ (55,57) IVUS ϩ TRFS imaging* — — ϩϩϩ (52) ϩϩ (41,49) ϩϩ (49,58) ϩ (51) ϩϩ (49,58)

Methods’ ability to identify plaque characteristics is graded as unable (—), low capability (ϩ), moderate capability (ϩϩ), and high capability (ϩϩϩ). CTCA ϭ computed tomographic coronary angiography; IVPA ϭ intravascular photoacoustic; IVUS ϭ intravascular ultrasound; NIRF ϭ near-infrared ﬂuorescence; NIRS ϭ near-infrared spectroscopic; OCT ϭ optical coherence tomography; RF-IVUS ϭ radiofrequency backscatter analysis of intravascular ultrasound signal; TRFS ϭ time-resolved ﬂuorescence spectroscopic. *These modalities are in their infancy, and therefore the data provided for these techniques are derived from small histology-based in vitro studies. technological advances that will enhance its application in the undertaken in upcoming years in inventing new imaging study of atherosclerosis. techniques, advancing catheter design, and developing Currently, there is a trend toward noninvasive imaging innovative fusion methodologies that will reveal unknown modalities, because these techniques are associated with aspects of plaque pathophysiology. Hybrid intravascular minimal risk for complications and allow complete study of imaging has a prosperous future and is anticipated to the coronary tree. Although they cannot provide details constitute a valuable and indispensable ally in this challeng- about luminal morphology and plaque, the fact that they can ing quest. be used in asymptomatic patients has attracted attention, and currently, broad-scale studies are under way that im- Reprint requests and correspondence: Dr. Patrick W. Serruys, plement CTCA to identify predictors of future cardiovas- Thoraxcenter, Erasmus Medical Center, ’s-Gravendijkwal 230, cular events (58). 3015 CE Rotterdam, the Netherlands. E-mail: p.w.j.c.serruys@ In this setting, and judging from our previous research erasmusmc.nl, OR Dr. Hector M. Garcia-Garcia, Thoraxcenter, experience, hybrid intravascular imaging will need time to Erasmus MC, z120 Dr. Molerwaterplein 403015 GD Rotterdam, be established and is anticipated to be restricted to small- the Netherlands. E-mail: [email protected]. scale studies. Although the implications of the composition of plaque and of rheology on the atherosclerotic evolution have been evident for many years, the Providing Regional REFERENCES Observations to Study Predictors of Events in the Coronary 1. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovas- Tree (PROSPECT) and PREDICTION trials have just cular diseases: part I: general considerations, the epidemiologic tran- recently been reported. The need to visualize with an sition, risk factors, and impact of urbanization. Circulation 2001;104: 2746–53. intravascular modality all 3 coronary arteries, the increased 2. Stone GW, Maehara A, Lansky AJ, et al. A prospective natural- time required to process the overwhelming data provided, as history study of coronary atherosclerosis. N Engl J Med 2011;364: well as our low capability to predict future culprit lesions 226–35. 3. Suter MJ, Nadkarni SK, Weisz G, et al. Intravascular optical imaging and the lack of evidence about how we should treat these technology for investigating the coronary artery. J Am Coll Cardiol patients, are considerations that at least at this stage will Img 2011;4:1022–39. hamper the conduction of invasive, large-scale studies of the 4. Puri R, Worthley MI, Nicholls SJ. Intravascular imaging of vulnerable coronary plaque: current and future concepts. Nat Rev Cardiol natural history of atherosclerosis. 2011;8:131–9. 5. Klein HM, Gunther RW, Verlande M, et al. 3D-surface reconstruc- Conclusions tion of intravascular ultrasound images using personal computer hardware and a motorized catheter control. Cardiovasc Intervent Cardiovascular research has focused in recent years on the Radiol 1992;15:97–101. 6. Wahle A, Prause GPM, DeJong SC, Sonka M. 3-D fusion of biplane study of coronary atherosclerosis, aiming to predict its angiography and intravascular ultrasound for accurate visualization and evolution and identify future culprit lesions. Consequently, volumetry. Lect Notes Comput Sc 1998;1496:146–55. considerable effort has been made to thoroughly visualize 7. Bourantas CV, Kourtis IC, Plissiti ME, et al. A method for 3D reconstruction of coronary arteries using biplane angiography and the coronary anatomy and pathology and understand in intravascular ultrasound images. Comput Med Imaging Graph 2005; detail the effect of local and systemic factors on plaque 29:597–606. progression. Although currently, hybrid intravascular imag- 8. Slager CJ, Wentzel JJ, Schuurbiers JC, et al. True 3-dimensional reconstruction of coronary arteries in patients by fusion of angiography ing has limited clinical and research applications, it has and IVUS (ANGUS) and its quantitative validation. Circulation considerable future potential. Further effort is expected to be 2000;102:511–6. JACC Vol. 61, No. 13, 2013 Bourantas et al. 1377 April 2, 2013:1369–78 Applications of Hybrid Intravascular Imaging

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